1. Phase I/II Study of Temozolomide Plus Nimustine Chemotherapy for Recurrent Malignant Gliomas: Kyoto Neuro-oncology Group.
- Author
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Aoki T, Arakawa Y, Ueba T, Oda M, Nishida N, Akiyama Y, Tsukahara T, Iwasaki K, Mikuni N, and Miyamoto S
- Subjects
- Adult, Aged, Dacarbazine therapeutic use, Female, Humans, Japan, Male, Middle Aged, Temozolomide, Antineoplastic Agents, Alkylating therapeutic use, Brain Neoplasms drug therapy, Dacarbazine analogs & derivatives, Glioma drug therapy, Neoplasm Recurrence, Local drug therapy, Nimustine therapeutic use
- Abstract
The objective of this phase I/II study was to examine the efficacy and toxicity profile of temozolomide (TMZ) plus nimustine (ACNU). Patients who had received a standard radiotherapy with one or two previous chemo-regimens were enrolled. In phase I, the maximum-tolerated dose (MTD) by TMZ (150 mg/m
2 /day) (Day 1-5) plus various doses of ACNU (30, 35, 40, 45 mg/m2 /day) (Day 15) per 4 weeks was defined on a standard 3 + 3 design. In phase II, these therapeutic activity and safety of this regimen were evaluated. Forty-nine eligible patients were enrolled. The median age was 50 years-old. Eighty percent had a KPS of 70-100. Histologies were glioblastoma (73%), anaplastic astrocytoma (22%), anaplastic oligodendroglioma (4%). In phase I, 15 patients were treated at four cohorts by TMZ plus ACNU. MTD was TMZ (150 mg/m2 ) plus ACNU (40 mg/m2 ). In phase II, 40 patients were treated at the dose of cohort 3 (MTD). Thirty-five percent of patients experienced grade 3 or 4 toxicities, mainly hematologic. The overall response rate was 11% (4/37). Sixty-eight percent (25/37) had stable disease. Twenty-two percent (8/37) showed progression. Progression-free survival (PFS) rates at 6 and 12 months were 24% (95% CI, 12-35%) and 8% (95% CI, 4-15%). Median PFS was 13 months (95% CI, 9.2-17.2 months). Overall survival (OS) at 6 and 12 were 78% (95% CI, 67-89%) and 49% (95% CI, 33-57%). Median OS was 11.8 months (95% CI, 8.2-14.5 months). This phase I/II study showed a moderate toxicity in hematology and may has a promising efficacy in OS, without inferiority in PFS., Competing Interests: The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices in the article. All authors who are members of The Japan Neurosurgical Society (JNS) have registered online Self-reported COI Disclosure Statement Forms through the website for JNS members. This manuscript has no COI that should be disclosed.- Published
- 2017
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