Adding oxaliplatin to fluoropyrimidine-based adjuvant chemotherapy significantly reduces the risk of recurrence of colon cancer, an analysis of pooled data published Jan. 25 from five modern adjuvant therapy trials suggests.
Among more than 12,000 patients enrolled in the randomized clinical trials, the addition of oxaliplatin to standard adjuvant chemotherapy with fluorouracil (FU) and leucovorin was associated with significant reductions in the risk of recurrence within the first 14 months following treatment in patients with stage II colon cancer, and within the first 4 years for patients with stage III disease, report Dr. Manish A. Shah of Weill Cornell Medical College and Presbyterian Hospital, New York, and his colleagues.
“[W]e found that oxaliplatin significantly reduces the risk of recurrence and death within the first 6 years post treatment, with the greatest benefit observed in patients with higher-risk cancers. The time course risk of recurrence for stage II colon cancer is significantly reduced compared with patients with stage III disease, with potential implications for surveillance strategies,” they wrote (J Clin Onc. 2016 Jan 25. doi: 10.1200/JCO.2015.63.0558).
The authors looked at pooled data from five randomized studies with oxaliplatin for which mature data are available: the NSABP C-07 (National Surgical Adjuvant Breast and Bowel Project) trial, the NSABP C-08 , the N0147 , MOSAIC (Multicenter International Study of Oxaliplatin/ 5FU-LV in the Adjuvant Treatment of Colon Cancer), and XELOXA (Adjuvant XELOX).
They plotted continuous-time hazards of recurrence and death from the time of randomization up to 6 years in all patients treated with oxaliplatin and in those randomized to FU/leucovorin with or without oxaliplatin.
They found that for patients treated with FU, leucovorin, and oxaliplatin, the maximum hazard for recurrence occurred at around 14 months post treatment, and then dwindled to nearly zero after about 6 years of follow-up. They also found that the risk of recurrence was lower with the addition of oxaliplatin at all-time points.
For the endpoint of death, oxaliplatin significantly reduced the risk from 2 to 6 years after treatment in patients with stage III disease. The addition of oxaliplatin, however, did not significantly reduce the risk of death for patients with stage II disease at any time point. The investigators also found that oxaliplatin was least effective at preventing recurrences in patients with stage II disease, suggesting a limited role for intensive adjuvant therapy in this group.
“These data support the hypothesis that the addition of oxaliplatin to fluoropyrimidine therapy provides sustained benefit over time, preventing recurrences that would ultimately lead to deaths in this large patient population,” the authors wrote.The analysis was supported by a grant from the National Cancer Institute. Dr. Shah disclosed consulting/advising Eli Lilly/ImClone Systems and Genentech, and institutional research funding from Sanofi and Genentech.