The prognosis of locally advanced or metastatic adenocarcinoma of the stomach is poor. In an attempt to improve therapeutic results, we undertook a phase II trial to investigate a combination of paclitaxel, carboplatin, and oral etoposide, all active drugs in this malignancy and with a synergistic effect in combination. Fourteen patients with advanced gastric adenocarcinoma were treated with paclitaxel 200 mg/m2 iv, carboplatin AUC-6 iv on d 1, and oral etoposide 50 mg/d alternating with 100 mg/d on d 1-10. Cycles were repeated every 3 wk. Of the 14 patients treated, partial response was observed in 3/12 (25%) evaluable patients. Median survival for the entire group was 7 mo. The treatment was associated with severe myelotoxicity. Neutropenic fever that required hospitalization developed in 7/14 (50%) of patients, and symptomatic anemia that required red blood cell transfusion was noted in 8/14 (57%). There was one drug-related death associated with neutropenic fever, Gram negative sepsis, grade 4 thrombocytopenia, and gastrointestinal bleeding. Nonhematological toxicity was moderate. We conclude that the current regimen of paclitaxel, carboplatin, and oral etoposide is not recommended in advanced gastric carcinoma owing to unacceptable myelotoxicity.