{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T09:20:46Z","timestamp":1789896046017,"version":"4.0.1"},"reference-count":21,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2004,5,1]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> Cisplatin and temozolomide (TMZ) are active in glioblastoma multiforme (GBM), with different profiles of toxicity. A bid regimen of TMZ achieves a strong inhibition of O<jats:sup>6<\/jats:sup>-alkylguanine DNA-alkyl transferase (AGAT), and cisplatin reduces AGAT activity in vitro, suggesting a possible synergic interaction. The primary end point of the present multicenter phase II study was progression-free survival (PFS) at 6 months (PFS-6); secondary end points included response, toxicity, and overall survival. <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> Chemotherapy-naive patients with GBM who experienced disease recurrence or progression after surgery and standard radiotherapy were eligible. Chemotherapy cycles consisted of cisplatin 75 mg\/m<jats:sup>2<\/jats:sup> on day 1, TMZ 130 mg\/m<jats:sup>2<\/jats:sup> bolus followed by nine doses of 70 mg\/m<jats:sup>2<\/jats:sup> every 12 hours (total of 5 days) from day 2 every 4 weeks. In the absence of hematologic toxicity, TMZ was escalated to 1,000 mg\/m<jats:sup>2<\/jats:sup> in 5 days. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> A total of 50 patients (median age, 53.4 years; range, 27 to 70 years; median Karnofsky performance status, 80; range, 60 to 100) were accrued in the study. PFS-6 was 34% (95% CI, 23% to 50%), and PFS-12 was 4% (95% CI, 0.3% to 16%). Median PFS was 18.4 weeks (95% CI, 13 to 25.9 weeks). Among 49 assessable patients, one complete response and nine partial responses were obtained, with an overall response rate of 20.4% (95% CI, 7.7% to 33%). Among 203 treatment cycles delivered, the most common grade 3 or grade 4 events included granulocytopenia in 7.9% of cycles, thrombocytopenia in 4%, and neurologic toxicity in three patients (6%). <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> The new cisplatin plus bid TMZ regimen appears active in chemotherapy-naive patients with recurrent GBM and incurs an acceptable toxicity. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2004.11.019","type":"journal-article","created":{"date-parts":[[2004,4,29]],"date-time":"2004-04-29T22:34:18Z","timestamp":1083278058000},"page":"1598-1604","source":"Crossref","is-referenced-by-count":88,"title":["First-Line Chemotherapy With Cisplatin Plus Fractionated Temozolomide in Recurrent Glioblastoma Multiforme: A Phase II Study of the Gruppo Italiano Cooperativo di Neuro-Oncologia"],"prefix":"10.1200","volume":"22","author":[{"given":"Alba A.","family":"Brandes","sequence":"first","affiliation":[{"name":"From the Departments of Medical Oncology and Neurological Sciences, Azienda Ospedale-University Hospital, Padova; 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