Hanrahan Emer O, Kies Merrill S, Glisson Bonnie S, Khuri Fadlo R, Feng Lei, Tran Hai T, Ginsberg Lawrence E, Truong Mylene T, Hong Waun K, Kim Edward S
Department of Thoracic/Head and Neck Medical Oncology, MD Anderson Cancer Center, University of Texas, Houston, TX 77030, USA.
Am J Clin Oncol. 2009 Jun;32(3):274-9. doi: 10.1097/COC.0b013e318187dd57.
Treatment options for recurrent squamous cell carcinoma of the head and neck (SCCHN) following platinum-based therapy are limited. Lonafarnib is a potent, specific inhibitor of farnesyl transferase that demonstrated marked antitumor activity as monotherapy in treatment-naive SCCHN in a phase Ib study. A phase II study of lonafarnib was conducted to determine its efficacy and safety in patients with recurrent, platinum-refractory SCCHN.
This was an open-label, phase II, single-center study in patients with recurrent SCCHN after platinum-based therapy. A Simon 2-stage design was used, with a plan to close the study to further accrual if <2 of the first 15 patients had objective responses. Patients were treated with lonafarnib 200 mg twice daily (b.i.d.) by mouth continuously in 4-week cycles.
Fifteen patients with baseline Eastern Cooperative Oncology Group PS 0-1 and median age 57 years were enrolled. Twelve patients had received at least 2 previous chemotherapy regimens. Median duration of treatment with lonafarnib was 61 days. No objective response was observed. Seven (47%) patients maintained stable disease through >or=3 cycles of therapy. Median time to progression and survival time were 2.04 and 9.17 months, respectively. Most treatment-related toxicities were grade 1-2, and there were no treatment-related deaths.
Lonafarnib at a dose of 200 mg b.i.d. was well-tolerated. However, there were no objective responses observed in the first 15 patients enrolled in this study, and the study was closed to further accrual, as per predefined criteria. Further evaluation of lonafarnib in platinum-refractory SCCHN is not planned.
铂类治疗后复发的头颈部鳞状细胞癌（SCCHN）的治疗选择有限。洛那法尼是一种有效的法尼基转移酶特异性抑制剂，在一项Ib期研究中，其作为单药疗法在未经治疗的SCCHN中显示出显著的抗肿瘤活性。开展了一项洛那法尼的II期研究，以确定其在复发的、铂难治性SCCHN患者中的疗效和安全性。
这是一项针对铂类治疗后复发的SCCHN患者的开放标签、II期、单中心研究。采用西蒙两阶段设计，若前15例患者中客观缓解者少于2例，则计划停止入组。患者接受洛那法尼200 mg，每日两次口服，持续4周为一个周期。
纳入15例东部肿瘤协作组体能状态（ECOG PS）为0 - 1且中位年龄57岁的患者。12例患者此前至少接受过2种化疗方案。洛那法尼的中位治疗持续时间为61天。未观察到客观缓解。7例（47%）患者经过≥3个周期的治疗病情维持稳定。中位疾病进展时间和生存时间分别为2.04个月和9.17个月。大多数治疗相关毒性为1 - 2级，且无治疗相关死亡。
洛那法尼剂量为200 mg每日两次时耐受性良好。然而，在本研究入组的前15例患者中未观察到客观缓解，根据预定义标准，该研究停止进一步入组。未计划对铂难治性SCCHN中的洛那法尼进行进一步评估。
