Phase I/II trial of triplet regimen with docetaxel, oxaliplatin and capecitabine in advanced gastric and gastroesophageal cancers

Background: Advanced and metastatic gastric cancers present at late stages and have very dismal prognosis. Many modifications have been tried for improving the outcome. Docetaxel, cisplatin and fluorouraciVepirubicin, cisplatin and fluorouracil regimen have been established as a standard combination in clinical trials; however, they are limited by their toxicities. Aim: We conducted a study to assess the maximal tolerated dose (MTD) of docetaxel given at days 1 and 8 along with fixed doses of oxaliplatin ( days I and 8) and capecitabine (days 1-14), toxicity profile, response rate and efficacy of the triplet combination in advanced/metastatic gastric and GEJ malignancies. Materials and Methods: Study was conducted in two phases; Phase I study assessed the MTD and Phase II assessed toxicity, response and efficacy of polychemotherapy. Escalating doses of docetaxel was tested in Phase I design along with oxaliplatin 50 mg/m(2) (days 1 and 8) and capecitabine 625 mg/m(2) (days 1-14). MTD dose of docetaxel was used in Phase II along with the other two drugs for assessment of primary and secondary endpoints. Results: A total of 24 patients were evaluated in Phase I design as per modified Fibonacci series. The MTD for docetaxel was 40 mg/m2 given on days 1 and 8. On evaluation of 27 patients in Phase II, hematological, neurological and biochemical toxicities were tolerable. Grade 3 diarrhea and hand-foot syndrome were the most common toxicities. Overall response rates were 66.6%. Median progression-free survival (PFS) was 8.4 months. Conclusion: The MTD of docetaxel was 40 mg/m(2) (days 1 and 8) administered along with oxaliplatin 50 mg/m(2) (days 1 and 8) and capecitabine 625 mg/m(2) (days 1-14). The regimen had proven to be efficacious with appreciable overall response rates, PFS with tolerable and manageable toxicities.