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Docetaxel/oxaliplatin/5-fluorouracil should be considered as either a primary or subsidiary component of treatments for advanced gastric cancer, according to the results of a study published online Nov. 21 in the Annals of Oncology.
“Recent attention has focused on newer platinum compounds such as oxaliplatin and the oral fluoropyrimidine capecitabine and on taxane-containing triplet combinations [and] the combination of docetaxel, cisplatin and infusional 5-FU (DCF) significantly improved progression-free survival (PFS) and overall survival (OS), compared with cisplatin/5-FU (CF),” wrote the authors, led by Dr. Eric Van Cutsem of University Hospitals Leuven (Belgium). “However, the DCF regimen has been associated with increased toxicity, compared with CF and has not been used extensively in clinical practice or as the preferred chemotherapy backbone in clinical trials evaluating new targeted agents,” they wrote (Ann. Oncol. 2014 [doi:10.1093/annonc/mdu496]).
In a prospective, multinational, randomized, phase II trial, investigators compared the efficacy of gastric cancer treatments with docetaxel/oxaliplatin (TE), docetaxel/oxaliplatin/5-FU (TEF), and docetaxel/oxaliplatin/capecitabine (TEX). Researchers determined the “optimal dose” for each regimen, after which a total of 254 patients – all of whom were aged at least 18 years, with Karnofsky Performance Status scores greater than 70, histologically proven metastatic or locally recurrent gastric adenocarcinoma – were randomized using “an interactive voice response system, with stratification by country, weight loss (≤5% or >5%), and disease measurability.”
Ultimately, 248 patients received full treatments of one of the three optimized dose regimens. Investigators took note of both PFS and OS rates, both of which had higher medians in the TEF group than in either the TE or the TEX: 7.66 months TEF versus 4.50 months TE and 5.55 months TEX for PFS and 14.59 months TEF versus 8.97 months TE and 11.30 months TEX for OS. Tumor response rates, complete or partial, were also higher in the TEF group: 46.6% versus 23.1% for TE and 25.6% for TEX. In terms of adverse effects and the frequency of such occurrences, the numbers were similar across all three groups. The most commonly reported side effects were fatigue (21%), sensory neuropathy (14%), and diarrhea (13%).
In order to account for potential toxicity, which would offset patient survival data, the investigators used a therapeutic index relating their PFS data to a measure of tolerability of febrile neutropenia, which was reported in all three groups: 2% TEF, 14% TE, and 9% TEX.
“Using this index, TEF was very favorable, compared with TE and TEX and also with historical data for DCF and CF, thus providing evidence of an improved benefit:risk profile with TEF, compared with the standard treatment in advanced GC,” Dr. Van Cutsem and his coauthors noted.
Dr. Van Cutsem and coauthor Dr. J. Tabernero have received research funding from Sanofi, which also supported the study. Dr. Tabernero has also acted as a consultant for and has received honoraria from Sanofi. All other coauthors reported no financial conflicts of interest.
Docetaxel/oxaliplatin/5-fluorouracil should be considered as either a primary or subsidiary component of treatments for advanced gastric cancer, according to the results of a study published online Nov. 21 in the Annals of Oncology.
“Recent attention has focused on newer platinum compounds such as oxaliplatin and the oral fluoropyrimidine capecitabine and on taxane-containing triplet combinations [and] the combination of docetaxel, cisplatin and infusional 5-FU (DCF) significantly improved progression-free survival (PFS) and overall survival (OS), compared with cisplatin/5-FU (CF),” wrote the authors, led by Dr. Eric Van Cutsem of University Hospitals Leuven (Belgium). “However, the DCF regimen has been associated with increased toxicity, compared with CF and has not been used extensively in clinical practice or as the preferred chemotherapy backbone in clinical trials evaluating new targeted agents,” they wrote (Ann. Oncol. 2014 [doi:10.1093/annonc/mdu496]).
In a prospective, multinational, randomized, phase II trial, investigators compared the efficacy of gastric cancer treatments with docetaxel/oxaliplatin (TE), docetaxel/oxaliplatin/5-FU (TEF), and docetaxel/oxaliplatin/capecitabine (TEX). Researchers determined the “optimal dose” for each regimen, after which a total of 254 patients – all of whom were aged at least 18 years, with Karnofsky Performance Status scores greater than 70, histologically proven metastatic or locally recurrent gastric adenocarcinoma – were randomized using “an interactive voice response system, with stratification by country, weight loss (≤5% or >5%), and disease measurability.”
Ultimately, 248 patients received full treatments of one of the three optimized dose regimens. Investigators took note of both PFS and OS rates, both of which had higher medians in the TEF group than in either the TE or the TEX: 7.66 months TEF versus 4.50 months TE and 5.55 months TEX for PFS and 14.59 months TEF versus 8.97 months TE and 11.30 months TEX for OS. Tumor response rates, complete or partial, were also higher in the TEF group: 46.6% versus 23.1% for TE and 25.6% for TEX. In terms of adverse effects and the frequency of such occurrences, the numbers were similar across all three groups. The most commonly reported side effects were fatigue (21%), sensory neuropathy (14%), and diarrhea (13%).
In order to account for potential toxicity, which would offset patient survival data, the investigators used a therapeutic index relating their PFS data to a measure of tolerability of febrile neutropenia, which was reported in all three groups: 2% TEF, 14% TE, and 9% TEX.
“Using this index, TEF was very favorable, compared with TE and TEX and also with historical data for DCF and CF, thus providing evidence of an improved benefit:risk profile with TEF, compared with the standard treatment in advanced GC,” Dr. Van Cutsem and his coauthors noted.
Dr. Van Cutsem and coauthor Dr. J. Tabernero have received research funding from Sanofi, which also supported the study. Dr. Tabernero has also acted as a consultant for and has received honoraria from Sanofi. All other coauthors reported no financial conflicts of interest.
Docetaxel/oxaliplatin/5-fluorouracil should be considered as either a primary or subsidiary component of treatments for advanced gastric cancer, according to the results of a study published online Nov. 21 in the Annals of Oncology.
“Recent attention has focused on newer platinum compounds such as oxaliplatin and the oral fluoropyrimidine capecitabine and on taxane-containing triplet combinations [and] the combination of docetaxel, cisplatin and infusional 5-FU (DCF) significantly improved progression-free survival (PFS) and overall survival (OS), compared with cisplatin/5-FU (CF),” wrote the authors, led by Dr. Eric Van Cutsem of University Hospitals Leuven (Belgium). “However, the DCF regimen has been associated with increased toxicity, compared with CF and has not been used extensively in clinical practice or as the preferred chemotherapy backbone in clinical trials evaluating new targeted agents,” they wrote (Ann. Oncol. 2014 [doi:10.1093/annonc/mdu496]).
In a prospective, multinational, randomized, phase II trial, investigators compared the efficacy of gastric cancer treatments with docetaxel/oxaliplatin (TE), docetaxel/oxaliplatin/5-FU (TEF), and docetaxel/oxaliplatin/capecitabine (TEX). Researchers determined the “optimal dose” for each regimen, after which a total of 254 patients – all of whom were aged at least 18 years, with Karnofsky Performance Status scores greater than 70, histologically proven metastatic or locally recurrent gastric adenocarcinoma – were randomized using “an interactive voice response system, with stratification by country, weight loss (≤5% or >5%), and disease measurability.”
Ultimately, 248 patients received full treatments of one of the three optimized dose regimens. Investigators took note of both PFS and OS rates, both of which had higher medians in the TEF group than in either the TE or the TEX: 7.66 months TEF versus 4.50 months TE and 5.55 months TEX for PFS and 14.59 months TEF versus 8.97 months TE and 11.30 months TEX for OS. Tumor response rates, complete or partial, were also higher in the TEF group: 46.6% versus 23.1% for TE and 25.6% for TEX. In terms of adverse effects and the frequency of such occurrences, the numbers were similar across all three groups. The most commonly reported side effects were fatigue (21%), sensory neuropathy (14%), and diarrhea (13%).
In order to account for potential toxicity, which would offset patient survival data, the investigators used a therapeutic index relating their PFS data to a measure of tolerability of febrile neutropenia, which was reported in all three groups: 2% TEF, 14% TE, and 9% TEX.
“Using this index, TEF was very favorable, compared with TE and TEX and also with historical data for DCF and CF, thus providing evidence of an improved benefit:risk profile with TEF, compared with the standard treatment in advanced GC,” Dr. Van Cutsem and his coauthors noted.
Dr. Van Cutsem and coauthor Dr. J. Tabernero have received research funding from Sanofi, which also supported the study. Dr. Tabernero has also acted as a consultant for and has received honoraria from Sanofi. All other coauthors reported no financial conflicts of interest.
FROM THE ANNALS OF ONCOLOGY
Key clinical point: Docetaxel/oxaliplatin/5-fluorouracil (TEF) should be considered as either a primary or subsidiary component of treatments for advanced gastric cancer.
Major finding: Median PFS and OS rates were higher with TEF than with docetaxel/oxaliplatin (TE) or docetaxel/oxaliplatin/capecitabine (TEX): 7.66 months TEF vs. 4.50 months TE and 5.55 months TEX for PFS, and 14.59 months TEF vs. 8.97 months TE and 11.30 months TEX for OS.
Data source: A prospective, multinational, randomized, phase II study.
Disclosures: Dr. Van Cutsem and coauthor Dr. J. Tabernero have received research funding from Sanofi, which also supported the study. Dr. Tabernero has also acted as a consultant for and has received honoraria from Sanofi. All other coauthors reported no financial conflicts of interest.