Elsevier

Auris Nasus Larynx

Volume 42, Issue 5, October 2015, Pages 396-400
Auris Nasus Larynx

Docetaxel, cisplatin, and fluorouracil for patients with inoperable recurrent or metastatic head and neck squamous cell carcinoma

https://doi.org/10.1016/j.anl.2015.02.009Get rights and content

Abstract

Objective

The first-line treatment for inoperable recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) has long been the combination of cisplatin and fluorouracil (PF). Recently, cetuximab has been shown to provide an additional survival benefit to PF. It remains unknown whether docetaxel adds additional benefits to PF. Therefore, we sought to evaluate the efficacy and toxicity of docetaxel, cisplatin, and fluorouracil (TPF) for inoperable recurrent or metastatic HNSCC.

Methods

A retrospective chart review from January 2005 to March 2013 identified patients who were treated with docetaxel 60 mg/m2 on day 1, followed by cisplatin 60 mg/m2 on day 1, and fluorouracil 600 mg/m2/day on days 1–5 (modified TPF) every 4 weeks for inoperable recurrent or metastatic HNSCC.

Results

Twenty-four patients were identified; seven and five patients had locoregional disease only and distant metastasis only, respectively, while 12 patients had locoregional disease and distant metastasis simultaneously. Of the 17 patients with distant metastasis, multiple organs were affected in 9 patients, with the most frequently affected organ being the lung (n = 11). Three patients had no prior treatment, whereas 21 patients underwent intensive prior treatment. In 17 of 21 patients who had received prior treatment, the treatment included chemoradiotherapy and/or chemotherapy. The median number of cycles of modified TPF was two (range, 1–5). One patient showed complete response, four patients showed partial response, two patients had stable disease, and 17 patients had progressive disease. Overall, the rate of objective response was 21%, with a 95% confidence interval (CI) of 9–40%. Median overall survival was 8.0 months (95%CI, 4.4–10.6 months). The treatment efficacy differed significantly according to extent of disease. Objective response in patients with distant metastasis alone was better than in patients with locoregional disease with or without distant metastasis (60% vs. 11%, respectively; P = 0.02). Median overall survival in the former patients was longer than in the latter patients (not reached vs. 7.0 months, respectively; P = 0.02). Fifteen patients (63%) had Grades 3–4 neutropenia, and seven patients (29%) developed Grade 3 febrile neutropenia. There were no toxic deaths.

Conclusion

The efficacy of modified TPF in the setting of first-line treatment for recurrent or metastatic HNSCC is not very high, while the toxicity is acceptable with extensive care. The development of more efficacious chemotherapeutic regimen is required.

Introduction

The first-line treatment for inoperable recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC) is a combination of cisplatin and fluorouracil (PF), but the clinical outcome is poor [1]. TAX323 is a phase III study that compared the efficacy of induction chemotherapy between PF and PF plus docetaxel (TPF) for locoregionally advanced HNSCC, and it was reported that TPF significantly improved progression-free and overall survival compared with PF [2]. This finding has established TPF as the standard regimen of induction chemotherapy, which led us to the assumption that TPF is effective for patients with inoperable recurrent or metastatic HNSCC.

The standard TPF regimen consists of docetaxel 75 mg/m2 on day 1, followed by cisplatin 75 mg/m2 on day 1, and fluorouracil 750 mg/m2/day on days 1–5 [2], whereas the recommended dose of docetaxel for HNSCC is 60 mg/m2 in Japan. It has been reported that the standard TPF regimen is highly toxic to Asian patients owing to severe myelosuppression when used as induction chemotherapy [3]. Moreover, it is generally understood that the physical status of patients with inoperable recurrent or metastatic HNSCC is poorer than patients with locoregionally advanced HNSCC, and that patients with inoperable recurrent or metastatic HNSCC have cachexia and are likely to be vulnerable to aggressive chemotherapy. Accordingly, we reduced the dosage of PF by 20% in proportion to the recommended dose of docetaxel to apply the TPF regimen to Japanese patients with inoperable recurrent or metastatic HNSCC. This modified TPF regimen consists of docetaxel 60 mg/m2 on day 1, followed by cisplatin 60 mg/m2 on day 1, and fluorouracil 600 mg/m2/day on days 1–5. Herein, we report the efficacy and toxicity of modified TPF as the first-line treatment for inoperable recurrent or metastatic HNSCC in a community setting at our single institution.

Section snippets

Patients and treatment

We performed a retrospective chart review from January 2005 to March 2013 to identify patients who had undergone modified TPF chemotherapy owing to inoperable recurrent or metastatic non-nasopharyngeal HNSCC. To be treated with modified TPF, patients were required to have an Eastern Cooperative Oncology Group performance status of 0–2, and adequate bone marrow, liver, and renal function. Patients were also required to have cardiopulmonary function tolerable to hydration. Additional exclusion

Patient characteristics

We identified 24 patients for inclusion in this study, whose baseline characteristics are summarized in Table 1. Seven and five patients had locoregional disease only and distant metastasis only, respectively, while 12 patients had locoregional disease and distant metastasis simultaneously. Of the 17 patients with distant metastasis, multiple organs were affected in 9 patients. The most frequently affected organ was the lung (n = 11), followed by bone (n = 8), mediastinal node (n = 4), liver (n = 3),

Discussion

In this retrospective study, we showed the efficacy of modified TPF as the first-line treatment for inoperable recurrent or metastatic HNSCC. Objective response rate, median overall survival, and 1-year overall survival rate were 21%, 8.0 months, and 18%, respectively. We also showed that the treatment efficacy differed significantly depending on disease extent. Tumor response in patients with distant metastasis alone was better than in patients with locoregional disease with or without distant

Conflicts of interest

The authors declare that they have no conflicts of interest.

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