Retrospective analysis of the international standard-dose FOLFIRI (plus bevacizumab) regimen in Japanese patients with unresectable advanced or recurrent colorectal carcinoma.

BACKGROUND: When applying the topoisomerase inhibitor irinotecan (CPT) with the infusional fluorouracil/levofolinate (FOLFIRI) ± bevacizumab chemotherapy regimen in cases of advanced colorectal carcinoma, the international standard dose for CPT is 180 mg/m(2). Despite this, 150 mg/m(2) CPT is widely prescribed and is the maximum dosage covered by Japanese health insurance. Consequently, the safety of dosing at the international standard has not been tested comprehensively and the efficacy of FOLFIRI in Japan may be underestimated.
METHODS: To evaluate the safety of FOLFIRI (+bevacizumab) in clinical practice using international standards, we reviewed medical records of 53 patients who received FOLFIRI (+bevacizumab) with CPT 180 mg/m(2) as first-line treatment between September 2004 and August 2009. The primary endpoint of the study was to measure the relative dose intensity (RDI) of CPT after four courses. The secondary endpoint was to assess treatment completion rate, adverse events, response rate, progression-free survival (PFS) and overall survival (OS) among all patients.
RESULTS: The RDI and the treatment completion rate were 88.9% and 69.8%, respectively, in the 53 patients. Accompanying grade 3 or 4 adverse events included neutropenia (35.8%), febrile neutropenia (7.5%), and diarrhea (3.8%). Supportive care managed all toxicity symptoms. Median durations for PFS and OS were 10.3 and 26.5 months, respectively.
CONCLUSION: FOLFIRI (+bevacizumab) with the international standard dose of CPT is feasible in clinical practice. In order to minimize deviation of the Japanese regimen from global best practice, international dose standards should be followed.