indinavir-sulfate and Lymphoma--Non-Hodgkin

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.. 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.. 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.. Either modified-dose or full-dose CHOP chemotherapy for HIV-NHL, delivered with HAART, is effective and tolerable.

Topics: Adult; Anti-HIV Agents; Antineoplastic Combined Chemotherapy Protocols; Antiretroviral Therapy, Highly Active; Combined Modality Therapy; Cyclophosphamide; Dose-Response Relationship, Drug; Doxorubicin; Female; Granulocyte Colony-Stimulating Factor; HIV Infections; Humans; Indinavir; Lamivudine; Lymphoma, AIDS-Related; Lymphoma, Non-Hodgkin; Male; Middle Aged; Neutropenia; Prednisone; Stavudine; Treatment Outcome; Vincristine; Viral Load

We have investigated whether chemotherapy for HIV-related systemic non-Hodgkin's lymphoma (NHL) affects the pharmacokinetics of protease inhibitors.. This was a prospective, open-label, non-randomized, two-way crossover trial in HIV-1-infected patients treated with highly active antiretroviral therapy and chemotherapy for NHL. Seven patients received indinavir at a dosage of 800 mg three times daily and three patients received nelfinavir at a dosage of 750 mg three times daily. Chemotherapy consisted of adriamycin, cyclophosphamide, vincristine and prednisolone (CHOP). Each patient had blood samples for protease inhibitor pharmacokinetics drawn concomitantly with or independently of the CHOP cycle.. When indinavir was given concomitantly with CHOP, the AUC(0-8) increased by 38% (20.5 +/- 9.0 versus 14.9 +/- 9.5 mg.h/L; P=0.03), and was comparable to historical controls. By contrast, the AUC(0-8) of indinavir administered without CHOP was lower than expected. A similar trend was observed with nelfinavir. Likewise, we observed a significant number of patients with C(0) and C(8) below the IC(50) for the wild-type virus (0.1 mg/L) when the drug was administered without CHOP.. Therapeutic drug monitoring of protease inhibitors should be part of the work-up in HIV-infected patients receiving chemotherapy for NHL.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Cross-Over Studies; Cyclophosphamide; Doxorubicin; Drug Interactions; Female; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Lymphoma, Non-Hodgkin; Male; Middle Aged; Nelfinavir; Prednisone; Prospective Studies; Vincristine

Combination therapy with protease inhibitors and nucleoside analogues dramatically suppresses plasma HIV-1 RNA and delays progression to AIDS, but the impact on HIV-associated malignancy remains to be established. We therefore examined incidence trends of Kaposi's sarcoma and non-Hodgkin's lymphoma in patients with advanced HIV infection in nine AIDS Clinical Trial Group studies of antiviral therapies for HIV and cytomegalovirus infections. Among a total of 6587 patients enrolled between November 1987 and February 1997, there were 280 cases of Kaposi's sarcoma and 68 cases of non-Hodgkin's lymphoma. Incidence rates per 100 person-years of both malignancies declined in concert with decreases in mortality, but the decreases in Kaposi's sarcoma were more profound and consistent than the decreases in non-Hodgkin's lymphoma. These data suggest that current therapies have ameliorated the incidence of Kaposi's sarcoma, but may not have had an equal effect on non-Hodgkin's lymphoma.

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiviral Agents; Clinical Trials as Topic; Cytomegalovirus Retinitis; Foscarnet; Ganciclovir; HIV Infections; Humans; Incidence; Indinavir; Lymphoma, AIDS-Related; Lymphoma, Non-Hodgkin; Retrospective Studies; Sarcoma, Kaposi