Docetaxel in advanced gastric cancer

Standard chemotherapy for advanced gastric cancer remains undefined. Two of the most popular regimens-ECF [epirubicin-cisplatin-5-fluorouracil (5-FU)] and PELF (cisplatin-epirubicin-5-FU-leucovorin)-have been shown to be active, but each has limitations. Phase II trials show that single-agent docetaxel is an active agent in advanced gastric cancer, producing overall response rates (ORRs) of 17.5-24%. Docetaxel has also been shown to lack cross-resistance with other drugs in gastric cancer, and is likely to be at least additive to cisplatin and 5-FU. Phase II results of docetaxel combinations in advanced gastric cancer are encouraging. Docetaxel-cisplatin has yielded response rates similar to those achieved by ECF and PELF. Adding 5-FU to docetaxel-cisplatin has achieved an ORR of 52 versus 45% for docetaxel-cisplatin in a randomized phase II trial. Docetaxel-based regimens demonstrate acceptable tolerability despite predictable hematotoxicity. Neutropenia, the major toxicity, is manageable by dose modification or by using prophylactic granulocyte colony stimulating factor. Several phase III trials are now ongoing, including a large-scale trial of docetaxel-cisplatin-5-FU versus cisplatin-5-FU. Results will show whether docetaxel improves overall response and survival, as suggested in the phase II setting.