Document 0118
 DOCN  M94A0118
 TI    Etoposide: current status and future perspectives in the management of
       malignant neoplasms.
 DT    9412
 AU    Belani CP; Doyle LA; Aisner J; University of Pittsburgh Medical Center,
       Pittsburgh Cancer; Institute, Division of Medical Oncology 15213.
 SO    Cancer Chemother Pharmacol. 1994;34 Suppl:S118-26. Unique Identifier :
       AIDSLINE MED/94349496
 AB    Etoposide has demonstrated highly significant clinical activity against
       a wide variety of neoplasms, including germ-cell malignancies,
       small-cell lung cancer, non-Hodgkin's lymphomas, leukemias, Kaposi's
       sarcoma, neuroblastoma, and soft-tissue sarcomas. It is also one of the
       important agents in the preparatory regimens given prior to bone marrow
       and peripheral stem-cell rescue. Despite its high degree of efficacy in
       a number of malignancies, the optimal dose, schedule, and dosing form
       remain to be defined. It is possible that continuous or prolonged
       inhibition of the substrate, i. e., topoisomerase II, may be the key
       factor for the cytotoxic effects of etoposide. Clinical studies have
       shown the activity of etoposide to be schedule-dependent, with prolonged
       dosing, best accomplished by the oral dosing form, offering a
       therapeutic advantage. This benefit awaits validation by prospective
       randomized studies, some of which are in progress. Recent clinical
       investigations have focused on the use of etoposide in combination with
       (a) cytokines to ameliorate myelosuppression, the dose-limiting toxicity
       of etoposide; (b) agents such as cyclosporin A and verapamil to alter
       the p-glycoprotein (mdr1) function; and (c) topoisomerase I inhibitors
       to modulate the substrate upon which it acts. There is continued
       interest in the development of etoposide to its maximal clinical
       dimensions and in the examination of alternative biochemical and
       mechanistic approaches to further our understanding of this highly
       active agent.
 DE    Acquired Immunodeficiency Syndrome/COMPLICATIONS  Antineoplastic Agents,
       Combined/*THERAPEUTIC USE  Carcinoma, Non-Small-Cell Lung/DRUG THERAPY
       Carcinoma, Small Cell/DRUG THERAPY  Etoposide/ADMINISTRATION &
       DOSAGE/*THERAPEUTIC USE  Germinoma/DRUG THERAPY  Human  Leukemia,
       Myelocytic, Acute/DRUG THERAPY  Lung Neoplasms/*DRUG THERAPY
       Lymphoma/DRUG THERAPY  Neoplasms/*DRUG THERAPY  Sarcoma, Kaposi's/DRUG
       THERAPY/ETIOLOGY  Stomach Neoplasms/DRUG THERAPY  JOURNAL ARTICLE
       REVIEW  REVIEW, ACADEMIC

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