Brouns Anita J W M, Hendriks Lizza E L, van der Noort Vincent, van de Borne Ben E E M, Schramel Franz M N H, Groen Harry J M, Biesma Bonne, Smit Hans J M, Dingemans Anne-Marie C
Department of Pulmonary Diseases, Zuyderland Medical Center, Sittard-Geleen, Netherlands.
Department of Pulmonary Diseases, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center+ (MUMC+), Maastricht, Netherlands.
Front Oncol. 2020 Jun 24;10:890. doi: 10.3389/fonc.2020.00890. eCollection 2020.
Approximately 80% of non-small cell lung cancer (NSCLC) patients with bone metastases have cancer induced bone pain (CIBP). The NVALT-9 was an open-label, single arm, phase II, multicenter study. Main inclusion criterion: bone metastasized NSCLC patients with uncontrolled CIBP [brief pain inventory [BPI] ≥ 5 over last 7 days]. Patients were treated with six milligram ibandronate intravenously (day 1-3) once a day. Main exclusion criteria: active secondary malignancy, systemic anti-tumor treatment and radiotherapy ≤4 weeks before study start, previous bisphosphonate treatment. Statistics: Simon's Optimal two-stage design with a 90% power to declare the treatment active if the pain response rate is ≥ 80% and 95% confidence to declare the treatment inactive if the pain response rate is ≤ 60%. If pain response is observed in ≤ 12 of the first 19 patients further enrollment will be stopped. Primary endpoint: bone pain response, defined as 25% decrease in worst pain score (PSc) over a 3-day period (day 5-7) compared to baseline PSc with maximum of 25% increase in mean analgesic consumption during the same period. Secondary endpoints: BPI score, quality of life, toxicity and World Health Organization Performance Score. Of the 19 enrolled patients in the first stage, 18 were evaluable for response. All completed ibandronate treatment according to protocol. In 4 (22.2%), a bone pain response was observed. According to the stopping rule, further enrollment was halted. Ibandronate loading doses lead to insufficient pain relief in NSCLC patients with CIBP.
约80%发生骨转移的非小细胞肺癌（NSCLC）患者有癌性骨痛（CIBP）。NVALT - 9是一项开放标签、单臂、II期、多中心研究。主要纳入标准：骨转移的NSCLC患者，CIBP未得到控制[过去7天简短疼痛量表（BPI）≥5]。患者每天静脉注射6毫克伊班膦酸钠（第1 - 3天）。主要排除标准：活动性继发性恶性肿瘤、研究开始前≤4周进行全身抗肿瘤治疗和放疗、既往使用过双膦酸盐治疗。统计学方法：采用西蒙最优两阶段设计，若疼痛缓解率≥80%，则有90%的把握判定治疗有效；若疼痛缓解率≤60%，则有95%的把握判定治疗无效。若在前19例患者中观察到≤12例有疼痛反应，则停止进一步入组。主要终点：骨痛反应，定义为与基线最差疼痛评分（PSc）相比，在3天时间（第5 - 7天）内最差疼痛评分降低25%，且同期平均镇痛药消耗量最多增加25%。次要终点：BPI评分、生活质量、毒性和世界卫生组织体能状态评分。在第一阶段入组的19例患者中，18例可评估反应。所有患者均按方案完成伊班膦酸钠治疗。4例（22.2%）观察到骨痛反应。根据停止规则，停止进一步入组。伊班膦酸钠负荷剂量对有CIBP的NSCLC患者的疼痛缓解不足。
