International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationPhase 2 Study of Docetaxel, Cisplatin, and Concurrent Radiation for Technically Resectable Stage III-IV Squamous Cell Carcinoma of the Head and Neck
Introduction
The contemporary organ-preserving treatment for locally advanced head and neck squamous cell carcinoma (HNSCC) is concurrent chemoradiation therapy (CRT) (1), with high-dose cisplatin (CDDP) and radiation as the standard regimen (2). Adding concurrent high-dose CDDP to radiation improves overall survival (OS) over radiation therapy alone, whereas this regimen increases both acute toxicity, including myelosuppression, renal injury, and vomiting, and severe late toxicity such as dysphagia (3), which compromise patients' quality of life. An optimal concurrent regimen with lower mortality and morbidity than high-dose CDDP is needed.
As docetaxel (DTX) serves as a radiosensitizer (4) and enhances cytotoxicity of CDDP by modifying intracellular platinum metabolism (5), DTX and CDDP in combination (DTX/CDDP) would be expected to synergistically affect concurrent radiation therapy. We conducted a phase 1 study of weekly administration of low-dose DTX/CDDP concurrent with conventionally fractionated radiation therapy (6). Hematologic toxicity, except for lymphocytopenia, renal injury, and vomiting, was minimal, but in-field mucositis was common and dose-limiting. We established 10 mg/m2 as the recommended dose for DTX and 20 mg/m2 for CDDP and proceeded to phase 2 study. Here, we report long-term results of this phase 2 study.
Section snippets
Patients
We recruited patients with previously untreated, measureable, nonmetastatic, histologically proven, technically resectable stage III or IV HNSCC, 20 to 75 years of age, with Eastern Cooperative Oncology Group performance status 0 to 1 and adequate bone marrow, liver, and renal function. We excluded those patients with T1N1 disease, previous radiation therapy above the clavicles, cancer diagnoses within the previous 2 years, excluding superficial disease, or another active cancer. The initial
Patient characteristics and treatment adherence
We enrolled 117 patients from March 29, 2004, to October 19, 2011, 116 of whom were analyzable (43 with oropharyngeal cancer, 54 with hypopharyngeal cancer, and 19 with laryngeal cancer) and 85 (73%) of whom had stage IV disease. One patient was excluded from analysis owing to protocol violation. Patient characteristics are shown in Table 1, and tumor-versus-node stage is shown in supplemental Table E1; available online at www.redjournal.com.
Of 116 patients, 82 (71%) completed treatment per
Discussion
The primary objective of this phase 2 trial was to determine whether overall CR rate would exceed 65%. We obtained an overall CR rate of 71%, with acceptable toxicity, and 2- and 4-year OS rates of 82% and 68%, respectively. Another series of phase 2 trials addressed the efficacy of taxane plus platin-based concurrent CRT. Tsao et al (12) used DTX, 15 mg/m2, and CDDP, 20 mg/m2 weekly, during weeks 1 to 4 with concomitant boost radiation of 72 Gy, which yielded 53% overall CR and 65% 2-year OS
Conclusions
In conclusion, weekly low-dose DTX/CDDP concurrent with standard fractionation radiation therapy for technically resectable stage III-IV HNSCC led to high local control and survival. Acute toxicity, such as mucositis, was common, but late toxicity, such as dysphagia, was uncommon. This regimen might be superior to high-dose CDDP regimen in terms of efficacy and/or toxicity. A randomized phase 3 study to address this issue is currently under consideration.
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Long-term efficacy and toxicity of concurrent chemoradiotherapy with nedaplatin and S-1 for head and neck squamous cell carcinoma
2019, Auris Nasus LarynxCitation Excerpt :Grade 3 or 4 acute adverse events were mainly leukopenia (24.5%), neutropenia (18.9%), mucositis (32.1%), and dermatitis (18.9%). The frequencies of these events were similar to those reported in previous studies on CDDP-based regimens (leukopenia, 12–37%; neutropenia, 5–18%; mucositis, 15–78%; dermatitis, 0–28%) [31,32,38,39]. On the other hand, the frequencies of grade 3 or higher anemia (1.9%) and thrombocytopenia (1.9%) were lower in this study than in previous studies on CDDP-based regimens (anemia, 0–13%; thrombocytopenia, 3–8%) [31,32,38,39].
In regard to Inohara et al
2015, International Journal of Radiation Oncology Biology PhysicsIn reply to Puthiyottil et al
2015, International Journal of Radiation Oncology Biology PhysicsDocetaxel, cisplatin, and fluorouracil for patients with inoperable recurrent or metastatic head and neck squamous cell carcinoma
2015, Auris Nasus LarynxCitation Excerpt :In 17 of 21 patients who underwent prior treatment, the treatment included chemoradiotherapy and/or chemotherapy. The regimen of the chemoradiotherapy consisted of six cycles of docetaxel 10 mg/m2 and cisplatin 20 mg/m2 concurrent with conventionally fractionated radiation of 66 Gy [5,6], while for chemotherapy treatment was the modified TPF. Median accumulative doses of chemotherapeutic reagents in prior treatments were 60 mg/m2 (range, 60–240 mg/m2) for docetaxel (n = 17), 120 mg/m2 (range, 60–240 mg/m2) for cisplatin (n = 17), and 1200 mg/m2 (range, 600–2400 mg/m2) for fluorouracil (n = 11).
Modified TPEx as first-line treatment for recurrent and/or metastatic head and neck cancer
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Conflict of interest: none.