The purpose of this trial was to test feasibility and tolerability of a multimodality treatment approach for patients with tumors in the upper gastrointestinal tract (EC, esophageal cancer; JC, cancer of the gastro-esophageal junction; GC, gastric cancer) including preoperative chemotherapy with the EAP-protocol as induction and a consecutive high-dose-chemotherapy for responding patients. Sixteen patients with locally advanced tumors of the esophagus, the gastro-esophageal junction or the stomach were treated with two cycles of EAP-chemotherapy (etoposide, 3x120 mg/m(2); adriamycin, 2x20 mg/m(2); cisplatin, 2x40 mg/m(2)). Responding (cPR, cCR) patients were included into a high-dose MCVB-chemotherapy protocol (mitomycin, 10 mg/m(2); cisplatin, 4x40 mg/m(2); vepeside, 5x200 mg/m(2); BCNU 300 mg/m(2)) and subsequent rescue with peripheral blood stem cells (PBSC). After a second restaging, surgery was performed in patients with no change or further response. Postoperative chemotherapy was given with either two cycles of EAP or FAMTX (methotrexate, 1,500 mg/m(2) + folinic acid rescue; 5-flourouracil, 1,500 mg/m(2); adriamycin, 30 mg/m(2)) according to pathological staging results. A total of 16 patients (EC, 7; JC, 6; GC 3) were treated within the protocol. Six patients achieved a major response upon EAP and 5/6 were included in the high-dose MCVB-protocol with stem cell rescue. All 5 could be yielded R(0) by definitive surgery and 2/5 had a pCR upon surgery. MCVB toxicity was predominantly hematologic (grade 4 in all 5 patients) with non-hematological toxicity not exceeding grade 2 (predominantly mucositis). Median survival time is 12 months for the non-responding patients and has not been reached for the MCVB patients. In conclusion, multimodality therapy including high-dose chemotherapy and stem cell rescue is feasible with tolerable toxicity in patients with locally advanced tumors of the upper gastrointestinal tract and should be further studied in phase II and III trials.