Phase II trial of 9-aminocamptothecin as a 72-h infusion in cutaneous T-cell lymphoma

Purpose: To evaluate the role of 9-aminocamptothecin (9-AC), a synthetic ca mptothecin analog, in advanced cutaneous T-cell lymphoma (CTCL). Methods: E ligible patients had stage IIB-IV CTCL. 9-AC was infused over 72 h at a dos e of 1,100 mug/m(2) per day (approximately 46 mug/m(2)/h) every 2 weeks, wi th granulocyte-colony stimulating factor (G-CSF) support. Results: Twelve p atients received a total of 30 cycles of 9-AC. Nine patients had stage IV d isease, 5 patients had circulating Sezary cells, and 2 patients had evidenc e of tranformation to a large cell lymphoma. Most of the patients were heav ily pretreated: 10 had received prior chemotherapy (83%), 5 of whom had rec eived 2 or more prior regimens, including a patient who had received high-d ose chemotherapy, and 7 had previously received total-skin electron beam th erapy. The study was prematurely terminated due to substantial toxicity. Si x patients (50%) developed an indwelling central venous catheter-related in fection, 5 during a period of neutropenia. Three patients died due to sepsi s 4-8 weeks after their last 9-AC treatment. Two of these patients had a pr evious history of bacterial sepsis. Four patients (33%) developed grade IV thrombocytopenia. Two partial responses were observed (response rate 17%), but the duration of response was brief, 4-8 weeks. Conclusion: 9-AC at this schedule and route of administration had activity but resulted in an unacc eptable rate of complicated neutropenia and septic deaths in heavily pretre ated patients with advanced CTCL who are susceptible to catheter-related in fections.