Document 2848
 DOCN  M94A2848
 TI    Safety of zalcitabine (ddC) in zidovudine (ZDV) intolerant individuals:
       results of the European Expanded Access Study.
 DT    9412
 AU    Moyle G; Goll A; Snape S; F. Hoffmann-La Roche Ltd, Basel, Switzerland.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):210 (abstract no. PB0268). Unique
       Identifier : AIDSLINE ICA10/94369727
 AB    OBJECTIVE: To assess the tolerability of ddC in HIV positive individuals
       intolerant to or had clinically failed on ZDV. METHODOLOGY: Patients
       intolerant to or had failed on ZDV were provided with ddC (0.75 mg tid,
       weight adjusted) via an open label access program. Recruitment ran from
       March 1992 to end July 1993. Demographic data were collected at baseline
       and patients were followed at 4 weekly intervals for drug related
       events, clinical events and changes in surrogate markers (CD4 cell
       count, weight, Karnofsky score). The relationship between baseline
       characteristics and and peripheral neuropathy was specifically examined.
       RESULTS: At closure of the program 517 patients had been enrolled with
       at least one follow-up available on 423 patients 70% of the patients
       were considered ZDV failures. 59% of patients had AIDS at baseline. The
       mean baseline CD4 count was 52 cells/mm3 with 70% of the patients having
       CD4 counts below 50 cells/mm3. Only 13% of patients terminated due to
       drug related adverse events. Table 1 shows the incidence of adverse
       events occurring during the study assessed as both related and unrelated
       to ddC. Peripheral neuropathy was the most common drug related event.
       Analysis of baseline characteristics suggest this toxicity occurred more
       frequently in patients with a baseline AIDS diagnosis (p = 0.002) (Table
       2). Data regarding changes in surrogate and clinical markers will also
       be presented. TABULAR DATA, SEE ABSTRACT VOLUME. CONCLUSIONS: ddC
       appears well tolerated in this patient population with unfavorable
       baseline characteristics. Peripheral neuropathy is the most common drug
       related toxicity occurring in 14.1% of the patients, and is more common
       in patients commencing ddC with a baseline AIDS diagnosis.
       Gastrointestinal disturbance including pancreatitis appears rare with
       ddC. Hematologic disturbance also appears infrequent.
 DE    Bone Marrow Diseases/CHEMICALLY INDUCED  Gastrointestinal
       Diseases/CHEMICALLY INDUCED  Human  HIV Infections/*DRUG THERAPY
       Pancreatitis/CHEMICALLY INDUCED  Patient Acceptance of Health Care
       Peripheral Nervous System Diseases/CHEMICALLY INDUCED  Safety  Treatment
       Failure  Zalcitabine/ADVERSE EFFECTS/*THERAPEUTIC USE
       Zidovudine/*ADVERSE EFFECTS  CLINICAL TRIAL  MEETING ABSTRACT
       MULTICENTER STUDY

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