Two phase I studies of concurrent radiation therapy with continuous-infusion 5-fluorouracil plus epirubicin, and either cisplatin or irinotecan for locally advanced upper gastrointestinal adenocarcinomas.

Purpose: Multimodality therapy with chemotherapy and radiation treatment may improve disease control and overall outcome of locally advanced upper gastrointestinal (UGI) malignancies including esophageal, gastric, pancreatic, and biliary tract carcinomas. However, more effective and less toxic chemotherapy regimens with concomitant radiotherapy are needed beyond concurrent continuous-infusion fluorouracil (CIFU) with radiation that is commonly applied in general practice. Epirubicin, cisplatin, and irinotecan are active cytotoxic chemotherapy agents in UGI cancers.

Methods: Two parallel phase I studies were designed to test the tolerability (dose-limited toxicity [DLT] and maximum tolerable dose [MTD]) of the combination of radiotherapy concurrently with CIFU, epirubicin, and cisplatin (ECF/radiation) or CIFU, epirubicin, and irinotecan (EIF/radiation) in the treatment of locally advanced upper GI malignancies. CIFU was administered through a portable infusion pump for 5 1/2 weeks during radiation treatment (50.4 Gy-a dose of 45 Gy in 25 fractions of 1.8 Gy, with additional comedown of 5.4 Gy). Epirubicin, cisplatin, or irinotecan were administered intravenously each week for 5 weeks (days 1, 8, 15, 22, and 29).

Results: The MTDs recommended for further studies are: 5-fluorouracil 200 mg/m²/day CI, weekly cisplatin 20 mg/m² and epirubicin 10 mg/m² for ECF/radiation combination; 5-fluorouracil 200 mg/m²/day CI, weekly irinotecan 30 mg/m² and epirubicin 10 mg/m² for EIF/radiation regimen. The DLTs are neutropenia, diarrhea/dehydration, and mucositis as expected.

Conclusions: Both regimens are safe with expected toxicities, and the efficacy of both regimens was encouraging. Further larger scale studies should be considered.