Cancer Res Treat. 2016;48(3):907-16.

The Effect of Induction Chemotherapy Using Docetaxel, Cisplatin, and Fluorouracil on Survival in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Meta-Analysis.

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제1저자 김률, 한서경 · 교신저자 김범석

PMID 26582394 PMC4946346 DOI 10.4143/crt.2015.359 IF 4.2 혈액종양내과

소속 (4)

Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Korea.
Department of Medicine, Seoul National University College of Medicine, Seoul, Korea.
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.

Abstract

PURPOSE The purpose of this study was to compare the survival of patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) undergoing concurrent chemoradiotherapy (CRT) alone with that of patients undergoing induction chemotherapy (IC) using docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by CRT.

MATERIALS AND METHODS A search of the PubMed, EMBASE, and Cochrane Library databases was performed in April 2015 and abstracts from the American Society of Clinical Oncology meetings (2008-2014) were reviewed. Summaries of the results were pooled using a fixed-effect model, and the risk of bias was evaluated using the Cochrane tool.

RESULTS A total of six relevant trials comprising 1,280 patients were identified. There was no statistically significant overall survival (OS) advantage for TPF prior to CRT (TPF/CRT) over CRT alone (hazard ratio [HR] 0.92; 95% confidence interval [CI], 0.79 to 1.09; p=0.339). Progression-free survival (PFS) was significantly longer in the TPF/CRT arms (HR, 0.82; 95% CI, 0.70 to 0.95; p=0.009). Patients with non-oropharyngeal LA-HNSCC obtained the greatest OS and PFS benefits from TPF (HR, 0.68; 95% CI, 0.47 to 0.99; p=0.043 and HR, 0.67; 95% CI, 0.48 to 0.94; p=0.022, respectively). The complete response rate was significantly increased (risk ratio [RR], 1.34; 95% CI, 1.14 to 1.56; p < 0.001), and the distant metastasis rate tended to decrease (RR, 0.65; 95% CI, 0.40 to 1.04; p=0.071) in the TPF/CRT arms.

CONCLUSION IC with TPF followed by CRT is not superior to CRT alone for OS. However, PFS and the complete response rate were significantly improved in the TPF/CRT arms. TPF/CRT for patients with nonoropharyngeal LA-HNSCC provided clear survival advantages.

Keywords

ChemoradiotherapyHead and neck neoplasmsInduction chemotherapyMeta-analysisReview

Figures

**Fig. 1.** Flow diagram for study review and inclusion. This search was performed in April 2015. ASCO, American Society of Clinical Oncology; NIH, National Institutes of Health; LA-HNSCC, locally-advanced head and neck squamous cell carcinoma; IC, induction chemotherapy; TPF, docetaxel, cisplatin, and 5-fluorouracil; CRT, concurrent chemoradiotherapy; RCT, randomized controlled trial.

**Fig. 2.** Survival outcomes from the six randomized controlled trials comparing TPF/CRT with CRT alone. (A) Forest plot of OS. (B) Forest plot of PFS. TPF, docetaxel, cisplatin, and 5-fluorouracil; CRT, concurrent chemoradiotherapy; OS, overall survival; HR, hazard ratio; CI, confidence interval; df, degrees of freedom; PFS, progression-free survival.

**Fig. 3.** Subgroup analysis for OS and PFS according to the primary tumor location. TPF, docetaxel, cisplatin, and 5-fluorouracil; CRT, concurrent chemoradiotherapy; HR, hazard ratio; CI, confidence interval; OS, overall survival; PFS, progression-free survival.

**Fig. 4.** Relative risks for ORR (A) and CRR (B) from the trials with available data. TPF, docetaxel, cisplatin, and 5-fluorouracil; CRT, concurrent chemoradiotherapy; ORR, overall response rate; RR, relative risk; CI, confidence interval; df, degrees of freedom; CRR, complete response rate.

**Fig. 5.** Forest plot of relative risk for failure of completing chemoradiotherapy. TPF, docetaxel, cisplatin, and 5-fluorouracil; CRT, concurrent chemoradiotherapy; RR, relative risk; df, degrees of freedom; CI, confidence interval; PF, cisplatin and 5-fluorouracil. ^a)Patients who did not complete two cycles of PF during CRT were considered to have failed completion of CRT, ^b)Among 155 patients in the TPF/CRT arm, 28 patients discontinued before the third cycle of TPF and 19 patients discontinued after the third cycle of TPF but before CRT. In addition, 18 patients discontinued during the CRT period. Among 128 patients in the CRT arm, ten patients did not receive treatment, and 21 patients discontinued during the CRT period, ^c)Patients who did not complete two cycles of PF or cetuximab for 7 weeks were considered to have failed completion of CRT.

그림 출처: PubMed Central 공개 논문 (PMC4946346)

Conflict of interest statement

Conflict of interest relevant to this article was not reported.

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