Xeloda or 5FU, leukovorin and gemcitabine for colorectal cancer
Posted Apr 14 2010 3:02pm
Fluoropyrimidines with oxaliplatin or irinotecan plus bevacizumab is the standard chemotherapy combination in patients with advanced colorectal cancer (CRC). Gemcitabine acts synergistically with fluoropyrimidines to enhance the binding of thymidylate synthase and increase inhibition of DNA synthesis. The patient appealed based on studies of Xeloda/Gemcitabine and assumes the identity of 5FU/leukovorin to Xeloda, which is far from proven in rectal cancer. Even if assuming such equivalence, it remains an experimental combination; A 2004 study concluded: "This combination regimen has an excellent tolerance in this heavily pretreated patients; the MTP, survival (OS) and the founding of some degree of activity are encouraging. Further studies of this treatment regimen are warranted." The regimen has more of a track record in pancreatic cancer and renal cell cancer. A recent review looked at forty-two advanced CRC patients who were evaluated in two Phase I studies and the maximum tolerated dose of gemcitabine was 900 - 1,000 mg/m(2) weekly with either bolus 5-fluorouracil (5-FU) or capecitabine. A total of 216 advanced CRC patients were evaluated in six Phase II studies. It found that "Fluoropyrimidine plus gemcitabine is clinically active in patients with refractory CRC demonstrating prolonged median time to progression and acceptable toxicity only when bolus 5-FU was not used." Clinicaltrials.gov lists one study that has been completed but for which no publication has yet been submitted.
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Merl M, Hoimes C, Pham T, Saif MW. Is there a palliative benefit of gemcitabine plus fluoropyrimidines in patients with refractory colorectal cancer? A review of the literature previously presented: poster at the 2008 Gastrointestinal Cancer Symposium (Abstract No. 512).Expert Opin Investig Drugs. 2009 Sep;18(9):1257-64.