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

Ryul Kim, Seokyung Hahn, Junghoon Shin, Chan-Young Ock, Miso Kim, Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim, Dae Seog Heo, Ryul Kim, Seokyung Hahn, Junghoon Shin, Chan-Young Ock, Miso Kim, Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim, Dae Seog Heo

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: Chemoradiotherapy; Head and neck neoplasms; Induction chemotherapy; Meta-analysis; Review.

Conflict of interest statement

Conflict of interest relevant to this article was not reported.

Figures

Fig. 1.
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.
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.
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.
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.
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.

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