Robbins K T, Vicario D, Seagren S, Weisman R, Pellitteri P, Kerber C, Orloff L, Los G, Howell S B
Department of Otolaryngology/Head and Neck Surgery, University of Tennessee, Memphis 38163.
Am J Surg. 1994 Nov;168(5):419-22. doi: 10.1016/s0002-9610(05)80089-3.
Hypothesizing that cisplatin (DDP) drug resistance is dose dependent and the radiosensitizing effect of DDP is clinically beneficial, we conducted a chemoradiation protocol using extremely high doses of DDP delivered intra-arterially (IA) to locally advanced head and neck tumors.
Twenty-nine patients with untreated stage IV disease received 4 weekly infusions of 150 mg/m2, simultaneous systemic DDP neutralization with intravenous (IV) bolus sodium thiosulfate, and concomitant radiotherapy (180 to 200 cGy/day x 35 fractions).
The complete response rate of the 24 evaluable patients as determined with repeat biopsies was 23/24 (96%). Of the 29 patients evaluable for toxicity, central nervous system complications related to the infusion technique occurred with 2/110 infusions, both of which were reversible. The rate of grade III to IV chemotoxicity was 13%. The median length of follow-up was 22 months. There have been 6 recurrences: 1 local; 3 regional; and 2 at distant sites. The projected overall and disease-free 3-year survival was 88% and 53%, respectively.
We conclude that the combination of rapid selective delivery of supradose DDP/IV thiosulfate neutralization and concomitant radiotherapy can be safely and effectively applied to patients with advanced head and neck cancer. Preliminary survival analysis indicates that this approach may improve the prognosis for patients with an otherwise devastating disease.
假设顺铂（DDP）耐药具有剂量依赖性，且DDP的放射增敏作用具有临床益处，我们采用动脉内（IA）给予极高剂量DDP的放化疗方案治疗局部晚期头颈部肿瘤。
29例未经治疗的IV期患者接受4周一次、每次150 mg/m²的输注，同时静脉推注硫代硫酸钠进行全身DDP中和，并同步进行放疗（180至200 cGy/天，共35次分割）。
通过重复活检确定的24例可评估患者的完全缓解率为23/24（96%）。在29例可评估毒性的患者中，与输注技术相关的中枢神经系统并发症在110次输注中出现2次，均为可逆性。III至IV级化学毒性发生率为13%。中位随访时间为22个月。出现6例复发：1例局部复发；3例区域复发；2例远处复发。预计3年总生存率和无病生存率分别为88%和53%。
我们得出结论，超剂量DDP快速选择性给药/静脉注射硫代硫酸钠中和与同步放疗相结合可安全有效地应用于晚期头颈癌患者。初步生存分析表明，这种方法可能改善这种原本预后不佳疾病患者的预后。
