The addition of oxaliplatin to fluorouracil (5-FU) plus leucovorin improved overall survival in patients younger than 70 years old participating in the National Surgical Adjuvant Breast and Bowel Project (NSABP) C-07 trial. Patients eligible for the trial had either stage II or III colon cancer and had undergone potentially curative surgical resection with no evidence of residual malignant disease. Of the 2,409 patients included in the analyses, 1,209 had been randomly assigned to the 5-FU/leucovorin arm and 1,200 to the 5-FU/leucovorin plus oxaliplatin arm.
“[Overall survival] did not differ significantly by treatment in the full cohort of this study,” according to updated NSABP C-07 trial results, including survival and subset analyses, published in the Journal of Clinical Oncology. The overall survival estimates at 5 years were 78.4% for 5-FU/leucovorin and 80.2% for 5-FU/leucovorin/oxaliplatin, an absolute difference of 1.8%, favoring the oxaliplatin-containing regimen, the authors reported.
In an exploratory subset analysis by age, however, overall survival was significantly improved with 5-FU/leucovorin/oxaliplatin compared with 5-FU/leucovorin for patients younger than 70 (HR = 0.80; 95% CI = 0.68–0.95; P = .013). The 5-year overall survival estimates were 78.8% for 5-FU/leucovorin and 81.8% with the addition of oxaliplatin, “a 3.1% improvement in patients younger than age 70 years,” the authors added.
Differences Related to Toxicity?
“Our finding that the effect of oxaliplatin differs by age group is provocative,” the authors stated. They suggest that the differences may be related to toxicity. Patients age 70 years or older were more likely to experience grade 4 or 5 toxicity with 5‑FU/leucovorin/oxaliplatin, while in younger patients the toxicity rates for the two treatments were similar. “These differences in toxicity are not conclusive, but they do suggest that older patients may be more likely to have adverse outcomes related to treatment with oxaliplatin,” the authors reported. “Patients age 70 years or older received approximately 25% less oxaliplatin overall compared with younger patients, but dose intensities were similar, which suggests that older patients received fewer cycles,” they added.
“Although a chronologic age of at least 70 years may not be an ideal marker for the true cause of differences in outcome, it appears to be the best marker currently available. In making treatment decisions for individual patients, we suggest that advanced age be one factor taken into account when oxaliplatin is being considered,” the authors continued. They advised caution in selecting patients of advanced age for oxaliplatin therapy. “Consideration should be given to the patient’s overall state of health and potential for tolerating adverse events,” they concluded. ■
Yothers G, et al: J Clin Oncol 29:3768-3774, 2011.