Phase I Study of Matuzumab in Combination with 5-fluorouracil, Leucovorin and Cisplatin (PLF) in Patients with Advanced Gastric and Esophagogastric Adenocarcinomas

Overview

Journal Invest New Drugs

Publisher Springer

Specialty Oncology

Date 2012 Jul 6

PMID 22763610

Citations 5

Authors

Tanja Trarbach

Marta Przyborek

Norbert Schleucher

Steffen Heeger

Christian Lupfert

Udo Vanhoefer

Affiliations

Soon will be listed here.

Abstract

Background: To evaluate the safety and tolerability of two different weekly doses of the fully humanized epidermal growth factor receptor (EGFR)-targeting monoclonal antibody matuzumab combined with high-dose 5-fluorouracil, leucovorin and cisplatin (PLF) in the first-line treatment of patients with EGFR-positive advanced gastric and esophagogastric adenocarcinomas.

Methods: Patients were treated in two matuzumab dose groups with the first cohort of patients receiving 400 mg matuzumab in combination with PLF. Based on the safety observations the next cohort of patients received 800 mg matuzumab. The study was conducted in two parts, with phase A, designed to assess the safety and tolerability of the combination, and phase B designed to be a treatment continuation for those patients benefiting from treatment. Treatment cycles were 7 weeks each. Each patient received the dose of matuzumab they were assigned to at study entry for the duration of the study.

Results: Fifteen EGFR-positive patients were enrolled into the two matuzumab dose groups; 400 mg dose n=7; 800 mg dose n=8. All patients experienced at least one adverse event (AE). No patient experienced any serious AE which was considered to be related to matuzumab. Two grade 3 AEs possibly related to matuzumab occurred in 2 different patients (13.3 %), both in the 800 mg dose group. No dose-limiting toxicity (DLT) was observed in the 400 mg group. The maximum tolerated dose of matuzumab was not reached. The best confirmed overall response rate was 26.7 %.

Conclusion: Matuzumab, in combination with PLF, demonstrated an acceptable safety profile with modest anti-tumor activity.

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