The current regimens of irinotecan, oxaliplatin, and molecular-targeted treatments prolong survival for patients with advanced colorectal cancer by several months compared with a few years ago when these treatments were unavailable, according to an Article in The Lancet Oncology to be published Online Thursday, September 20.
According to Professor Ioannidis (University of Ioannina School of Medicine, Greece) and colleagues, while previous studies have noted survival benefits for the newer regimens, the magnitude of these benefits across diverse regimens is less clear. To ascertain whether certain regimens are associated with better survival and delayed disease progression and to assess the magnitude of these benefits, they did a meta-analysis of 242 randomised trials to compare systemic treatment regimens in patients with advanced colorectal cancer during the last 40 years.
The Greek authors noted that for patients who would be expected to live for 1 year on fluorouracil and leucovorin, the estimated absolute survival benefit of additional treatment with irinotecan plus bevacizumab was 8 months. Survival benefits were also noted for the addition of oxaliplatin plus bevacizumab or irinotecan plus oxaliplatin (4.7 months prolongation for each regimen).
Because newer and more intensive regimens have higher toxicity, this type of quantification is needed to ascertain the incremental survival benefits of each type of chemotherapy compared with the older regimens so that toxic effects can be balanced with improved efficacy, say the authors. They caution that although definite progress has been made in prolonging the survival of these patients, multidrug combinations can cause serious toxic effects, and call for the collection of additional and longer-term follow-up data on toxicity in different settings and on the newest regimens: "The fluorouracil, leucovorin, irinotecan, plus bevacizumab regimen especially, which has the highest probability to be the best in improving survival according to our analysis, might be complicated by up to 84.9% of grade 3 or 4 adverse events, including a 1.5% chance of gastrointestinal perforation." ..."[These]existing uncertainties suggest that more data are needed, especially for the newest regimens", they add.