Platinum-based chemotherapy plus cetuximab for the first-line treatment of Japanese patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: results of a phase II trial

Takayuki Yoshino, Yasuhisa Hasegawa, Shunji Takahashi, Nobuya Monden, Akihiro Homma, Kenji Okami, Yusuke Onozawa, Masato Fujii, Takahide Taguchi, Barbara de Blas, Frank Beier, Makoto Tahara, Takayuki Yoshino, Yasuhisa Hasegawa, Shunji Takahashi, Nobuya Monden, Akihiro Homma, Kenji Okami, Yusuke Onozawa, Masato Fujii, Takahide Taguchi, Barbara de Blas, Frank Beier, Makoto Tahara

Abstract

Objective: To assess the efficacy and safety of cetuximab in combination with cisplatin and 5-fluorouracil for first-line treatment of Japanese patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck.

Methods: In this open-label, single-arm, multicenter, Phase II study conducted in Japan, patients with confirmed recurrent and/or metastatic squamous cell carcinoma of the head and neck received weekly cetuximab (week 1, 400 mg/m(2); subsequent weeks, 250 mg/m(2)) plus a maximum of six three-weekly cycles of cisplatin (100 mg/m(2), day 1) and 5-fluorouracil (1000 mg/m(2)/day, 24-h infusion, days 1-4). The primary endpoint was the best overall response assessed by an independent review committee according to the modified World Health Organization criteria.

Results: In total, 33 patients received treatment. The most frequent primary tumor site was the hypopharynx (42%), and most patients had metastatic disease (85%). The best overall response rate as assessed by the independent review committee was 36% (95% confidence interval: 20, 55) and was significantly greater (P = 0.002) than the protocol-specified threshold of 15% at the one-sided 5% level. The disease control rate was 88%. The median progression-free survival and overall survival were 4.1 and 14.1 months, respectively. There were no unexpected safety concerns. Grade 3 or 4 adverse events were experienced by nearly all patients (32, 97%). No adverse events were fatal.

Conclusions: The demonstrated efficacy and safety of cetuximab in combination with cisplatin and 5-fluorouracil for the first-line treatment of Japanese patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck justify the further use of this combination treatment in this patient population .

Trial registration: ClinicalTrials.gov NCT00971932.

Figures

Figure 1.
Figure 1.
Kaplan–Meier estimates of (a) progression-free survival and (b) overall survival. CI, confidence interval.
Figure 2.
Figure 2.
Serum cetuximab concentrations after a dose of 250 mg/m2 on day 22. Linear plot. Points are mean ± standard deviation.
Figure 3.
Figure 3.
Serum cetuximab peak and trough concentrations.

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