Regular Article

British Journal of Cancer (2000) 83, 588–593. doi:10.1054/bjoc.2000.1316 www.bjcancer.com
Published online 8 August 2000

A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse

W K A Yung1, R E Albright2, J Olson3, R Fredericks4, K Fink5, M D Prados6, M Brada7, A Spence8, R J Hohl9, W Shapiro10, M Glantz11, H Greenberg12, R G Selker13, N A Vick14, R Rampling15, H Friedman16, P Phillips17, J Bruner1, N Yue18, D Osoba19, S Zaknoen20 and V A Levin1

  1. 1Department of Neuro-Oncology, UTMD Anderson Cancer Center, Box 100, 1515 Holcombe Boulevard, Houston, Texas, 77030, USA
  2. 2Barret Cancer Center, 234 Goodman Street, Cincinnati, Ohio, 45267, USA
  3. 3Department of Neurosurgery, Emory University, 1327 Clifton Road, Atlanta, Georgia, 30322, USA
  4. 4University of Mississippi Medical Center, 2500 North State Street, Jackson, Mississippi, 39216, USA
  5. 5Department of Neurology, University of Texas, Southwestern Medical School, 5323 Harry Hines Boulevard, Dallas, Texas, 75235, USA
  6. 6Department of Neurosurgery, University of California San Francisco, 533 Parnassus Street, Room U107, San Francisco, California, 94143, USA
  7. 7The Royal Marsden NHS Trust and the Institute of Cancer Research, Royal Marsden Hospital, Downs Road, Sutton, Surrey, SM2 5PT, United Kingdom
  8. 8Department of Neurology, University of Washington, Box 356465, 1959 N.E. Pacific Street, Seattle, Washington, 98195, USA
  9. 9University of Iowa, Hospitals and Clinics, 200 Hawkins Drive, Iowa City, Iowa, 52242, USA
  10. 10Division of Neurology, Barrow Neurological Institute, 350 West Thomas Road, Phoenix, Arizona, 85013, USA
  11. 11Memorial Hospital of Rhode Island, 710 Robinson Road, PO Box 665, Hinsdale, Massachusetts, 01235, USA
  12. 12Department of Neurology, University of Michigan Medical Center, 1500 East Medical Center Drive, 1914 Taubman Center, Box 0316, Ann Arbor, Michigan, 48109, USA
  13. 13West Penn Hospital, Center for Neuro-Oncology, 4800 Friendship Avenue – Suite 1614, Pittsburgh, Pennsylvania, 15224, USA
  14. 14Division of Neurology, Evanston Hospital, 2650 Ridge Avenue, Evanston, Illinois, 60201, USA
  15. 15Beatson Oncology Centre, Western Infirmary, Glasgow, G11 6NT, United Kingdom
  16. 16Department of Pediatric Hematology-Oncology, Duke University Medical Center, Duke North – Room 5418, Erwin Road, Durham, North Carolina, 27710, USA
  17. 17Department of Neuroscience, University of Pennsylvania Medical Center, Abramson 516, 3400 Civic Center Boulevard, Philadelphia, Pennsylvania, 19104, USA
  18. 18MRI Reading Center at St. Joseph, 8216 Carrbridge Circle, Baltimore, Maryland, 21204, USA
  19. 19British Columbia Cancer Agency, 1515 Larch Street, Vancouver, British Columbia, V6K 3N6, Canada
  20. 20Schering-Plough Research Institute, 2000 Galloping Hill Road, Kenilworth, New Jersey, 07033, USA

Received 13 August 1999; Revised 23 April 2000; Accepted 1 May 2000.

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Abstract

A randomized, multicentre, open-label, phase II study compared temozolomide (TMZ), an oral second-generation alkylating agent, and procarbazine (PCB) in 225 patients with glioblastoma multiforme at first relapse. Primary objectives were to determine progression-free survival (PFS) at 6 months and safety for TMZ and PCB in adult patients who failed conventional treatment. Secondary objectives were to assess overall survival and health-related quality of life (HRQL). TMZ was given orally at 200 mg/m2/day or 150 mg/m2/day (prior chemotherapy) for 5 days, repeated every 28 days. PCB was given orally at 150 mg/m2/day or 125 mg/m2/day (prior chemotherapy) for 28 days, repeated every 56 days. HRQL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 [+3]) and the Brain Cancer Module 20 (BCM20). The 6-month PFS rate for patients who received TMZ was 21%, which met the protocol objective. The 6-month PFS rate for those who received PCB was 8% (P = 0.008, for the comparison). Overall PFS significantly improved with TMZ, with a median PFS of 12.4 weeks in the TMZ group and 8.32 weeks in the PCB group (P = 0.0063). The 6-month overall survival rate for TMZ patients was 60% vs. 44% for PCB patients (P = 0.019). Freedom from disease progression was associated with maintenance of HRQL, regardless of treatment received. TMZ had an acceptable safety profile; most adverse events were mild or moderate in severity. © 2000 Cancer Research Campaign

Keywords:

malignant glioma, temozolomide, procarbazine, glioblastoma multiforme

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