@article{35d4f9278c9e46dc8c18dfe01289e89f,
title = "A phase i study afatinib/carboplatin/paclitaxel induction chemotherapy followed by standard chemoradiation in HPV-negative or high-risk HPV-positive locally advanced stage III/IVa/IVb head and neck squamous cell carcinoma",
abstract = "Introduction Afatinib is an ERBB family receptor inhibitor with efficacy in head and neck squamous cell carcinoma (HNSCC). A phase I trial was conducted to determine the maximally tolerated dose (MTD) of afatinib in combination with carboplatin and paclitaxel as induction chemotherapy (IC). Material and methods Patients with newly diagnosed, locally advanced HPV-negative or HPV-positive HNSCC with a significant smoking history were enrolled. Afatinib alone was given daily for two weeks as lead-in and subsequently given with carboplatin AUC 6 mg/ml min and paclitaxel 175 mg/m2 every 21 days as IC. Afatinib was started at a dose of 20 mg daily and dose escalated using a modified Fibonacci design. After completion of IC, afatinib was discontinued and patients received concurrent cisplatin 40 mg/m2 weekly and standard radiation. Toxicity was assessed using CTCAE version 4.0. Results Seven of nine patients completed afatinib lead-in and IC. Five patients had partial response and two patients had stable disease after IC. Dose level 1 (afatinib 20 mg) was well tolerated with one grade 3 (ALT elevation) and one grade 4 (neutropenia) toxicities. However, dose level 2 (afatinib 30 mg) was not well tolerated with nine grade 3 (pneumonia, abdominal pain, diarrhea, pancytopenia, and UTI), two grade 4 (sepsis) and one grade 5 (death) toxicities. Conclusions The MTD of afatinib given with carboplatin AUC 6 mg/ml min and paclitaxel 175 mg/m2 is 20 mg daily. Combination of afatinib at doses higher than 20 mg with carboplatin and paclitaxel should be administered with caution due to the toxicities.",
keywords = "ABCB1, Afatinib, Carboplatin, Efficacy, Head and neck squamous cell carcinoma, Paclitaxel, Phase I trial, Toxicity",
author = "Chung, {Christine H.} and Rudek, {Michelle A.} and Hyunseok Kang and Shanthi Marur and Pritish John and Nancy Tsottles and Sarah Bonerigo and Andy Veasey and Ana Kiess and Harry Quon and Anthony Cmelak and Murphy, {Barbara A.} and Jill Gilbert",
note = "Funding Information: The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). These studies were supported by Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI) through National Comprehensive Cancer Network Oncology Research Program (ORP). BIPI had no role in the design, analysis or interpretation of the results in this study; BIPI was given the opportunity to review the manuscript for medical and scientific accuracy as it relates to BIPI substances, as well as intellectual property considerations. The project described was also supported by the Analytical Pharmacology Core of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (NIH Grants P30 CA006973 and UL1 TR 001079 ). Grant No. UL1 TR 001079 is from the National Center for Advancing Translational Sciences (NCATS) a component of the NIH, and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the Johns Hopkins ICTR, NCATS or NIH. Funding Information: Christine H. Chung received research funding from Boehringer Ingelheim for preclinical research. Sarah Bonerigo received honorarium from Boehringer Ingelheim for serving in a focus group. All other authors have no conflict of interest. Funding Information: The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). These studies were supported by Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI) through National Comprehensive Cancer Network Oncology Research Program (ORP). BIPI had no role in the design, analysis or interpretation of the results in this study; BIPI was given the opportunity to review the manuscript for medical and scientific accuracy as it relates to BIPI substances, as well as intellectual property considerations. The project described was also supported by the Analytical Pharmacology Core of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (NIH Grants P30 CA006973 and UL1 TR 001079). Grant No. UL1 TR 001079 is from the National Center for Advancing Translational Sciences (NCATS) a component of the NIH, and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the Johns Hopkins ICTR, NCATS or NIH. Christine H. Chung received research funding from Boehringer Ingelheim for preclinical research. Sarah Bonerigo received honorarium from Boehringer Ingelheim for serving in a focus group. All other authors have no conflict of interest. Publisher Copyright: {\textcopyright} 2015 Elsevier Ltd. All rights reserved.All rights reserved.",
year = "2016",
month = feb,
day = "1",
doi = "10.1016/j.oraloncology.2015.11.020",
language = "English (US)",
volume = "53",
pages = "54--59",
journal = "Oral Oncology",
issn = "1368-8375",
publisher = "Elsevier Limited",
}