PHASE-II PILOT TRIAL OF PREOPERATIVE HIGH-DOSE CHEMOTHERAPY IN PATIENTS WITH MALIGNANT-TUMORS OF THE UPPER GASTROINTESTINAL-TRACT

The purpose of this trial was to test feasibility and tolerability of a multimodality treatment approach for patients with tumors in the upp er gastrointestinal tract (EC, esophageal cancer; JC, cancer of the ga stro-esophageal junction; GC, gastric cancer) including preoperative c hemotherapy with the EAP-protocol as induction and a consecutive high- dose-chemotherapy for responding patients. Sixteen patients with local ly advanced tumors of the esophagus, the gastro-esophageal junction or the stomach were treated with two cycles of EAP-chemotherapy (etoposi de, 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-ch emotherapy protocol (mitomycin, 10 mg/m(2); cisplatin, 4x40 mg/m(2); v epeside, 5x200 mg/m(2); BCNU 300 mg/m(2)) and subsequent rescue with p eripheral blood stem cells (PBSC). After a second restaging, surgery w as performed in patients with no change or further response. Postopera tive chemotherapy was given with either two cycles of EAP or FAMTX (me thotrexate, 1,500 mg/m(2) + folinic acid rescue; 5-flourouracil, 1,500 mg/m(2); adriamycin, 30 mg/m(2)) according to pathological staging re sults. 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. A ll 5 could be yielded R(0) by definitive surgery and 2/5 had a pCR upo n surgery. MCVB toxicity was predominantly hematologic (grade 4 in all 5 patients) with non-hematological toxicity not exceeding grade 2 (pr edominantly 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 an d stem cell rescue is feasible with tolerable toxicity in patients wit h locally advanced tumors of the upper gastrointestinal tract and shou ld be further studied in phase II and III trials.