Liposome-Encapsulated Doxorubicin in Combination With Standard Agents (cyclophosphamide, vincristine, prednisone) in Patients With Newly Diagnosed AIDS-Related Non-Hodgkin's Lymphoma: Results of Therapy and Correlates of Response

• Published in: Journal of clinical oncology Vol. 22; no. 13; pp. 2662 - 2670
• Main Authors: LEVINE, Alexandra M, TULPULE, Anil, ESPINA, Byron, SHERROD, Andy, BOSWELL, William D, LIEBERMAN, Robert D, NATHWANI, Bharat N, WELLES, Lauri
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 01.07.2004; Lippincott Williams & Wilkins
• Subjects: Antibiotics, Antineoplastic - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; ATP-Binding Cassette, Sub-Family B, Member 1 - biosynthesis; Biological and medical sciences; CD4 Lymphocyte Count; Cyclophosphamide - administration & dosage; Dose-Response Relationship, Drug; Doxorubicin - administration & dosage; Hematologic and hematopoietic diseases; Human viral diseases; Humans; Infectious diseases; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Liposomes; Lymphoma, AIDS-Related - drug therapy; Lymphoma, AIDS-Related - pathology; Medical sciences; Prednisone - administration & dosage; Survival Analysis; Treatment Outcome; Vincristine - administration & dosage; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Antineoplastic agent; Early stage; Drug carrier; Standard; Doxorubicin; Alkaloid; Isomerases; Lymphoproliferative syndrome; Antimitotic; Human; Corticosteroid; DNA topoisomerase (ATP-hydrolysing); Immunopathology; Enzyme; Controlled release form; Antiinflammatory agent; Enzyme inhibitor; Liposome; AIDS; Malignant hemopathy; Prednisone; Non Hodgkin lymphoma; Immune deficiency; Vincristine; Standards; Infection; Alkylating agent; Oxazaphosphinane derivatives; Antibiotic; Cyclophosphamide; Treatment; Nitrogen mustard; Viral disease; Adrenal hormone; Anthracyclins; Immunosuppressive agent
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2004.10.093

To evaluate the safety and efficacy of liposomal doxorubicin (Myocet; Medeus Pharma Ltd, Herts,UK) when substituted for doxorubicin in the CHOP regimen (cyclophosphamide, doxorubicin, vincristine, prednisone) in patients with newly diagnosed AIDS-related non-Hodgkin's lymphoma (AIDS-NHL). Secondary objectives were to assess the impact of HIV viral control on response and survival, and to correlate MDR-1 expression with outcome. Liposomal doxorubicin at doses of 40, 50, 60, and 80 mg/m(2) was given with fixed doses of cyclophosphamide, vincristine, and prednisone every 21 days. All patients received concurrent highly active antiretroviral therapy. NHL tissues were evaluated for multidrug resistance (MDR-1) expression. Twenty-four patients were accrued. 67% had high or high-intermediate International Prognostic Index scores; the median CD4 lymphocyte count was 112/mm(3) (range, 19/mm(3) to 791/mm(3)). No dose-limiting toxicities were observed at any level, with myelosuppression being the most frequent toxicity. Overall response rate was 88%, with 75% complete responses (CRs), and 13% partial responses. The median duration of CR was 15.6+ months (range, 1.7 to 43.5+ months). Effective HIV viral control during chemotherapy was associated with significantly improved survival (P =.027), but CRs were attained independent of HIV viral control. MDR-1 expression did not correlate with response, suggesting that the liposomal doxorubicin may evade this resistance mechanism. Liposomal doxorubicin in combination with cyclophosphamide, vincristine, and prednisone is active in AIDS-NHL, with complete remissions achieved in 75% independent of HIV viral control or tissue MDR-1 expression. HIV viral control is associated with a significant improvement in survival. Additional studies are warranted.