Forty-seven patients with solid
tumors were treated on a phase I study of
menogaril administered by mouth once per week.
Nausea and
vomiting were excessive at weekly doses of 350 and 450 mg/m2/week but were tolerable and controlled reasonably well by
antiemetics at lower doses. There appeared to be a relatively shallow dose-vs-
granulocytopenia curve above a
menogaril dose of 180 mg/m2/week. No patient receiving chronic
dexamethasone for
cerebral edema developed
granulocytopenia, even at
menogaril doses of 350-450 mg/m2/week. Two patients developed neutropenic
infection. No patient developed
thrombocytopenia. Mild arrhythmias were seen in 3 patients. Two patients suffered possible
myocardial infarcts that may not have been related to treatment. Asymptomatic blood pressure fluctuations were common and were probably not related to treatment.
Diarrhea was dose-related but was generally not severe.
Alopecia and
stomatitis occurred occasionally. Minor responses were seen in two patients with
gliomas, and three of five evaluable
prostate cancer patients experienced marked
pain relief. The dose recommended for phase II studies is 250-300 mg/m2/week with
antiemetic pretreatment. This schedule appears to allow an oral
menogaril dose-intensity that is approximately double that attainable with other oral schedules that have been studied.