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


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


RESULTS
From 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 4 weeks later. The disease-control rate was 83.7% (95% CI, 73.4-94.0). The median follow-up duration was 25.6 months (range, 20.9-28.8 months). The median survival of all patients was 21.8 months (95% CI, 14.4, 29.2). The median TTP was 9.9 months (95% CI, 6.4, 13.3). No patients experienced additional adverse effect that was definitely caused by simvastatin drug therapy in this trial.


CONCLUSIONS
The combination of simvastatin plus FOLFIRI was a feasible regimen with promising antitumor activity.
Lee
Jeeyun
J
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Kangnam-Gu, Seoul, Korea.
Jung
Kyung Hae
KH
Park
Young Suk
YS
Ahn
Joong Bae
JB
Shin
Sang Jun
SJ
Im
Seock-Ah
SA
Oh
Do Youn
DY
Shin
Dong Bok
DB
Kim
Tae Won
TW
Lee
Namsu
N
Byun
Jae Ho
JH
Hong
Yong Sang
YS
Park
Joon Oh
JO
Park
Se Hoon
SH
Lim
Ho Yeong
HY
Kang
Won Ki
WK
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D019821:Simvastatin / Q000008:administration & dosage
D000077146:Irinotecan; D019821:Simvastatin; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin