Choi K N, Rotman M, Aziz H, Sohn C K, Schulsinger A, Torres C, Har-El G, Chandra P, Bradley T, Rosenthal C J
State University of New York, Health Science Center at Brooklyn, Department of Radiation Oncology, 11203-2098, USA.
Int J Radiat Oncol Biol Phys. 1997 Nov 1;39(4):823-9. doi: 10.1016/s0360-3016(97)00462-8.
This is a prospective study to improve the therapeutic ratio in the treatment of patients with locally advanced nasopharyngeal and paranasal sinus tumors by using split-course concomitant infusion cisplatin chemotherapy and hyperfractionated radiotherapy.
From 1983 to 1993, 21 patients with locally advanced nasopharyngeal and paranasal sinus tumors (T3 and T4, or recurrent tumors involving the facial bones and/or the base of the skull) were treated with a regimen of split-course hyperfractioned radiotherapy (1.2 Gy/fraction/bid) and concomitant infusion cisplatin (5-10 mg/m2/24 h). The therapy was given in three separate 2-week sessions with 1 to 2 week breaks between sessions. Seventeen of 21 patients were treated with curative intent with cumulative radiation doses ranging from 64.8 to 70.8 Gy. Four patients were treated with palliative intent to a total dose of less than 60 Gy or to a limited field due to previous irradiation.
Sixteen of 17 patients (94%) treated curatively achieved a complete response. Of the 16 patients who achieved complete response, 7 patients (50%) were alive at the time of analysis (36 to 126 months). One patient was alive at 4 years with no evidence of disease, and died in 10 years at the age of 80 of unknown cause. Two patients died of local recurrence at 21 and 45 months and one patient died of a cerebrovascular accident at 12 months with disease status unknown. Five patients died of distant metastases. The one patient who had a partial response died in 25 months with local disease and metastases to the bone and lung. Four patients that were previously irradiated received a reduced total dose or treated to a limited irradiation field. All had near complete responses, but died within a year of treatment, with the exception of one patient who died at 23 months. Acute reactions included intense erythema of the mucosa in all patients. Five of 21 (23%) developed punctate mucositis and 3 of 21 (14%) developed confluent mucositis. Hematologically, one patient developed neutropenia (1800 WBC/mm3) and one developed thrombocytopenia (38,000/mm3). A rising creatinine was observed in three patients (2.0, 1.7, 1.7) all of whom were treated with the higher 10 mg/m2/day dose of infusional cisplatin. In all three of these cases, the creatinine slowly returned to normal over a 6-month period. Hormonal evaluations were performed in three patients and all were within normal ranges. There was no evidence of neck fibrosis or trismus. One patient with gross recurrent disease of the orbit developed blindness of the involved eye due to corneal opacification. The orbital area had been reirradiated in this patient.
Concomitant infusion cisplatinum with hyperfractionated radiation improved tumor control, but did not increase normal tissue injury. Acute reactions were minimized by splitting the treatment with a 1- to 2-week break after each 2 weeks of radiation treatment. Late complications were not increased by using a hyperfractionated radiation regimen. The local failure rate was only 18% (3 of 17 patients), but the distant failure rate was 35% (6 patients). Further investigation is needed to prove if adjuvant chemotherapy after concomitant chemoradiation improves survival by decreasing the distant failure in such advanced cases.
本前瞻性研究旨在通过采用分程同步输注顺铂化疗和超分割放疗，提高局部晚期鼻咽癌和鼻窦肿瘤患者的治疗比。
1983年至1993年，21例局部晚期鼻咽癌和鼻窦肿瘤患者（T3和T4期，或复发肿瘤累及面骨和/或颅底）接受了分程超分割放疗（每次1.2 Gy，每日两次）和同步输注顺铂（5 - 10 mg/m²/24小时）的治疗方案。治疗分三个独立的2周疗程进行，疗程之间休息1至2周。21例患者中有17例接受了根治性治疗，累积放疗剂量为64.8至70.8 Gy。4例患者因先前接受过放疗，接受了姑息性治疗，总剂量小于60 Gy或照射野受限。
17例接受根治性治疗的患者中有16例（94%）达到完全缓解。在这16例达到完全缓解的患者中，7例（50%）在分析时存活（36至126个月）。1例患者在4年时存活且无疾病证据，10年后80岁时因不明原因死亡。2例患者分别在21个月和45个月死于局部复发，1例患者在12个月时死于脑血管意外，疾病状态不明。5例患者死于远处转移。1例部分缓解的患者在25个月时死于局部疾病以及骨和肺转移。4例先前接受过放疗的患者接受了降低的总剂量或有限照射野的治疗。所有患者均接近完全缓解，但除1例在23个月时死亡外，其余均在治疗后一年内死亡。急性反应包括所有患者黏膜出现强烈红斑。21例中有5例（23%）出现点状黏膜炎，21例中有3例（14%）出现融合性黏膜炎。血液学方面，1例患者出现中性粒细胞减少（白细胞计数1800/mm³），1例出现血小板减少（血小板计数38,000/mm³）。3例患者（肌酐值分别为2.0、1.7、1.7）肌酐升高，这3例患者均接受了较高剂量1mg/m²/天的顺铂输注治疗。在所有这3例病例中，肌酐在6个月内缓慢恢复正常。对3例患者进行了激素评估，结果均在正常范围内。没有颈部纤维化或牙关紧闭的证据。1例眼眶有明显复发疾病的患者因角膜混浊导致患眼失明。该患者眼眶区域曾接受再次放疗。
同步输注顺铂与超分割放疗可改善肿瘤控制，但未增加正常组织损伤。通过在每2周放疗后休息1至2周来分程治疗，可将急性反应降至最低。采用超分割放疗方案并未增加晚期并发症。局部失败率仅为18%（17例患者中有3例），但远处失败率为35%（6例患者）。需要进一步研究以证实同步放化疗后辅助化疗是否能通过降低此类晚期病例的远处失败率来提高生存率。
