Phase I study of imatinib, cisplatin and 5-fluoruracil or capecitabine in advanced esophageal and gastric adenocarcinoma
1 Department of Internal Medicine II, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
2 Institute for Pathology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
3 Department of Medicine II, University Hospital Mannheim, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany
4 Department of Medicine III, University Hospital Mannheim, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany
5 Novartis Pharma GmbH, Nürnberg, Germany
6 Institute of Pathology, Christian-Albrechts Universität, Kiel, Germany
BMC Cancer 2012, 12:587 doi:10.1186/1471-2407-12-587Published: 10 December 2012
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.
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/m2 d1 q 3w)/ capecitabine (1250 mg/m2 bid d1-14 q 21) or cisplatin (50 mg/m2 d1 q 2w)/ 5-fluoruracil (2 g/m2 d1, q 1w). Imatinib was started d - 4 with dose escalation from 300 to 700 mg QD in 100 mg steps.
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.
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.
European Clinical Trials Database: Eudra-CT2006-005792-17 and Clinical Trials Database: NCT00601510