title: A phase I study of nelfinavir concurrent with temozolomide and radiotherapy in patients with glioblastoma multiforme.
abstract: We conducted a phase I trial to examine the maximally tolerated dose (MTD) of the oral protease inhibitor nelfinavir (NFV) in combination with temozolomide and concurrent radiotherapy in patients with glioblastoma and to gather preliminary data for response. The study was conducted in patients with newly diagnosed glioblastoma after surgical resection. Patients were treated with standard radiotherapy (6,000 cGy to the gross tumor volume), temozolomide (75 mg/m(2) daily) together with daily oral NFV starting 7-10 days prior to chemoradiotherapy continuing for the duration of chemoradiation for 6 weeks. Temozolomide (150-200 mg/m(2)) was resumed 4 weeks after completion of chemoradiotherapy. Two dose levels of NFV were investigated: 625 mg twice daily (bid) and 1,250 mg bid in a cohort escalation design. A total of 21 patients were enrolled. At the maximum tolerated dose, 18 subjects were enrolled to further evaluate toxicity and for preliminary estimate of efficacy for further phase II study. No dose-limiting toxicity was noted at 625 mg bid. At 1,250 mg bid, 3 dose-limiting episodes of hepatotoxicity were noted and one dose-limiting episode of diarrhea. The MTD for this study was 1,250 mg bid. NFV (1,250 mg bid) concurrent with temozolomide and radiotherapy is tolerated in most patients with glioblastoma. At the 1,250 mg bid dose level, patients should be monitored for hepatotoxicity and GI side effects.
authors.affiliation: Department of Radiation Oncology, Smilow Center for Translational Research 8-135, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd, Bldg 421, Philadelphia, PA 19104, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Alonso-Basanta
authors.affiliation: Department of Radiation Oncology, Smilow Center for Translational Research 8-135, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd, Bldg 421, Philadelphia, PA 19104, USA.
authors.forename: Penny
authors.initials: P
authors.lastname: Fang
authors.affiliation: Department of Radiation Oncology, Smilow Center for Translational Research 8-135, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd, Bldg 421, Philadelphia, PA 19104, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Maity
authors.affiliation: Department of Radiation Oncology, Smilow Center for Translational Research 8-135, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd, Bldg 421, Philadelphia, PA 19104, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hahn
authors.affiliation: Department of Radiation Oncology, Smilow Center for Translational Research 8-135, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd, Bldg 421, Philadelphia, PA 19104, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Lustig
authors.affiliation: Department of Radiation Oncology, Smilow Center for Translational Research 8-135, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd, Bldg 421, Philadelphia, PA 19104, USA.
authors.forename: Jay F
authors.initials: JF
authors.lastname: Dorsey
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001921:Brain / Q000473:pathology; D015331:Cohort Studies; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000532:radiotherapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019888:Nelfinavir / Q000627:therapeutic use*; D017063:Outcome Assessment, Health Care; D000077204:Temozolomide; D013997:Time Factors
chemical_list: D018906:Antineoplastic Agents, Alkylating; D017320:HIV Protease Inhibitors; D003606:Dacarbazine; D019888:Nelfinavir; D000077204:Temozolomide