Phase I clinical trial of irinotecan with oral capecitabine in patients with gastrointestinal and other solid malignancies

Sanjay Goel, Minaxi Jhawer, Lakshmi Rajdev, Una Hopkins, Karen Fehn, Cheryl Baker, Hoo G. Chun, Della F. Makower, Leon C. Landau, Anthony Hoffman, Scott Wadler, Sridhar Mani

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The purpose of this study was to determine the safety of irinotecan and capecitabine in patients with advanced solid tumors. Thirty-four patients received 122 courses of irinotecan 200 to 300 mg/m2 as an intravenous infusion during 30 minutes on day 1 and capecitabine 1,500 to 3,000 mg/d orally 12 hours apart starting on day 2 for 14 days, repeated every 21 days (one course). Three to seven patients were treated in six dose-escalation cohorts. Three of 7 (43%) patients treated with irinotecan 300 mg/m2 and capecitabine 2,300 mg/d had course 1 dose-limiting toxicity (DLT) defining maximum tolerated dosage (MTD). Fatigue and diarrhea were the major DLTs, and other events included neutropenia, anorexia, and hand-foot syndrome. At one dose level below the MTD, none of 7 patients treated with irinotecan 275 mg/m2, and capecitabine 2,300 mg/d (36 courses) had course 1 DLT. Grade III to IV toxicities beyond course 1 included neutropenia (11% of all courses), fatigue (3.4%) and hand-foot syndrome (3.4%). There were only two episodes of febrile grade II neutropenia. There were no toxic deaths. Transient antitumor response was noted in one patient with irinotecan and 5-fluorouracil-refractory colon cancer. The combination of irinotecan 275 mg/m2 and capecitabine 2,300 mg/d represents a safe, favorable, and convenient outpatient regimen warranting further phase II evaluation.

Original languageEnglish (US)
Pages (from-to)528-534
Number of pages7
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume25
Issue number5
DOIs
StatePublished - Oct 2002

Fingerprint

irinotecan
Clinical Trials, Phase I
Neutropenia
Hand-Foot Syndrome
Neoplasms
Fatigue
Poisons
Anorexia
Intravenous Infusions
Fluorouracil
Colonic Neoplasms
Capecitabine
Diarrhea
Fever
Outpatients

Keywords

  • Cancer
  • Capecitabine
  • Colorectal
  • CPT-11
  • Irinotecan
  • Phase I

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Phase I clinical trial of irinotecan with oral capecitabine in patients with gastrointestinal and other solid malignancies. / Goel, Sanjay; Jhawer, Minaxi; Rajdev, Lakshmi; Hopkins, Una; Fehn, Karen; Baker, Cheryl; Chun, Hoo G.; Makower, Della F.; Landau, Leon C.; Hoffman, Anthony; Wadler, Scott; Mani, Sridhar.

In: American Journal of Clinical Oncology: Cancer Clinical Trials, Vol. 25, No. 5, 10.2002, p. 528-534.

Research output: Contribution to journalArticle

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abstract = "The purpose of this study was to determine the safety of irinotecan and capecitabine in patients with advanced solid tumors. Thirty-four patients received 122 courses of irinotecan 200 to 300 mg/m2 as an intravenous infusion during 30 minutes on day 1 and capecitabine 1,500 to 3,000 mg/d orally 12 hours apart starting on day 2 for 14 days, repeated every 21 days (one course). Three to seven patients were treated in six dose-escalation cohorts. Three of 7 (43{\%}) patients treated with irinotecan 300 mg/m2 and capecitabine 2,300 mg/d had course 1 dose-limiting toxicity (DLT) defining maximum tolerated dosage (MTD). Fatigue and diarrhea were the major DLTs, and other events included neutropenia, anorexia, and hand-foot syndrome. At one dose level below the MTD, none of 7 patients treated with irinotecan 275 mg/m2, and capecitabine 2,300 mg/d (36 courses) had course 1 DLT. Grade III to IV toxicities beyond course 1 included neutropenia (11{\%} of all courses), fatigue (3.4{\%}) and hand-foot syndrome (3.4{\%}). There were only two episodes of febrile grade II neutropenia. There were no toxic deaths. Transient antitumor response was noted in one patient with irinotecan and 5-fluorouracil-refractory colon cancer. The combination of irinotecan 275 mg/m2 and capecitabine 2,300 mg/d represents a safe, favorable, and convenient outpatient regimen warranting further phase II evaluation.",
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AU - Baker, Cheryl

AU - Chun, Hoo G.

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AU - Mani, Sridhar

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