Ari J Rosenberg1,2, Nishant Agrawal3,4, Alexander T Pearson5,3, Zhen Gooi4, Elizabeth Blair3,4, Louis Portugal3,4, John F Cursio6, Aditya Juloori3,7, Jeffrey Chin5, Kathryn Rouse5, Victoria M Villaflor8, Tanguy Y Seiwert9, Evgeny Izumchenko5,3, Mark W Lingen3,10, Daniel J Haraf3,7, Everett E Vokes5,3. 1. Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA. Arirosenberg@medicine.bsd.uchicago.edu. 2. University of Chicago Comprehensive Cancer Center, Chicago, IL, USA. Arirosenberg@medicine.bsd.uchicago.edu. 3. University of Chicago Comprehensive Cancer Center, Chicago, IL, USA. 4. Section of Otolaryngology-Head and Neck Surgery, University of Chicago, Chicago, IL, USA. 5. Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA. 6. Department of Public Health Sciences, University of Chicago, Chicago, IL, USA. 7. Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, USA. 8. City of Hope Comprehensive Cancer Center, Duarte, CA, USA. 9. Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA. 10. Department of Pathology, University of Chicago, Chicago, IL, USA.
Abstract
BACKGROUND: Recurrent head and neck squamous cell carcinoma (HNSCC) is associated with poor overall survival (OS). Prior studies suggested incorporation of nab-paclitaxel (A) may improve outcomes in recurrent HNSCC. METHODS: This Phase I study evaluated induction with carboplatin and A followed by concomitant FHX (infusional 5-fluorouracil, hydroxyurea and twice-daily radiation therapy administered every other week) plus A with cohort dose escalation ranging from 10-100 mg/m2 in recurrent HNSCC. The primary endpoint was maximally tolerated dose (MTD) and dose-limiting toxicity (DLT) of A when given in combination with FHX (AFHX). RESULTS: Forty-eight eligible pts started induction; 28 pts started AFHX and were evaluable for toxicity. Two DLTs occurred (both Grade 4 mucositis) at a dose level 20 mg/m2. No further DLTs were observed with subsequent dose escalation. The MTD and recommended Phase II dose (RP2D) of A was 100 mg/m2. CONCLUSIONS: In this Phase I study, the RP2D of A with FHX is 100 mg/m2 (AFHX). The role of re-irradiation with immunotherapy warrants further investigation. CLINICAL TRIAL INFORMATION: This clinical trial was registered with ClinicalTrials.gov identifier: NCT01847326.
BACKGROUND: Recurrent head and neck squamous cell carcinoma (HNSCC) is associated with poor overall survival (OS). Prior studies suggested incorporation of nab-paclitaxel (A) may improve outcomes in recurrent HNSCC. METHODS: This Phase I study evaluated induction with carboplatin and A followed by concomitant FHX (infusional 5-fluorouracil, hydroxyurea and twice-daily radiation therapy administered every other week) plus A with cohort dose escalation ranging from 10-100 mg/m2 in recurrent HNSCC. The primary endpoint was maximally tolerated dose (MTD) and dose-limiting toxicity (DLT) of A when given in combination with FHX (AFHX). RESULTS: Forty-eight eligible pts started induction; 28 pts started AFHX and were evaluable for toxicity. Two DLTs occurred (both Grade 4 mucositis) at a dose level 20 mg/m2. No further DLTs were observed with subsequent dose escalation. The MTD and recommended Phase II dose (RP2D) of A was 100 mg/m2. CONCLUSIONS: In this Phase I study, the RP2D of A with FHX is 100 mg/m2 (AFHX). The role of re-irradiation with immunotherapy warrants further investigation. CLINICAL TRIAL INFORMATION: This clinical trial was registered with ClinicalTrials.gov identifier: NCT01847326.
Authors: T Y Seiwert; C C Foster; E A Blair; T G Karrison; N Agrawal; J M Melotek; L Portugal; R J Brisson; A Dekker; S Kochanny; Z Gooi; M W Lingen; V M Villaflor; D T Ginat; D J Haraf; E E Vokes Journal: Ann Oncol Date: 2019-10-01 Impact factor: 32.976
Authors: S A Spencer; J Harris; R H Wheeler; M Machtay; C Schultz; W Spanos; M Rotman; R Meredith Journal: Int J Radiat Oncol Biol Phys Date: 2001-12-01 Impact factor: 7.038
Authors: Ari J Rosenberg; Nishant Agrawal; Alexander Pearson; Zhen Gooi; Elizabeth Blair; John Cursio; Aditya Juloori; Daniel Ginat; Adam Howard; Jeffrey Chin; Sara Kochanny; Corey Foster; Nicole Cipriani; Mark Lingen; Evgeny Izumchenko; Tanguy Y Seiwert; Daniel Haraf; Everett E Vokes Journal: Oral Oncol Date: 2021-10-18 Impact factor: 5.972
Authors: Sharon A Spencer; Jonathan Harris; Richard H Wheeler; Mitchell Machtay; Christopher Schultz; William Spanos; Marvin Rotman; Ruby Meredith; Kie-Kian Ang Journal: Head Neck Date: 2008-03 Impact factor: 3.147
Authors: V M Villaflor; J M Melotek; T G Karrison; R J Brisson; E A Blair; L Portugal; J A De Souza; D T Ginat; K M Stenson; A Langerman; M Kocherginsky; M T Spiotto; N Hannigan; T Y Seiwert; E E W Cohen; E E Vokes; D J Haraf Journal: Ann Oncol Date: 2016-02-15 Impact factor: 32.976
Authors: Tanguy Y Seiwert; James M Melotek; Elizabeth A Blair; Kerstin M Stenson; Joseph K Salama; Mary Ellyn Witt; Ryan J Brisson; Apoorva Chawla; Allison Dekker; Mark W Lingen; Masha Kocherginsky; Victoria M Villaflor; Ezra E W Cohen; Daniel J Haraf; Everett E Vokes Journal: Int J Radiat Oncol Biol Phys Date: 2016-05-07 Impact factor: 7.038
Authors: Barbara Burtness; Kevin J Harrington; Richard Greil; Denis Soulières; Makoto Tahara; Gilberto de Castro; Amanda Psyrri; Neus Basté; Prakash Neupane; Åse Bratland; Thorsten Fuereder; Brett G M Hughes; Ricard Mesía; Nuttapong Ngamphaiboon; Tamara Rordorf; Wan Zamaniah Wan Ishak; Ruey-Long Hong; René González Mendoza; Ananya Roy; Yayan Zhang; Burak Gumuscu; Jonathan D Cheng; Fan Jin; Danny Rischin Journal: Lancet Date: 2019-11-01 Impact factor: 79.321
Authors: Robert L Ferris; George Blumenschein; Jerome Fayette; Joel Guigay; A Dimitrios Colevas; Lisa Licitra; Kevin Harrington; Stefan Kasper; Everett E Vokes; Caroline Even; Francis Worden; Nabil F Saba; Lara C Iglesias Docampo; Robert Haddad; Tamara Rordorf; Naomi Kiyota; Makoto Tahara; Manish Monga; Mark Lynch; William J Geese; Justin Kopit; James W Shaw; Maura L Gillison Journal: N Engl J Med Date: 2016-10-08 Impact factor: 91.245
Authors: Matthew C Ward; Nadeem Riaz; Jimmy J Caudell; Neal E Dunlap; Derek Isrow; Sara J Zakem; Joshua Dault; Musaddiq J Awan; John A Vargo; Dwight E Heron; Kristin A Higgins; Jonathan J Beitler; Samuel Marcrom; Drexell H Boggs; Comron Hassanzadeh; Chandana A Reddy; James A Bonner; Min Yao; Mitchell Machtay; Farzan Siddiqui; Andy M Trotti; Nancy Y Lee; Shlomo A Koyfman Journal: Int J Radiat Oncol Biol Phys Date: 2017-06-17 Impact factor: 8.013