title: Irinotecan (CPT-11) in combination with infusional 5-fluorouracil and leucovorin (de Gramont regimen) as first-line treatment in patients with advanced colorectal cancer: a multicenter phase II study.
abstract: The combination of CPT-11 with 5-fluorouracil (5-FU) in advanced colorectal cancer (ACC) represents an attractive approach. A phase II study was conducted to assess the tolerance and efficacy of CPT-11 in combination with leucovorin-modulated bolus plus infusional 5-FU given according to the de Gramont regimen in chemonaive patients with ACC. Fifty-four patients with histologically confirmed ACC were enrolled. The patients' median age was 65 years; 30 (55.5%) patients were men; performance status (World Health Organization) was 0 in 27 (50%) patients, 1 in 22 (41%), and 2 in 5 (9%). Patients received leucovorin (200 mg/m2/d) as a 2-hour intravenous infusion, followed by 5-FU as an intravenous bolus at 400 mg/m2/d, and then as a 22-hour continuous infusion at 600 mg/m2/d, repeated on 2 consecutive days. CPT-11 (180 mg/m2; 30-minute intravenous infusion) was administered on day 1, simultaneously with leucovorin administration. This cycle was repeated every 2 weeks. Complete response was achieved in 4 patients (8%) and partial response in 19 (37%) (overall response rate: 45%; 95% CI: 24-50.5%). Stable disease was achieved in 16 (31%) patients and progressive disease in 13 (25%). The median duration of response and the median TTP were 5 and 8 months, respectively. After a median follow-up period of 11 months, 33 (61%) patients are still alive; the median overall survival has not yet been reached. Thrombocytopenia and anemia were very rare. Grade III/IV neutropenia developed in 19 patients (36%); febrile neutropenia developed in 4 patients, and 1 of them died of sepsis. Grade IV diarrhea was seen in 7 (13%) patients, and 4 of them required hospitalization. Grade III and IV mucositis was observed in two (4%) and one (2%) patients, respectively. Other toxicities were mild. The combination of CPT-11 and bolus plus infusional 5-FU is a relatively well-tolerated and effective first-line treatment in ACC. Final results from large phase III trials are awaited to clarify whether the CPT-11/5-FU combinations should be considered as "standard" first-line treatment in ACC.
authors.affiliation: Department of Medical Oncology, University General Hospital of Heraklion, Heraklion 71110, Crete, Greece.
authors.forename: L
authors.initials: L
authors.lastname: Vamvakas
authors.forename: S
authors.initials: S
authors.lastname: Kakolyris
authors.forename: C
authors.initials: C
authors.lastname: Kouroussis
authors.forename: K
authors.initials: K
authors.lastname: Kandilis
authors.forename: D
authors.initials: D
authors.lastname: Mavroudis
authors.forename: N
authors.initials: N
authors.lastname: Ziras
authors.forename: N
authors.initials: N
authors.lastname: Androulakis
authors.forename: K
authors.initials: K
authors.lastname: Kalbakis
authors.forename: E
authors.initials: E
authors.lastname: Sarra
authors.forename: J
authors.initials: J
authors.lastname: Souglakos
authors.forename: V
authors.initials: V
authors.lastname: Georgoulias
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / 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; D012074:Remission Induction; D016019:Survival Analysis
chemical_list: D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin