A Study of Chemotherapy Plus Azidothymidine in the Treatment of Kaposi's Sarcoma in Patients With AIDS
A Study of Chemotherapy Plus Azidothymidine in the Treatment of Kaposi's Sarcoma in Patients With AIDS
To study the safety and maximum tolerated dose (MTD) of combined chemotherapy when it is
 administered to patients with advanced Kaposi's sarcoma together with one of two different
 doses of zidovudine (AZT).

 The combination of AZT and chemotherapy may be effective in treating the tumor as well as
 preventing the life-threatening infections when used for patients with AIDS and Kaposi's
 sarcoma. The MTD of combined chemotherapy is being determined so that the information will be
 available for future studies, when the relative effectiveness of the two doses of AZT has
 been learned.
The combination of AZT and chemotherapy may be effective in treating the tumor as well as
 preventing the life-threatening infections when used for patients with AIDS and Kaposi's
 sarcoma. The MTD of combined chemotherapy is being determined so that the information will be
 available for future studies, when the relative effectiveness of the two doses of AZT has
 been learned.

 AMENDED: AZT by mouth. If the treatment is well tolerated, subsequent groups of patients are
 started on increasing doses of doxorubicin combined with the same dose of bleomycin and
 vincristine. After determination of the MTD of chemotherapy in combination with AZT, the 2nd
 phase begins in which AZT is given and the first group of patients is given bleomycin and
 vincristine only. If this combination is well tolerated, then the subsequent groups are
 started on increasing doses of doxorubicin with the same dose of bleomycin, vincristine and
 AZT. The MTD of chemotherapy in combination with AZT is then determined. Patients achieving
 maximum response to the tumor are maintained on AZT alone. This is an outpatient study, and
 patients are seen every 2 weeks for evaluation, with a physical examination every month.
 Original design: The combination of chemotherapy and AZT is given to groups of four patients
 each, the first group beginning with bleomycin and vincristine, without the addition of
 doxorubicin. The chemotherapy is given intravenously every 2 weeks. This is combined first
 with AZT by mouth.
Inclusion Criteria

 Concurrent Medication:

 Allowed:

 -  Medication for grades 1 and 2 oral toxicity. Antiemetic agents, except steroids, for
 gastrointestinal toxicity. Toxicity grades according to NIAID Recommendations for
 Grading of Acute and Subacute Toxic Effects (Adults).

 Patients must demonstrate any of the following clinical and laboratory findings:

 -  25 or more mucocutaneous lesions with or without lymphedema.

 -  Progressive Kaposi's sarcoma (KS) with 10 or more new lesions in the month prior to
 study entry or visceral involvement.

 -  Oral mucosal lesion(s) requiring therapy.

 -  Prior history of Pneumocystis carinii pneumonia (PCP) or Mycobacterium avium
 intracellulare.

 Patients with any of the following constitutional symptoms with no etiology established may
 be included:

 -  Temperature > 38 degrees C and/or drenching night sweats for more than 1 month.

 -  Watery diarrhea (= or > 3 stools/day) for 2 or more weeks.

 -  Weight loss > 10 percent of normal. Patients with carcinoma in situ of the cervix or
 localized squamous or basal cell carcinoma of the skin may be included.

 Active alcohol or drug abuse sufficient to prevent adequate compliance with study therapy.

 Exclusion Criteria

 Co-existing Condition:

 Patients with the following conditions will be excluded:

 -  Peripheral sensory or motor neuropathy.

 -  Opportunistic infections requiring therapy.

 -  Significant pulmonary (exertional dyspnea with minimal exercise) or cardiac
 insufficiency (New York Heart Association, status > 2).

 -  Serious neuropsychiatric illness which would prevent informed consent of intensive
 treatment.

 Concurrent Medication:

 Excluded:

 -  Any drugs causing anemia, neutropenia, or significant risk of nephrotoxicity. Patients
 with a history of other systemic malignancies or lymphomas, except carcinoma in situ
 of the cervix or localized squamous or basal cell carcinoma of the skin, will be
 excluded from the study.

 Prior Medication:

 Excluded:

 -  Systemic antineoplastic chemotherapy.

 -  Excluded within 30 days of study entry:

 -  Any other investigational therapy.

 -  Antiretroviral agents (zidovudine, ribavirin).

 -  Immunomodulating agents (steroids, interferons, naltrexone, isoprinosine, and
 interleukin-2).