Parimi Sunil, Eliasziw Misha, North Scott, Trudeau Marc, Winquist Eric, Chi Kim N, Ruether Dean, Cheng Tina, Eigl Bernhard J
Department of Medical Oncology, BC Cancer Agency, Vancouver Cancer Centre, 600 West 10th Avenue, Vancouver, BC, V5Z 4E6, Canada.
Tufts University, Boston, MA, USA.
Invest New Drugs. 2016 Dec;34(6):771-776. doi: 10.1007/s10637-016-0386-z. Epub 2016 Aug 26.
Background Docetaxel is a standard first-line treatment option for men with metastatic castration resistant prostate cancer (mCRPC). Sunitinib is attractive as a maintenance therapy due to its mechanism of action, oral route of administration, and acceptable toxicity profile. We designed a phase II study of sunitinib in patients with mCRPC who responded to docetaxel. Methods Patients with responding or stable disease at the completion of docetaxel treatment received 50 mg of sunitinib on 4 week on 2 week off cycles. Treatment continued until disease progression (either by RECIST 1.1 criteria or by cancer related symptomatic progression), intolerable toxicity, start of new cancer therapy, withdrawal of consent, or death. The primary endpoint was progression free survival. Secondary endpoints included PSA response rate and safety. Results Twenty-three patients were enrolled and treated. The mean number of prior cycles of docetaxel given was 8.6 (range 4-12). The median number of cycles of sunitinib administered was 4 (range 1-11). Adverse events were generally grade 1-2 with 12 % grade ≥ 3 which were of a type and severity expected for sunitinib. Median PFS was 4.4 months (95 % CI: 1.6-5.1). Most patients had immediate PSA increases without other evidence of disease progression, with the mean increases in PSA over baseline being 197 %, 342 %, and 1437 % in Cycles 1, 2, and 3, respectively. Conclusion Sunitinib was tolerable as maintenance therapy but median PFS was significantly lower than the predefined threshold of 6 months.
多西他赛是转移性去势抵抗性前列腺癌（mCRPC）男性患者的标准一线治疗选择。舒尼替尼因其作用机制、口服给药途径和可接受的毒性特征，作为维持治疗具有吸引力。我们设计了一项针对对多西他赛有反应的mCRPC患者的舒尼替尼II期研究。方法：多西他赛治疗结束时病情缓解或稳定的患者接受舒尼替尼50mg，每4周服用2周，停药2周。治疗持续至疾病进展（根据RECIST 1.1标准或癌症相关症状进展）、不可耐受的毒性、开始新的癌症治疗、撤回同意或死亡。主要终点是无进展生存期。次要终点包括PSA反应率和安全性。结果：23名患者入组并接受治疗。多西他赛之前给予的平均周期数为8.6（范围4 - 12）。舒尼替尼给药的中位周期数为4（范围1 - 11）。不良事件一般为1 - 2级，12%为≥3级，这是舒尼替尼预期的类型和严重程度。中位无进展生存期为4.4个月（95%CI：1.6 - 5.1）。大多数患者PSA立即升高，无其他疾病进展证据，第1、2和3周期PSA相对于基线的平均升高分别为197%、342%和1437%。结论：舒尼替尼作为维持治疗可耐受，但中位无进展生存期显著低于预先定义的6个月阈值。
