Concurrent Weekly Cisplatin and Radiotherapy With or Without Induction Docetaxel, Cisplatin & Capecitabine Plus Isotretinoin in Locally Advanced Nasopharyngeal Squamous Cell Carcinoma, ALI A. ZEIN EL-DEEN and AHMAD AL-ADLY
Abstract
Background: Induction chemotherapy can decrease tumor size before the standard concurrent chemo-radiotherapy and reduce distant metastases rates. Oral capecitabine in replace-ment of 5-fluorouracil may have lower toxicity and better compliance. Retinoids induce differentiation and have syner-gistic action with cisplatin.
Methods: A total of 36 patients with non-metastatic stage III-IVB nasopharyngeal squamous cell carcinoma were ran-domized into two arms (A & B), all patients received concurrent chemoradiation (CRT) with weekly cisplatin 30mg/m2. Arm A patients received induction chemotherapy DCX consisted of Docetaxel 75mg/m2 D1, Cisplatin 60mg/m2 D1 & Capecit-abine 2500mg/m2 in two divided doses for 7 days every 21 days for 3 cycles with filgrastim support and concomitant daily oral isotretinoin 0.5mg/kg in two divided doses daily all through treatment.
Results: Treatment was tolerable in both arms, the main early toxicity G3-4 was neutropenia, and mucositis occurred in 16% and 11% in arm A vs. 5% and 17% in arm B, respec-tively, while the main late toxicity in arm A was G3 dysgeusia and xerostomia occurred in 22% and 17% vs. 28% and 22% of patients in arm B, respectively. Complete response rate was 83% in arm A vs. 72% in arm B. The 4-year overall survival in arm A was 72.5% vs. 65% in arm B, p=0.69. The 4-year progression free survival in arm A was 67% vs. 61% in arm B, p=0.72. Distant metastases free survival at 3 & 4 years in arm A: 100% & 88% vs. 81 & 71% in arm B, respec-tively, p=0.16 while the loco-regional failure free survival at 2, 3 and 4 years were 83%, 77% and 76% in arm A vs. 78%, 77%, 76% in arm B, respectively, p=0.87.
Conclusion: The induction protocol DCX before CRT and concurrent oral isotretinoin was at least of equivalent efficacy and tolerable toxicity to the standard CRT alone with reduced distant metastases and deserves larger randomized trials.