beta-2--deoxythioguanosine and Colonic-Neoplasms

The Eastern Cooperative Oncology Group assessed the activity of diglycoaldehyde (DGA), VP-16-213, and the combination of methyl-CCNU and beta-2'-deoxythioguanosine in previously treated patients with advanced colorectal cancer. Objective responses were seen in two of 40 evaluable patients receiving methyl-CCNU and beta-2'-deoxythioguanosine and in one of 35 patients receiving DGA. None of 33 patients responded to VP-16-213, but one death related to sepsis and bone marrow failure occurred. Survival of patients whose previous chemotherapy included a nitrosourea was markedly shortened compared to those who had not been exposed to nitrosoureas. With the possible exception of DGA, further treatment of patients with colorectal cancer with these therapies is not warranted.

Topics: Aldehydes; Colonic Neoplasms; Deoxyguanosine; Drug Evaluation; Drug Therapy, Combination; Etoposide; Female; Humans; Inosine; Male; Nitrosourea Compounds; Podophyllotoxin; Rectal Neoplasms; Semustine; Thionucleosides

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

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