Fran Lowry

ORLANDO — Every patient with type 1 or type 2 diabetes should be screened annually for the presence of diabetic kidney disease, according to comprehensive guidelines developed by the National Kidney Foundation as part of its Kidney Disease Outcomes Quality Initiative.

The clinical practice guidelines offer “simple, clear messages about managing risk factors not only for kidney disease but also for cardiovascular disease,” Dr. Katherine R. Tuttle said at a meeting sponsored by the National Kidney Foundation.

The working group that drafted the guidelines included representatives of the American College of Physicians, the American Diabetes Association, and the American Heart Association, as well as the NKF. An estimated 21 million people in the United States have diabetes and over half of them have kidney damage. The incidence of diabetic kidney disease is expected to double by the year 2030.

The guidelines recommend measurements of urinary albumin-to-creatinine ratio in a spot urine sample, and measurement of serum creatinine to estimate the glomerular filtration rate.

“We recommended a spot urine sample rather than 24-hour urine collection so that this [measurement] can actually be done in an internist's or other primary care provider's office. Plus, it's cheap,” said Dr. Tuttle, medical and scientific director of research at Providence Medical Research Center, Spokane, Wash.

The guidelines are available online at www.kdoqi.org

ORLANDO — Every patient with type 1 or type 2 diabetes should be screened annually for the presence of diabetic kidney disease, according to comprehensive guidelines developed by the National Kidney Foundation as part of its Kidney Disease Outcomes Quality Initiative.

The clinical practice guidelines offer “simple, clear messages about managing risk factors not only for kidney disease but also for cardiovascular disease,” Dr. Katherine R. Tuttle said at a meeting sponsored by the National Kidney Foundation.

The working group that drafted the guidelines included representatives of the American College of Physicians, the American Diabetes Association, and the American Heart Association, as well as the NKF. An estimated 21 million people in the United States have diabetes and over half of them have kidney damage. The incidence of diabetic kidney disease is expected to double by the year 2030.

The guidelines recommend measurements of urinary albumin-to-creatinine ratio in a spot urine sample, and measurement of serum creatinine to estimate the glomerular filtration rate.

“We recommended a spot urine sample rather than 24-hour urine collection so that this [measurement] can actually be done in an internist's or other primary care provider's office. Plus, it's cheap,” said Dr. Tuttle, medical and scientific director of research at Providence Medical Research Center, Spokane, Wash.

The guidelines are available online at www.kdoqi.org

ORLANDO — Every patient with type 1 or type 2 diabetes should be screened annually for the presence of diabetic kidney disease, according to comprehensive guidelines developed by the National Kidney Foundation as part of its Kidney Disease Outcomes Quality Initiative.

The clinical practice guidelines offer “simple, clear messages about managing risk factors not only for kidney disease but also for cardiovascular disease,” Dr. Katherine R. Tuttle said at a meeting sponsored by the National Kidney Foundation.

The working group that drafted the guidelines included representatives of the American College of Physicians, the American Diabetes Association, and the American Heart Association, as well as the NKF. An estimated 21 million people in the United States have diabetes and over half of them have kidney damage. The incidence of diabetic kidney disease is expected to double by the year 2030.

The guidelines recommend measurements of urinary albumin-to-creatinine ratio in a spot urine sample, and measurement of serum creatinine to estimate the glomerular filtration rate.

“We recommended a spot urine sample rather than 24-hour urine collection so that this [measurement] can actually be done in an internist's or other primary care provider's office. Plus, it's cheap,” said Dr. Tuttle, medical and scientific director of research at Providence Medical Research Center, Spokane, Wash.

The guidelines are available online at www.kdoqi.org

A new technique for delivering an old nonsteroidal anti-inflammatory drug is just as effective as oral celecoxib for relieving the pain of knee osteoarthritis, German researchers report.

The NSAID ketoprofen, approved in both the United States and Europe, when combined in a gel that is capable of penetrating the skin directly to arthritic joints, was significantly better than placebo and comparable with celecoxib in relieving pain associated with an acute flare of knee osteoarthritis. Moreover, it did so without entering the systemic circulation, said Dr. Matthias Rother, head of research and development of IDEA AG, Munich, Germany, and colleagues.

The toxicities of systemic NSAID treatment are well known, and the newer COX-2 inhibitors are associated with elevated cardiovascular risks. Hence, the need for safer therapies, the investigators wrote.

The new technology, called Transfersome, is a special gel made up of nanoparticles too large to be absorbed into the microcirculatory barrier of the skin, Dr. Rother said in a telephone interview.

Numerous gel and cream NSAID preparations are available in Europe. All work by diffusion, with the drugs absorbed systemically when they are applied to the skin. But when an NSAID, in this case ketoprofen, is mixed with the nanoparticle gel, it is able to penetrate into deep muscle and joints and be released. The mixture of ketoprofen and Transfersomes is called IDEA-033, Dr. Rother said.

“Transfersomes are ultradeformable carriers loaded with an active substance and applied epicutaneously in an aqueous suspension. Once they are on the skin, the water in the suspension begins to evaporate, and this draws the carriers containing ketoprofen through the skin barrier to the specific target areas,” he explained.

To compare this form of ketoprofen delivery with celecoxib and placebo in the relief of knee OA, the investigators randomized patients for at least 6 months to either 110 mg epicutaneous ketoprofen in 4.8 g Transfersome plus oral placebo (138 patients), 100 mg oral celecoxib plus placebo gel (132 patients), or both placebo formulations (127 patients) twice a day for 6 weeks.

Efficacy was assessed by measuring the changes in the Western Ontario and McMaster Universities (WOMAC) Index of Osteoarthritis pain subscale, physical function subscale, and patient global assessment (PGA) of response from baseline to the end of the study, in the index knee.

Overall, the mean WOMAC pain subscale scores were reduced by 18.2 in patients who received IDEA-033, by 20.3 in patients who received celecoxib, and by 9.9 in those patients who received placebo.

The mean physical function subscale score was reduced by 14.6 in patients who received IDEA-033, 16.6 in those receiving celecoxib, and 10.2 in the placebo group.

The mean PGA of response scores were 1.8 in the IDEA-033 group, 1.7 in the celecoxib group, and 1.3 in the placebo group.

The differences in change between IDEA-033 and placebo were statistically significant for pain subscale (P = .0041) and PGA of response (P = .0015).

Gastrointestinal adverse events with IDEA-033 were similar to placebo, the investigators wrote. No GI bleeding occurred. The rate of nonserious GI adverse events for IDEA-033, at 9.4%, was similar to placebo and numerically lower than for celecoxib (13.6%).

One patient treated with celecoxib had a myocardial infarction, one patient treated with placebo had angina, and no serious cardiovascular events occurred in patients treated with IDEA-033.

The IDEA-033 patients had more erythema and more skin irritations than the group receiving placebo gel, the investigators added (ARD Online First, published online by the British Medical Journal on March 15, 2007, as 10.1136/ard.2006.065128).

Systemic exposure in the IDEA-033 group was between 1% and 5%, compared with that of celecoxib, Dr. Rother said.

A new technique for delivering an old nonsteroidal anti-inflammatory drug is just as effective as oral celecoxib for relieving the pain of knee osteoarthritis, German researchers report.

The NSAID ketoprofen, approved in both the United States and Europe, when combined in a gel that is capable of penetrating the skin directly to arthritic joints, was significantly better than placebo and comparable with celecoxib in relieving pain associated with an acute flare of knee osteoarthritis. Moreover, it did so without entering the systemic circulation, said Dr. Matthias Rother, head of research and development of IDEA AG, Munich, Germany, and colleagues.

The toxicities of systemic NSAID treatment are well known, and the newer COX-2 inhibitors are associated with elevated cardiovascular risks. Hence, the need for safer therapies, the investigators wrote.

The new technology, called Transfersome, is a special gel made up of nanoparticles too large to be absorbed into the microcirculatory barrier of the skin, Dr. Rother said in a telephone interview.

Numerous gel and cream NSAID preparations are available in Europe. All work by diffusion, with the drugs absorbed systemically when they are applied to the skin. But when an NSAID, in this case ketoprofen, is mixed with the nanoparticle gel, it is able to penetrate into deep muscle and joints and be released. The mixture of ketoprofen and Transfersomes is called IDEA-033, Dr. Rother said.

“Transfersomes are ultradeformable carriers loaded with an active substance and applied epicutaneously in an aqueous suspension. Once they are on the skin, the water in the suspension begins to evaporate, and this draws the carriers containing ketoprofen through the skin barrier to the specific target areas,” he explained.

To compare this form of ketoprofen delivery with celecoxib and placebo in the relief of knee OA, the investigators randomized patients for at least 6 months to either 110 mg epicutaneous ketoprofen in 4.8 g Transfersome plus oral placebo (138 patients), 100 mg oral celecoxib plus placebo gel (132 patients), or both placebo formulations (127 patients) twice a day for 6 weeks.

Efficacy was assessed by measuring the changes in the Western Ontario and McMaster Universities (WOMAC) Index of Osteoarthritis pain subscale, physical function subscale, and patient global assessment (PGA) of response from baseline to the end of the study, in the index knee.

Overall, the mean WOMAC pain subscale scores were reduced by 18.2 in patients who received IDEA-033, by 20.3 in patients who received celecoxib, and by 9.9 in those patients who received placebo.

The mean physical function subscale score was reduced by 14.6 in patients who received IDEA-033, 16.6 in those receiving celecoxib, and 10.2 in the placebo group.

The mean PGA of response scores were 1.8 in the IDEA-033 group, 1.7 in the celecoxib group, and 1.3 in the placebo group.

The differences in change between IDEA-033 and placebo were statistically significant for pain subscale (P = .0041) and PGA of response (P = .0015).

Gastrointestinal adverse events with IDEA-033 were similar to placebo, the investigators wrote. No GI bleeding occurred. The rate of nonserious GI adverse events for IDEA-033, at 9.4%, was similar to placebo and numerically lower than for celecoxib (13.6%).

One patient treated with celecoxib had a myocardial infarction, one patient treated with placebo had angina, and no serious cardiovascular events occurred in patients treated with IDEA-033.

The IDEA-033 patients had more erythema and more skin irritations than the group receiving placebo gel, the investigators added (ARD Online First, published online by the British Medical Journal on March 15, 2007, as 10.1136/ard.2006.065128).

Systemic exposure in the IDEA-033 group was between 1% and 5%, compared with that of celecoxib, Dr. Rother said.

A new technique for delivering an old nonsteroidal anti-inflammatory drug is just as effective as oral celecoxib for relieving the pain of knee osteoarthritis, German researchers report.

The NSAID ketoprofen, approved in both the United States and Europe, when combined in a gel that is capable of penetrating the skin directly to arthritic joints, was significantly better than placebo and comparable with celecoxib in relieving pain associated with an acute flare of knee osteoarthritis. Moreover, it did so without entering the systemic circulation, said Dr. Matthias Rother, head of research and development of IDEA AG, Munich, Germany, and colleagues.

The toxicities of systemic NSAID treatment are well known, and the newer COX-2 inhibitors are associated with elevated cardiovascular risks. Hence, the need for safer therapies, the investigators wrote.

The new technology, called Transfersome, is a special gel made up of nanoparticles too large to be absorbed into the microcirculatory barrier of the skin, Dr. Rother said in a telephone interview.

Numerous gel and cream NSAID preparations are available in Europe. All work by diffusion, with the drugs absorbed systemically when they are applied to the skin. But when an NSAID, in this case ketoprofen, is mixed with the nanoparticle gel, it is able to penetrate into deep muscle and joints and be released. The mixture of ketoprofen and Transfersomes is called IDEA-033, Dr. Rother said.

“Transfersomes are ultradeformable carriers loaded with an active substance and applied epicutaneously in an aqueous suspension. Once they are on the skin, the water in the suspension begins to evaporate, and this draws the carriers containing ketoprofen through the skin barrier to the specific target areas,” he explained.

To compare this form of ketoprofen delivery with celecoxib and placebo in the relief of knee OA, the investigators randomized patients for at least 6 months to either 110 mg epicutaneous ketoprofen in 4.8 g Transfersome plus oral placebo (138 patients), 100 mg oral celecoxib plus placebo gel (132 patients), or both placebo formulations (127 patients) twice a day for 6 weeks.

Efficacy was assessed by measuring the changes in the Western Ontario and McMaster Universities (WOMAC) Index of Osteoarthritis pain subscale, physical function subscale, and patient global assessment (PGA) of response from baseline to the end of the study, in the index knee.

Overall, the mean WOMAC pain subscale scores were reduced by 18.2 in patients who received IDEA-033, by 20.3 in patients who received celecoxib, and by 9.9 in those patients who received placebo.

The mean physical function subscale score was reduced by 14.6 in patients who received IDEA-033, 16.6 in those receiving celecoxib, and 10.2 in the placebo group.

The mean PGA of response scores were 1.8 in the IDEA-033 group, 1.7 in the celecoxib group, and 1.3 in the placebo group.

The differences in change between IDEA-033 and placebo were statistically significant for pain subscale (P = .0041) and PGA of response (P = .0015).

Gastrointestinal adverse events with IDEA-033 were similar to placebo, the investigators wrote. No GI bleeding occurred. The rate of nonserious GI adverse events for IDEA-033, at 9.4%, was similar to placebo and numerically lower than for celecoxib (13.6%).

One patient treated with celecoxib had a myocardial infarction, one patient treated with placebo had angina, and no serious cardiovascular events occurred in patients treated with IDEA-033.

The IDEA-033 patients had more erythema and more skin irritations than the group receiving placebo gel, the investigators added (ARD Online First, published online by the British Medical Journal on March 15, 2007, as 10.1136/ard.2006.065128).

Systemic exposure in the IDEA-033 group was between 1% and 5%, compared with that of celecoxib, Dr. Rother said.

ORLANDO — Chronic use of nonsteroidal anti-inflammatory agents promotes sodium-retention weight gain and can cause blood pressure to rise by an average of 5 mm Hg, Dr. Matthew R. Weir said at a meeting sponsored by the National Kidney Foundation.

The increase is “not insignificant” when one considers how widely used these drugs are, said Dr. Weir, professor of medicine at the University of Maryland, Baltimore.

Most clinicians are familiar with the renal syndromes caused by NSAIDs and tend to be concerned about kidney disease or dysfunction. But these effects tend to be reversible.

The effects of NSAIDs on blood pressure may pose a more serious issue, Dr. Weir said. “One has to view NSAIDs as antinatriuretic compounds. This is a concern because, depending on how much salt you eat, the actual dose of the NSAID you are taking, and your preexisting levels of blood pressure, you can get very different effects on overall changes in blood pressure over time.”

The age-related changes in renal blood supply that occur over time may be an important issue in older patients, who are more likely to be using NSAIDs to relieve the pain of chronic conditions such as arthritis.

To avoid adverse cardiovascular effects, always use the lowest possible dose of anti-inflammatory drug, regardless of class. Consider using shorter-acting agents, which may allow the kidney to restore its sodium and water balance, he advised.

Counsel patients taking NSAIDs to try to avoid dietary sodium. “Quite clearly, when you give chemicals that engender sodium sensitivity … you should tell your patients that they really need to avoid dietary sodium as best they can,” said Dr. Weir.

Blood pressure must be monitored carefully in persons taking NSAIDs, and blood pressure medications adjusted accordingly. Calcium channel blockers in particular appear to retain their lowering effect on blood pressure despite chronic NSAID use.

“We are not sure why, but calcium channel blockers may have natriuretic properties that are independent of so-called prostaglandin-dependent mechanisms within the kidney. We studied this years ago and found that calcium channel blockers helped alleviate any blood pressure-associated change with nonsteroidal anti-inflammatory drugs,” Dr. Weir said.

Nonprescription drugs should not be overlooked, he added. “We should take a careful history on the use of over-the-counter NSAIDs. They don't often appear on medication lists.”

Calcium channel blockers have been shown to help alleviate any blood pressure-related change with NSAIDs. DR. WEIR

ORLANDO — Chronic use of nonsteroidal anti-inflammatory agents promotes sodium-retention weight gain and can cause blood pressure to rise by an average of 5 mm Hg, Dr. Matthew R. Weir said at a meeting sponsored by the National Kidney Foundation.

The increase is “not insignificant” when one considers how widely used these drugs are, said Dr. Weir, professor of medicine at the University of Maryland, Baltimore.

Most clinicians are familiar with the renal syndromes caused by NSAIDs and tend to be concerned about kidney disease or dysfunction. But these effects tend to be reversible.

The effects of NSAIDs on blood pressure may pose a more serious issue, Dr. Weir said. “One has to view NSAIDs as antinatriuretic compounds. This is a concern because, depending on how much salt you eat, the actual dose of the NSAID you are taking, and your preexisting levels of blood pressure, you can get very different effects on overall changes in blood pressure over time.”

The age-related changes in renal blood supply that occur over time may be an important issue in older patients, who are more likely to be using NSAIDs to relieve the pain of chronic conditions such as arthritis.

To avoid adverse cardiovascular effects, always use the lowest possible dose of anti-inflammatory drug, regardless of class. Consider using shorter-acting agents, which may allow the kidney to restore its sodium and water balance, he advised.

Counsel patients taking NSAIDs to try to avoid dietary sodium. “Quite clearly, when you give chemicals that engender sodium sensitivity … you should tell your patients that they really need to avoid dietary sodium as best they can,” said Dr. Weir.

Blood pressure must be monitored carefully in persons taking NSAIDs, and blood pressure medications adjusted accordingly. Calcium channel blockers in particular appear to retain their lowering effect on blood pressure despite chronic NSAID use.

“We are not sure why, but calcium channel blockers may have natriuretic properties that are independent of so-called prostaglandin-dependent mechanisms within the kidney. We studied this years ago and found that calcium channel blockers helped alleviate any blood pressure-associated change with nonsteroidal anti-inflammatory drugs,” Dr. Weir said.

Nonprescription drugs should not be overlooked, he added. “We should take a careful history on the use of over-the-counter NSAIDs. They don't often appear on medication lists.”

Calcium channel blockers have been shown to help alleviate any blood pressure-related change with NSAIDs. DR. WEIR

ORLANDO — Chronic use of nonsteroidal anti-inflammatory agents promotes sodium-retention weight gain and can cause blood pressure to rise by an average of 5 mm Hg, Dr. Matthew R. Weir said at a meeting sponsored by the National Kidney Foundation.

The increase is “not insignificant” when one considers how widely used these drugs are, said Dr. Weir, professor of medicine at the University of Maryland, Baltimore.

Most clinicians are familiar with the renal syndromes caused by NSAIDs and tend to be concerned about kidney disease or dysfunction. But these effects tend to be reversible.

The effects of NSAIDs on blood pressure may pose a more serious issue, Dr. Weir said. “One has to view NSAIDs as antinatriuretic compounds. This is a concern because, depending on how much salt you eat, the actual dose of the NSAID you are taking, and your preexisting levels of blood pressure, you can get very different effects on overall changes in blood pressure over time.”

The age-related changes in renal blood supply that occur over time may be an important issue in older patients, who are more likely to be using NSAIDs to relieve the pain of chronic conditions such as arthritis.

To avoid adverse cardiovascular effects, always use the lowest possible dose of anti-inflammatory drug, regardless of class. Consider using shorter-acting agents, which may allow the kidney to restore its sodium and water balance, he advised.

Counsel patients taking NSAIDs to try to avoid dietary sodium. “Quite clearly, when you give chemicals that engender sodium sensitivity … you should tell your patients that they really need to avoid dietary sodium as best they can,” said Dr. Weir.

Blood pressure must be monitored carefully in persons taking NSAIDs, and blood pressure medications adjusted accordingly. Calcium channel blockers in particular appear to retain their lowering effect on blood pressure despite chronic NSAID use.

“We are not sure why, but calcium channel blockers may have natriuretic properties that are independent of so-called prostaglandin-dependent mechanisms within the kidney. We studied this years ago and found that calcium channel blockers helped alleviate any blood pressure-associated change with nonsteroidal anti-inflammatory drugs,” Dr. Weir said.

Nonprescription drugs should not be overlooked, he added. “We should take a careful history on the use of over-the-counter NSAIDs. They don't often appear on medication lists.”

Calcium channel blockers have been shown to help alleviate any blood pressure-related change with NSAIDs. DR. WEIR

ORLANDO — For hemodialysis patients with diabetes who refuse to take insulin at home, delivering insulin during dialysis is a good way to improve glycemic control, researchers reported at a meeting sponsored by the National Kidney Foundation.

Patients with diabetes make up roughly half of the end-stage renal disease (ESRD) population in the United States, and good glycemic control is essential to slow the progression of both microvascular and macrovascular disease.

But sometimes, having to take insulin is just too much for these patients, said Dr. Kalyana Janga of Maimonides Medical Center, New York. “It's like the straw that broke the camel's back. Dialysis patients with diabetes can be very noncompliant. They have to take so many different medications and they can be very dissatisfied with the complexity of their treatment.”

When such a patient came to his dialysis center, Dr. Janga and his associates decided to try a novel approach for delivering insulin. Postulating that Lantus, a long-acting insulin, would continue to exert its effect until the next dialysis treatment and thereby improve glycemic control, they persuaded the patient to allow the dialysis nurse to give him his insulin after his dialysis session.

The patient was 72 years old and had been on maintenance hemodialysis for 3 years. In addition to being hypertensive and having coronary artery disease, the patient had poor glycemic control despite being on maximum doses of two oral hypoglycemic agents. He had had type 2 diabetes for 20 years, Dr. Janga said.

“His fasting glucose was more than 200 mg/dL, and greater than 250 mg/dL prelunch. His hemoglobin A_1c was 13.3%. He refused to take insulin at home; he was afraid to take it.”

The patient was placed on a regimen of Lantus three times a week post dialysis. Lantus was begun at 5 units and progressively increased to 17 units after each dialysis, based on fasting glucose levels which the patient measured at home, and on prelunch glucose levels measured at dialysis.

After 3 months, the fasting blood glucose levels dropped to 100–110 mg/dL and the prelunch glucose levels decreased to 125–135 mg/dL. After 4 months, hemoglobin A_1c levels decreased from 13.3% to 8.4%, and at 8 months, hemoglobin A_1c had decreased even further, to 7.9%, Dr. Janga reported.

So successful was this treatment regimen that the patient was actually able to come off dialysis and became a kidney transplant recipient. “His wife donated a kidney. He's surviving and doing very well. We are so happy to see him when he visits us at the clinic,” Dr. Janga said.

He added that this type of regimen should be considered in all diabetics who are noncompliant with their insulin therapy. “Giving them their insulin when they show up at the dialysis center reduces the cost and complexity burden to these patients … If we can at least take care of their diabetes, we can do something of major importance” for them.

ORLANDO — For hemodialysis patients with diabetes who refuse to take insulin at home, delivering insulin during dialysis is a good way to improve glycemic control, researchers reported at a meeting sponsored by the National Kidney Foundation.

Patients with diabetes make up roughly half of the end-stage renal disease (ESRD) population in the United States, and good glycemic control is essential to slow the progression of both microvascular and macrovascular disease.

But sometimes, having to take insulin is just too much for these patients, said Dr. Kalyana Janga of Maimonides Medical Center, New York. “It's like the straw that broke the camel's back. Dialysis patients with diabetes can be very noncompliant. They have to take so many different medications and they can be very dissatisfied with the complexity of their treatment.”

When such a patient came to his dialysis center, Dr. Janga and his associates decided to try a novel approach for delivering insulin. Postulating that Lantus, a long-acting insulin, would continue to exert its effect until the next dialysis treatment and thereby improve glycemic control, they persuaded the patient to allow the dialysis nurse to give him his insulin after his dialysis session.

The patient was 72 years old and had been on maintenance hemodialysis for 3 years. In addition to being hypertensive and having coronary artery disease, the patient had poor glycemic control despite being on maximum doses of two oral hypoglycemic agents. He had had type 2 diabetes for 20 years, Dr. Janga said.

“His fasting glucose was more than 200 mg/dL, and greater than 250 mg/dL prelunch. His hemoglobin A_1c was 13.3%. He refused to take insulin at home; he was afraid to take it.”

The patient was placed on a regimen of Lantus three times a week post dialysis. Lantus was begun at 5 units and progressively increased to 17 units after each dialysis, based on fasting glucose levels which the patient measured at home, and on prelunch glucose levels measured at dialysis.

After 3 months, the fasting blood glucose levels dropped to 100–110 mg/dL and the prelunch glucose levels decreased to 125–135 mg/dL. After 4 months, hemoglobin A_1c levels decreased from 13.3% to 8.4%, and at 8 months, hemoglobin A_1c had decreased even further, to 7.9%, Dr. Janga reported.

So successful was this treatment regimen that the patient was actually able to come off dialysis and became a kidney transplant recipient. “His wife donated a kidney. He's surviving and doing very well. We are so happy to see him when he visits us at the clinic,” Dr. Janga said.

He added that this type of regimen should be considered in all diabetics who are noncompliant with their insulin therapy. “Giving them their insulin when they show up at the dialysis center reduces the cost and complexity burden to these patients … If we can at least take care of their diabetes, we can do something of major importance” for them.

ORLANDO — For hemodialysis patients with diabetes who refuse to take insulin at home, delivering insulin during dialysis is a good way to improve glycemic control, researchers reported at a meeting sponsored by the National Kidney Foundation.

Patients with diabetes make up roughly half of the end-stage renal disease (ESRD) population in the United States, and good glycemic control is essential to slow the progression of both microvascular and macrovascular disease.

But sometimes, having to take insulin is just too much for these patients, said Dr. Kalyana Janga of Maimonides Medical Center, New York. “It's like the straw that broke the camel's back. Dialysis patients with diabetes can be very noncompliant. They have to take so many different medications and they can be very dissatisfied with the complexity of their treatment.”

When such a patient came to his dialysis center, Dr. Janga and his associates decided to try a novel approach for delivering insulin. Postulating that Lantus, a long-acting insulin, would continue to exert its effect until the next dialysis treatment and thereby improve glycemic control, they persuaded the patient to allow the dialysis nurse to give him his insulin after his dialysis session.

The patient was 72 years old and had been on maintenance hemodialysis for 3 years. In addition to being hypertensive and having coronary artery disease, the patient had poor glycemic control despite being on maximum doses of two oral hypoglycemic agents. He had had type 2 diabetes for 20 years, Dr. Janga said.

“His fasting glucose was more than 200 mg/dL, and greater than 250 mg/dL prelunch. His hemoglobin A_1c was 13.3%. He refused to take insulin at home; he was afraid to take it.”

The patient was placed on a regimen of Lantus three times a week post dialysis. Lantus was begun at 5 units and progressively increased to 17 units after each dialysis, based on fasting glucose levels which the patient measured at home, and on prelunch glucose levels measured at dialysis.

After 3 months, the fasting blood glucose levels dropped to 100–110 mg/dL and the prelunch glucose levels decreased to 125–135 mg/dL. After 4 months, hemoglobin A_1c levels decreased from 13.3% to 8.4%, and at 8 months, hemoglobin A_1c had decreased even further, to 7.9%, Dr. Janga reported.

So successful was this treatment regimen that the patient was actually able to come off dialysis and became a kidney transplant recipient. “His wife donated a kidney. He's surviving and doing very well. We are so happy to see him when he visits us at the clinic,” Dr. Janga said.

He added that this type of regimen should be considered in all diabetics who are noncompliant with their insulin therapy. “Giving them their insulin when they show up at the dialysis center reduces the cost and complexity burden to these patients … If we can at least take care of their diabetes, we can do something of major importance” for them.

ORLANDO — Echocardiography overestimates the true prevalence of primary pulmonary hypertension in hemodialysis patients with end-stage renal disease, according to a study presented at a meeting sponsored by the National Kidney Foundation.

For this reason, hemodialysis patients with echocardiographic evidence of pulmonary artery hypertension (PAH) should undergo right heart catheterization for confirmation, Dr. Ifeanyi Isaiah and colleagues, of Temple University, Philadelphia, wrote in a poster.

The reported prevalence of PAH in hemodialysis patients ranges from 27% to 40%, but these numbers are based on studies that relied exclusively on echocardiographic estimates of pulmonary arterial pressures to make the diagnosis.

The more accurate way of making the diagnosis is with right heart catheterization, Dr. Isaiah and colleagues wrote.

To establish the true prevalence of PAH in this population, the investigators conducted a retrospective, observational analysis of all echocardiographic and right heart catheterization studies done in their outpatient hemodialysis unit from January 2000 to December 2006.

Of the 502 patients included in the analysis, the majority (439 patients, or 87.5%) had undergone echocardiography. Pulmonary arterial pressure greater than 40 mm Hg, suggesting the presence ofPAH, was documented in 127 of the echocardiography patients (28.9%).

Data for right heart catheterization, which were available for 22 of these 127 patients, showed that 11 (50%) of them had elevated pulmonary arterial pressure.

Although the results showed that pulmonary hypertension may be overestimated, the study also “confirms a higher prevalence of pulmonary hypertension in end-stage renal disease patients receiving hemodialysis than [in] the general population,” the investigators wrote.

In addition to providing a more accurate diagnosis of PAH in hemodialysis patients, right heart catheterization is valuable in distinguishing those patients whose elevated pulmonary pressure results from heart failure from those who have isolated PAH with no heart failure, they added.

ORLANDO — Echocardiography overestimates the true prevalence of primary pulmonary hypertension in hemodialysis patients with end-stage renal disease, according to a study presented at a meeting sponsored by the National Kidney Foundation.

For this reason, hemodialysis patients with echocardiographic evidence of pulmonary artery hypertension (PAH) should undergo right heart catheterization for confirmation, Dr. Ifeanyi Isaiah and colleagues, of Temple University, Philadelphia, wrote in a poster.

The reported prevalence of PAH in hemodialysis patients ranges from 27% to 40%, but these numbers are based on studies that relied exclusively on echocardiographic estimates of pulmonary arterial pressures to make the diagnosis.

The more accurate way of making the diagnosis is with right heart catheterization, Dr. Isaiah and colleagues wrote.

To establish the true prevalence of PAH in this population, the investigators conducted a retrospective, observational analysis of all echocardiographic and right heart catheterization studies done in their outpatient hemodialysis unit from January 2000 to December 2006.

Of the 502 patients included in the analysis, the majority (439 patients, or 87.5%) had undergone echocardiography. Pulmonary arterial pressure greater than 40 mm Hg, suggesting the presence ofPAH, was documented in 127 of the echocardiography patients (28.9%).

Data for right heart catheterization, which were available for 22 of these 127 patients, showed that 11 (50%) of them had elevated pulmonary arterial pressure.

Although the results showed that pulmonary hypertension may be overestimated, the study also “confirms a higher prevalence of pulmonary hypertension in end-stage renal disease patients receiving hemodialysis than [in] the general population,” the investigators wrote.

In addition to providing a more accurate diagnosis of PAH in hemodialysis patients, right heart catheterization is valuable in distinguishing those patients whose elevated pulmonary pressure results from heart failure from those who have isolated PAH with no heart failure, they added.

ORLANDO — Echocardiography overestimates the true prevalence of primary pulmonary hypertension in hemodialysis patients with end-stage renal disease, according to a study presented at a meeting sponsored by the National Kidney Foundation.

For this reason, hemodialysis patients with echocardiographic evidence of pulmonary artery hypertension (PAH) should undergo right heart catheterization for confirmation, Dr. Ifeanyi Isaiah and colleagues, of Temple University, Philadelphia, wrote in a poster.

The reported prevalence of PAH in hemodialysis patients ranges from 27% to 40%, but these numbers are based on studies that relied exclusively on echocardiographic estimates of pulmonary arterial pressures to make the diagnosis.

The more accurate way of making the diagnosis is with right heart catheterization, Dr. Isaiah and colleagues wrote.

To establish the true prevalence of PAH in this population, the investigators conducted a retrospective, observational analysis of all echocardiographic and right heart catheterization studies done in their outpatient hemodialysis unit from January 2000 to December 2006.

Of the 502 patients included in the analysis, the majority (439 patients, or 87.5%) had undergone echocardiography. Pulmonary arterial pressure greater than 40 mm Hg, suggesting the presence ofPAH, was documented in 127 of the echocardiography patients (28.9%).

Data for right heart catheterization, which were available for 22 of these 127 patients, showed that 11 (50%) of them had elevated pulmonary arterial pressure.

Although the results showed that pulmonary hypertension may be overestimated, the study also “confirms a higher prevalence of pulmonary hypertension in end-stage renal disease patients receiving hemodialysis than [in] the general population,” the investigators wrote.

In addition to providing a more accurate diagnosis of PAH in hemodialysis patients, right heart catheterization is valuable in distinguishing those patients whose elevated pulmonary pressure results from heart failure from those who have isolated PAH with no heart failure, they added.

ORLANDO — Chronic use of non-steroidal anti-inflammatory agents promotes sodium-retention weight gain and can cause blood pressure to rise by an average of 5 mm Hg, Dr. Matthew R. Weir said at a meeting sponsored by the National Kidney Foundation.

The increase is “not insignificant” when one considers how widely used these drugs are, said Dr. Weir, professor of medicine at the University of Maryland, Baltimore.

“Depending on how much salt you eat, the actual dose of the NSAID you are taking, and your preexisting levels of blood pressure, you can get very different effects on overall changes in blood pressure over time.”

The age-related changes in renal blood supply that occur over time may be an important issue in older patients, who are more likely to be using NSAIDs for conditions such as arthritis.

To avoid adverse cardiovascular effects, always use the lowest possible dose of anti-inflammatory drug, regardless of class. Consider using shorter-acting agents, which may allow the kidney to restore its sodium and water balance, Dr. Weir advised.

Advise patients taking NSAIDs to try to avoid dietary sodium. Blood pressure must be monitored carefully in persons taking NSAIDs, and blood pressure medications adjusted accordingly.

Calcium channel blockers in particular appear to retain their lowering effect on blood pressure despite chronic NSAID use.

“We should take a careful history on the use of over-the-counter nonsteroidal anti-inflammatory drugs,” Dr. Weir concluded. “They don't often appear on medication lists.”

The increase is 'not insignificant' when one considers how widely used these drugs are. DR. WEIR

ORLANDO — Chronic use of non-steroidal anti-inflammatory agents promotes sodium-retention weight gain and can cause blood pressure to rise by an average of 5 mm Hg, Dr. Matthew R. Weir said at a meeting sponsored by the National Kidney Foundation.

The increase is “not insignificant” when one considers how widely used these drugs are, said Dr. Weir, professor of medicine at the University of Maryland, Baltimore.

“Depending on how much salt you eat, the actual dose of the NSAID you are taking, and your preexisting levels of blood pressure, you can get very different effects on overall changes in blood pressure over time.”

The age-related changes in renal blood supply that occur over time may be an important issue in older patients, who are more likely to be using NSAIDs for conditions such as arthritis.

To avoid adverse cardiovascular effects, always use the lowest possible dose of anti-inflammatory drug, regardless of class. Consider using shorter-acting agents, which may allow the kidney to restore its sodium and water balance, Dr. Weir advised.

Advise patients taking NSAIDs to try to avoid dietary sodium. Blood pressure must be monitored carefully in persons taking NSAIDs, and blood pressure medications adjusted accordingly.

Calcium channel blockers in particular appear to retain their lowering effect on blood pressure despite chronic NSAID use.

“We should take a careful history on the use of over-the-counter nonsteroidal anti-inflammatory drugs,” Dr. Weir concluded. “They don't often appear on medication lists.”

The increase is 'not insignificant' when one considers how widely used these drugs are. DR. WEIR

ORLANDO — Chronic use of non-steroidal anti-inflammatory agents promotes sodium-retention weight gain and can cause blood pressure to rise by an average of 5 mm Hg, Dr. Matthew R. Weir said at a meeting sponsored by the National Kidney Foundation.

The increase is “not insignificant” when one considers how widely used these drugs are, said Dr. Weir, professor of medicine at the University of Maryland, Baltimore.

“Depending on how much salt you eat, the actual dose of the NSAID you are taking, and your preexisting levels of blood pressure, you can get very different effects on overall changes in blood pressure over time.”

The age-related changes in renal blood supply that occur over time may be an important issue in older patients, who are more likely to be using NSAIDs for conditions such as arthritis.

To avoid adverse cardiovascular effects, always use the lowest possible dose of anti-inflammatory drug, regardless of class. Consider using shorter-acting agents, which may allow the kidney to restore its sodium and water balance, Dr. Weir advised.

Advise patients taking NSAIDs to try to avoid dietary sodium. Blood pressure must be monitored carefully in persons taking NSAIDs, and blood pressure medications adjusted accordingly.

Calcium channel blockers in particular appear to retain their lowering effect on blood pressure despite chronic NSAID use.

“We should take a careful history on the use of over-the-counter nonsteroidal anti-inflammatory drugs,” Dr. Weir concluded. “They don't often appear on medication lists.”

The increase is 'not insignificant' when one considers how widely used these drugs are. DR. WEIR

ORLANDO — Every patient with type 1 or type 2 diabetes should be screened annually for the presence of diabetic kidney disease, according to comprehensive guidelines developed by the National Kidney Foundation as part of its Kidney Disease Outcomes Quality Initiative.

The clinical practice guidelines offer “simple, clear messages about managing risk factors not only for kidney disease but also for cardiovascular disease,” Dr. Katherine R. Tuttle said at a meeting that was sponsored by the National Kidney Foundation.

The working group that drafted the guidelines included representatives of the American Diabetes Association, the American Heart Association, and the American College of Physicians, as well as the NKF.

An estimated 21 million people in the United States have diabetes and over half of them have kidney damage. The incidence of diabetic kidney disease is expected to double by the year 2030.

The guidelines recommend measurements of urinary albumin-to-creatinine ratio in a spot urine sample, and measurement of serum creatinine to estimate the glomerular filtration rate.

“We recommended a spot urine sample rather than 24-hour urine collection so that this [measurement] can actually be done in an internist's or other primary care provider's office. Plus, it's cheap,” said Dr. Tuttle, who is the medical and scientific director of research at Providence Medical Research Center, Spokane, Wash.

Screening is essential because strategies that slow or prevent chronic kidney disease and its complications are available. “Simple, clear messages are very powerful. And that's what we're after,” she said.

The guidelines, under the title “KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease” (Am. J. Kidney Dis. 2007;49[2 suppl. 2]:S12–154) are available online at www.kdoqi.org

We recommended a spot urine sample that can be done in a provider's office. 'Plus, it's cheap.' DR. TUTTLE

ORLANDO — Every patient with type 1 or type 2 diabetes should be screened annually for the presence of diabetic kidney disease, according to comprehensive guidelines developed by the National Kidney Foundation as part of its Kidney Disease Outcomes Quality Initiative.

The clinical practice guidelines offer “simple, clear messages about managing risk factors not only for kidney disease but also for cardiovascular disease,” Dr. Katherine R. Tuttle said at a meeting that was sponsored by the National Kidney Foundation.

The working group that drafted the guidelines included representatives of the American Diabetes Association, the American Heart Association, and the American College of Physicians, as well as the NKF.

An estimated 21 million people in the United States have diabetes and over half of them have kidney damage. The incidence of diabetic kidney disease is expected to double by the year 2030.

The guidelines recommend measurements of urinary albumin-to-creatinine ratio in a spot urine sample, and measurement of serum creatinine to estimate the glomerular filtration rate.

“We recommended a spot urine sample rather than 24-hour urine collection so that this [measurement] can actually be done in an internist's or other primary care provider's office. Plus, it's cheap,” said Dr. Tuttle, who is the medical and scientific director of research at Providence Medical Research Center, Spokane, Wash.

Screening is essential because strategies that slow or prevent chronic kidney disease and its complications are available. “Simple, clear messages are very powerful. And that's what we're after,” she said.

The guidelines, under the title “KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease” (Am. J. Kidney Dis. 2007;49[2 suppl. 2]:S12–154) are available online at www.kdoqi.org

We recommended a spot urine sample that can be done in a provider's office. 'Plus, it's cheap.' DR. TUTTLE

ORLANDO — Every patient with type 1 or type 2 diabetes should be screened annually for the presence of diabetic kidney disease, according to comprehensive guidelines developed by the National Kidney Foundation as part of its Kidney Disease Outcomes Quality Initiative.

The clinical practice guidelines offer “simple, clear messages about managing risk factors not only for kidney disease but also for cardiovascular disease,” Dr. Katherine R. Tuttle said at a meeting that was sponsored by the National Kidney Foundation.

The working group that drafted the guidelines included representatives of the American Diabetes Association, the American Heart Association, and the American College of Physicians, as well as the NKF.

An estimated 21 million people in the United States have diabetes and over half of them have kidney damage. The incidence of diabetic kidney disease is expected to double by the year 2030.

The guidelines recommend measurements of urinary albumin-to-creatinine ratio in a spot urine sample, and measurement of serum creatinine to estimate the glomerular filtration rate.

“We recommended a spot urine sample rather than 24-hour urine collection so that this [measurement] can actually be done in an internist's or other primary care provider's office. Plus, it's cheap,” said Dr. Tuttle, who is the medical and scientific director of research at Providence Medical Research Center, Spokane, Wash.

Screening is essential because strategies that slow or prevent chronic kidney disease and its complications are available. “Simple, clear messages are very powerful. And that's what we're after,” she said.

The guidelines, under the title “KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease” (Am. J. Kidney Dis. 2007;49[2 suppl. 2]:S12–154) are available online at www.kdoqi.org

We recommended a spot urine sample that can be done in a provider's office. 'Plus, it's cheap.' DR. TUTTLE

ORLANDO — Many patients with colorectal cancer are willing to undergo adjuvant chemotherapy in the hopes of warding off a recurrence, even though the likelihood of recurrence is slight.

In a survey of 150 patients, just over one-third of those who had received adjuvant chemotherapy with 5-fluorouracil and oxaliplatin said they would go through chemotherapy again to reduce their chance of cancer relapse by 1%, and 57% said they would be treated again for a 3% reduction, said Dr. Neil Love, president of Research to Practice, an oncology education company in Miami, at a symposium on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

At the other end of the spectrum, even when chemotherapy would result in a 1 in 10 chance that they would avoid relapse, about 10% of patients said they would forgo treatment, he said at the symposium, also sponsored by the AGA Institute, the American Society for Therapeutic Radiology and Oncology, and the Society of Surgical Oncology.

These responses came after the patients were given educational CDs and videos, and had the opportunity to talk with oncologists about adjuvant chemotherapy.

Dr. Love and his associates did a parallel survey of 150 oncologists and clinical investigators who specialized in gastrointestinal cancers, asking them to predict what their patients would choose. The oncologists and investigators thought that far fewer patients, just 19%, would choose to undergo chemotherapy for a 1% reduction in cancer recurrence risk.

More than half the patients in the survey expected to have severe nausea and vomiting and lose their hair as a result of their chemotherapy, despite being told otherwise by their doctors. “Patients seem to be getting a lot of misinformation from friends and relatives about the chemotherapy that is used for colorectal cancer, which usually doesn't cause those side effects because of the medications we have today,” Dr. Love said.

These results suggest that “doctors are not getting the right information across to their patients [and] that patients may be far more willing to receive cytotoxic therapy for what others might view as modest potential treatment benefits,” he said.

'Patients may be far more willing to receive cytotoxic therapy for what others might view as modest … benefits.' DR. LOVE

ORLANDO — Many patients with colorectal cancer are willing to undergo adjuvant chemotherapy in the hopes of warding off a recurrence, even though the likelihood of recurrence is slight.

In a survey of 150 patients, just over one-third of those who had received adjuvant chemotherapy with 5-fluorouracil and oxaliplatin said they would go through chemotherapy again to reduce their chance of cancer relapse by 1%, and 57% said they would be treated again for a 3% reduction, said Dr. Neil Love, president of Research to Practice, an oncology education company in Miami, at a symposium on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

At the other end of the spectrum, even when chemotherapy would result in a 1 in 10 chance that they would avoid relapse, about 10% of patients said they would forgo treatment, he said at the symposium, also sponsored by the AGA Institute, the American Society for Therapeutic Radiology and Oncology, and the Society of Surgical Oncology.

These responses came after the patients were given educational CDs and videos, and had the opportunity to talk with oncologists about adjuvant chemotherapy.

Dr. Love and his associates did a parallel survey of 150 oncologists and clinical investigators who specialized in gastrointestinal cancers, asking them to predict what their patients would choose. The oncologists and investigators thought that far fewer patients, just 19%, would choose to undergo chemotherapy for a 1% reduction in cancer recurrence risk.

More than half the patients in the survey expected to have severe nausea and vomiting and lose their hair as a result of their chemotherapy, despite being told otherwise by their doctors. “Patients seem to be getting a lot of misinformation from friends and relatives about the chemotherapy that is used for colorectal cancer, which usually doesn't cause those side effects because of the medications we have today,” Dr. Love said.

These results suggest that “doctors are not getting the right information across to their patients [and] that patients may be far more willing to receive cytotoxic therapy for what others might view as modest potential treatment benefits,” he said.

'Patients may be far more willing to receive cytotoxic therapy for what others might view as modest … benefits.' DR. LOVE

ORLANDO — Many patients with colorectal cancer are willing to undergo adjuvant chemotherapy in the hopes of warding off a recurrence, even though the likelihood of recurrence is slight.

In a survey of 150 patients, just over one-third of those who had received adjuvant chemotherapy with 5-fluorouracil and oxaliplatin said they would go through chemotherapy again to reduce their chance of cancer relapse by 1%, and 57% said they would be treated again for a 3% reduction, said Dr. Neil Love, president of Research to Practice, an oncology education company in Miami, at a symposium on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

At the other end of the spectrum, even when chemotherapy would result in a 1 in 10 chance that they would avoid relapse, about 10% of patients said they would forgo treatment, he said at the symposium, also sponsored by the AGA Institute, the American Society for Therapeutic Radiology and Oncology, and the Society of Surgical Oncology.

These responses came after the patients were given educational CDs and videos, and had the opportunity to talk with oncologists about adjuvant chemotherapy.

Dr. Love and his associates did a parallel survey of 150 oncologists and clinical investigators who specialized in gastrointestinal cancers, asking them to predict what their patients would choose. The oncologists and investigators thought that far fewer patients, just 19%, would choose to undergo chemotherapy for a 1% reduction in cancer recurrence risk.

More than half the patients in the survey expected to have severe nausea and vomiting and lose their hair as a result of their chemotherapy, despite being told otherwise by their doctors. “Patients seem to be getting a lot of misinformation from friends and relatives about the chemotherapy that is used for colorectal cancer, which usually doesn't cause those side effects because of the medications we have today,” Dr. Love said.

These results suggest that “doctors are not getting the right information across to their patients [and] that patients may be far more willing to receive cytotoxic therapy for what others might view as modest potential treatment benefits,” he said.

'Patients may be far more willing to receive cytotoxic therapy for what others might view as modest … benefits.' DR. LOVE

ORLANDO — Patients with metastatic colorectal cancer who have mild skin reactions or no reactions at all when treated with standard doses of cetuximab can be safely treated with escalated doses of cetuximab to achieve an improved tumor response, according to a randomized trial presented at a symposium on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

Increasing the cetuximab dose boosted the response rate in these patients, Dr. Eric Van Cutsem, professor of medicine at University Hospital Gasthuisberg, Leuven, Belgium, said at the symposium, also sponsored by the AGA Institute, the American Society for Therapeutic Radiology and Oncology, and the Society of Surgical Oncology. Positive responses to cetuximab, an epidermal growth factor receptor blocker that inhibits the growth of EGFR-expressing tumors, correlate with the intensity of the associated skin reaction.

The EVEREST trial sought to determine whether escalating the dose in EGFR-expressing patients with metastatic colorectal cancer who had no or slight skin reactions when treated with a standard dose would cause them to develop the acnelike rash that indicates they are benefiting from the drug, said Dr. Van Cutsem, speaking on behalf of the EVEREST investigators.

The study randomized 45 patients who had failed to exhibit a skin reaction greater than grade 1 to continue a cetuximab dose of 250 mg/m

Outcomes in these two arms were compared with those of 77 patients who were ineligible for randomization because they had demonstrated more severe skin reactions when treated with the standard regimen. This group, arm C, continued to receive their standard treatment.

After 24 weeks of treatment, arm B patients had a higher complete response rate than those in arm A (30% vs. 13%, respectively), while patients in arm C had a 34% complete response rate.

Dr. Van Cutsem disclosed that he is a consultant or adviser for Sanofi-Aventis, Roche, Pfizer, and Merck.

Cetuximab dose escalation in patients with no or mild skin reaction on standard dose treatment may improve response. DR. VAN CUTSEM

ORLANDO — Patients with metastatic colorectal cancer who have mild skin reactions or no reactions at all when treated with standard doses of cetuximab can be safely treated with escalated doses of cetuximab to achieve an improved tumor response, according to a randomized trial presented at a symposium on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

Increasing the cetuximab dose boosted the response rate in these patients, Dr. Eric Van Cutsem, professor of medicine at University Hospital Gasthuisberg, Leuven, Belgium, said at the symposium, also sponsored by the AGA Institute, the American Society for Therapeutic Radiology and Oncology, and the Society of Surgical Oncology. Positive responses to cetuximab, an epidermal growth factor receptor blocker that inhibits the growth of EGFR-expressing tumors, correlate with the intensity of the associated skin reaction.

The EVEREST trial sought to determine whether escalating the dose in EGFR-expressing patients with metastatic colorectal cancer who had no or slight skin reactions when treated with a standard dose would cause them to develop the acnelike rash that indicates they are benefiting from the drug, said Dr. Van Cutsem, speaking on behalf of the EVEREST investigators.

The study randomized 45 patients who had failed to exhibit a skin reaction greater than grade 1 to continue a cetuximab dose of 250 mg/m

Outcomes in these two arms were compared with those of 77 patients who were ineligible for randomization because they had demonstrated more severe skin reactions when treated with the standard regimen. This group, arm C, continued to receive their standard treatment.

After 24 weeks of treatment, arm B patients had a higher complete response rate than those in arm A (30% vs. 13%, respectively), while patients in arm C had a 34% complete response rate.

Dr. Van Cutsem disclosed that he is a consultant or adviser for Sanofi-Aventis, Roche, Pfizer, and Merck.

Cetuximab dose escalation in patients with no or mild skin reaction on standard dose treatment may improve response. DR. VAN CUTSEM

ORLANDO — Patients with metastatic colorectal cancer who have mild skin reactions or no reactions at all when treated with standard doses of cetuximab can be safely treated with escalated doses of cetuximab to achieve an improved tumor response, according to a randomized trial presented at a symposium on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

Increasing the cetuximab dose boosted the response rate in these patients, Dr. Eric Van Cutsem, professor of medicine at University Hospital Gasthuisberg, Leuven, Belgium, said at the symposium, also sponsored by the AGA Institute, the American Society for Therapeutic Radiology and Oncology, and the Society of Surgical Oncology. Positive responses to cetuximab, an epidermal growth factor receptor blocker that inhibits the growth of EGFR-expressing tumors, correlate with the intensity of the associated skin reaction.

The EVEREST trial sought to determine whether escalating the dose in EGFR-expressing patients with metastatic colorectal cancer who had no or slight skin reactions when treated with a standard dose would cause them to develop the acnelike rash that indicates they are benefiting from the drug, said Dr. Van Cutsem, speaking on behalf of the EVEREST investigators.

The study randomized 45 patients who had failed to exhibit a skin reaction greater than grade 1 to continue a cetuximab dose of 250 mg/m

Outcomes in these two arms were compared with those of 77 patients who were ineligible for randomization because they had demonstrated more severe skin reactions when treated with the standard regimen. This group, arm C, continued to receive their standard treatment.

After 24 weeks of treatment, arm B patients had a higher complete response rate than those in arm A (30% vs. 13%, respectively), while patients in arm C had a 34% complete response rate.

Dr. Van Cutsem disclosed that he is a consultant or adviser for Sanofi-Aventis, Roche, Pfizer, and Merck.

Cetuximab dose escalation in patients with no or mild skin reaction on standard dose treatment may improve response. DR. VAN CUTSEM

Available evidence does not support the early use of androgen-deprivation therapy in men whose prostate cancer recurs after treatment, according to clinical practice guidelines issued by the American Society of Clinical Oncology.

In addressing the controversial issue, the ASCO guidelines recommend that hormone therapy be deferred in such patients until they experience symptoms of their disease.

The expert panel that drafted the document—an update of ASCO's 2004 guidelines for the initial management of androgen-sensitive prostate cancer that is metastatic, recurrent, or progressive—failed to find an overall survival advantage for early use of hormone therapy, compared with later use (J. Clin. Oncol. 2007 April 2 [Epub DOI:10.1200/ JCO. 2006.10.1949]).

After performing a meta-analysis of seven studies that involved more than 5,000 patients, the panel concluded that early hormone therapy was associated with a 17% decrease in mortality from prostate cancer, but a 15% increase in mortality from other causes.

“Hormones are not benign. We have been thinking that they are bothersome because they cause hot flashes, fatigue, low sex drive, and thin bones. But the more we study this, the more aware we become that there are serious side effects associated with the hormones,” lead author Dr. Andrew Loblaw said in an interview.

One of the most serious of these side effects is hip fracture due to osteoporosis. Many patients are unaware that a hip fracture increases mortality risk by 33% within the first month and 67% within the first year.

Doctors should discuss with their patients the risks and benefits of early hormone therapy, compared with deferred therapy. If a patient prefers to defer therapy, he should have regular visits with his physician every 3–6 months to monitor the disease, said Dr. Loblaw, of the Toronto-Sunnybrook Regional Cancer Centre, Toronto.

The panel suggested either bilateral orchiectomy or injections with luteinizing hormone-releasing hormone (LHRH) analogues as initial androgen-deprivation treatments. It also suggested that combined androgen blockade—nonsteroidal anti-androgen therapy with an orchiectomy or LHRH analogues—be considered for the treatment of locally advanced or metastatic prostate cancer.

It also stated that a newer nonsteroidal antiandrogen agent, bicalutamide, is preferable to older agents such as flutamide. “New data suggest bicalutamide combined with injection might improve survival by up to 20% and has fewer side effects, such as nausea and night blindness, than the older agents. Physicians should be aware of this,” Dr. Loblaw said.

Still, he said, the struggle continues to distinguish the minority of men who will die from their prostate cancer from the majority of men who will die with it. “We know that prostate cancer kills 40,000 Americans and 4,000 Canadians every year, so we have to be able to separate out the bad actors.” Dr. Loblaw and Canadian coinvestigators recently began accrual to the Early vs. Late Androgen Ablation Therapy (ELAAT) trial in the hope of doing just that.

ELAAT will enroll 11,000 patients who have recurrent prostate cancer after radiation therapy and will randomize them either to immediate hormone treatment or to hormone treatment once their prostate-specific-antigen level reaches 25 ng/mL.

“If men have symptoms after the cancer comes back, they should have hormone treatments. But the PSA when that occurs is around 100 [ng/mL]. So, we are only going to wait until the PSA rises to 25 [ng/mL]. It might be OK to wait, because hormone treatment has so many dangerous side effects,” he said.

'The more we study this, the more aware we become that there are serious side effects associated with the hormones.' DR. LOBLAW

Available evidence does not support the early use of androgen-deprivation therapy in men whose prostate cancer recurs after treatment, according to clinical practice guidelines issued by the American Society of Clinical Oncology.

In addressing the controversial issue, the ASCO guidelines recommend that hormone therapy be deferred in such patients until they experience symptoms of their disease.

The expert panel that drafted the document—an update of ASCO's 2004 guidelines for the initial management of androgen-sensitive prostate cancer that is metastatic, recurrent, or progressive—failed to find an overall survival advantage for early use of hormone therapy, compared with later use (J. Clin. Oncol. 2007 April 2 [Epub DOI:10.1200/ JCO. 2006.10.1949]).

After performing a meta-analysis of seven studies that involved more than 5,000 patients, the panel concluded that early hormone therapy was associated with a 17% decrease in mortality from prostate cancer, but a 15% increase in mortality from other causes.

“Hormones are not benign. We have been thinking that they are bothersome because they cause hot flashes, fatigue, low sex drive, and thin bones. But the more we study this, the more aware we become that there are serious side effects associated with the hormones,” lead author Dr. Andrew Loblaw said in an interview.

One of the most serious of these side effects is hip fracture due to osteoporosis. Many patients are unaware that a hip fracture increases mortality risk by 33% within the first month and 67% within the first year.

Doctors should discuss with their patients the risks and benefits of early hormone therapy, compared with deferred therapy. If a patient prefers to defer therapy, he should have regular visits with his physician every 3–6 months to monitor the disease, said Dr. Loblaw, of the Toronto-Sunnybrook Regional Cancer Centre, Toronto.

The panel suggested either bilateral orchiectomy or injections with luteinizing hormone-releasing hormone (LHRH) analogues as initial androgen-deprivation treatments. It also suggested that combined androgen blockade—nonsteroidal anti-androgen therapy with an orchiectomy or LHRH analogues—be considered for the treatment of locally advanced or metastatic prostate cancer.

It also stated that a newer nonsteroidal antiandrogen agent, bicalutamide, is preferable to older agents such as flutamide. “New data suggest bicalutamide combined with injection might improve survival by up to 20% and has fewer side effects, such as nausea and night blindness, than the older agents. Physicians should be aware of this,” Dr. Loblaw said.

Still, he said, the struggle continues to distinguish the minority of men who will die from their prostate cancer from the majority of men who will die with it. “We know that prostate cancer kills 40,000 Americans and 4,000 Canadians every year, so we have to be able to separate out the bad actors.” Dr. Loblaw and Canadian coinvestigators recently began accrual to the Early vs. Late Androgen Ablation Therapy (ELAAT) trial in the hope of doing just that.

ELAAT will enroll 11,000 patients who have recurrent prostate cancer after radiation therapy and will randomize them either to immediate hormone treatment or to hormone treatment once their prostate-specific-antigen level reaches 25 ng/mL.

“If men have symptoms after the cancer comes back, they should have hormone treatments. But the PSA when that occurs is around 100 [ng/mL]. So, we are only going to wait until the PSA rises to 25 [ng/mL]. It might be OK to wait, because hormone treatment has so many dangerous side effects,” he said.

'The more we study this, the more aware we become that there are serious side effects associated with the hormones.' DR. LOBLAW

Available evidence does not support the early use of androgen-deprivation therapy in men whose prostate cancer recurs after treatment, according to clinical practice guidelines issued by the American Society of Clinical Oncology.

In addressing the controversial issue, the ASCO guidelines recommend that hormone therapy be deferred in such patients until they experience symptoms of their disease.

The expert panel that drafted the document—an update of ASCO's 2004 guidelines for the initial management of androgen-sensitive prostate cancer that is metastatic, recurrent, or progressive—failed to find an overall survival advantage for early use of hormone therapy, compared with later use (J. Clin. Oncol. 2007 April 2 [Epub DOI:10.1200/ JCO. 2006.10.1949]).

After performing a meta-analysis of seven studies that involved more than 5,000 patients, the panel concluded that early hormone therapy was associated with a 17% decrease in mortality from prostate cancer, but a 15% increase in mortality from other causes.

“Hormones are not benign. We have been thinking that they are bothersome because they cause hot flashes, fatigue, low sex drive, and thin bones. But the more we study this, the more aware we become that there are serious side effects associated with the hormones,” lead author Dr. Andrew Loblaw said in an interview.

One of the most serious of these side effects is hip fracture due to osteoporosis. Many patients are unaware that a hip fracture increases mortality risk by 33% within the first month and 67% within the first year.

Doctors should discuss with their patients the risks and benefits of early hormone therapy, compared with deferred therapy. If a patient prefers to defer therapy, he should have regular visits with his physician every 3–6 months to monitor the disease, said Dr. Loblaw, of the Toronto-Sunnybrook Regional Cancer Centre, Toronto.

The panel suggested either bilateral orchiectomy or injections with luteinizing hormone-releasing hormone (LHRH) analogues as initial androgen-deprivation treatments. It also suggested that combined androgen blockade—nonsteroidal anti-androgen therapy with an orchiectomy or LHRH analogues—be considered for the treatment of locally advanced or metastatic prostate cancer.

It also stated that a newer nonsteroidal antiandrogen agent, bicalutamide, is preferable to older agents such as flutamide. “New data suggest bicalutamide combined with injection might improve survival by up to 20% and has fewer side effects, such as nausea and night blindness, than the older agents. Physicians should be aware of this,” Dr. Loblaw said.

Still, he said, the struggle continues to distinguish the minority of men who will die from their prostate cancer from the majority of men who will die with it. “We know that prostate cancer kills 40,000 Americans and 4,000 Canadians every year, so we have to be able to separate out the bad actors.” Dr. Loblaw and Canadian coinvestigators recently began accrual to the Early vs. Late Androgen Ablation Therapy (ELAAT) trial in the hope of doing just that.

ELAAT will enroll 11,000 patients who have recurrent prostate cancer after radiation therapy and will randomize them either to immediate hormone treatment or to hormone treatment once their prostate-specific-antigen level reaches 25 ng/mL.

“If men have symptoms after the cancer comes back, they should have hormone treatments. But the PSA when that occurs is around 100 [ng/mL]. So, we are only going to wait until the PSA rises to 25 [ng/mL]. It might be OK to wait, because hormone treatment has so many dangerous side effects,” he said.

'The more we study this, the more aware we become that there are serious side effects associated with the hormones.' DR. LOBLAW