Vrdoljak Eduard, Géczi Lajos, Mardiak Jozef, Ciuleanu Tudor-Eliade, Leyman Sophie, Zhang Ke, Sajben Peter, Torday Laszlo
Medical School Split, Center of Oncology, University Hospital Split, Spinciceva 1, 21000, Split, Croatia,
Pathol Oncol Res. 2015 Jul;21(3):775-82. doi: 10.1007/s12253-014-9889-0. Epub 2015 Jan 4.
A global, open-label, expanded-access trial (EAT) provided sunitinib treatment on a compassionate-use basis to patients with metastatic renal cell carcinoma (mRCC) between 2005 and 2011. This retrospective analysis examines outcomes in patients from Central and East European (CEE) countries participating in the global EAT. Sunitinib (starting dose 50 mg orally once daily, with dose reduction for toxicity) was administered in repeated 6-week cycles (4 weeks on and 2 weeks off) until occurrence of disease progression or unacceptable toxicity. Tumor assessments were guided by Response Evaluation Criteria in Solid Tumors (RECIST) criteria but were performed according to local standards of care. In total, 401 CEE patients received sunitinib (median treatment duration 9.6 months), of whom 378 were evaluable for tumor response. The most frequent grade ≥3 toxicities were fatigue (7.5 %), hypertension (7.0 %), thrombocytopenia (6.5 %), diarrhea (4.2 %), nausea and hand-foot syndrome (both 3.7 %) and neutropenia (3.0 %). Median overall survival was 30.7 months (95 % CI 23.3, ‒ months). Overall survival tended to be longer in cytokine-naïve than cytokine-experienced patients (median 60.8 vs. 27.5 months; P = 0.1324). Among patients with evaluable tumors, 4.0 % achieved a complete and 14.6 % a partial response [objective response rate (ORR) 18.5 % (95 % CI 14.7, 22.8 %)]. Median progression-free survival was 11.6 months (95 % CI 10.3, 12.8 months). Sunitinib demonstrates safety and effectiveness in real-world mRCC patients in CEE countries. Expanded-access program patients showed a lower tumor response rate but similar survival outcomes to patients in the pivotal Phase III clinical trial of sunitinib in mRCC.
一项全球、开放标签、扩大准入试验（EAT）在2005年至2011年期间，基于同情用药原则为转移性肾细胞癌（mRCC）患者提供了舒尼替尼治疗。这项回顾性分析考察了参与全球EAT的中东欧（CEE）国家患者的治疗结果。舒尼替尼（起始剂量为口服50mg，每日一次，根据毒性情况减量）以重复的6周周期给药（4周用药，2周停药），直至疾病进展或出现不可接受的毒性。肿瘤评估以实体瘤疗效评价标准（RECIST）为指导，但根据当地的医疗标准进行。共有401名CEE患者接受了舒尼替尼治疗（中位治疗持续时间为9.6个月），其中378名患者可评估肿瘤反应。最常见的≥3级毒性反应为疲劳（7.5%）、高血压（7.0%）、血小板减少（6.5%）、腹泻（4.2%）、恶心和手足综合征（均为3.7%）以及中性粒细胞减少（3.0%）。中位总生存期为30.7个月（95%CI为23.3，-个月）。未接受过细胞因子治疗的患者总生存期往往比接受过细胞因子治疗的患者更长（中位生存期分别为60.8个月和27.5个月；P = 0.1324）。在可评估肿瘤的患者中，4.0%达到完全缓解，14.6%达到部分缓解[客观缓解率（ORR）为18.5%（95%CI为14.7，22.8%）]。中位无进展生存期为11.6个月（95%CI为10.3，12.8个月）。舒尼替尼在CEE国家的真实世界mRCC患者中显示出安全性和有效性。扩大准入项目患者的肿瘤反应率较低，但生存结果与舒尼替尼用于mRCC的关键III期临床试验中的患者相似。
