Document 0421
 DOCN  M9650421
 TI    Cyclosporin A does not reverse clinical resistance to paclitaxel in
       patients with relapsed non-Hodgkin's lymphoma.
 DT    9605
 AU    Sarris AH; Younes A; McLaughlin P; Moore D; Hagemeister F; Swan F;
       Rodriguez MA; Romaguera J; North L; Mansfield P; Callendar D; Mesina O;
       Cabanillas F; Department of Hematology, University of Texas M.D.
       Anderson; Cancer Center, Houston 77030, USA.
 SO    J Clin Oncol. 1996 Jan;14(1):233-9. Unique Identifier : AIDSLINE
       MED/96140305
 AB    PURPOSE: Cyclosporin A has been shown to reverse paclitaxel resistance
       in vitro by inhibiting P-gp function. Therefore, we determined whether
       addition of cyclosporine to paclitaxel reversed clinical paclitaxel
       resistance in patients with non-Hodgkin's lymphoma (NHL). PATIENTS AND
       METHODS: Patients with relapsed NHL were eligible if they had no
       intervening treatment after failure to respond to paclitaxel (200 mg/m2
       over 3 hours), and if they had adequate marrow, renal, and hepatic
       function, no serious cardiac disease, no CNS involvement, and no
       antibodies to human immunodeficiency virus-1. A cyclosporin A bolus dose
       (5 mg/kg over 3 hours) was followed by intravenous infusion (15 mg/kg)
       over 24 hours. Six hours after the beginning of cyclosporin A, the
       immediately preceding paclitaxel dose was administered over 3 hours. All
       patients were premedicated with dexamethasone, diphenhydramine, and
       cimetidine. Response was assessed after two cycles, and those patients
       who achieved at least a partial response received a maximum of six
       courses. RESULTS: All 26 patients entered were assessable for toxicity
       and 25 were assessable for response. One patient whose disease had
       progressed during paclitaxel treatment had a partial remission after the
       addition of cyclosporin A (response rate, 4%; 95% confidence interval,
       1% to 20%). Disease progressed in 17 patients (71%) and did not respond
       in seven (25%). Serum cyclosporin A A levels measured at the time of
       initiation of paclitaxel infusion were greater than 2,000 ng/mL during
       81% of cycles. Treatment toxicity included peripheral neuropathy in 57%,
       myalgia or arthralgia in 30%, neutropenia in 53%, neutropenic fever in
       8%, and thrombocytopenia in 42% of patients. One patient with
       preexisting asthma had an acute bronchospasm during the first cycle and
       was removed from the study. There were no renal or hepatic toxicity and
       no infectious or hemorrhagic deaths. CONCLUSION: Cyclosporin A
       administered on this schedule did not reverse established clinical
       resistance to paclitaxel, which suggests that P-gp-mediated drug efflux
       is unlikely to be the only cause of paclitaxel resistance in this
       patient population.
 DE    Adult  Aged  Antineoplastic Agents, Combined/ADVERSE
       EFFECTS/*THERAPEUTIC USE  Cimetidine/ADMINISTRATION & DOSAGE  Cross-Over
       Studies  Cyclosporine/BLOOD/*THERAPEUTIC USE
       Dexamethasone/ADMINISTRATION & DOSAGE  Diphenhydramine/ADMINISTRATION &
       DOSAGE  Drug Administration Schedule  Drug Resistance, Neoplasm  Female
       Human  Infusions, Intravenous  Lymphoma, Non-Hodgkin's/*DRUG THERAPY
       Male  Membrane Glycoproteins/ANTAGONISTS & INHIB  Middle Age  Neoplasm
       Proteins/ANTAGONISTS & INHIB  Paclitaxel/*THERAPEUTIC USE  Premedication
       Propoxyphene/THERAPEUTIC USE  Recurrence  Remission Induction  CLINICAL
       TRIAL  JOURNAL ARTICLE  RANDOMIZED CONTROLLED TRIAL

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