title: Chemotherapy of advanced measurable colon and rectal carcinoma with oral 5-fluorouracil, alone or in combination with cyclophosphamide or 6-thioguanine, with intravenous 5-fluorouracil or beta-2'-deoxythioguanosine or with oral 3(4-methyl-cyclohexyl)-1(2-chlorethyl)-1-nitrosourea: a Phase II-III study of the Eastern Cooperative Oncology Group (EST 4273).
abstract: In a randomized multi-institutional trial of the Eastern Cooperative Oncology Group, 316 patients with advanced measurable colorectal adenocarcinoma were treated with a weekly schedule of 5-fluorouracil given orally and intravenously with oral-5-fluorouracil in combination with cyclophosphamide or 6-thioguanine, or with oral Methyl CCNU administered once every eight weeks. On failure or progression, 133 protocol patients crossed-over to a secondary therapy, while 116 other patients previously treated with 5-fluorouracil off protocol were randomized to treatment with Methyl CCNU or B-2'-deoxythioguanosine. Response rates among patients who had received no prior chemotherapy were 18% to oral 5-FU, 15% to intravenous 5-FU and to MeCCNU, 12% to 5-FU and 6-thioguanine and 5% to cyclophosphamide and 5-FU, with little activity (3% response rate) in crossover or previously treated patients. Treatment with 5-FU, particularly oral 5-FU was associated with the least drug-related toxicity. Hematologic toxicity was greatest with Methyl CCNU, but was no more frequent in previously treated than in untreated patients. A tendency toward cumulative bone marrow depression was noted. 5-FU was effective only in ambulatory patients, whereas responses among non-ambulatory patients were seen only in the group treated with Methyl-CCNU.
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001853:Bone Marrow / Q000187:drug effects; D002986:Clinical Trials as Topic; D003110:Colonic Neoplasms / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003849:Deoxyguanosine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis / Q000188:drug therapy; D012004:Rectal Neoplasms / Q000188:drug therapy*; D012673:Semustine / Q000008:administration & dosage; D013866:Thioguanine / Q000008:administration & dosage; D013872:Thionucleosides / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D013872:Thionucleosides; D012673:Semustine; C010438:beta-2'-deoxythioguanosine; D003520:Cyclophosphamide; D013866:Thioguanine; D003849:Deoxyguanosine; D005472:Fluorouracil