Phase II trial of docetaxel (T), cisplatin (P), and cetuximab (E) followed by concurrent radiation (RT), P, and E in locally advanced head and neck squamous cell carcinoma (HNSCC)

Abstract

6051 Background: E is a chimeric IgG1 monoclonal antibody against the external domain of the epidermal growth factor receptor that may enhance the efficacy of RT and chemotherapy. Our goal was to incorporate E in the induction and subsequent chemoradiotherapy of HNSCC. We report our preliminary results with TPE induction. Methods: Patients (pts) had pathologically documented HNSCC stage III/IV or selected stage II (base of tongue, hypopharynx, or nasopharynx), no prior therapy, ECOG PS 0–1, and adequate hematologic, kidney and liver laboratory parameters. Induction consisted of T 75 mg/m2 day 1, P 75 mg/m2 day 1, and E 250 mg/m2 days 1,8, and 15 (after an initial dose of 400 mg/m2 on cycle 1, day 1), repeated every 21 days × 3 cycles. Subsequently, pts received RT 70 Gy (2 Gy/day) with concurrent P 30 mg/m2 and E 250 mg/m2 weekly, followed by maintenance E for 6 months. Prophylactic antibiotics were given on days 5–14 of each TPE cycle. Tumor assessment was performed after induction (primary endpoint) and 8 weeks after RT. Sample size was 39; one-stage design; target overall response rate (ORR): 80%. Results: 21 pts have been enrolled to date: median age 55 (39–74); Male/Female: 18/3; primary site: oropharynx (n=13), larynx (n=5), and other (n=3); stage III/IV: 4/17. In 16 evaluable pts, ORR to TPE was 15/16 (94%), CR: 2, PR 13, SD 1. For the primary site (12 evaluable): CR 6, PR 5, SD 1; for the lymph nodes (14 evaluable): CR 1, PR: 12, SD 1. The pt with SD discontinued E in the first cycle due to recurring infusion reaction. Another patient had a grade (G) 3 infusion reaction on the first E administration and was removed from study. Other serious toxicities during TPE (n=20): grade (G) 3/4 neutropenia (n=4/n=7) without incidence of neutropenic fever, G 3 anemia (n=1), G 3 thrombocytopenia (n=1), G 3/4 hypomagnesemia (n=2/n=1), G 3 rash (n=1), G 3 fatigue (n=4), and G 3 diarrhea (n=1). 1 pt had sudden death due to myocardial infarction (autopsy) after the third cycle of TPE. Subsequent RT plus P and E was feasible. 10 pts completed RT and all remain progression-free. Conclusions: Preliminary results suggest that TPE has predictable and manageable toxicities and high activity in HNSCC. Accrual is ongoing and updated data will be available. No significant financial relationships to disclose.

Molecular targeting agents in the context of primary chemoradiation strategies

“…In this context, we would like to report about a phase II clinical trial initiated by a group from the University of Pittsburgh. First results of this trial were presented at the ASCO meeting in 2007 and again in 2008, 2009, and 2010 19–22. In 2010, they published their data in the Journal of Clinical Oncology 23.…”

Recent results of cetuximab use in the treatment of squamous cell carcinoma of the head and neck

“…Hematologic and skin toxicities were the most relevant adverse events also in this study. 37 Langer and colleagues have presented preliminary data of the ECOG 3303 study in which concurrent radiotherapy, cisplatin and cetuximab was given to 61 patients. The overall response rate was only 48% in this study.…”

Multidisciplinary Management of Locally Advanced SCCHN: Optimizing Treatment Outcomes

“…A weakness of this trial by the current benchmark is that the control group received RT alone-the standard of care at the time of study designrather than CRT, the current standard. Preliminary efficacy results of cetuximab plus CRT are encouraging [75][76][77][78][79] (this combination also seems to be feasible for esophageal cancer [80]), and an ongoing phase III trial (RTOG-0522) is evaluating whether cetuximab improves disease-free survival when added to CRT in LA-SCCHN [81]. Other recently completed or ongoing trials are evaluating cetuximab combined with induction CT [82] or adjuvant CRT [83], or as maintenance therapy following CRT [84].…”