germanium and Nervous-System-Diseases

The National Cancer Institute of Canada Clinical Trials Group conducted a phase II study of spirogermanium given daily for 5 days every 3 weeks to patients with poor prognosis non-Hodgkin's lymphomas. All patients had had a maximum of one prior treatment regimen. No responses were seen in 13 evaluable patients. Toxicity was primarily neurologic and mild or moderate in most patients. There is no evidence of activity of spirogermanium given in this schedule in this subset of lymphoma patients.

Topics: Aged; Antineoplastic Agents; Drug Evaluation; Germanium; Humans; Lymphoma; Middle Aged; Nervous System Diseases; Organometallic Compounds; Prognosis; Spiro Compounds

Spirogermanium, an azaspirane compound, has recently had limited clinical trials using a schedule of intravenous injection one to three times every week. The observation of clinical antitumor activity and lack of myelosuppression prompted us to investigate further the clinical effects of spirogermanium administered on various schedules. A total of 52 patients with advanced metastatic tumors refractory to standard therapy were treated with spirogermanium. Three different schedules of drug administration were evaluated. Initially, a short daily IV infusion for 5 days every week was evaluated, starting with a dose of 30 mg/m2/day. A total of 22 patients received 69 courses with a dose range of 30-120 mg/m2/day for 5 days every week. The maximum tolerated dose was 100 mg/m2/day IV over 1 hr and 120 mg/m2 over 2-3 hr. In the second phase of the study, 12 patients received 41 courses of spirogermanium as a 24-hr continuous infusion for 5 days/wk at a dose of 150-375 mg/m2/day. The maximum tolerated dose was 200 mg/m2/day for 5 days. In the third phase of the study, 18 patients received spirogermanium as a continuous infusion daily for a median of 30 days (range 6-77 days) in a dose range of 100-200 mg/m2/day. The maximum tolerated dose was 150 mg/m2/day. Of the 44 assessable patients, 3 demonstrated a partial response and 3 had minor tumor regression; all responses occurred in lymphoma patients. The dose-limiting toxicity of spirogermanium was neurologic; other side effects consisted of mild anorexia, nausea and vomiting, and possible lung toxicity. There was no clear evidence of cumulative toxicity despite daily administration of spirogermanium. Our data suggest that spirogermanium can be administered daily by several different schedules, and the optimum dose depends on the infusion time and the duration of therapy. The delivery of drug by continuous infusion permitted administration of twofold higher dose levels compared to the standard IV schedules used in previous studies.

Topics: Adult; Aged; Colonic Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Evaluation; Female; Germanium; Humans; Infusions, Parenteral; Lymphoma; Male; Middle Aged; Nausea; Nervous System Diseases; Organometallic Compounds; Ovarian Neoplasms; Spiro Compounds