mitoguazone and Rectal-Neoplasms

The Eastern Cooperative Oncology Group (ECOG) entered 326 patients with advanced measurable colorectal cancer into four phase II drug or drug combination trials. Previously treated and chemotherapy-naive patients were eligible. Chlorozotocin was administered to 83 patients (51 previously treated), methyl-glyoxal-bis-guanylhydrozone (MGBG) to 90 patients (58 previously treated), and two regimens of the three-drug combination of cyclophosphamide, vincristine, and methotrexate (COM) to 153 patients (120 previously treated). The multidrug regimen had been developed specifically for previously treated patients. In this trial, chemotherapy-naive patients were no more likely to respond than were members of the previously-treated group. Even among previously untreated patients, response rates did not exceed 10% in any of these phase II programs. They are not recommended for further trials in patients with colorectal cancers.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Cyclophosphamide; Drug Evaluation; Humans; Methotrexate; Mitoguazone; Rectal Neoplasms; Streptozocin; Vincristine

We have tested methyl glyoxal bis-guanyl hydrazone (NSC 32946) for antitumor activity in patients with colorectal carcinoma and non-small cell bronchogenic carcinoma. The drug dose was 500 mg/m2 administered by single weekly injection, and with a provision dose escalation. No responses were seen in 38 evaluable patients with colorectal cancer, including 17 who had received no prior chemotherapy. Three responses were seen among 42 patients with bronchogenic carcinoma. These included one each with epidermoid carcinoma, adenocarcinoma and large cell anaplastic carcinoma. None of these responders had received prior chemotherapy. Toxicity of the drug was predominantly gastrointestinal, namely nausea, vomiting and diarrhea, and tended to increase with repeated drug doses. Neurologic symptoms of various sorts were also prominent. We conclude that methyl-G is of marginal benefit in this dose and schedule to patients with bronchogenic carcinoma.

Topics: Adult; Aged; Antineoplastic Agents; Carcinoma; Carcinoma, Bronchogenic; Colonic Neoplasms; Drug Administration Schedule; Drug Evaluation; Female; Gastrointestinal Diseases; Guanidines; Humans; Lung Neoplasms; Male; Middle Aged; Mitoguazone; Rectal Neoplasms

Forty-four patients with advanced colon or rectal cancer were treated with methyl-GAG on a weekly schedule. Of the 40 evaluable patients, 35 (87%) had received prior chemotherapy. Objective tumor regression was seen in six patients (one CR, five PR's). An additional nine patients had stable disease for a median of 42 weeks. The median survival (42+ weeks) for responding and stable disease patients was significantly better (p = 0.0001 Wilcoxan test) than those with progressive disease (11 weeks). Toxicity was reversible and included mild to moderate mucositis, nausea, vomiting, diarrhea, and thrombocytopenia. Responses observed in this study warrant further trials in patients with colon cancer who have no prior chemotherapy.

Topics: Adult; Aged; Colonic Neoplasms; Drug Evaluation; Female; Guanidines; Humans; Male; Middle Aged; Mitoguazone; Rectal Neoplasms