Efficacy and Tolerability of Cisplatin Plus Alternating Weekly Temozolomide in Recurrent High-grade Gliomas

Efficacy and Tolerability of Cisplatin Plus Alternating Weekly Temozolomide in Recurrent High-grade Gliomas: A Single-arm Prospective Phase II Clinical Study

Currently, the prognosis of recurrent high-grade gliomas is still dismal with no standard treatment protocol established. Cisplatin (CDDP), recommended by National Comprehensive Cancer Network (NCCN) as a chemotherapeutic agent in salvage treatment for recurrent high-grade gliomas, was shown to reduce O6-alkylguanine DNA-alkyl transferase (AGAT) activity and potentially capable of enhancing the antitumor effects of temozolomide (TMZ). Compared to the standard 5-day TMZ regimen, alternating weekly regimen that deliver more prolonged exposure of TMZ may lead to higher cumulative doses, and may deplete more O6-methylguanine DNA methyltransferase (MGMT), thus reducing the resistance of tumor cells to TMZ.

The investigators therefore initiate a single-arm Phase II study to evaluate the efficacy and tolerability of CDDP plus alternating weekly TMZ regimen in patients with recurrent high-grade gliomas.

Inclusion Criteria:

• Histological diagnosis of primary tumor as high-grade gliomas (WHO III or IV)
• All patients should complete radiation therapy for primary gliomas.
• MRI showed unequivocal evidence of tumor recurrence or progression.
• The time to be enrolled should be more than 90 days after the radiation therapy.
• Written informed consent
• Eastern Cooperative Oncology Group(ECOG) score: 0-2
• The patients with recurrent gliomas were treated without dose-dense TMZ therapy before enrollment.
• Surgical interventions for recurrent gliomas are permitted and patients with no residual tumor are permitted

Exclusion Criteria:

• Abnormal function of liver or renal (value more than 1.5 fold normal upper limit)
• Blood routing: Hb < 90g/L, absolute neutrophil count≤1.5*10^9/L, platelet < 100*10^9/L
• Pregnant or lactating women
• Allergic to administered drugs
• Radiation therapy in the previous 90 days before enrollment
• The patients with recurrent gliomas were treated with dose-dense TMZ therapy before enrollment.
• Acute infection in need of antibiotics intravenously
• Participation in other clinical trials in the 90 days before enrollment