Transplantation Laboratory and Haartman Institute and Finnish Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland.
Int J Radiat Oncol Biol Phys. 2010 Sep 1;78(1):42-9. doi: 10.1016/j.ijrobp.2009.07.1731. Epub 2009 Dec 11.
To estimate the safety and tolerability of daily administration of 250 mg of gefitinib given concurrently with three-dimensional conformal radiotherapy for patients with nonmetastatic prostate cancer.
A total of 42 patients with T2-T3N0M0 tumors were treated in a nonrandomized single-center study. A prostate-specific antigen (PSA) level of <20 and a good performance status (WHO, 0-1) were required. Adjuvant or neoadjuvant hormone treatments were not allowed. A daily regimen of 250 mg of gefitinib was started 1 week before radiation therapy began and lasted for the duration of radiation therapy. A dose of 50.4 Gy (1.8 Gy/day) was administered to the tumor, prostate, and seminal vesicles, followed by a 22-Gy booster (2 Gy/day) for a total dose of 72.4 Gy. Correlative studies included analysis of epidermal growth factor receptor (EGFR), EGFRvIII, and phosphorylated EGFR in tumors and tumor necrosis factor, interleukin-1alpha (IL-1alpha), and IL-6 in serum.
Maximum tolerated dose was not reached in phase I (12 patients), and 30 additional patients were treated in phase II. Thirty (71.4%) patients completed trial medication. Dose-limiting toxicities were recorded for 16 (38.1%) patients, the most common of which was a grade 3 to 4 increase in transaminase (6 patients). After a median follow-up of 38 months, there were no deaths due to prostate cancer. The estimated PSA relapse-free survival rate at 4 years (Kaplan-Meier) was 97%, the salvage therapy-free survival rate was 91%, and the overall survival rate was 87%. These figures compared favorably with those of matched patients treated with radiation only at higher doses.
The combination of gefitinib and radiation is reasonably well tolerated and has promising activity against nonmetastatic prostate cancer.
评估每日给予 250mg 吉非替尼联合三维适形放疗治疗非转移性前列腺癌患者的安全性和耐受性。
42 例 T2-T3N0M0 期肿瘤患者参与了这项非随机单中心研究。要求患者前列腺特异性抗原（PSA）水平＜20ng/ml，且体能状态良好（WHO，0-1 级）。不允许接受辅助或新辅助激素治疗。在开始放疗前 1 周开始每日给予 250mg 吉非替尼，持续整个放疗期间。肿瘤、前列腺和精囊给予 50.4Gy（1.8Gy/天）剂量，随后给予 22Gy 增强剂量（2Gy/天），总剂量为 72.4Gy。相关研究包括肿瘤中表皮生长因子受体（EGFR）、EGFRvIII 和磷酸化 EGFR 的分析，以及血清中肿瘤坏死因子、白细胞介素-1α（IL-1α）和白细胞介素-6（IL-6）的分析。
在 I 期（12 例患者）未达到最大耐受剂量，随后在 II 期又治疗了 30 例患者。30 例（71.4%）患者完成了试验药物治疗。16 例（38.1%）患者出现剂量限制性毒性，最常见的是 3-4 级转氨酶升高（6 例）。中位随访 38 个月后，无前列腺癌相关死亡。4 年（Kaplan-Meier）时的估计 PSA 无复发生存率为 97%，挽救性治疗无复发生存率为 91%，总生存率为 87%。这些数据与接受更高剂量放疗的匹配患者的结果相比具有优势。
吉非替尼联合放疗具有良好的耐受性，对非转移性前列腺癌具有有前景的活性。
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