Increased tolerability of bimonthly 12-hour timed flat infusion 5-fluorouracil/irinotecan regimen in advanced colorectal cancer: A dose-finding study

Corrado Ficorella, E. Ricevuto, M. F. Morelli, R. Morese, K. Cannita, G. Cianci, G. Porzio, Z. C. Di Rocco, F. De Galitiis, M. De Tursi, N. Tinari, S. Iacobelli, P. Marchetti

Research output: Contribution to journalArticlepeer-review

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 (d1,15) and escalating doses of 5-FU 600-1200 mg/m 2 on days 1-4 and 15-18 (d1-4,15-18). 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/d1-4,15-18; CPT-11 180 mg/m 2/d1,15 [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.

Original languageEnglish
Pages (from-to)1345-1350
Number of pages6
JournalOncology Reports
Volume15
Issue number5
Publication statusPublished - May 2006

Keywords

  • 5-fluorouracil
  • Advanced colorectal cancer
  • Irinotecan

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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