M G Fury1, E J Sherman2, S S Rao3, S Wolden3, S Smith-Marrone2, B Mueller4, K K Ng2, P R Dutta5, D Y Gelblum2, J L Lee6, R Shen7, S Kurz2, N Katabi8, S Haque9, N Y Lee3, D G Pfister2. 1. Departments of Medicine. Electronic address: furym@mskcc.org. 2. Departments of Medicine. 3. Radiation Oncology. 4. Radiation Oncology, MSKCC Regional Network Affiliate, Sleepy Hollow. 5. Radiation Oncology, MSKCC Regional Network Affiliate, Rockville Center. 6. Radiation Oncology, MSKCC Regional Network Affiliate, Commack, USA. 7. Epidemiology and Biostatistics. 8. Pathology. 9. Radiology, Memorial Sloan-Kettering Cancer Center (MSKCC), New York.
Abstract
BACKGROUND: There is a clinical need to improve the efficacy of standard cetuximab + concurrent intensity-modulated radiation therapy (IMRT) for patients with locally and/or regionally advanced HNSCC. Taxanes have radiosensitizing activity against HNSCC, and nab-paclitaxel may offer therapeutic advantage in comparison with other taxanes. PATIENTS AND METHODS: This was a single-institution phase I study with a modified 3 + 3 design. Four dose levels (DLs) of weekly nab-paclitaxel were explored (30, 45, 60, and 80 mg/m(2)), given with standard weekly cetuximab (450 mg/m(2) loading dose followed by 250 mg/m(2) weekly) and concurrent IMRT (total dose, 70 Gy). RESULTS: Twenty-five eligible patients (20 M, 5 F) enrolled, with median age 58 years (range, 46-84 years). Primary tumor sites were oropharynx, 19 (10 human papillomavirus [HPV] pos, 8 HPV neg, 1 not done); neck node with unknown primary, 2; larynx 2; and oral cavity and maxillary sinus, 1 each. Seven patients had received prior induction chemotherapy. Maximum tolerated dose (MTD) was exceeded at DL4 (nab-paclitaxel, 80 mg/m(2)) with three dose-limiting toxicities (DLTs) (grade 3 neuropathy, grade 3 dehydration, with grade 3 mucositis grade 3 anemia) among five assessable patients. There was only one DLT (grade 3 supraventricular tachycardia) among six patients at DL3 (nab-paclitaxel, 60 mg/m(2)), and this was deemed the MTD. Among 23 assessable patients, the most common ≥ g3 AEs were lymphopenia 100%, functional mucositis 65%, and pain in throat/oral cavity 52%. At a median follow-up of 33 months, 2-year failure-free survival (FFS) is 65% [95% confidence interval (CI) 42% to 81%] and 2-year overall survival (OS) is 91% (95% CI 69-97). CONCLUSION: The recommended phase II dose for nab-paclitaxel is 60 mg/m(2) weekly when given standard weekly cetuximab and concurrent IMRT. This regimen merits further study as a nonplatinum alternative to IMRT + cetuximab alone. CLINICALTRIALSGOV ID: NCT00736619.
BACKGROUND: There is a clinical need to improve the efficacy of standard cetuximab + concurrent intensity-modulated radiation therapy (IMRT) for patients with locally and/or regionally advanced HNSCC. Taxanes have radiosensitizing activity against HNSCC, and nab-paclitaxel may offer therapeutic advantage in comparison with other taxanes. PATIENTS AND METHODS: This was a single-institution phase I study with a modified 3 + 3 design. Four dose levels (DLs) of weekly nab-paclitaxel were explored (30, 45, 60, and 80 mg/m(2)), given with standard weekly cetuximab (450 mg/m(2) loading dose followed by 250 mg/m(2) weekly) and concurrent IMRT (total dose, 70 Gy). RESULTS: Twenty-five eligible patients (20 M, 5 F) enrolled, with median age 58 years (range, 46-84 years). Primary tumor sites were oropharynx, 19 (10 human papillomavirus [HPV] pos, 8 HPV neg, 1 not done); neck node with unknown primary, 2; larynx 2; and oral cavity and maxillary sinus, 1 each. Seven patients had received prior induction chemotherapy. Maximum tolerated dose (MTD) was exceeded at DL4 (nab-paclitaxel, 80 mg/m(2)) with three dose-limiting toxicities (DLTs) (grade 3 neuropathy, grade 3 dehydration, with grade 3 mucositis grade 3 anemia) among five assessable patients. There was only one DLT (grade 3 supraventricular tachycardia) among six patients at DL3 (nab-paclitaxel, 60 mg/m(2)), and this was deemed the MTD. Among 23 assessable patients, the most common ≥ g3 AEs were lymphopenia 100%, functional mucositis 65%, and pain in throat/oral cavity 52%. At a median follow-up of 33 months, 2-year failure-free survival (FFS) is 65% [95% confidence interval (CI) 42% to 81%] and 2-year overall survival (OS) is 91% (95% CI 69-97). CONCLUSION: The recommended phase II dose for nab-paclitaxel is 60 mg/m(2) weekly when given standard weekly cetuximab and concurrent IMRT. This regimen merits further study as a nonplatinum alternative to IMRT + cetuximab alone. CLINICALTRIALSGOV ID: NCT00736619.
Entities:
Keywords:
cetuximab; head and neck; nab-paclitaxel; radiation; squamous
Authors: Douglas Adkins; Jessica Ley; Kathryn Trinkaus; Wade Thorstad; James Lewis; Tanya Wildes; Barry A Siegel; Farrokh Dehdashti; Hiram Gay; Paul Mehan; Brian Nussenbaum Journal: Cancer Date: 2012-09-18 Impact factor: 6.860
Authors: Begoña Jiménez; José M Trigo; Bella I Pajares; Maria I Sáez; Cristina Quero; Victor Navarro; Casilda Llácer; Laura Medina; Antonio Rueda; Emilio Alba Journal: Oral Oncol Date: 2012-09-28 Impact factor: 5.337
Authors: B Damascelli; G Cantù; F Mattavelli; P Tamplenizza; P Bidoli; E Leo; F Dosio; A M Cerrotta; G Di Tolla; L F Frigerio; F Garbagnati; R Lanocita; A Marchianò; G Patelli; C Spreafico; V Tichà; V Vespro; F Zunino Journal: Cancer Date: 2001-11-15 Impact factor: 6.860
Authors: Mohan Suntharalingam; Young Kwok; Olga Goloubeva; Arti Parekh; Rodney Taylor; Jeffrey Wolf; Ann Zimrin; Scott Strome; Robert Ord; Kevin J Cullen Journal: Int J Radiat Oncol Biol Phys Date: 2011-05-19 Impact factor: 7.038
Authors: Gregory Vlacich; Roberto Diaz; Steven W Thorpe; Barbara A Murphy; Wyndee Kirby; Robert J Sinard; Bashar Shakhtour; Yu Shyr; Patrick Murphy; James L Netterville; Wendell G Yarbrough; Anthony J Cmelak Journal: Oncologist Date: 2012-05-01
Authors: Lawrence Koutcher; Eric Sherman; Matthew Fury; Suzanne Wolden; Zhigang Zhang; Qianxing Mo; Laschelle Stewart; Karen Schupak; Daphna Gelblum; Richard Wong; Dennis Kraus; Jatin Shah; Michael Zelefsky; David Pfister; Nancy Lee Journal: Int J Radiat Oncol Biol Phys Date: 2010-10-13 Impact factor: 7.038
Authors: Aaron E Sosa; Juan J Grau; Luis Feliz; Verónica Pereira; Diego Alcaraz; Carmen Muñoz-García; Miguel Caballero Journal: Eur Arch Otorhinolaryngol Date: 2013-05-04 Impact factor: 2.503
Authors: Thomas Kuhnt; Andreas Schreiber; Anett Pirnasch; Matthias G Hautmann; Peter Hass; Frank P Sieker; Rita Engenhart-Cabillic; Michael Richter; Kathrin Dellas; Jürgen Dunst Journal: Strahlenther Onkol Date: 2017-05-12 Impact factor: 3.621
Authors: Allison N DuRoss; Megan J Neufeld; Shushan Rana; Charles R Thomas; Conroy Sun Journal: Adv Drug Deliv Rev Date: 2019-07-04 Impact factor: 15.470
Authors: Alexandra Iulia Irimie; Laura Sonea; Ancuta Jurj; Nikolay Mehterov; Alina Andreea Zimta; Liviuta Budisan; Cornelia Braicu; Ioana Berindan-Neagoe Journal: Int J Nanomedicine Date: 2017-06-26
Authors: William T Arscott; Kevin T Nead; Adham Bear; Sriram Venigalla; Jacob Shabason; John N Lukens; John P Plastaras; Andrzej Wojcieszynski; James Metz; Mark O'Hara; Kim A Reiss; Ursina Teitelbaum; Arturo Loaiza-Bonilla; Jeffrey Drebin; Major K Lee; Stuti G Shroff; Edgar Ben-Josef Journal: Am J Clin Oncol Date: 2021-09-01 Impact factor: 2.339