beta-2--deoxythioguanosine and Adenocarcinoma

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.

Topics: Adenocarcinoma; Antineoplastic Agents; Bone Marrow; Clinical Trials as Topic; Colonic Neoplasms; Cyclophosphamide; Deoxyguanosine; Drug Therapy, Combination; Female; Fluorouracil; Humans; Male; Neoplasm Metastasis; Rectal Neoplasms; Semustine; Thioguanine; Thionucleosides

Phase II trials of several single agents demonstrated only minimal objective response rates in patients with pancreatic carcinoma and measurable tumors: hexamethylmelamine (7%; four responses among 55 patients); dianhydrogalactitol (2.5%; one response among 40 patients); razoxane (7%; two responses among 29 patients); and beta-2'-deoxythioguanosine (6%; two responses among 32 patients). Among patients with a good performance status (0-2) and no prior chemotherapy, response rates were 8% for hexamethylmelamine (two responses among 26 patients); 8% for dianhydrogalactitol (one response among 13 patients); 8% for razoxane (one response among 12 patients); and 10% for beta-2'-deoxythioguanosine (two responses among 20 patients). None of these agents given by the methods of this study offers substantive benefit to the patient with advanced pancreatic cancer.

Topics: Adenocarcinoma; Altretamine; Antineoplastic Agents; Deoxyguanosine; Dianhydrogalactitol; Drug Evaluation; Humans; Leukopenia; Pancreatic Neoplasms; Piperazines; Razoxane; Sugar Alcohols; Thionucleosides; Thrombocytopenia; Triazines

Two hundred twenty eligible patients with metastatic colorectal carcinoma were treated with a combination of beta-2'-deoxythioguanosine (BTG), plus methyl-CCNU or mitomycin. There was no significant difference in overall response (CR/PR + stable) among fully evaluable patients between the mitomycin plus BTG arm 19/96 (19.7%) and the MeCCNU arm 26/87 (29.8%). Median survival of eligible patients was 19 weeks with mitomycin plus BTG versus 21 weeks with MeCCNU plus BTG: no difference. Median survival of responders (40 weeks) and patients with stable disease (35 weeks) was significantly better than patients with increasing disease (17 weeks): p + 0.001.

Topics: Adenocarcinoma; Colonic Neoplasms; Deoxyguanosine; Drug Evaluation; Drug Therapy, Combination; Humans; Leukopenia; Lomustine; Mitomycins; Nausea; Nitrosourea Compounds; Thionucleosides; Thrombocytopenia

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Cattle; Chromatography; Deoxyguanosine; Mammary Neoplasms, Animal; Mammary Neoplasms, Experimental; Metabolism; Mice; Neoplasms, Experimental; Nucleosides; Pharmacology; Research; Sulfhydryl Compounds; Thioguanine; Thionucleosides; Ultraviolet Rays

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Chemistry, Pharmaceutical; Deoxyguanosine; DNA; DNA, Neoplasm; Mammary Neoplasms, Animal; Mammary Neoplasms, Experimental; Metabolism; Mice; Nucleosides; Pharmacology; Research; RNA; RNA, Neoplasm; Thioguanine; Thionucleosides