title: 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.
authors.affiliation: Division of Medical Oncology A, National Cancer Institute, Aviano, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Vaccher
authors.forename: M
authors.initials: M
authors.lastname: Spina
authors.forename: G
authors.initials: G
authors.lastname: di Gennaro
authors.forename: R
authors.initials: R
authors.lastname: Talamini
authors.forename: G
authors.initials: G
authors.lastname: Nasti
authors.forename: O
authors.initials: O
authors.lastname: Schioppa
authors.forename: G
authors.initials: G
authors.lastname: Vultaggio
authors.forename: U
authors.initials: U
authors.lastname: Tirelli
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000209:etiology / Q000517:prevention & control; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D001761:Bleomycin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004347:Drug Interactions; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D012189:Retrospective Studies; D013713:Teniposide / Q000008:administration & dosage; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D001761:Bleomycin; D014750:Vincristine; D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide; D013713:Teniposide; D011241:Prednisone