Phase I study of the EGFR tyrosine kinase inhibitor erlotinib in combination with docetaxel and radiation in locally advanced squamous cell cancer of the head and neck (SCCHN)

Abstract

5545 Background: EGFR is highly expressed in SCCHN, representing a promising therapeutic target. Erlotinib (E) is an EGFR tyrosine kinase inhibitor that may potentiate the efficacy of concurrent radiation (RT) and docetaxel (D). We sought to establish the MTD, toxicities and preliminary efficacy of the combination of RT, D and E in patients (pts) with SCCHN. Methods: Patients with previously untreated stage III-IVB SCCHN were enrolled in a phase I dose-escalating study with standard once-daily RT (70.2 Gy, 1.8 Gy/day), weekly D for the duration of RT and daily E for two weeks prior, during and up to two years following RT. 4 dose levels (DL) were evaluated [D (mg/m2)/E (mg): 15/50, 15/100, 20/100, 20/150]. A 3+3 escalation design was followed. Pharmacokinetic studies (PK) were performed. Results: A total of 23 patients were enrolled (6 pts at each DL 1–3, 5 pts at DL4). Primary site: oral cavity (n = 1), pharynx (n = 15) and larynx (n = 7). 20 patients (87%) had stage IV disease. Three dose-limiting toxicities were observed, 1 at each DL (1–3), including a death within 30 days from last treatment (DL1), grade 3 mucositis resulting in holding RT (>5 days) (DL2) and grade 4 mucositis (DL3). No DLT to date on DL4 with 3/5 pts evaluable. In patients enrolled at DL 1–3 (n = 18), post concurrent chemoRT, best response was CR (n = 15), not evaluable (n = 2), death on study (n = 1). 3/3 pts who underwent planned neck dissection had a pathologic CR. 9 patients are currently receiving adjuvant E and 1 has completed the 2-year course. 3 patients have relapsed. Interpatient variability of E peak plasma concentrations measured after the first dose was observed at all dose levels: 458 ± 173 ng/mL (DL1), 686 ± 364 (DL2), 1017 ± 241 (DL3), 833 ± 222 (DL4) (mean ± s.d., n = 6, 6, 6, 2 at DL1–4 respectively). Adjuvant erlotinib plasma concentration data will be presented separately. No significant PK interaction of erlotinib with docetaxel was noted. Conclusions: The combination of daily erlotinib with weekly docetaxel and RT for pts with stage III-IVB SCCHN is feasible and active. A phase II trial is planned. Supported in part by NIH grants nos. CA62502 and M01 RR-000080. No significant financial relationships to disclose.

Phase II study of erlotinib and docetaxel with concurrent intensity‐modulated radiotherapy in locally advanced head and neck squamous cell carcinoma

“…[18][19][20] We have completed a phase I trial combining erlotinib, docetaxel, and concurrent radiation in HNSCC and found the regimen to be feasible and tolerated. 18 We are now reporting a phase II trial of this treatment regimen.…”

“…Human tumor xenograft studies have indicated that cetuximab is more effective in combination with docetaxel and radiation than with cisplatin and radiation . Our group has extensive experience in studying the efficacy and toxicity of targeted therapies added to a docetaxel‐based CRT regimen both in phase I and phase II setting . We have completed a phase I trial combining erlotinib, docetaxel, and concurrent radiation in HNSCC and found the regimen to be feasible and tolerated .…”

“…Our group has extensive experience in studying the efficacy and toxicity of targeted therapies added to a docetaxel‐based CRT regimen both in phase I and phase II setting . We have completed a phase I trial combining erlotinib, docetaxel, and concurrent radiation in HNSCC and found the regimen to be feasible and tolerated . We are now reporting a phase II trial of this treatment regimen.…”

Phase II study of bevacizumab in combination with docetaxel and radiation in locally advanced squamous cell carcinoma of the head and neck

“…[10][11][12] Our group has extensive experience in studying the efficacy and toxicities of targeted therapies added to a docetaxel-based CRT both in phase I and phase II settings. 13,14 Initial selection of docetaxel was based on its documented potent radiosensitizing effects and favorable toxicity profile when compared to cisplatin. We developed the first protocol combining radiotherapy (RT) with the doublet of docetaxel/bevacizumab in the effort to identify a non-cisplatin concurrent CRT regimen.…”

“…Our group has extensive experience in studying the efficacy and toxicities of targeted therapies added to a docetaxel‐based CRT both in phase I and phase II settings . Initial selection of docetaxel was based on its documented potent radiosensitizing effects and favorable toxicity profile when compared to cisplatin.…”