title: Phase I and II clinical study of anhydro-ara-5-fluorocytosine (AAFC) and ICRF-159 combination in adenocarcinoma of digestive origin.
abstract: The results of a phase I--II study of a combination chemotherapy with AAFC and ICRF-159 in advanced adenocarcinoma of digestive origin are presented. Myelosuppression was the dose-limiting toxicity with anemia, leukopenia, and thrombocytopenia. The maximum tolerated dose of AAFC in the combination program was 650 mg/m2 I.V. weekly. ICRF-159 was given in a 3-day course every 3 weeks and the dose was escalated from 125 mg/m2 to 500 mg/m2 daily. Bone marrow toxicity was noticied at the first escalation level and all dose levels were similarly toxic. The results of this combination chemotherapy were: two partial responses in 14 patients with gastric cancer; no responses in nine patients with colorectal cancer; no responses in three patients with pancreatic cancer; and no responses in two patients with biliary tree cancer. In conclusion, AAFC and ICRF-159 combination chemotherapy demonstrated a low level of activity in advanced carcinoma of digestive origin. The peculiar hematologic toxicity found at the low-level dose requires further documentation and could make this drug association suitable for a phase II study in leukemia and/or lymphoma.
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D003504:Ancitabine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D001853:Bone Marrow / Q000187:drug effects; D003561:Cytarabine / Q000031:analogs & derivatives*; D004067:Digestive System Neoplasms / Q000188:drug therapy*; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D011929:Razoxane / Q000008:administration & dosage* / Q000633:toxicity; D012075:Remission, Spontaneous
chemical_list: D010879:Piperazines; D003561:Cytarabine; D011929:Razoxane; C011168:5-fluoro-2,2'-cyclocytidine; D003504:Ancitabine