Joensuu H, De Braud F, Coco P, De Pas T, Putzu C, Spreafico C, Bono P, Bosselli S, Jalava T, Laurent D, Casali P G
Department of Oncology, University Central Hospital of Helsinki, Helsinki, Finland.
Ann Oncol. 2008 Jan;19(1):173-7. doi: 10.1093/annonc/mdm419. Epub 2007 Aug 14.
We evaluated safety and efficacy of PTK787/ZK222584 (PTK/ZK), a novel tyrosine kinase inhibitor of KIT, platelet-derived growth factor receptors and vascular endothelial cell growth factor receptors (VEGFRs), in patients with imatinib-resistant gastrointestinal stromal tumor (GIST). This is the first study of PTK/ZK in this population.
Patients with metastatic GIST that had progressed after >/= 4-week treatment with imatinib mesylate were eligible. Prior VEGFR-2 inhibitor therapy was not permitted. PTK/ZK 1250 mg orally once-daily was administered to 15 patients (accrued as a two-stage procedure), most of whom (n = 11) had been unsuccessfully treated with imatinib 800 mg daily, until treatment failure. Patients were monitored at 4- to 8-week intervals.
All 15 patients enrolled were eligible; two (13%) achieved partial response (PR), eight (53%) had stable disease (SD) >/=3 months, and five (33%) progressed. The clinical benefit rate (PR + SD) was 67% (95% CI 38% to 86%). Median time to progression was 8.5 months (range 0.9-24.8+ months). Three patients had not progressed at the time of analysis, including one PR at 24.8 months and two SDs at 16.6 and 18.6 months on treatment. PTK/ZK was generally well tolerated.
PTK/ZK 1250 mg p.o. once daily is active and well tolerated in patients with imatinib-resistant GIST.
我们评估了新型酪氨酸激酶抑制剂PTK787/ZK222584（PTK/ZK）对伊马替尼耐药的胃肠道间质瘤（GIST）患者的安全性和有效性，该抑制剂可抑制KIT、血小板衍生生长因子受体及血管内皮细胞生长因子受体（VEGFRs）。这是针对该人群进行的第一项关于PTK/ZK的研究。
符合条件的患者为接受甲磺酸伊马替尼治疗≥4周后病情进展的转移性GIST患者。既往不允许接受VEGFR-2抑制剂治疗。15例患者（分两阶段入组）口服PTK/ZK 1250mg，每日1次，其中大多数患者（n = 11）每日服用800mg伊马替尼治疗失败，直至治疗失败。每隔4至8周对患者进行监测。
所有入组的15例患者均符合条件；2例（13%）达到部分缓解（PR），8例（53%）疾病稳定（SD）≥3个月，5例（33%）病情进展。临床获益率（PR + SD）为67%（95%CI 38%至86%）。中位疾病进展时间为8.5个月（范围0.9 - 24.8 +个月）。3例患者在分析时病情未进展，包括1例在24.8个月时达到PR，2例在治疗16.6个月和18.6个月时处于SD。PTK/ZK总体耐受性良好。
每日口服1250mg PTK/ZK对伊马替尼耐药的GIST患者有效且耐受性良好。
