mitoguazone and Vomiting

Eflornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, and mitoguazone (MGBG), a competitive inhibitor of S-adenosylmethionine decarboxylase, were evaluated in a phase I-II study for patients with primary recurrent malignant brain tumors. All patients had failed prior radiation therapy and most had also failed prior chemotherapy. Two dose schedules were used, with the second schedule (Group II) a modification of the first schedule (Group I). The Group II schedule, with different dose levels, was better tolerated than the Group I schedule. Gastrointestinal and myelotoxicity were dose-limiting in most patients, and tinnitus was dose-limiting in two patients. Nineteen of 33 evaluable patients had anaplastic gliomas, in whom response was observed in 21%, stable disease in 53%, and immediate progression after one course of therapy in 26%. Of six patients with glioblastoma multiforme, two had brief stabilization of disease. An additional patient with brainstem glioma and ependymoma also had disease stabilization. Four patients with medulloblastoma, a spinal cord mixed glioma, and one with oligodendroglioma failed DFMO-MGBG. Based on this study, we believe that a combination of DFMO and MGBG is well-tolerated and deserves further evaluation for patients with anaplastic gliomas, particularly those that appear to be biologically slow growing.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Child; Drug Evaluation; Eflornithine; Humans; Leukopenia; Middle Aged; Mitoguazone; Nausea; Neoplasm Recurrence, Local; Thrombocytopenia; Tinnitus; Vomiting

Methylglyoxal bis (guanylhydrazone) (MGBG) is an inhibitor of polyamine synthesis. In vitro studies demonstrate the accumulation of some tumor cells in S and G2 phases of the cell cycle. Nineteen patients with advanced head and neck cancer were entered in a Phase II trial of MGBG. MGBG, 500 mg/M2, was administered as a brief intravenous infusion weekly for 4 weeks, then every 2 weeks. Dose modifications were based on cumulative toxicity after 2 weekly treatments. All but three patients had prior exposure to chemotherapy for disease recurrence. Of 17 patients evaluable for response and toxicity, one brief partial response was observed. The most common toxicities were mild to moderate nausea, vomiting, diarrhea, and stomatitis. Myelosuppression occurred in three patients. Dose modifications were required in four patients; a maximum dose of 700 mg/M2 was tolerated. The results of four other Phase II single and combination chemotherapy trials of MGBG in head and neck cancer are reviewed. The single agent response rate in 59 patients was 22% (range, 6%-41%). The poor response rate observed in this trial was similar to that in other trials in which a heavily pretreated group of patients was evaluated. It is concluded that single agent MGBG is not a useful drug in heavily pretreated recurrent disease patients. However, because of its biochemical effects, further testing in combination with cycle specific agents and in larger numbers of patients with minimal prior treatment may be warranted.

Topics: Aged; Animals; Cats; Diarrhea; Drug Evaluation; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Mitoguazone; Nausea; Vomiting

Eighteen patients with measurable or evaluable lesions from squamous cancer of the esophagus received a regimen combining four active agents on an outpatient basis. Nine of 14 evaluable patients (64%, or 50% of 18 patients entered) responded: four of five with previously untreated regional disease and five of nine with recurrent or metastatic disease. Median duration of response in the latter group was 5 months (longest response, 13). Treatment was well-tolerated in all patients but one, who developed signs of severe methotrexate toxicity and died of sepsis.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Creatinine; Esophageal Neoplasms; Female; Hemoglobins; Humans; Leukocyte Count; Male; Methotrexate; Middle Aged; Mitoguazone; Platelet Count; Vomiting

Thirty-nine patients received 600 mg/m2 OF MGBG intravenously every week for the treatment of advanced refractory ovarian cancer. Twenty-seven of these received adequate trials, and only two had partial remissions lasting 3 1/2 and 4 months each. Toxicity was substantial, with severe hematologic toxicity in 26%, diarrhea in 22% (severe in 7%), skin rash in 26% (severe in 7%), and vomiting in 70% (severe in 11%). Fatigue, facial paresthesias, and flushing during drug administration were frequent. It appears that MGBG in this dose and schedule has little activity against advanced ovarian cancer.

Topics: Blood; Drug Evaluation; Fatigue; Female; Guanidines; Humans; Mitoguazone; Ovarian Neoplasms; Vomiting

Topics: Drug Evaluation; Guanidines; Humans; Kidney Neoplasms; Middle Aged; Mitoguazone; Neuralgia; Vomiting

Fourteen patients with metastatic renal cell carcinoma received methyl-G weekly at a starting dose of 600 mg/m2 (five patients) and 500 mg/m2 (nine patients) intravenously. All 14 patients are evaluable for response and toxicity. No antitumor responses were observed. Six patients achieved stabilization of disease for 8 to 42 weeks. Toxicity was nonhematologic and included nausea or vomiting (35%), fever with shaking chills (28%), diarrhea (21%), myalgia (63%), paresthesia (49%), and bilateral foot drop (7%). Methyl-G does not appear to have activity against renal cell carcinoma.

Topics: Adenocarcinoma; Adult; Aged; Dose-Response Relationship, Drug; Drug Evaluation; Drug Resistance; Female; Guanidines; Humans; Male; Middle Aged; Mitoguazone; Nausea; Neoplasm Metastasis; Neoplasms; Paresthesia; Vomiting