title: First-line sunitinib plus FOLFIRI in Japanese patients with unresectable/metastatic colorectal cancer: a phase II study.
abstract: This phase II, open-label, single-arm study investigated sunitinib + FOLFIRI in Japanese patients with treatment-naïve unresectable/metastatic colorectal cancer. Patients received i.v. FOLFIRI (levo-leucovorin 200 mg/m(2) + irinotecan 180 mg/m(2), followed by 5-fluorouracil 400 mg/m(2) bolus then 2400 mg/m(2) 46-h infusion) every 2 weeks, and oral sunitinib 37.5 mg/day on Schedule 4/2 (4 weeks on, 2 weeks off), until disease progression or treatment withdrawal. Progression-free survival (PFS) was the primary endpoint, with a target median of 10.8 months (35% improvement over FOLFIRI alone). Seventy-one patients started a median of 3 (range 1-11) sunitinib cycles (median relative dose intensity, <60%). The median PFS was 6.7 months (95% confidence interval, 4.7-9.2) by independent review, 7.2 months (95% confidence interval, 5.4-9.5) by investigator assessment. Objective response rate (complete responses + partial responses) was 36.6% (independent review) and 42.3% (investigator assessment). Clinical benefit rate (complete responses + partial responses + stable disease) was 83.1% (independent review) and 88.7% (investigator assessment). Common all-causality, any-grade, adverse events were: neutropenia and leukopenia (both 97.2%); thrombocytopenia (84.5%); diarrhea and nausea (both 78.9%); decreased appetite (74.6%); and fatigue (66.2%). Neutropenia (96%) was the most frequent grade 3/4 adverse event. This study was closed early due to findings from a concurrent phase III study of sunitinib + FOLFIRI in non-Japanese patients with metastatic colorectal cancer. In conclusion, the median PFS for sunitinib + FOLFIRI in Japanese patients was shorter than the 10.8 month target, indicating that sunitinib did not add to the antitumor activity of FOLFIRI. This study was registered with www.ClinicalTrials.gov (NCT00668863).
authors.affiliation: Department of Medical Oncology, KKR Sapporo Medical Center Tonan Hospital, Hokkaido, Japan. ytsuji@tonan.gr.jp
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tsuji
authors.forename: Taroh
authors.initials: T
authors.lastname: Satoh
authors.forename: Akihito
authors.initials: A
authors.lastname: Tsuji
authors.forename: Kei
authors.initials: K
authors.lastname: Muro
authors.forename: Motoki
authors.initials: M
authors.lastname: Yoshida
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nishina
authors.forename: Michitaka
authors.initials: M
authors.lastname: Nagase
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Komatsu
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kato
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Miyata
authors.forename: Naoko
authors.initials: N
authors.lastname: Mizutani
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hashigaki
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Lechuga
authors.forename: Tadamichi
authors.initials: T
authors.lastname: Denda
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D007211:Indoles; D011758:Pyrroles; D002955:Leucovorin; D005472:Fluorouracil; D000077210:Sunitinib; D002166:Camptothecin