title: Simvastatin plus irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) as first-line chemotherapy in metastatic colorectal patients: a multicenter phase II study.
abstract: 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.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Kangnam-Gu, Seoul, Korea.
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Lee
authors.forename: Kyung Hae
authors.initials: KH
authors.lastname: Jung
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Park
authors.forename: Joong Bae
authors.initials: JB
authors.lastname: Ahn
authors.forename: Sang Jun
authors.initials: SJ
authors.lastname: Shin
authors.forename: Seock-Ah
authors.initials: SA
authors.lastname: Im
authors.forename: Do Youn
authors.initials: DY
authors.lastname: Oh
authors.forename: Dong Bok
authors.initials: DB
authors.lastname: Shin
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Kim
authors.forename: Namsu
authors.initials: N
authors.lastname: Lee
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Byun
authors.forename: Yong Sang
authors.initials: YS
authors.lastname: Hong
authors.forename: Joon Oh
authors.initials: JO
authors.lastname: Park
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Park
authors.forename: Ho Yeong
authors.initials: HY
authors.lastname: Lim
authors.forename: Won Ki
authors.initials: WK
authors.lastname: Kang
mesh_terms: 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
chemical_list: D000077146:Irinotecan; D019821:Simvastatin; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin