A multicenter phase II trial of paclitaxel, carboplatin, and cetuximab followed by chemoradiotherapy in patients with unresectable locally advanced squamous cell carcinoma of the head and neck

Abstract

Background Induction chemotherapy (IC) in locally advanced squamous cell carcinoma of the head and neck (LA‐SCCHN) often compromises compliance with subsequent chemoradiotherapy (CRT), which negatively affects outcomes. Here, we assessed the combination of paclitaxel (PTX), carboplatin (CBDCA), and cetuximab (Cmab) as IC for unresectable LA‐SCCHN. Methods Induction chemotherapy consisted of weekly CBDCA area under the plasma concentration‐time curve = 1.5, PTX 80 mg/m2 and Cmab with an initial dose of 400 mg/m2 followed by 250 mg/m2 for 8 weeks. Following IC, CDDP (20 mg/m2, 4 days × 3 cycles) and concurrent radiotherapy (70 Gy/35 fr) were started. Primary endpoint was the proportion of CRT completion (%CRT completion). PCE was planned to be deemed effective if the Bayesian posterior probability (PP), defined as the probability that %CRT completion was larger than the threshold value of 65%, exceeded 84%. Results Thirty‐five patients were enrolled. Cases were hypopharynx/oropharynx/larynx in 17/17/1 patients, all at Stage IV. Of 35 patients, 34 (97%) completed IC and 32 received CRT and met the criteria of full analysis set (FAS). In FAS, the %CRT completion was 96.9%, and PP was 99.9%, exceeding the prespecified boundary of 84%. Mean cumulative dose and relative to dose intensity of CDDP in CRT was 232.5 mg/m2 and 100%, respectively. Response rate was 88.6% by IC and 93.8% in the CRT phase. Three year overall survival was 83.5%. Main grade 3 toxicities included neutropenia (11.4%) and skin rash (5.7%) during IC; and oral mucositis (31.3%) and neutropenia (12.5%) during CRT. No grade 4 toxicity or treatment‐related death was seen. Conclusions PCE as IC was feasible, with promising efficacy and no effect on compliance with subsequent CRT in unresectable LA‐SCCHN.

Efficacy and toxicity of weekly paclitaxel, carboplatin, and cetuximab as induction chemotherapy or in cases of metastases or relapse for head and neck cancer with a focus on elderly or frail patients

“…Thirty-one patients were elderly or frail (EF). The most common reasons patients did not receive cisplatin were performance status (13 patients), hearing loss (11), concern for nephrotoxicity (6) and age (5).…”

“…9 Several studies have showed this regimen yields promising results when used as an induction chemotherapy for locally advanced disease, with response rates ranging from 70% to 97%. 5,[10][11][12][13] PCC has also been studied for patients with metastatic or recurrent incurable disease, and has shown promising response with tolerable toxicity rates. 14 Although it is thought that this treatment combination is less toxic than some of the other standard-of-care systemic therapies, and it is often used as induction therapy prior to radiation or surgery in more frail patients as well as in patients with recurrent or metastatic disease, there is a relative dearth of evidence supporting its use.…”

“…Replacing 5‐FU with a taxane significantly decreases toxicity, and multiple preclinical studies have shown that cetuximab, taxane agents, and platinum agents have synergistic pro‐apoptotic and immunomodulatory functions 9 . Several studies have showed this regimen yields promising results when used as an induction chemotherapy for locally advanced disease, with response rates ranging from 70% to 97% 5,10–13 . PCC has also been studied for patients with metastatic or recurrent incurable disease, and has shown promising response with tolerable toxicity rates 14 …”

A phase I, single-center, open-label study of RM-1929 photoimmunotherapy in Japanese patients with recurrent head and neck squamous cell carcinoma

“…Head and neck squamous cell carcinoma (HNSCC) accounts for 90% of head and neck cancers [5]. Approximately, 70% of patients with primary HNSCC present with locally or regionally advanced disease (stage III or IV) [6], which recurs in approximately 40-65% of cases after primary therapy with surgery and radiation, with or without chemotherapy [6][7][8][9][10]. Patients with locally advanced HNSCC have a very poor prognosis, with a 5 year survival rate of only 10-50%, depending on the stage and location of the lesion [6].…”

Current Perspectives on Taxanes: Focus on Their Bioactivity, Delivery and Combination Therapy

“…Antibody-dependent cellular cytotoxicity, the main mechanism of anticancer action of cetuximab, can be further increased by paclitaxel [ 148 ]. Co-administration of cetuximab and paclitaxel was reported to be effective not only for the treatment of head and neck carcinoma but also for cervical, esophageal, urothelial, or non-small cell lung carcinoma, on which there are currently active clinical trials [ 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 ]. Another recently reported promising combination of paclitaxel with immunotherapy involves pamrevlumab (FG-3019; FibroGen, Inc., San Francisco, USA).…”