Nishimura Yasumasa, Nakagawa Kazuhiko, Takeda Koji, Tanaka Masahiro, Segawa Yoshihiko, Tsujino Kayoko, Negoro Shunichi, Fuwa Nobukazu, Hida Toyoaki, Kawahara Masaaki, Katakami Nobuyuki, Hirokawa Keiko, Yamamoto Nobuyuki, Fukuoka Masahiro, Ariyoshi Yutaka
Department of Radiation Oncology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan.
Int J Radiat Oncol Biol Phys. 2007 Nov 1;69(3):786-92. doi: 10.1016/j.ijrobp.2007.04.008. Epub 2007 May 23.
This Phase I/II trial was conducted to assess the efficacy and safety of PR-350, a novel hypoxic cell radiosensitizer, when administered with thoracic radiation therapy (RT) after induction chemotherapy (CT) for locally advanced non-small-cell lung cancer (NSCLC).
Two cycles of cisplatin (80 mg/m(2)) and paclitaxel (180 mg/m(2)), or carboplatin (AUC = 6) and paclitaxel (200 mg/m(2)) were given before RT of 60 Gy in 30 fractions. In the Phase I portion, the starting dosage of PR-350 was 10 daily administrations (2000 mg/m(2)) in combination with RT, and this number was increased in increments of 10 for successive groups to 30 doses.
In total, 37 patients were enrolled. In Phase I (n = 20), PR-350 could be administered 30 times with concurrent thoracic RT. Thus, in Phase II (n = 17), PR-350 was administered 30 times. The major toxicity was radiation pneumonitis, with Grade 3 or more pneumonitis noted in 6 patients (16%) including 2 with treatment-related deaths. However, no Grade 3 or more esophageal toxicity was noted, and only Grade 1 peripheral neuropathy was noted in 9 patients (24%). For all 37 patients, the median survival time (MST) and the 2-year survival rate were 15.9 months and 24%, respectively. For 18 patients receiving 21 to 30 doses of PR-350, the MST and 2-year survival rate were 20.9 months and 33%, respectively.
Thoracic RT combined with 30 daily administrations of PR-350 after induction CT was well tolerated and promising for locally advanced NSCLC.
本I/II期试验旨在评估新型低氧细胞放射增敏剂PR - 350与诱导化疗（CT）后胸部放疗（RT）联合应用于局部晚期非小细胞肺癌（NSCLC）时的疗效和安全性。
在60 Gy、分30次的放疗前给予两个周期的顺铂（80 mg/m²）和紫杉醇（180 mg/m²），或卡铂（AUC = 6）和紫杉醇（200 mg/m²）。在I期部分，PR - 350的起始剂量为每日10次给药（2000 mg/m²）并联合放疗，后续组依次以每次增加10次的方式递增至30次给药。
共纳入37例患者。在I期（n = 20），PR - 350可与同期胸部放疗联合给药30次。因此，在II期（n = 17），PR - 350给药30次。主要毒性为放射性肺炎，6例患者（16%）出现3级或更高级别的肺炎，其中2例与治疗相关死亡。然而，未观察到3级或更高级别的食管毒性，仅9例患者（24%）出现1级周围神经病变。对于所有37例患者，中位生存时间（MST）和2年生存率分别为15.9个月和24%。对于接受21至30次PR - 350给药的18例患者，MST和2年生存率分别为20.9个月和33%。
诱导化疗后胸部放疗联合每日30次给予PR - 350耐受性良好，对局部晚期NSCLC有前景。
