The Oncologist, Vol. 2, No. 3, 192–192,
June 1997
© 1997 AlphaMed Press
SPECIAL FEATURE
BRIEF REPORT |
Liposomally Encapsulated Daunorubicin (DaunoXome) in the Treatment of Non-Hodgkin's Lymphoma
Anil Tulpule, M.D.
Kenneth Norris Jr. Cancer Hospital, 1441 Eastlake Avenue, Room 162, Los Angeles, CA 90033
Liposomal encapsulation of Daunorubicin markedly alters the toxicity profile usually seen with anthracyclines. The initial phase I/II clinical work with DaunoXome was performed at the University of Southern California School of Medicine in Los Angeles. The maximum tolerated dose was between 100 mg/m2 and 120 mg/m2 given every three weeks. The dose-limiting toxicity was myelosuppression. However, other characteristic anthracycline toxicities were markedly diminished or absent. For example, there was little or no nausea and vomiting; alopecia and mucositis were rarely seen. Most notably, patients were able to remain on therapy for prolonged periods of time, after cumulative doses in excess of 2,000 mg/m2 without evidence of cardiac toxicity. Phase II trials of DaunoXome showed good antitumor activity in patients with AIDS-related Kaposi’s sarcoma (KS). Thus, a pivotal phase III trial was conducted in AIDS-related KS. The result of this study showed DaunoXome had comparable activity to standard treatment with combination chemotherapy (ABV) and with a more favorable toxicity profile. Based on the results of this study, DaunoXome was recently licensed by the FDA for first-line therapy in AIDS-KS.
Due to the favorable profile and antitumor activity of this formulation, we have conducted a phase II study to evaluate the safety and efficacy of DaunoXome in patients with low- and intermediate-grade NHL with refractory disease or relapse from prior chemotherapy. Patients were treated with DaunoXome at a dose of 100 mg/m2 given intravenously over two hours every three weeks. If hematologically stable, dose escalations of 20 mg/m2 per cycle were allowed up to a maximum of 140 mg/m2. Thus far, 14 patients have been enrolled (11 males, 3 females), with a median age of 67 (range 39-75). Twelve had low-grade histologies; two had intermediate-grade (follicular large cell and diffuse small cleaved in one patient each). Eleven (79%) had stage IV disease with bone marrow involvement. Eight (57%) had received two or more prior regimens while the others received one prior regimen. Four (29%) patients had received prior anthracycline therapy. Thus far, a median of two cycles of DaunoXome has been delivered (range 1-11). Of the 14 patients, six attained a partial response, three have stable disease and the remaining five have progression of disease. Three of the responders received prior anthracycline therapy. Six patients experienced grade 3 or 4 neutropenia. There was no other grade 3 or 4 toxicities. Other related side effects were all mild and consisted of fatigue, nausea, vomiting and alopecia. We conclude that DaunoXome at 100 mg/m2 every three weeks is an active agent in this patient population. Further accrual is ongoing and additional data will be reported.
