Concomitant cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy plus highly active antiretroviral therapy in patients with human immunodeficiency virus-related, non-Hodgkin lymphoma

Abstract

BACKGROUND The feasibility and efficacy of concomitant chemotherapy and highly active antiretroviral therapy (HAART) is still unknown in patients with human immunodeficiency virus (HIV)‐related malignancies. To evaluate the impact of chemotherapy plus HAART on the clinical course of patients with HIV‐related, systemic, non‐Hodgkin lymphoma (HIV‐NHL), the authors compared retrospectively a group of 24 patients with HIV‐NHL who were treated with the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy regimen plus HAART with a group of 80 patients who were treated with CHOP chemotherapy or a CHOP‐like regimen (i.e., cyclophosphamide, doxorubicin, teniposide, and prednisone with vincristine plus bleomycin) without receiving antiretroviral therapy. METHODS All patients were enrolled in two sequential trials performed at the Aviano Cancer Center, Italy, from April 1988 to December 1998. HAART was included with combination therapy from January 1997. Antiretroviral regimens consisted of two reverse transcriptase inhibitors and one protease inhibitor. RESULTS The two treatment groups were well matched with regard to patient demographics, NHL characteristics, HIV status, and treatment, i.e., the number of cycles and chemotherapy dose. The response rates were similar between the two groups. Severe anemia (Grade 3–4 according to the World Health Organization criteria) was significantly greater in the patients who received CHOP‐HAART compared with the patients who received CHOP alone (33% vs. 7%, respectively; P = 0.001). Leukopenia was similar between the two groups, but colony stimulating factor support was significantly greater in the CHOP‐HAART group than in the control group (92% vs. 66%, respectively; P = 0.03). Seventeen percent of CHOP‐HAART patients developed severe autonomic neurotoxicity, whereas none of the CHOP patients developed neurotoxicity (P = 0.002). At similar median follow‐up, opportunistic infection (OI) rates and mortality were significantly lower in the CHOP‐HAART patients than in the CHOP patients (18% vs. 52%, respectively; P = 0.05; and 38% vs. 85%, respectively; P = 0.001). The median survival for CHOP‐HAART patients was not reached, whereas the medial survival of CHOP patients was 7 months (P = 0.03). CONCLUSIONS The combination of CHOP plus HAART is feasible and may reduce the morbidity from OIs in HIV‐NHL patients. However, careful attention must be directed to cross toxicity and possible pharmacokinetic interactions between antiretroviral and antineoplastic drugs. The impact of the combined chemotherapy plus HAART treatment on patient survival needs urgently to be evaluated in prospective studies. Cancer 2001;91:155–63. © 2001 American Cancer Society.

Effect of highly active antiretroviral therapy on survival among HIV‐infected men with Kaposi sarcoma or non‐Hodgkin lymphoma

“…42 Although our study did not take into consideration the role of specific neoplastic therapy, other investigators have found the effect of HAART on outcomes, including partial and complete remission of tumors, disease-free survival and overall survival to be independent of the commonly used cancer therapies. In one study, Vaccher et al 43 found reduced opportunistic infections and mortality among patients exposed to HAART and combination cyclophosphamide, hydroxydoxorubicin, vincristine and prednisone chemotherapy (CHOP) compared to those exposed only to CHOP. Similarly, Navarro et al 44 found response to CHOP to be higher among those on HAART compared to those not receiving HAART.…”

Plasmablastic Lymphoma in a Previously Undiagnosed Aids Patient: A Case Report

“…However, toxicity, drug interactions, and poor compliance with antiretroviral and antineoplastic drugs are still a challenge [27].…”

“…Chemotherapy is the standard treatment for PBL but controversy still remains regarding when starting chemotherapy regimens, such as CHOP, EPOCH, or other protocols in severely immunocompromised patients undergoing HAART. When these regimens are added, some authors recommend the optimal dose should be adjusted to avoid toxicity [4,5,8,9,[24][25][26][27][28]. Other protocols also require the interruption of HAART during chemotherapy to decrease adverse interactions [9,15,26].…”

Therapeutic approaches to AIDS-related malignancies

“…The investigators concluded that the decreased clearance of cyclophosphamide was not associated with adverse effects and that either low-or full-dose CHOP combined with HAART could be safely and effectively administrated to patients with AIDS-NHL. Vaccher et al (2001) have assessed the impact of HAART on CT in a matched case control retrospective analysis of 24 patients with AIDS-NHL treated with CHOP and HAART compared with 80 patients treated with CHOP or CHOP-like regimens without HAART. Antiretroviral regimens were selected based on the patient's prior therapy.…”