Simvastatin plus irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) as first-line chemotherapy in metastatic colorectal patients: a multicenter phase II study

Abstract

BackgroundSimvastatin has demonstrated anti-tumor activity in preclinical studies via tumor cell senescence, anti-angiogenesis, and
apoptosis. This phase II trial evaluated the efficacy and toxicity profile of conventional FOLFIRI chemotherapy plus simvastatin
in metastatic colorectal cancer patients.

MethodsPatients received irinotecan 180mg/m2 as a 90-min infusion followed by leucovorin 200mg/m2 in a 2-h infusion, and then 5-FU 400mg/m2 bolus injection followed by 2,400mg/m2 as a 46-h continuous infusion. Treatment cycles were repeated every 2weeks until documented disease progression, unacceptable
toxicity, or patient’s refusal. Simvastatin 40mg tablet was given once daily per oral everyday during the period of chemotherapy
without a rest.

ResultsFrom October 2005 to June 2006, 49 patients were enrolled. The overall response rate (ORR) was 46.9% (95% CI, 31.0–58.8) by
intent-to-treat analysis and 45.8% (95% CI, 33.3–62.8) by per-protocol analysis. There were one complete response (CR) and
22 partial responses (PRs). Both CR and PRs were confirmed at least 4weeks later. The disease-control rate was 83.7% (95%
CI, 73.4–94.0). The median follow-up duration was 25.6months (range, 20.9–28.8months). The median survival of all patients
was 21.8months (95% CI, 14.4, 29.2). The median TTP was 9.9months (95% CI, 6.4, 13.3). No patients experienced additional
adverse effect that was definitely caused by simvastatin drug therapy in this trial.

ConclusionThe combination of simvastatin plus FOLFIRI was a feasible regimen with promising antitumor activity.