title: Controlled phase III clinical study of 4-epi-doxorubicin + 5-fluorouracil versus 5-fluorouracil alone in metastatic gastric and rectosigmoid cancer.
abstract: The combination of 4-epi doxorubicin (4-epi-DX) and 5-fluorouracil (5-FU) versus 5-FU alone was studied in previously untreated patients with metastatic gastric and rectosigmoid cancer. 5-FU alone was administered at the dose of 12 mg/kg/day i.v. on days 1, 2, 3, 4 and 5 every 3-4 weeks. The combination regimen included 4-epi-DX 40 mg/m2/day i.v., on days 1 and 2 (80 mg/m2/cycle) and 5-FU administered as in the single-agent schedule, but at a somewhat lower dose (10 mg/m2/day i.v. on days 1, 2, 3, 4 and 5). Sixty-two patients with gastric cancer were evaluable, 30 in the 5-FU group and 32 in 4-epi-DX + 5-FU group. The results showed 6 partial remissions out of 30 patients treated with 5-FU alone (response rate 20%) with a median remission duration of 4 months. With 4-epi-DX + 5FU the response rate was 41% (13/32) with 1 complete and 12 partial remissions. The median remission duration was 8 months. The difference in treatment results was statistically significant (p less than 0.05). In rectosigmoid cancer the group on 5-FU included 26 patients who showed a response rate of 19% (5/26). 4-epi-DX + 5-FU resulted in 6 responses (2 complete remissions, 4 partial remissions) out of 27 patients treated (22%). Median remission duration in the 5-FU group was 3 months whereas it was 6 months in the 4-epi-DX + 5-FU group. Toxicity was mild and well tolerated in both treatment modalities. The results of the study in gastric cancer showed a clear-cut superiority of 4-epi-DX + 5-FU over 5-FU alone, while no difference in response rate was observed between the two approaches in rectosigmoid cancer. Nevertheless, rectal localization of primary tumors showed a slightly better response to 4-epi-DX + 5-FU (33 vs. 16%).
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D015251:Epirubicin; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006331:Heart Diseases / Q000139:chemically induced; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008207:Lymphatic Metastasis / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D012004:Rectal Neoplasms / Q000188:drug therapy*; D012811:Sigmoid Neoplasms / Q000188:drug therapy*; D013274:Stomach Neoplasms / Q000188:drug therapy*
chemical_list: D015251:Epirubicin; D004317:Doxorubicin; D005472:Fluorouracil