Journal Article

Phase I study of imatinib, cisplatin and 5-fluoruracil or capecitabine in advanced esophageal and gastric adenocarcinoma

Schulte, Nadine, Hofheinz, Ralf, Mayr, Martina, Krause, Annekatrin, Röcken, Christoph, Becker, Karen, Ebert, Matthias P, Schmid, Roland M, Belle, Sebastian

2012

Overview

Background Despite all benefit provided by established therapies prognosis of gastric cancer remains poor. Targeted inhibition of platelet derived growth factor receptor (PDGFR) by imatinib may influence tumor growth and amplify chemotherapeutic effects. Methods This phase I study evaluated dose limiting toxicity (DLT) of imatinib combinated with chemotherapy according to a 3-patient cohort dose-escalating design. Thirty-five patients received cisplatin (60 mg/m 2 d1 q 3w)/ capecitabine (1250 mg/m 2 bid d1-14 q 21) or cisplatin (50 mg/m 2 d1 q 2w)/ 5-fluoruracil (2 g/m 2 d1, q 1w). Imatinib was started d - 4 with dose escalation from 300 to 700 mg QD in 100 mg steps. Results At imatinib dose level 1 (300mg) one DLT was observed, three more patients were enrolled without further DLT. At dose level 5 (700 mg) two gastric perforations occurred, so 600 mg imatinib emerged as the maximum tolerated dose. Major grade 3/4 toxicities were nausea (6%), anemia (6%) and fatigue (3%). Response evaluation revealed partial response in 27% and stable disease in 43% of the assessable patients. Conclusions Combination of imatinib and chemotherapy is well tolerated. Response rates were not superior to those of standard therapy. Further investigations of a larger group of patients are required to confirm the amplification of chemotherapy effects by imatinib. Trial registration European Clinical Trials Database: Eudra-CT2006-005792-17 and Clinical Trials Database: NCT00601510

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adenocarcinoma - drug therapy / Adenocarcinoma - metabolism / Adult / Aged / Anemia / Antimitotic agents / Antineoplastic agents / Antineoplastic Combined Chemotherapy Protocols - adverse effects / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Benzamides - administration & dosage / Benzamides - adverse effects / Biomedical and Life Sciences / Biomedicine / Cancer / Cancer Research / Cancer therapies / Capecitabine / Chemotherapy / Cisplatin / Cisplatin - administration & dosage / Cisplatin - adverse effects / Clinical trials / Complications and side effects / Deoxycytidine - administration & dosage / Deoxycytidine - adverse effects / Deoxycytidine - analogs & derivatives / Dosage and administration / Drug therapy / Esophageal cancer / Esophageal Neoplasms - drug therapy / Esophageal Neoplasms - metabolism / Female / Fluorouracil / Fluorouracil - administration & dosage / Fluorouracil - adverse effects / Fluorouracil - analogs & derivatives / Gastric cancer / Health aspects / Health Promotion and Disease Prevention / Hospitals / Humans / Imatinib / Imatinib Mesylate / Male / Maximum Tolerated Dose / Medicine/Public Health / Middle Aged / Oncology / Pathology / Patients / PDGF / Piperazines - administration & dosage / Piperazines - adverse effects / Platelet-derived growth factor / Prognosis / Proto-Oncogene Proteins c-kit - metabolism / Pyrimidines - administration & dosage / Pyrimidines - adverse effects / Receptors, Platelet-Derived Growth Factor - metabolism / Research Article / Signal transduction / Stomach cancer / Stomach Neoplasms - drug therapy / Stomach Neoplasms - metabolism / Studies / Surgical Oncology / Tumors