This evidence-based series was developed by the Gastrointestinal Cancer Disease Site Group (DSG) of Cancer Care Ontario's (CCO's) Program in Evidence-based Care (PEBC). The series is a convenient and up-to-date source of the best available evidence on oxaliplatin (L-OHP) combined with 5-fluorouracil (5-FU) and folinic acid (FA) in advanced colorectal cancer, developed through systematic review, evidence synthesis, and input from practitioners in Ontario.
Disease Site Group Consensus Process
Note: The Gastrointestinal DSG consensus process was based on an earlier draft of the present guideline document. That draft did not contain any of the evidence regarding the addition of bevacizumab to regimens of infusional 5FU/FA plus oxaliplatin.
The present systematic review found one first-line therapy trial that demonstrated infusional 5FU/FA/oxaliplatin (FOLFOX) to be superior to bolus 5FU/FA/irinotecan (IFL), with more-favourable median survival and tumour response rates. Compared with IFL, FOLFOX has lower incidences of severe nausea, vomiting, diarrhea, and febrile neutropenia, but a higher incidence of peripheral neuropathy. Therefore, for first-line treatment, short-term infusional 5FU/FA in combination with either oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) is acceptable for fit patients when combination therapy is the preferred treatment. Choice of first-line therapy may rely on patient factors and preferences—for example, less neuropathy with irinotecan versus less alopecia with oxaliplatin.
For second-line treatment after progression on first-line anti-thymidylate synthase (TS) monotherapy (for example, 5FU/FA, capecitabine), irinotecan is standard therapy. For patients with contraindications to the use of second-line irinotecan, FOLFOX is a reasonable alternative. After progression on both irinotecan and an anti-TS agent, FOLFOX is the preferred therapy.
The role of radiation therapy, either alone or in combination with chemotherapy, for locally advanced unresectable colorectal cancer was not addressed in this guideline. In addition, the use of chronomodulated (CM) regimens is a topic that intersects with the use of oxaliplatin/5FU combinations, particularly CM 5FU in those combinations. Chronomodulation of oxaliplatin has not been extensively studied and was not addressed, because the topic is beyond the scope of this guideline.
In conclusion, the Gastrointestinal DSG acknowledges that the combination of oxaliplatin with short-term infusional 5FU and FA (FOLFOX) is an important component of first- and second-line treatment of advanced colon cancer, and the DSG recommends that oxaliplatin be made available for the treatment of advanced colorectal cancer.