PHASE-II AND DOSE-ESCALATION WITH OR WITHOUT GRANULOCYTE-COLONY-STIMULATING FACTOR STUDY OF 9-AMINOCAMPTOTHECIN IN RELAPSED AND REFRACTORY LYMPHOMAS

Purpose: To assess the efficacy and maximum dose-intensity of a new to poisomerase I (topa I)-targeting agent, 9-aminocamptothecin (9-AC), in patients with relapsed or refractory lymphomas. Patients and Methods: Eligible patients had measurable disease and were considered incurabl e. 9-AC was infused over 72 hours at an initial dose rate of 40 mu g/m (2)/h every 3 weeks with subsequent intrapatient escalations or reduct ions in 10-mu g/m(2)/h increments based on toxicity, To assess the imp act of granulocyte-colony stimulating factor (G-CSF) on dose-intensity , the first 16 patients received no G-CSF and the subsequent 29 patien ts received G-CSF on all cycles. Results: Forty-five patients received a total of 142 cycles of 9-AC, The patients' median age was 55 years, 73% had stage IV disease, and histologies included indolent and aggre ssive non-Hodgkin's lymphoma (NHL) in 33% and 58% of patients, respect ively, and Hodgkin's lymphoma in 9%, Patients had received a median of two prior chemotherapy regimens, and 67% of patients had chemotherapy -sensitive disease. Of 40 assessable patients, 10 (25%) achieved a par tial response (PR). Chemotherapy-sensitive patients had a 32% response rate compared with 8% in chemotherapy-resistant patients. With a medi an follow-up duration of 35 months, the median event-free survival (EF S) and overall survival times were 1.5 and 12.5 months, respectively, and the median duration of response wets 5 months (range, 1 to 10). G- CSF significantly reduced the incidence of neutropenia and diarrhea, b ut did not permit a significant increase in dose-intensity.Conclusion: 9-AC had a reasonable response rate of 25% in heavily pretreated pati ents. The low response rate in patients with chemotherapy-resistant di sease suggests that there is cross-resistance between 9-AC and standar d chemotherapy. However, there was no association between 9-AC respons e and the number of prior regimens. Due to dose-limiting thrombocytope nia, C-CSF support did not increase dose-intensity, although individua l patients benefited from the use of G-CSF. (C) 1998 by American Socie ty of Clinical Oncology.