title: Neoadjuvant chemotherapy followed by concurrent chemoradiation for locally advanced nasopharyngeal carcinoma.
abstract: 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 5 fluorouracil (5-Fu) (TPF) followed by radiotherapy and concurrent cisplatin in patients with stage III and IV(A - B) NPC. This article is the preliminary report on treatment related toxicities and response.
  
  
  METHODS
  Graded according to the 2002 American Joint Committee on Cancer (AJCC) staging criteria, only patients with stage III or IV(A-B) poorly differentiated or undifferentiated NPC (World Health Organization type II/III) were included. We planned to recruit 52 patients with stage III disease and 64 patients with stage IV(A - B) disease. All patients received neoadjuvant chemotherapy with TPF (docetaxel 75 mg/m(2), day 1; cisplatin 75 mg/m(2), day 1; 5 Fu 500 mg/(m2 x day), continuous intravenous infusion for 120 h), every 3 weeks for 3 cycles, followed by weekly cisplatin (40 mg/m(2)) concurrent with radiotherapy. Three dimensional conformal radiotherapy (3D CRT) and intensity modulated radiotherapy (IMRT) were used. Gross disease planning target volume (PTV), high risk and low risk 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
  Fifty nine patients were evaluable for treatment response. Thirty patients had stage III disease and 29 patients had stage IV(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 follow up of 14.3 months, we observed 5 treatment failures and 2 deaths. The 1 year overall survival, distant metastasis free survival, and locoregional relapse free 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 treatment related 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.
authors.affiliation: Department of Radiation Oncology, Fudan University, Shanghai Cancer Center, Shanghai 200032, PR China. konglinj@gmail.com
authors.forename: Lin
authors.initials: L
authors.lastname: Kong
authors.forename: You-Wang
authors.initials: YW
authors.lastname: Zhang
authors.forename: Chao-Su
authors.initials: CS
authors.lastname: Hu
authors.forename: Ye
authors.initials: Y
authors.lastname: Guo
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced / Q000209:etiology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D059248:Chemoradiotherapy / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000473:pathology / Q000628:therapy*; D009325:Nausea / Q000139:chemically induced / Q000209:etiology; D020360:Neoadjuvant Therapy / Q000009:adverse effects; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced / Q000209:etiology; D020266:Radiotherapy, Conformal; D050397:Radiotherapy, Intensity-Modulated; D012074:Remission Induction; D015996:Survival Rate; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D043823:Taxoids; D002945:Cisplatin; D005472:Fluorouracil