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 fluorouracil/epirubicin, 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 1 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/m ² 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.