title: Increased tolerability of bimonthly 12-hour timed flat infusion 5-fluorouracil/irinotecan regimen in advanced colorectal cancer: A dose-finding study.
abstract: A dose-finding study was designed to determine the maximum tolerated dose (MTD) of a bimonthly 12-h (10:00 p.m to 10:00 a.m), timed flat infusion (TFI) of 5-fluorouracil (5-FU) plus irinotecan (CPT-11), without leucovorin (LV), for metastatic colorectal carcinoma (CRC). A total of 33 patients were treated. Seven dose levels included a fixed CPT-11 dose of 180 mg/m2 on days 1 and 15 (d(1,15)) and escalating doses of 5-FU 600-1200 mg/m2 on days 1-4 and 15-18 (d(1-4,15-18)). Dose-limiting toxicities (DLTs) were: grade 3-4 non-hematologic, grade 4 hematologic and any toxicity causing a more than a 2-week delay in treatment. The MTD was reached at the seventh dose level. DLTs were observed in 5/8 patients (63%): G3 diarrhea, 2 patients, associated with G3 mucositis in one instance; G4 neutropenia, 2 patients, associated with severe asthenia in 1 patient; G3 hand-foot syndrome, 1 patient. The recommended doses (RDs) were established at the sixth dose level: 5-FU, 1100 mg/m2/d(1-4,15-18); CPT-11 180 mg/m2/d(1,15) [5-FU and CPT-11 dose intensity (DI), 2200 and 90 mg/m2 per week (w), respectively]. At the recommended dose, the DLTs in 38 cycles were: mucositis, 2 cycles (5%); afebrile G4 neutropenia and hand-foot syndrome, 1 cycle (3%). In 24 assessable patients, the overall response rate was 37.5%. The present CPT-11/5-FU schedule is highly tolerable in an outpatient setting using the highest recommended 5-FU dose effective in advanced CRC.
authors.affiliation: Medical Oncology, Department of Experimental Medicine, University of L'Aquila,Coppito, L'Aquila 67100, Italy. ficorella@interfree.it
authors.forename: C
authors.initials: C
authors.lastname: Ficorella
authors.forename: E
authors.initials: E
authors.lastname: Ricevuto
authors.forename: M F
authors.initials: MF
authors.lastname: Morelli
authors.forename: R
authors.initials: R
authors.lastname: Morese
authors.forename: K
authors.initials: K
authors.lastname: Cannita
authors.forename: G
authors.initials: G
authors.lastname: Cianci
authors.forename: G
authors.initials: G
authors.lastname: Porzio
authors.forename: Z C
authors.initials: ZC
authors.lastname: Di Rocco
authors.forename: F
authors.initials: F
authors.lastname: De Galitiis
authors.forename: M
authors.initials: M
authors.lastname: De Tursi
authors.forename: N
authors.initials: N
authors.lastname: Tinari
authors.forename: S
authors.initials: S
authors.lastname: Iacobelli
authors.forename: P
authors.initials: P
authors.lastname: Marchetti
mesh_terms: D000293:Adolescent; 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; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D013997:Time Factors
chemical_list: D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin