title: Phase II trial of carboplatin and infusional cyclosporine with alpha-interferon in recurrent ovarian cancer: a California Cancer Consortium Trial.
abstract: The purpose of this study was to estimate the response rate of 26-h continuous infusion cyclosporine A (CSA) combined with carboplatin (CBDCA) and subcutaneous alpha-interferon (IFN), in recurrent ovarian cancer (OC), and to measure their effects on CBDCA pharmacokinetics. OC patients relapsing following platinum-based chemotherapy received CBDCA area under the curve (AUC 3) with CSA and IFN, every 3 weeks. The pharmacokinetics of CSA and CBDCA were determined in a subset of patients. Thirty patients received 84 courses of therapy. Three partial responses were observed. Nine patients were stable for >4 months. Toxicity was similar to that observed in our previously reported phase I study and consisted of myelosuppression, nausea, vomiting, and headache. The mean end of infusion CSA level (high-performance liquid chromatographic assay [HPLC]) was 1109 +/- 291 microg/mL (mean +/- SD). CBDCA pharmacokinetics revealed a measured AUC of 3.61 versus a targeted AUC of 3, suggesting a possible effect of IFN on CBDCA levels versus errors in the estimation of CBDCA clearance using measured creatinine clearance. Steady-state levels of >1 microg/mL CSA (HPLC assay) are achievable in vivo. Insufficient clinical resistance reversal was observed in this study to warrant further investigation of this combination.
authors.affiliation: Division of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA 91010, USA. rmorgan@coh.org
authors.forename: R J
authors.initials: RJ
authors.lastname: Morgan
authors.forename: T W
authors.initials: TW
authors.lastname: Synold
authors.forename: D
authors.initials: D
authors.lastname: Gandara
authors.forename: F
authors.initials: F
authors.lastname: Muggia
authors.forename: S
authors.initials: S
authors.lastname: Scudder
authors.forename: E
authors.initials: E
authors.lastname: Reed
authors.forename: K
authors.initials: K
authors.lastname: Margolin
authors.forename: J
authors.initials: J
authors.lastname: Raschko
authors.forename: L
authors.initials: L
authors.lastname: Leong
authors.forename: S
authors.initials: S
authors.lastname: Shibata
authors.forename: M
authors.initials: M
authors.lastname: Tetef
authors.forename: S
authors.initials: S
authors.lastname: Vasilev
authors.forename: K
authors.initials: K
authors.lastname: McGonigle
authors.forename: J
authors.initials: J
authors.lastname: Longmate
authors.forename: Y
authors.initials: Y
authors.lastname: Yen
authors.forename: W
authors.initials: W
authors.lastname: Chow
authors.forename: G
authors.initials: G
authors.lastname: Somlo
authors.forename: M
authors.initials: M
authors.lastname: Carroll
authors.forename: J H
authors.initials: JH
authors.lastname: Doroshow
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002140:California; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D002277:Carcinoma / Q000188:drug therapy*; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D016898:Interferon-alpha; D016572:Cyclosporine; D016190:Carboplatin