Low dose methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone with zalcitabine in patients with acquired immunodeficiency syndrome-related lymphoma. Effect on human immunodeficiency virus and serum interleukin-6 levels over time.
BACKGROUND
Use of multiagent chemotherapy has been associated with complete remission (CR) in approximately 50% of patients with newly diagnosed acquired immunodeficiency syndrome (AIDS)-lymphoma, although additional AIDS-related complications may occur. Both chemotherapy and antiretroviral therapy were employed in an attempt to ascertain if the combination was safe, and associated with changes in human immunodeficiency virus (HIV) p24 antigen levels during the course of treatment.


METHODS
Low dose methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone(M-BACOD) chemotherapy and zalcitabine (ddC) were employed in 28 patients. Since both vincristine and zalcitabine may cause peripheral neuropathy, a Phase I/II study design was employed. Serum was analyzed for immune complex dissociated (ICD) HIV p24 antigen and interleukin (IL)-6 levels during therapy.


RESULTS
CR was achieved in 14 of 25 patients (56%), with partial response (PR) in 5 (20%). CRs were equivalent in patients with good or poor prognostic indicators, including a history of AIDS prior to lymphoma (CR = 60%); and/or CD4 lymphocytes < 200/mm3 (CR = 53%). Five patients with a CR subsequently relapsed (36%); median survival of CR patients was 29.2 months (4.1-61+), whereas that of all of the treated patients was 8.1 months. No significant peripheral neuropathy or other toxicity was observed. Serum ICD p24 antigen levels either fell (7/14) or remained consistently negative (2/14) in 9 of 14 patients (64%), whereas 36% experienced an increase. Elevated serum IL-6 levels at diagnosis were associated with systemic "B" symptoms (P = 0.023), whereas changes in IL-6 correlated with response to therapy over time (P = 0.006).


CONCLUSIONS
Combination antineoplastic and zalcitabine antiretroviral therapy may be safely administered to patients with AIDS-related lymphoma, resulting in CR in 56%, lack of significant neurotoxicity, and favorable effect on HIV p24 antigen in 50%. Elevation of serum IL-6 is associated with systemic "B" symptoms, whereas changes in serum IL-6 may correlate with response.
Levine
A M
AM
Department of Medicine, Division of Hematology, University of Southern California School of Medicine, Los Angeles, USA.
Tulpule
A
A
Espina
B
B
Boswell
W
W
Buckley
J
J
Rasheed
S
S
Stain
S
S
Parker
J
J
Nathwani
B
B
Gill
P S
PS
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000188:drug therapy / Q000821:virology*; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D016655:HIV Core Protein p24 / Q000032:analysis; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D016483:Lymphoma, AIDS-Related / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D012074:Remission Induction; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects; D016047:Zalcitabine / Q000009:adverse effects / Q000627:therapeutic use*
D000998:Antiviral Agents; D016655:HIV Core Protein p24; D015850:Interleukin-6; D001761:Bleomycin; D014750:Vincristine; D016047:Zalcitabine; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D002955:Leucovorin; D008727:Methotrexate