Neoadjuvant chemotherapy followed by concurrent chemoradiation for locally advanced nasopharyngeal carcinoma

Lin Kong , You-Wang Zhang, Chao-Su Hu , Ye Guo

Department of Radiation Oncology, Fudan University, Shanghai Cancer Center, Shanghai 200032, P. R. China. konglinj@gmail.com

[Abstract] Background and Objective: Concurrent chemoradiation therapy (CCRT) is the standard treatment for patients with locally advanced nasopharyngeal carcinoma (NPC). The effect of neoadjuvant chemotherapy followed by CCRT has not been determined. Therefore, we conducted 2 phase II studies to evaluate the efficacy and safety of neoadjuvant chemotherapy with a regimen of docetaxel, cisplatin, and 5ª²fluorouracil (5ª²Fu) (TPF) followed by radiotherapy and concurrent cisplatin in patients with stageª²III and ª²IV(A - B) NPC. This article is the preliminary report on treatmentª²related toxicities and response. Methods: Graded according to the 2002 American Joint Committee on Cancer (AJCC) staging criteria, only patients with stageª²III or ª²IV(A ª² B) poorly differentiated or undifferentiated NPC (World Health Organization type II/III) were included. We planned to recruit 52 patients with stageª²III disease and 64 patients with stageª²IV(A - B) disease. All patients received neoadjuvant chemotherapy with TPF (docetaxel 75 mg/m², day 1; cisplatin 75 mg/m², day 1; 5ª²Fu 500 mg/(m2¡¤day), continuous intravenous infusion for 120 h), every 3 weeks for 3 cycles, followed by weekly cisplatin (40 mg/m²) concurrent with radiotherapy. Threeª²dimensional conformal radiotherapy (3Dª²CRT) and intensityª²modulated radiotherapy (IMRT) were used. Gross disease planning target volume (PTV), highª²risk and lowª²risk subclinical PTV doses were prescribed at 70-76 Gy, 66-70 Gy, and 60-61.25 Gy at 1.75-2.0 Gy per fraction. The lower neck or supraclavicular fields may be treated with conventional AP/PA fields for a total of 54 Gy at 1.8 Gy per fraction. Patients were evaluated for tumor response after the completion of neoadjuvant chemotherapy, and at 3 months after radiation according to the Response Evaluation Criteria In Solid Tumors (RECIST). The latest version of the National Cancer Institute¡¯s Common Terminology Criteria for Adverse Events (NCI CTCAE 3.0) was used for grading all adverse events. Results: Fiftyª²nine patients were evaluable for treatment response. Thirty patients had stageª²III disease and 29 patients had stageª²IV(A-B). All patients completed RT to the prescribed dose and 2 cycles of neoadjuvant chemotherapy, with 51 patients (86.4%) completing 3 cycles. A total of 50 (84.7%) and 39 patients (66.1%) completed 4 weeks and 5 weeks of cisplatin during CCRT, respectively. The overall response rate in the primary site and the neck region were 94.9% [complete response (CR) in 25.4%] and 100% (CR in 19.6%) after completing neoadjuvant chemotherapy. At 3 months after RT, the CR rates increased to 96.6% and 90.2%, respectively. After a median followª²up of 14.3 months, we observed 5 treatment failures and 2 deaths. The 1ª²year overall survival, distant metastasisª²free survival, and locoregional relapseª²free survival rates were 100%, 95.7%, and 97.7%, respectively. The rates of grade 3/4 myelosuppression and anorexia/nausea/vomiting during neoadjuvant chemotherapy were 55.9% and 16.9%, respectively. The corresponding rates were 11.9% and 23.7% during CCRT. Grade 3/4 mucositis, skin desquamation, and xerostomia occurred in 6.8%, 44.1%, and 27.1% of patients, respectively. There were no treatmentª²related deaths. Conclusions: Neoadjuvant chemotherapy with TPF followed by CCRT was well tolerated with a manageable toxicity profile. Preliminary results are encouraging and warrant further investigation.

Chinese Journal of Cancer 2010, Volume: 29, Issue 5, Page: 551-555

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