Intensive chemotherapy with cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) for human immunodeficiency virus-associated Burkitt lymphoma

Cancer. 2003 Sep 15;98(6):1196-205. doi: 10.1002/cncr.11628.

Abstract

Background: In the era of highly active antiretroviral therapy (HAART), standard-dose chemotherapy for human immunodeficiency virus (HIV)-associated diffuse large B-cell lymphoma is becoming the standard of care. In contrast, the safety and efficacy of intensive regimens have not been established for Burkitt lymphoma (BL), a highly aggressive lymphoma for which moderate-dose chemotherapy is substandard in the HIV-negative population.

Methods: To evaluate the feasibility of intensive chemotherapy in HIV-associated BL, the authors retrospectively reviewed 14 HIV-positive adults with BL treated at their center between 1988 and 2000. Eight patients were treated between 1996 and 2000 with cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC), one of the currently preferred intensive-dose chemotherapy regimens for BL. Six received other chemotherapy. Outcomes were compared with those of 24 HIV-negative adult patients with BL who had similar patient characteristics and were treated concomitantly (13 with CODOX-M/IVAC; 11 with other regimens).

Results: Of the 14 HIV-positive patients, 63% had a complete response after CODOX-M/IVAC treatment, compared with 67% of patients receiving other chemotherapy. The 2-year event-free survival (EFS) rates were 60% and 60% after CODOX-M/IVAC or other regimens, respectively. Similar outcomes were seen despite the fact that 88% of CODOX-M/IVAC-treated HIV-positive patients had Stage IV disease, compared with one-third of HIV-positive patients treated with other chemotherapy. HIV status did not adversely affect long-term EFS independent of the treatment regimen (P = 0.88). When EFS was evaluated according to chemotherapy regimen independent of HIV status, CODOX-M/IVAC was found to be associated with improved EFS (P = 0.05) in all patients, and particularly those at high risk. HIV-positive patients treated with CODOX-M/IVAC tolerated chemotherapy well with similar rates of myelosuppression and infectious complications as HIV-negative patients.

Conclusions: The current nonrandomized retrospective study suggested that intensive chemotherapy with CODOX-M/IVAC is feasible and well tolerated in HIV-positive adults with BL. In the post-HAART era, intensive chemotherapy such as CODOX-M/IVAC may be appropriate in all adult patients with BL, and especially those with poor prognostic factors, regardless of HIV status.

Publication types

  • Comparative Study
  • Evaluation Study

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Burkitt Lymphoma / drug therapy*
  • Burkitt Lymphoma / mortality
  • Cyclophosphamide / administration & dosage
  • Cytarabine / administration & dosage*
  • Cytarabine / adverse effects
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Etoposide / administration & dosage*
  • Etoposide / adverse effects
  • Female
  • Humans
  • Ifosfamide / administration & dosage*
  • Ifosfamide / adverse effects
  • Lymphoma, AIDS-Related / drug therapy*
  • Lymphoma, AIDS-Related / mortality
  • Male
  • Methotrexate / administration & dosage
  • Middle Aged
  • Retrospective Studies

Substances

  • Cytarabine
  • Etoposide
  • Doxorubicin
  • Cyclophosphamide
  • Ifosfamide
  • Methotrexate

Supplementary concepts

  • IVAC protocol