Mirmiran Alireza, McClay Edward, Spear Matthew A
Radiation Oncology, UCSD Cancer Center, UCSD Medical Center, 200 W Arbor Dr, San Diego, CA, 92103, USA.
Med Oncol. 2007;24(2):147-53. doi: 10.1007/BF02698033.
A phase I/II trial was conducted to determine the toxicities and efficacy (overall response, overall survival, and progression-free survival) of the combination of topotecan and whole brain radiation therapy (XRT) in patients with brain metastases. Patients received 30 Gy XRT given in 10 fractions to the whole brain. In phase I, patients were treated in groups of three at each topotecan dose level; dose escalation proceeded until the maximum tolerated dose (MTD) was identified. The dose-limiting toxicity proved to be grade IV neutropenia at 0.6 mg/m2/d, resulting in an MTD of 0.5 mg/m2/d. One of nine patients showed a response to treatment, and that was partial (OR 11%). Three had stable disease (33%), and four experienced progressive disease (44%). Median progression-free survival was 60 d; median overall survival was 102 d. Intravenous topotecan at 0.5 mg/m2/d concomitant to XRT with 30 Gy in 3-Gy fractions is tolerable in patients with brain metastases. This regimen has the additional advantage of providing systemic treatment to patients with metastases in other locations while whole brain radiation is in progress. Although response and survival outcomes in this small study do not appear higher than expected from historical controls, these were not primary end points, and larger studies on this topic would be useful to elucidate the efficacy of this combination treatment regimen.
开展了一项I/II期试验，以确定拓扑替康与全脑放射治疗（XRT）联合应用于脑转移患者的毒性和疗效（总缓解率、总生存期和无进展生存期）。患者接受全脑10次分割共30 Gy的XRT。在I期，每组3名患者在每个拓扑替康剂量水平接受治疗；剂量递增直至确定最大耐受剂量（MTD）。剂量限制性毒性为0.6 mg/m²/d时的IV级中性粒细胞减少，导致MTD为0.5 mg/m²/d。9名患者中有1名对治疗有反应，为部分缓解（OR 11%）。3名患者病情稳定（33%），4名患者病情进展（44%）。无进展生存期的中位数为60天；总生存期的中位数为102天。对于脑转移患者，0.5 mg/m²/d的静脉拓扑替康与30 Gy、每次3 Gy分割的XRT联合应用是可耐受的。该方案的额外优势在于，在进行全脑放疗时可为其他部位有转移的患者提供全身治疗。尽管这项小型研究中的缓解和生存结果似乎并不高于历史对照的预期，但这些并非主要终点，关于该主题的更大规模研究将有助于阐明这种联合治疗方案的疗效。
