Neurotoxicity tempers case for oxaliplatin in older adults with colorectal cancer

SAN FRANCISCO – Oxaliplatin has substantial neurotoxicity in older adults with colorectal cancer that should be factored into treatment decision making, suggests a study reported at the Gastrointestinal Cancers Symposium.

The Canadian analysis of more than 3,500 patients found that those aged 70 years or older who received oxaliplatin as part of their adjuvant chemotherapy had a doubling of the risk of a new diagnosis of peripheral neuropathy. The 3-year cumulative incidence in this group approached 8%.

Susan London/Frontline Medical News

“Hopefully, this study will allow patients to make more informed decisions with their clinicians,” first author Dr. Michael J. Raphael said in an interview. “We are able to say to patients that there is a significant risk of developing a neuropathy. Patients need to consider this in terms of their quality of life because as we are curing more and more people with colorectal cancer, even in the elderly, survivorship is becoming a very big issue. And it becomes an individual choice for the patient, if they survive, what level of toxicity are they willing to accept?”

The study didn’t look at oxaliplatin’s efficacy in older adults, he noted. However, some research has called into question the drug’s benefit in this population as well.

“We know that fluorouracil-based chemotherapy is the standard of care for patients with colorectal cancer stage II high risk and stage III, and the addition of oxaliplatin has provided significant survival benefits for the majority of the colon cancer population,” elaborated Dr. Raphael, who is a resident in the Department of Medicine, University of Toronto, and an investigator with the Institute for Clinical Evaluative Sciences, also in Toronto. “But retrospective subgroup analyses of some of the major trials – MOSAIC and NSABP C-07 – suggest that there may not be a benefit of giving oxaliplatin to patients over the age of 70.”

For the study, the investigators used a population-based database to capture all cases of colorectal cancer diagnosed in Ontario between 2007 and 2011. They restricted analyses to 3,607 patients aged 66 years or older with stage II or III disease and adjusted for potential confounders and the competing risk of death, which is important in an older population, he noted. Overall, 43% received oxaliplatin, Dr. Raphael reported at the symposium, sponsored by ASCO, ASTRO, the American Gastroenterological Association, and the Society of Urologic Oncology.

Results showed that in the 66 to 69 age-group, patients given oxaliplatin as part of their chemotherapy did not have a significantly elevated adjusted risk of a new diagnosis of peripheral neuropathy, but they did have an elevated risk of a new prescription for a neuropathic pain medication (hazard ratio, 1.92; P = .005).

In the 70 and older age-group, those given oxaliplatin had elevated adjusted risks of both a new diagnosis of peripheral neuropathy (HR, 2.07; P less than .001) and a new prescription for a neuropathic pain medication (HR, 1.86; P less than .001).

The 3-year cumulative incidence of neuropathy among those 66 to 69 years old was 5.17% with oxaliplatin and 5.06% without it. But among those 70 years old and older, it was 7.65% with the drug and 3.70% without it.

The clinical impact of the observed neuropathy is not yet known, noted Dr. Raphael. The investigators have therefore undertaken another study looking at possible correlates in this population, such as an uptick in visits to the emergency department for falls or fractures.

SAN FRANCISCO – Oxaliplatin has substantial neurotoxicity in older adults with colorectal cancer that should be factored into treatment decision making, suggests a study reported at the Gastrointestinal Cancers Symposium.

The Canadian analysis of more than 3,500 patients found that those aged 70 years or older who received oxaliplatin as part of their adjuvant chemotherapy had a doubling of the risk of a new diagnosis of peripheral neuropathy. The 3-year cumulative incidence in this group approached 8%.

Susan London/Frontline Medical News

“Hopefully, this study will allow patients to make more informed decisions with their clinicians,” first author Dr. Michael J. Raphael said in an interview. “We are able to say to patients that there is a significant risk of developing a neuropathy. Patients need to consider this in terms of their quality of life because as we are curing more and more people with colorectal cancer, even in the elderly, survivorship is becoming a very big issue. And it becomes an individual choice for the patient, if they survive, what level of toxicity are they willing to accept?”

The study didn’t look at oxaliplatin’s efficacy in older adults, he noted. However, some research has called into question the drug’s benefit in this population as well.

“We know that fluorouracil-based chemotherapy is the standard of care for patients with colorectal cancer stage II high risk and stage III, and the addition of oxaliplatin has provided significant survival benefits for the majority of the colon cancer population,” elaborated Dr. Raphael, who is a resident in the Department of Medicine, University of Toronto, and an investigator with the Institute for Clinical Evaluative Sciences, also in Toronto. “But retrospective subgroup analyses of some of the major trials – MOSAIC and NSABP C-07 – suggest that there may not be a benefit of giving oxaliplatin to patients over the age of 70.”

For the study, the investigators used a population-based database to capture all cases of colorectal cancer diagnosed in Ontario between 2007 and 2011. They restricted analyses to 3,607 patients aged 66 years or older with stage II or III disease and adjusted for potential confounders and the competing risk of death, which is important in an older population, he noted. Overall, 43% received oxaliplatin, Dr. Raphael reported at the symposium, sponsored by ASCO, ASTRO, the American Gastroenterological Association, and the Society of Urologic Oncology.

Results showed that in the 66 to 69 age-group, patients given oxaliplatin as part of their chemotherapy did not have a significantly elevated adjusted risk of a new diagnosis of peripheral neuropathy, but they did have an elevated risk of a new prescription for a neuropathic pain medication (hazard ratio, 1.92; P = .005).

In the 70 and older age-group, those given oxaliplatin had elevated adjusted risks of both a new diagnosis of peripheral neuropathy (HR, 2.07; P less than .001) and a new prescription for a neuropathic pain medication (HR, 1.86; P less than .001).

The 3-year cumulative incidence of neuropathy among those 66 to 69 years old was 5.17% with oxaliplatin and 5.06% without it. But among those 70 years old and older, it was 7.65% with the drug and 3.70% without it.

The clinical impact of the observed neuropathy is not yet known, noted Dr. Raphael. The investigators have therefore undertaken another study looking at possible correlates in this population, such as an uptick in visits to the emergency department for falls or fractures.

SAN FRANCISCO – Oxaliplatin has substantial neurotoxicity in older adults with colorectal cancer that should be factored into treatment decision making, suggests a study reported at the Gastrointestinal Cancers Symposium.

The Canadian analysis of more than 3,500 patients found that those aged 70 years or older who received oxaliplatin as part of their adjuvant chemotherapy had a doubling of the risk of a new diagnosis of peripheral neuropathy. The 3-year cumulative incidence in this group approached 8%.

Susan London/Frontline Medical News

“Hopefully, this study will allow patients to make more informed decisions with their clinicians,” first author Dr. Michael J. Raphael said in an interview. “We are able to say to patients that there is a significant risk of developing a neuropathy. Patients need to consider this in terms of their quality of life because as we are curing more and more people with colorectal cancer, even in the elderly, survivorship is becoming a very big issue. And it becomes an individual choice for the patient, if they survive, what level of toxicity are they willing to accept?”

The study didn’t look at oxaliplatin’s efficacy in older adults, he noted. However, some research has called into question the drug’s benefit in this population as well.

“We know that fluorouracil-based chemotherapy is the standard of care for patients with colorectal cancer stage II high risk and stage III, and the addition of oxaliplatin has provided significant survival benefits for the majority of the colon cancer population,” elaborated Dr. Raphael, who is a resident in the Department of Medicine, University of Toronto, and an investigator with the Institute for Clinical Evaluative Sciences, also in Toronto. “But retrospective subgroup analyses of some of the major trials – MOSAIC and NSABP C-07 – suggest that there may not be a benefit of giving oxaliplatin to patients over the age of 70.”

For the study, the investigators used a population-based database to capture all cases of colorectal cancer diagnosed in Ontario between 2007 and 2011. They restricted analyses to 3,607 patients aged 66 years or older with stage II or III disease and adjusted for potential confounders and the competing risk of death, which is important in an older population, he noted. Overall, 43% received oxaliplatin, Dr. Raphael reported at the symposium, sponsored by ASCO, ASTRO, the American Gastroenterological Association, and the Society of Urologic Oncology.

Results showed that in the 66 to 69 age-group, patients given oxaliplatin as part of their chemotherapy did not have a significantly elevated adjusted risk of a new diagnosis of peripheral neuropathy, but they did have an elevated risk of a new prescription for a neuropathic pain medication (hazard ratio, 1.92; P = .005).

In the 70 and older age-group, those given oxaliplatin had elevated adjusted risks of both a new diagnosis of peripheral neuropathy (HR, 2.07; P less than .001) and a new prescription for a neuropathic pain medication (HR, 1.86; P less than .001).

The 3-year cumulative incidence of neuropathy among those 66 to 69 years old was 5.17% with oxaliplatin and 5.06% without it. But among those 70 years old and older, it was 7.65% with the drug and 3.70% without it.

The clinical impact of the observed neuropathy is not yet known, noted Dr. Raphael. The investigators have therefore undertaken another study looking at possible correlates in this population, such as an uptick in visits to the emergency department for falls or fractures.