Chemotherapy for human immunodeficiency virus-associated non-Hodgkin's lymphoma in combination with highly active antiretroviral therapy.
OBJECTIVE
This study investigated the efficacy, toxicity, and pharmacokinetic interactions resulting from simultaneous combination chemotherapy and highly active antiretroviral therapy (HAART) for patients with human immunodeficiency virus (HIV)-associated non-Hodgkin's lymphoma (NHL). In addition, the effects on viral load, CD4 counts, and opportunistic infections were examined with the use of combination chemotherapy combined with HAART.


METHODS
Sixty-five patients with previously untreated and measurable disease at any stage of HIV-associated NHL of intermediate or high grade were entered onto this study at 17 different centers. The first 40 patients entered onto the study received reduced doses of cyclophosphamide and doxorubicin, combined with vincristine and prednisone (modified CHOP [mCHOP]), whereas the subsequent 25 patients entered onto the study received full doses of CHOP combined with granulocyte colony-stimulating factor (G-CSF). All patients also received stavudine, lamivudine, and indinavir.


RESULTS
The complete response rates were 30% and 48% among patients who received mCHOP and full-dose CHOP combined with HAART, respectively. Grade 3 or 4 neutropenia occurred in 25% of patients receiving mCHOP and 12% of those receiving full-dose CHOP combined with G-CSF (25% v 12%). There were similar numbers of patients with grade 3 or 4 hyperbilirubinemia (12% and 17%), constipation and abdominal pain (18% and 17%), and transaminase elevation (48% and 52%) on the modified and full-dose arms of the study, respectively. Doxorubicin clearance and indinavir concentration curves were similar among patients on this study and historical controls, whereas cyclophosphamide clearance was 1.5-fold reduced as compared with control values. Human immunodeficiency virus (HIV) load declined from a median baseline value of 29,000 copies/mL to a median minimum value on therapy of 500 copies/mL.


CONCLUSIONS
Either modified-dose or full-dose CHOP chemotherapy for HIV-NHL, delivered with HAART, is effective and tolerable.
Ratner
L
L
AIDS Malignancy Consortium Operation Center, University of Alabama, Birmingham, USA. lratner@imgate.wustl.edu
Lee
J
J
Tang
S
S
Redden
D
D
Hamzeh
F
F
Herndier
B
B
Scadden
D
D
Kaplan
L
L
Ambinder
R
R
Levine
A
A
Harrington
W
W
Grochow
L
L
Flexner
C
C
Tan
B
B
Straus
D
D
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D019469:Indinavir / Q000008:administration & dosage; D019259:Lamivudine / Q000008:administration & dosage; D016483:Lymphoma, AIDS-Related / Q000188:drug therapy* / Q000473:pathology / Q000821:virology*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D011241:Prednisone / Q000008:administration & dosage; D018119:Stavudine / Q000008:administration & dosage; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage; D019562:Viral Load
D019380:Anti-HIV Agents; D016179:Granulocyte Colony-Stimulating Factor; D019259:Lamivudine; D014750:Vincristine; D019469:Indinavir; D004317:Doxorubicin; D003520:Cyclophosphamide; D018119:Stavudine; D011241:Prednisone