Clinical Study

British Journal of Cancer (2006) 95, 1155–1160. doi:10.1038/sj.bjc.6603376 www.bjcancer.com
Published online 3 October 2006

Temozolomide 3 weeks on and 1 week off as first-line therapy for recurrent glioblastoma: phase II study from gruppo italiano cooperativo di neuro-oncologia (GICNO)

Presented in part at the European Association of Neuro-Oncology, Edinburgh, May 5–8, 2005.

A A Brandes1, A Tosoni2, G Cavallo1, R Bertorelle3, V Gioia4, E Franceschi1, M Biscuola3, V Blatt2, L Crinò5 and M Ermani6

  1. 1Department of Medical Oncology, Bellaria Hospital, 40139 Bologna, Italy
  2. 2Department of Medical Oncology, Istituto Oncologico Veneto-IRCCS, 35128 Padova, Italy
  3. 3Servizio di Immunologia e Diagnostica Molecolare Oncologica – Istituto Oncologico Veneto-IRCCS, 35128 Padova, Italy
  4. 4Dipartimento Farmaceutico – Azienda USL of Bologna, 40139 Bologna, Italy
  5. 5Department of Medical Oncology Perugia Hospital, 06100 Perugia
  6. 6Department of Neurological Sciences, Azienda Ospedale-Università of Padova, 35100 Padova, Italy

Correspondence: Dr AA Brandes, E-mail: aa.brandes@yahoo.it

Received 24 July 2006; Revised 24 August 2006; Accepted 24 August 2006; Published online 3 October 2006.

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Abstract

The efficacy of temozolomide strongly depends on O6-alkylguanine DNA-alkyl transferase (AGAT), which repairs DNA damage caused by the drug itself. Low-dose protracted temozolomide administration can decrease AGAT activity. The main end point of the present study was therefore to test progression-free survival at 6 months (PFS-6) in glioblastoma patients following a prolonged temozolomide schedule. Chemonaïve glioblastoma patients with disease recurrence or progression after surgery and standard radiotherapy were considered eligible. Chemotherapy cycles consisted of temozolomide 75 mg/m2/daily for 21 days every 28 days until disease progression. O6-methyl-guanine-DNA-methyl-tranferase (MGMT) was determined in 22 patients (66.7%). A total of 33 patients (median age 57 years, range 31–71) with a median KPS of 90 (range 60–100) were accrued. The overall response rate was 9%, and PFS-6 30.3% (95% CI:18–51%). No correlation was found between the MGMT promoter methylation status of the tumours and the overall response rate, time to progression and survival. In 153 treatment cycles delivered, the most common grade 3/4 event was lymphopoenia. The prolonged temozolomide schedule considered in the present study is followed by a high PFS-6 rate; toxicity is acceptable. Further randomised trials should therefore be conducted to confirm the efficacy of this regimen.

Keywords:

clinical trials, glioblastoma, MGMT, prolonged temozolomide