A Phase II Study of Two-Step Intensity Modulated Radiation Therapy (IMRT) with Chemotherapy for Loco-Regionally Advanced Nasopharyngeal Cancer (NPC) (JCOG1015)

Abstract

A phase II study of adaptive two-step IMRT with chemotherapy (Cx) for NPC (JCOG1015, UMIN-CTR: UMIN000005448) was conducted to evaluate the efficacy and safety. Acute toxicities and treatment compliance had been reported, and this is the final report on efficacy. Patients (pts) aged 20-75 years with stages II-IVB NPC with performance status of 0-1 were enrolled. As adaptive two-step IMRT, computed tomography planning was done twice before the start of IMRT for initial plan of 46 Gy/23 fractions (fr) and at the third or fourth week of treatment for boost plan of 24 Gy/12 fr with a total radiation dose of 70 Gy/ 35 fr. Individual case review was performed. Cx (cisplatin 80 mg/ m2 /3-weeks × 3 cycles) was given concurrently with IMRT, followed by adjuvant Cx (cisplatin 70 mg/ m2 with 5-FU 700 mg/m2 for 5 days/4-weeks × 3 cycles). The primary endpoint was 3-year overall survival (OS). The sample size was set as 75 pts by precision-base so that the 95% confidence interval (CI) for the estimated 3-year OS would be ±10% around the expected value of 74% based on the predicted proportion of stage (UICC 7th) II:III:IV = 20%:40%:40%. If upper limit of the 95% CI of estimated 3-year OS based on the actual proportion of stage was not lower than the expected value of target population by the conventional treatment, we conclude that adaptive two-step IMRT method was to be considered as a standard treatment. As a secondary endpoint, xerostomia score was evaluated. The expected incidences of Grade 2 or more xerostomia at 1, 2, and 3 years after IMRT were 30%, 25%, and 20%. From April 2011 to October 2014, 75 pts were enrolled from 12 institutions. The pts consisted of 60 men and 15 women with the median age of 55 years (range, 28-75). At least 2 cycles of concurrent Cx with a total dose of 70 Gy was completed in 74 pts (99%). However, the full protocol treatment including 3 cycles of adjuvant Cx was completed for 39 pts (52%). The 3-year OS for the 75 pts was 88% [95% CI; 78%-94%]. The upper and lower limit of the 95% CI of the 3-year OS (94%) was higher than the target population’s expected 3-year OS of 75% adjusted by the stage with actual proportion of stage II:III:IV = 21%:44%:35%; thus the primary endpoint was met. The 3-year progression-free survival (PFS) and loco-regional PFS were 71% [59%-80%] and 77% [66%-85%]. Loco-regional recurrences were noted in 13 pts (17%). In terms of late toxicities, 15 pts (20%) showed grade 3 toxicities including hearing impaired, aspiration, and dysphagia. No grade 4-5 toxicities were noted. Grade 2 or more xerostomia was noted in 26% (18/70), 12% (8/69), and 9% (6/65) at 1, 2, and 3 years after start of IMRT. Adaptive two-step IMRT for NPC showed an excellent 3-year OS with acceptable toxicities, and the incidence of xerostomia was satisfactorily low. This method would be a new standard treatment for locally advanced NPC.