Zhenyu Pan, Xiaojun Ye, Yushan Huang, Panpan Tai, Miaomiao Liu, Xingru Sun, Ran Tang, Anyan Gu, Zhuo Wang, Longhai Shen, Xiaochuan Pang, Tingting Yuan, Guozi Yang
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引用次数: 0
Abstract
Purpose: This phase I/II study aimed to determine the maximum-tolerated dose (MTD) of intrathecal pemetrexed (IP) with vitamin supplementation, and to evaluate its safety, feasibility and therapeutic activity for newly diagnosed leptomeningeal metastasis (LM) from solid tumors.
Methods: The phase I study followed the classic 3 + 3 design, with IP dose escalating from 15 mg. The recommended dose was applied in the phase II study. IP was administered first as induction therapy twice weekly for 2 weeks, followed by consolidation therapy, once weekly for 4 weeks, then maintenance therapy once monthly. Vitamin supplementation was initiated prior to the first IP dose. The MTD, adverse events (AEs), overall survival (OS), clinical response rate (CRR) and disease control rate (DCR) were evaluated.
Results: A total of 34 patients were enrolled. In the phase I study, 2 patients in the 20 mg group experienced dose-limiting toxicity, including grade 4 leukopenia and grade 5 chemical arachnoiditis. The MTD was established as 15 mg. Among 28 patients in the MTD group, 24 completed induction therapy, 19 completed consolidation therapy and 11 proceeded to maintenance therapy. The overall AEs rate was 74% (25/34), and severe AEs rate (> grade 3) was 15% (5/34). In the MTD group, the CRR, DCR and median OS were 46% (13/28), 75% (21/28) and 8.1 months (95% CI, 6.5-11.9).
Conclusion: IP at 15 mg, with folic acid and vitamin B12 supplementation initiated before the first IP dose, demonstrated feasibility and exhibited controllable toxicity. This regimen offers a new treatment option with therapeutic activity for newly diagnosed LM patients with solid tumors.
期刊介绍：
The Journal of Neuro-Oncology is a multi-disciplinary journal encompassing basic, applied, and clinical investigations in all research areas as they relate to cancer and the central nervous system. It provides a single forum for communication among neurologists, neurosurgeons, radiotherapists, medical oncologists, neuropathologists, neurodiagnosticians, and laboratory-based oncologists conducting relevant research. The Journal of Neuro-Oncology does not seek to isolate the field, but rather to focus the efforts of many disciplines in one publication through a format which pulls together these diverse interests. More than any other field of oncology, cancer of the central nervous system requires multi-disciplinary approaches. To alleviate having to scan dozens of journals of cell biology, pathology, laboratory and clinical endeavours, JNO is a periodical in which current, high-quality, relevant research in all aspects of neuro-oncology may be found.
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