title: Safety and efficacy of patupilone in patients with advanced ovarian, primary fallopian, or primary peritoneal cancer: a phase I, open-label, dose-escalation study.
abstract: PURPOSE To evaluate the safety, maximum tolerated dose (MTD), and pharmacokinetics of patupilone administered once every 3 weeks with proactive standardized diarrhea management in patients with resistant or refractory ovarian, fallopian, or peritoneal cancer. PATIENTS AND METHODS Patients received patupilone (6.5 to 11.0 mg/m(2)) every 3 weeks via 20-minute infusion. Adverse events, dose-limiting toxicities (DLT), MTD, and tumor response were determined. The tumor response was measured by Response Evaluation Criteria in Solid Tumors (RECIST) and cancer antigen 125 levels. Results Forty-five patients were enrolled. Adverse events were mild to moderate in intensity, and grade 3 diarrhea (13%) was the most commonly reported serious adverse event. Grade 3 peripheral neuropathy was noted in two patients (4%). Diarrhea, peripheral neuropathy, and fatigue were the most common DLTs; however, these were uncommon in the first cycle and the MTD was therefore not reached in this study. Overall response (OR; complete and partial responses; median cycles, 8) per RECIST in patients with measurable disease (n = 36) was 19.5%. Median duration of disease stabilization (complete and partial responses and stable disease) was 15.8 months. These results appear improved from a previous study in a similar patient population using a weekly schedule (2.5 mg/m(2)/week; N = 53; OR, 5.7%). CONCLUSION Patupilone once every 3 weeks was well-tolerated at doses up to 11.0 mg/m(2). Patupilone demonstrated promising antitumor activity in patients with drug-resistant/refractory disease. An ongoing phase III study in this patient population is testing the 10.0 mg/m(2) dose.
authors.affiliation: MD (Lon), FRCPC, Princess Margaret Hospital, University Health Network, University of Toronto, 610 University Ave 5-700, Toronto, Ontario, Canada, M5G 2M9.
authors.forename: Wim W
authors.initials: WW
authors.lastname: Ten Bokkel Huinink
authors.forename: Jozef
authors.initials: J
authors.lastname: Sufliarsky
authors.forename: Willem M
authors.initials: WM
authors.lastname: Smit
authors.forename: Stanislav
authors.initials: S
authors.lastname: Spanik
authors.forename: Maria
authors.initials: M
authors.lastname: Wagnerova
authors.forename: Hal W
authors.initials: HW
authors.lastname: Hirte
authors.forename: Stan
authors.initials: S
authors.lastname: Kaye
authors.forename: Anandhi R
authors.initials: AR
authors.lastname: Johri
authors.forename: Amit M
authors.initials: AM
authors.lastname: Oza
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D034261:Epothilones / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010534:Peritoneal Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D034261:Epothilones; C093788:epothilone B