Division of Oncology, Department of Internal Medicine, University of Texas, Health Science Center at Houston (Medical School)/Memorial Hermann Cancer Center, Houston, TX 77030, USA.
Clin Genitourin Cancer. 2012 Sep;10(3):153-8. doi: 10.1016/j.clgc.2012.03.001. Epub 2012 May 1.
Sorafenib has been demonstrated as second-line therapy, with limited significant adverse events at a dose of 400 mg twice a day (b.i.d.) in patients with metastatic renal cell carcinoma. This study evaluated the ability of patients to dose-escalate, response rate, progression-free survival (PFS), and overall survival.
The initial dose of sorafenib was 400 mg b.i.d.. Dose escalation of sorafenib to 600 mg b.i.d. occurred from days 29-56 and increased to 800 mg b.i.d. on day 57 and beyond as tolerated. Dose modifications were performed for toxicity per the National Cancer Institute Common Toxicity Criteria version 3.0. The patients were evaluated every 2 cycles (8 weeks) by using Response Evaluation Criteria in Solid Tumors version 1.0.
Forty-four patients were evaluable for response. Median age was 62.5 years, 39 patients had a Karnofsky Perfomance Status of 100%. Twenty-two patients received no prior therapy. Of the evaluable patients, 42 were dose escalated to 600 mg b.i.d., and 74% (31) of these were further dose escalated to 800 mg b.i.d.. Eight patients had a complete response (CR), 13 patients demonstrated a partial response (PR), and 21 patients had stable disease. Common treatment-related adverse events included hypertension, hand-foot syndrome, skin rash, diarrhea, dry skin, alopecia, and facial redness.
The majority of patients were escalated to 600 mg b.i.d. or 800 mg b.i.d.. Intrapatient dose-escalated sorafenib has promising antitumor activity as demonstrated by a 48% CR-PR rate (21 patients). Antitumor activity is further suggested by a prolonged PFS ≥6 months in 64% (28) of patients. Significant antitumor activity and reversible adverse events has been demonstrated in escalated doses of sorafenib.
索拉非尼已被证明是二线治疗药物，对于转移性肾细胞癌患者，每天两次口服 400mg 的剂量下，其不良反应有限且不明显。本研究评估了患者增加剂量的能力、缓解率、无进展生存期（PFS）和总生存期。
索拉非尼的初始剂量为每天两次口服 400mg。从第 29 天至第 56 天开始，每天两次口服 600mg 剂量递增，第 57 天及以后耐受时增加至每天两次口服 800mg。根据国家癌症研究所通用毒性标准 3.0 版对毒性进行剂量调整。每 2 个周期（8 周）对患者进行评估，使用实体瘤反应评价标准 1.0 版进行评估。
44 例患者可评估疗效。中位年龄为 62.5 岁，39 例患者 Karnofsky 表现状态评分为 100%。22 例患者未接受过既往治疗。在可评估的患者中，42 例患者增加剂量至每天两次口服 600mg，其中 74%（31 例）进一步增加剂量至每天两次口服 800mg。8 例患者完全缓解（CR），13 例患者部分缓解（PR），21 例患者病情稳定。常见的治疗相关不良事件包括高血压、手足综合征、皮疹、腹泻、皮肤干燥、脱发和面部潮红。
大多数患者增加剂量至每天两次口服 600mg 或 800mg。在本研究中，每天两次口服 800mg 或 600mg 剂量递增的索拉非尼具有显著的抗肿瘤活性，CR-PR 率为 48%（21 例）。在 64%（28 例）的患者中，PFS 延长至 6 个月以上，进一步提示了抗肿瘤活性。在递增剂量的索拉非尼中已证明具有显著的抗肿瘤活性和可逆转的不良反应。
