Document 3015
 DOCN  M94A3015
 TI    A phase II study of oral etoposide (VP-16) in AIDS-related Kaposi's
       sarcoma (KS).
 DT    9412
 AU    Mans D; Sprinz E; Sander I; Kalakun F; Jung G; Prolla G; Schwartsmann G;
       South American Office for Anticancer Drug Development, Brasil.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):173 (abstract no. PB0118). Unique
       Identifier : AIDSLINE ICA10/94369560
 AB    OBJECTIVE: To access the toxicity and antitumor activity of oral VP-16
       monotherapy in relation to plasma pharmacokinetics in patients with
       advanced AIDS-related KS. POPULATION & METHODS: Sixteen homo/bisexual
       male patients with AIDS-related KS NYU stage HIA-IVB were enrolled in
       the study. The mean age was 36 years (21-50) and performance status 1
       (0-2). Oral VP-16 was administered at the dose of 25 mg/m2 bid for 7
       days followed one week rest. In case of leucopenia grade 3-4 and/or
       thrombocytopenia, there was a 50% dose reduction. RESULTS: Complete and
       partial responses were achieved in 3 and 5 patients, respectively (56%).
       The mean duration response was 12 weeks (4-48 weeks). The most common
       adverse effects were leucopenia and nausea, and in 5 (31%) patients
       etoposide was reduced or discontinued due to severe toxicity. The plasma
       concentration versus time plots showed a mono- (2 patients) or biphasic
       decay (3 patients), consistent with a two- or three-compartment open
       model, respectively. Cytotoxic plasma concentrations (> 1 microgram/ml),
       were maintained for at least 6 hours during each administration. Mean
       peak levels after 2 hours were 2.1 micrograms/ml (range 1.3-2.5), which
       are usually bellow myelotoxic levels (> 3 micrograms/ml). The mean
       elimination half-life was 6.9 hours (range 4.5-9.3). CONCLUSIONS: Oral
       VP-16 is effective, relatively safe and well-tolerated in AIDS-related
       KS. This is probably due to the prolonged maintenance of cytotoxic
       plasma concentrations of the drug while avoiding toxic peak levels. Oral
       VP-16 is suitable for outpatient treatment. Future studies will exploit
       its use as a tid oral administration with a 25% dose escalation.
 DE    Acquired Immunodeficiency Syndrome/BLOOD/*DRUG THERAPY  Administration,
       Oral  Adult  Bisexuality  Dose-Response Relationship, Drug  Drug
       Administration Schedule  Etoposide/*ADMINISTRATION & DOSAGE/ADVERSE
       EFFECTS/  PHARMACOKINETICS  Homosexuality  Human  Male  Metabolic
       Clearance Rate  Middle Age  Sarcoma, Kaposi's/BLOOD/*DRUG THERAPY
       CLINICAL TRIAL  CLINICAL TRIAL, PHASE II  MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).