Thirty-nine adults with solid
tumors were treated on a Phase I study of
menogaril administered i.v. once each week.
Granulocytopenia was dose-limiting at a
menogaril dose of 115 mg/m2/wk. Ten patients required delays in treatment of 1-4 weeks (median, 1 week) at some point during their treatment until they recovered from
granulocytopenia. The average dose intensity possible on this schedule was at least 80% higher than that possible using a single-day or a five-times-daily schedule every 4 weeks. One patient developed
infection while neutropenic, and only one patient developed
thrombocytopenia.
Dexamethasone appeared to reduce the degree of myelosuppression. Gastrointestinal toxicity was quite mild, and
alopecia was uncommon. Arm vein
phlebitis frequently followed
menogaril administration, requiring the use of Hickman
catheters (or equivalents). Two patients had
myocardial infarcts while on treatment. It was unclear if the
menogaril was in any way responsible. Reversible
dyspnea and
cough (with no evidence of
congestive heart failure) were seen in some patients. Responses were seen in patients with
gliomas,
renal-cell carcinoma, and bladder
carcinoma, and marked subjective improvement occurred in a single patient with
prostate cancer. We plan to conduct a Phase II study in
astrocytoma patients using a
menogaril dose of 115 mg/m2/wk i.v.