Lack of efficacy of 9-aminocamptothecin in adults with newly diagnosed glioblastoma multiforme and recurrent high-grade astrocytoma

9-Aminocamptothecin (9-AC) was administered as a 72-h i.v. infusion every 2 weeks to a total of 99 adults with high-grade astrocytomas, Fifty-one pati ents with newly diagnosed glioblastoma multiforme received 9-AC treatment p rior to radiation therapy and 48 patients with high-grade astrocytomas were treated at the time of tumor recurrence. Upon entrance into these research protocols, all patients had measurable disease that was evaluated on a mon thly basis with volumetric CT or MRI scans. A partial response was defined by greater than or equal to 50% reduction in the contrast enhancing volume on stable or decreasing doses of glucocorticoids, The study specified that all apparent responders would have central review of their radiologic studi es and histopathology, The initial patients treated with 9-AC were also rec eiving anticonvulsants and were noted to have minimal myelosuppression with this chemotherapy. Thus, 9-AC doses were escalated from the previously rep orted maximum tolerated dose (MTD) of 850 mug/m(2)/24 h, We then establishe d new MTDs for patients receiving enzyme-inducing anticonvulsants, We defin ed these MTDs to be 1776 pg/m(2)/24 h for newly diagnosed, previously untre ated patients and 1611 pg/m2/24 h for patients with recurrent disease. Twen ty-two patients with newly diagnosed glioblastoma multiforme received 9-AC at doses greater than or equal to 1776 mug/m(2)/24 h, Of these, 18 had eval uable disease on central review, and 0 of 18 (0%) demonstrated a partial or complete response. Twenty-one patients with recurrent high-grade astrocyto mas were treated at 1611 mug/m(2)/24 h; 20 had evaluable disease and 0 of 2 0 (0%) had a partial or complete response. Thus, the overall response rate in the 38 evaluable patients treated at the MTD was 0 of 38 (0%), Furthermo re, of the 51 evaluable patients who were treated at doses less than the MT D, only one partial response was observed, yielding an overall response rat e of 2%, Evidence of drug failure was rapid with tumor progression in one-h alf of patients after 2 drug cycles. 9-AC lacks evidence of substantial act ivity in patients with newly diagnosed or recurrent high-grade astrocytomas .