NEW YORKEarly studies of pixantrone, a chemotherapeutic agent in clinical development primarily in lymphoma, suggest that it is active and potentially less cardiotoxic than other anthracenedione agents. John P. Leonard, MD, clinical director of the Center for Lymphoma and Myeloma and associate professor of medicine at Weill Medical College of Cornell University/New York Presbyterian Hospital, outlined early findings about pixantrone at the Chemotherapy Foundation Symposium XXIV. The agent is being developed by Cell Therapeutics, Inc. (CTI) in Seattle.
In recent years, about 300 patients have been treated with pixantrone in phase I and II trials, Dr. Leonard said. All the studies included cardiac monitoring and strict screening for cardiac issues. Of 80 patients in three phase I single-agent trials, 26 had recurrent non-Hodgkin's lymphoma (NHL) or chronic lymphocytic leukemia. Of these 26 patients, 6 responded (23%, 1 CR).
In a phase II single-agent trial of 33 patients with relapsed aggressive lymphomas, 9 responded (27%, 5 CRs). The median duration of response was 11+ months. The main toxicity was neutropenia. Dr. Leonard noted that these patients had received a median prior cumulative dose of doxorubicin of 300 mg/m2. "Seven patients had an asymptomatic LVEF [left ventricular ejection fraction] decline; they had previously all received significant doses of anthracyclines. These were generally mild. Only one patient had a greater than 20% decline," he said.
In three phase I-II lymphoma trials, pixantrone was substituted for agents in standard chemotherapeutic regimens, replacing etoposide in ESHAP, mitoxantrone in FND-R, and doxorubicin in CHOP-based regimens. In a phase II trial presented by Camboni at ASCO in 2004, pixantrone was substituted for etoposide in the ESHAP regimen in patients with relapsed/aggressive NHL. Of 18 evaluable patients, 61% had a response (7 CRs). Half of the responding patients went on to stem cell transplant.
The principal toxicity was hematologic, with mild decreases in LVEF seen in eight patients. "So, acceptable toxicity, meaningful activity in these pretreated patients," Dr. Leonard said. Positive results were also seen in the other two combination studies.
Finally, he took note of a phase III study by Santoro et al that looked at the combination of pixantrone and rituximab (Rituxan) vs rituximab alone in relapsed indolent lymphoma patients with up to five prior regimens. Pixantrone was added to the standard four doses of rituximab. The study, which had to be closed because of slow accrual, was presented at ASCO this year. A total of 32 patients were enrolled. Even with that small number, the response rate more than doubled with the addition of pixantrone, from 33% to 75% (P = .02). Progression-free survival was also significantly better.