Abstract
108 Background: Trastuzumab (T) improves efficacy of doublet chemotherapy (TOGA trial) in HER2 positive patients with advanced gastro-esophageal (GE) cancer but safety and efficacy with triple chemotherapy is presently unknown. We initiated a dose-finding trial to establish a safe 4 drug combination of docetaxel (D), short-time infusion of oxaliplatin (O), continuously capecitabine (C) and trastuzumab (T). Methods: This phase I, dose-finding trial was approved by the local etic committee. All pts had histologically confirmed GE adenocarcinoma. Therapy was given day 1 with escalating doses of D (42mg/m2 to 51 mg/m2 as a 60 minutes infusion), O (100 mg/m2 as a 30 minutes infusion) and C (1,250 mg/m2/day continuously). DOC was repeated every 3 weeks for a maximum of 6 courses. T was given as a loading dose (8 mg/kg) followed by 6 mg/kg every 3 weeks until PD or unacceptable toxicity. Toxicity was evaluated according to NCIC-CTC 3.0. DLT was evaluated after the first course and defined as non-haematological toxicity grade ≥ 3, neutropenia grade 4 more than 7 days or febrile neutropenia. Response was evaluated by the investigator according to RECIST 1.0 every 9th weeks. Data was updated September 1, 2013. Results: From May 2010 to October 2012 we included 11 pts. Median age was 62years (range 32-73), 5/11 pts had PS 0, all pts had metastatic disease. Neutropenia grade 3-4 was observed in two pts, one had febrile neutropenia grade 3 after four courses. Two pts had grade 3 vomiting, fatigue, or nausea, respectively and one patient had diarrhoea grade 3. Only one pt developed a DLT (grade 3 vomiting, nausea and fatigue). Dose-intensity, after six courses, in all 11 pts was: D = 89%, O= 88% C = 81% and T = 100%. Median number of DOC was 6; all pts continued T to a median of 12 courses and one pt is presently receiving T. Partial response was obtained in 9 pts (81%). Progression free survival was 8.8 months and overall survival was 16.5 months. Five pts are presently alive. Conclusions: DOC-T in HER2 positive GE pts is safe and easily administered in an out-patient setting. The recommended doses for further evaluation are: D 51 mg/m2, O 100 mg/m2, C 1,250 mg/m2. Efficacy is very promising and deserves evaluation in larger trials. Clinical trial information: NCT01295086.
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