Journal of Clinical Oncology, Vol 1, 331-336, Copyright © 1983 by American Society of Clinical Oncology
Phase I study of spirogermanium given daily
SS Legha, JA Ajani and GP Bodey
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.
