Low-dose compared with standard-dose m-BACOD chemotherapy for non-Hodgkin's lymphoma associated with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group.
BACKGROUND
Reduced doses of cytotoxic chemotherapy or standard-dose therapy plus a myeloid colony-stimulating factor decreases hematologic toxicity and its complications in patients with non-Hodgkin's lymphoma associated with infection with the human immunodeficiency virus (HIV). However, the effect of reducing the doses of cytotoxic chemotherapeutic agents on clinical outcome is not known.


METHODS
We randomly assigned 198 HIV-seropositive patients with previously untreated, aggressive non-Hodgkin's lymphoma to receive standard-dose therapy with methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD) along with granulocyte-macrophage colony-stimulating factor (GM-CSF; n=94) or reduced-dose m-BACOD with GM-CSF administered only as indicated (n=98).


RESULTS
A complete response was achieved in 39 of the 94 assessable patients assigned to low-dose therapy (41 percent) and in 42 of the 81 assessable patients assigned to standard-dose therapy (52 percent, P= 0.56). There were no significant differences in overall or disease-free survival; median survival times were 35 weeks for patients receiving low-dose therapy and 31 weeks for those receiving standard-dose therapy (risk ratio for death in the standard-dose group=1.17; 95 percent confidence interval, 0.84 to 1.63; P=0.25). Toxic effects of chemotherapy rated grade 3 or higher occurred in 66 of 94 patients assigned to standard-dose therapy (70 percent) and 50 of 98 patients assigned to low-dose treatment (51 percent, P=0.008). Hematologic toxicity accounted for the difference.


CONCLUSIONS
As compared with treatment with standard doses of cytotoxic chemotherapy (m-BACOD), reduced doses caused significantly fewer hematologic toxic effects yet had similar efficacy in patients with HIV-related lymphoma. Dose-modified chemotherapy should be considered for most HIV-infected patients with lymphoma.
Kaplan
L D
LD
Department of Medicine, San Francisco General Hospital, CA 94110, USA.
Straus
D J
DJ
Testa
M A
MA
Von Roenn
J
J
Dezube
B J
BJ
Cooley
T P
TP
Herndier
B
B
Northfelt
D W
DW
Huang
J
J
Tulpule
A
A
Levine
A M
AM
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D015658:HIV Infections / Q000150:complications* / Q000276:immunology / Q000401:mortality; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D001761:Bleomycin; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide; D008727:Methotrexate