trimethoprim--sulfamethoxazole-drug-combination and Herpes-Zoster

Topics: 2-Aminopurine; Acyclovir; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Antiprotozoal Agents; Antiretroviral Therapy, Highly Active; Antitubercular Agents; Antiviral Agents; Atovaquone; Azithromycin; Clarithromycin; Cytomegalovirus Infections; Drug Therapy, Combination; Famciclovir; Herpes Simplex; Herpes Zoster; Humans; Mycobacterium avium-intracellulare Infection; Mycoses; Naphthoquinones; Pneumonia, Pneumocystis; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary; Valacyclovir; Valine

Topics: Adolescent; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antifungal Agents; Blood Sedimentation; Female; Fluconazole; Foot Dermatoses; Hand Dermatoses; Hepatomegaly; Herpes Zoster; HIV Infections; Humans; Hypergammaglobulinemia; Immunocompromised Host; Onychomycosis; Tinea; Trimethoprim, Sulfamethoxazole Drug Combination

Purine analogs and alkylating agents are the most active drugs in the treatment of patients with chronic lymphocytic leukemia (CLL). Although fludarabine is the most widely tested purine analog in CLL, myelosuppression has limited its use in combination chemotherapy regimens. Because pentostatin (Nipent; SuperGen, San Ramon, CA), a related purine analog with proven activity in CLL, has less myelosuppression, we postulated that it would prove advantageous and could be more readily combined with alkylating agents. We are conducting a phase I/II trial of combination chemotherapy with pentostatin and cyclophosphamide for previously treated patients with CLL. Patients need to have Rai high-risk disease or "active" intermediate-risk disease. The treatment regimen consists of a fixed dose of pentostatin (4 mg/m2) combined with an increasing dose of cyclophosphamide. We plan to treat cohorts of three patients each at cyclophosphamide dose levels of 600, 900, 1,200, 1,500, and 2,000 mg/m2. Cycles will be repeated every 21 days. If unacceptable toxicity is encountered at one dose level, then three additional patients (total of six patients) will be accrued to that dose level before further dose escalations will be permitted. A second instance of unacceptable toxicity will close that dose level and identify the preceding level as the phase II dose. Additional patients will be accrued to the phase II dose level to better assess response. Supportive measures include the use of granulocyte colony-stimulating factor (5 microg/kg/d) to limit neutropenia. Sulfamethoxazole/trimethoprim will be given as prophylaxis against Pneumocystis carinii pneumonia and acyclovir will be administered as prophylaxis for herpes zoster. Response will be assessed according to standard criteria, and flow cytometry and fluorescent in situ hybridization will be used to assess for minimal residual disease in patients with trisomy 12.

Topics: Acyclovir; Anti-Infective Agents; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Chemoprevention; Chromosomes, Human, Pair 12; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Cohort Studies; Cyclophosphamide; Dose-Response Relationship, Drug; Flow Cytometry; Granulocyte Colony-Stimulating Factor; Herpes Zoster; Humans; Immunosuppressive Agents; In Situ Hybridization, Fluorescence; Leukemia, Lymphocytic, Chronic, B-Cell; Neutropenia; Patient Selection; Pentostatin; Pneumonia, Pneumocystis; Remission Induction; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Trisomy

We report a case of recurrent varicella-zoster virus infection in a patient with severe acquired immune deficiency syndrome in whom the infection has become clinically unresponsive to treatment with acyclovir.

Topics: Acquired Immunodeficiency Syndrome; Acute Disease; Acyclovir; Adult; Drug Combinations; Drug Therapy, Combination; Herpes Zoster; Herpesvirus 3, Human; Homosexuality; Humans; Immune Tolerance; Male; Recurrence; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination