Phase II Study of Zidovudine and Recombinant Alpha-2A Interferon in the Treatment of Patients With AIDS-Associated Kaposi's Sarcoma

In a recent study, the combination of IFN-A2a and AZT in the treatment of patients with AIDS-associated KS was evaluated and safe doses of both AZT and IFN-A2a were determined. In addition, it appeared that there was a substantial reduction in KS lesions with this therapy. Potential benefits of this combined therapy include resolution of KS lesions, prolonged survival, a decrease in the frequency and severity of opportunistic infections, improvement in CD4 cells, and a decrease in serum p24 antigens.

Following evaluation studies, patients who participate in the study receive IFN-A2a and AZT. IFN-A2a is administered as a single subcutaneous injection once a day. AZT is given in a single capsule every 4 hours through the day for a total of six capsules. The first phase of treatment continues for 8 weeks followed by a 1-week rest period, during which time AZT only is given. Subjects who have had an interruption in interferon during the first 8 weeks of the study for a toxicity may skip the rest period. Patients experiencing a complete response will be placed on maintenance therapy. Patients without progression of their KS can continue on the treatment of AZT and IFN-A2a until a complete response is obtained or until study is terminated, whichever comes first. Patients with complete anti-tumor response can continue on a maintenance phase, in which they receive IFN-A2a as a single injection 3 times a week on nonconsecutive days and a single capsule of AZT q4h 6 x /day until the study is terminated on February 1, 1992. Patients are required to visit the clinic weekly for the first 12 weeks (except during the week 9 rest period), every other week for the next 8 weeks, every month for up to 52 weeks of the study and every 3 months thereafter. Throughout the study, frequent blood samples will be taken to monitor the effectiveness and safety of the treatment.

Inclusion criteria

Concurrent Medication:

Allowed:

• Inhalation pentamidine for the prevention of Pneumocystis carinii pneumonia (PCP) at a dose of 300 mg once every 4 weeks.
• AMENDED: Trimethoprim - sulfamethoxazole or dapsone only if on the maintenance phase of the study.

Concurrent Treatment:

Allowed:

• Blood transfusions.

Patients must have a positive antibody to HIV by any federally licensed ELISA test. All lab tests must be within 7 days of entry into the study.

Exclusion criteria

Concurrent Medication:

Excluded:

• Other antiretroviral agents.
• Immunomodulators.
• Corticosteroids.
• Cytotoxic chemotherapy.
• Aspirin.
• H2 blockers.
• Barbiturates and myelosuppressive drugs should be particularly avoided as they may interfere with the metabolism or enhance the toxicities of either zidovudine or interferon alfa-2a.
• Other experimental medications.

Concurrent Treatment:

Excluded:

• Radiation therapy.

Patients with prior experience of Grade 4 toxicity to zidovudine therapy will be excluded from the study.

Prior Medication:

Excluded:

• Interferon therapy.
• Excluded within 30 days of study entry:
• Immunomodulators.
• Corticosteroids.
• Cytotoxic chemotherapeutic agents.
• Excluded within 14 days of study entry:
• Zidovudine (AZT).

Prior Treatment:

Excluded within 30 days of study entry:

• Blood transfusions.
• Radiation therapy.

Patients may not have any of the following diseases or symptoms:

• Active opportunistic infection associated with AIDS.
• Significant neurologic disease associated with AIDS, as manifested by motor abnormalities including impaired rapid eye movement or ataxia, motor weakness in the lower extremities, sensory deficit consistent with a peripheral neuropathy, bladder or bowel incontinence.
• Internal organ involvement with Kaposi's sarcoma, i.e., nonnodal visceral Kaposi's sarcoma, excluding minimal gastrointestinal disease of less than 5 lesions.
• Tumor-associated edema.
• Current neoplasm other than Kaposi's sarcoma.
• Significant cardiac disease, including a recent history of myocardial infarction or significant current cardiac arrhythmias.

Active drug or alcohol abuse.