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 camptothecin analog, in advanced cutaneous T-cell lymphoma (CTCL). Methods: Eligible patients had stage IIB-IV CTCL. 9-AC was infused over 72 h at a dose of 1,100 mug/m(2) per day (approximately 46 mug/m(2)/h) every 2 weeks, with granulocyte-colony stimulating factor (G-CSF) support. Results: Twelve patients received a total of 30 cycles of 9-AC. Nine patients had stage IV disease, 5 patients had circulating Sezary cells, and 2 patients had evidence of tranformation to a large cell lymphoma. Most of the patients were heavily pretreated: 10 had received prior chemotherapy (83%), 5 of whom had received 2 or more prior regimens, including a patient who had received high-dose chemotherapy, and 7 had previously received total-skin electron beam therapy. The study was prematurely terminated due to substantial toxicity. Six patients (50%) developed an indwelling central venous catheter-related infection, 5 during a period of neutropenia. Three patients died due to sepsis 4-8 weeks after their last 9-AC treatment. Two of these patients had a previous 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 unacceptable rate of complicated neutropenia and septic deaths in heavily pretreated patients with advanced CTCL who are susceptible to catheter-related infections.