A phase I-II, dose-escalating trial of ZD9331 in combination with irinotecan (CPT11) in previously pretreated metastatic colorectal cancer patients.

Abstract:

BACKGROUND:To establish the recommended dose (RD) of the thymidylate-synthase inhibitor ZD9331 administered with irinotecan (CPT-11) in patients with pretreated metastatic colorectal cancer, and to assess toxicity profile, pharmacokinetics (PK), and anti-tumor activity in a phase I/II open, multicenter, intrapatient chemotherapy dose escalating trial. PATIENTS AND METHODS:Twenty-one patients who failed first-line therapy (5-fluorouracil/leucovorin +/- oxaliplatin) received every 2 weeks CPT-11 180 mg/m2 D1, followed by ZD9331 30-minute infusion D2 at three dose levels: 90, 120 and 150 mg/m2. RESULTS:RD of ZD9331 was established at 90 mg/m2 for the first two cycles, with possibility to escalate at 120 mg/m2 according to safety evaluation. Grade 3-4 toxicities were neutropenia (67% of patients), grade 3 vomiting (14%), grade 3 nausea (10%) and grade 3 diarrhea (5%). ZD9331 dose level does not affect the PK of CPT-11 or SN-38. Tumor growth control (PR + SD) was achieved for 14 (66.7%) patients. Median time to progression was 6 months, and median survival was 8.4 months. CONCLUSION:ZD9331 90 mg/m2 combined with CPT-11 180 mg/m2 may be a viable option for treatment of metastatic colorectal cancer, with possible escalation to 120 mg/m2 of ZD9331 according to safety evaluation.

journal_name

Bull Cancer

journal_title

Bulletin du cancer

authors

Louvet C,André T,Gamelin E,Garcia ML,Saavedra A,Lenaers G,de Gramont A,Méry-Mignard D,Kalla S

subject

Has Abstract

pub_date

2004-12-01 00:00:00

pages

279-84

issue

12

eissn

0007-4551

issn

1769-6917

journal_volume

91

pub_type

临床试验,杂志文章,多中心研究
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    pub_type: 杂志文章,多中心研究

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