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.
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).
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.
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.
This is a preview of subscription content, access via your institution
Subscribe to Journal
Get full journal access for 1 year
only $4.96 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
All data are available upon request.
Mody MD, Rocco JW, Yom SS, Haddad RI, Saba NF. Head and neck cancer. Lancet. 2021;398:P2289–99.
Brockstein B, Haraf DJ, Rademaker AW, Kies MS, Stenson KM, Rosen F, et al. Patterns of failure, prognostic factors and survival in locoregionally advanced head and neck cancer treated with concomitant chemoradiotherapy: a 9-year, 337-patient, multi-institutional experience. Ann Oncol. 2004;15:1179–86.
Vokes EE, Weichselbaum RR, Lippman SM, Hong WK. Head and neck cancer. N. Engl J Med. 1993;328:184–94.
Guo T, Qualliotine JR, Ha PK, Califano JA, Kim Y, Saunders JR, et al. Surgical salvage improves overall survival for patients with HPV-positive and HPV-negative recurrent locoregional and distant metastatic oropharyngeal cancer. Cancer. 2015;121:1977–84.
National Comprehensive Cancer Network. Head and Neck Cancers (Version 2.2020). https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf.
Burtness B, Harrington KJ, Greil R, Soulieres D, Tahara M, de Castro G Jr, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019;394:1915–28.
Vokes EE, Panje WR, Schilsky RL, Mick R, Awan AM, Moran WJ, et al. Hydroxyurea, fluorouracil, and concomitant radiotherapy in poor-prognosis head and neck cancer: a phase I-II study. J Clin Oncol. 1989;7:761–8.
Haraf DJ, Weichselbaum RR, Vokes EE. Re-irradiation with concomitant chemotherapy of unresectable recurrent head and neck cancer: a potentially curable disease. Ann Oncol. 1996;7:913–8.
Vokes EE, Haraf DJ, Mick R, McEvilly JM, Weichselbaum RR. Intensified concomitant chemoradiotherapy with and without filgrastim for poor-prognosis head and neck cancer. J Clin Oncol. 1994;12:2351–9.
Salama JK, Vokes EE, Chmura SJ, Milano MT, Kao J, Stenson KM, et al. Long-term outcome of concurrent chemotherapy and reirradiation for recurrent and second primary head-and-neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 2006;64:382–91.
Spencer SA, Harris J, Wheeler RH, Machtay M, Schultz C, Spanos W, et al. RTOG 96-10: reirradiation with concurrent hydroxyurea and 5-fluorouracil in patients with squamous cell cancer of the head and neck. Int J Radiat Oncol Biol Phys. 2001;51:1299–304.
Spencer SA, Harris J, Wheeler RH, Machtay M, Schultz C, Spanos W, et al. Final report of RTOG 9610, a multi-institutional trial of reirradiation and chemotherapy for unresectable recurrent squamous cell carcinoma of the head and neck. Head Neck. 2008;30:281–8.
Villaflor VM, Melotek JM, Karrison TG, Brisson RJ, Blair EA, Portugal L, et al. Response-adapted volume de-escalation (RAVD) in locally advanced head and neck cancer. Ann Oncol. 2016;27:908–13.
Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16.
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–81.
Seiwert TY, Foster CC, Blair EA, Karrison TG, Agrawal N, Melotek JM, et al. OPTIMA: a phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer. Ann Oncol. 2019;30:1673.
Oppelt P, Ley J, Daly M, Rich J, Paniello R, Jackson RS, et al. nab-Paclitaxel and cisplatin followed by cisplatin and radiation (Arm 1) and nab-paclitaxel followed by cetuximab and radiation (Arm 2) for locally advanced head and neck squamous-cell carcinoma: a multicenter, non-randomized phase 2 trial. Med Oncol. 2021;38:35.
Weiss J, Gilbert J, Deal AM, Weissler M, Hilliard C, Chera B, et al. Induction chemotherapy with carboplatin, nab-paclitaxel and cetuximab for at least N2b nodal status or surgically unresectable squamous cell carcinoma of the head and neck. Oral Oncol. 2018;84:46–51.
Adkins D, Ley J, Oppelt P, Wildes TM, Gay HA, Daly M, et al. nab-Paclitaxel-based induction chemotherapy with or without cetuximab for locally advanced head and neck squamous cell carcinoma. Oral Oncol. 2017;72:26–31.
Rosenberg AJ, Agrawal N, Pearson A, Gooi Z, Blair E, Cursio J, et al. Risk and response adapted de-intensified treatment for HPV-associated oropharyngeal cancer: Optima paradigm expanded experience. Oral Oncol. 2021;122:105566.
Langer CJ, Harris J, Horwitz EM, Nicolaou N, Kies M, Curran W, et al. Phase II study of low-dose paclitaxel and cisplatin in combination with split-course concomitant twice-daily reirradiation in recurrent squamous cell carcinoma of the head and neck: results of Radiation Therapy Oncology Group Protocol 9911. J Clin Oncol. 2007;25:4800–5.
Janot F, de Raucourt D, Benhamou E, Ferron C, Dolivet G, Bensadoun RJ, et al. Randomized trial of postoperative reirradiation combined with chemotherapy after salvage surgery compared with salvage surgery alone in head and neck carcinoma. J Clin Oncol. 2008;26:5518–23.
Ward MC, Riaz N, Caudell JJ, Dunlap NE, Isrow D, Zakem SJ, et al. Refining patient selection for reirradiation of head and neck squamous carcinoma in the IMRT era: a multi-institution cohort study by the MIRI collaborative. Int J Radiat Oncol Biol Phys. 2018;100:586–94.
Ferris RL, Blumenschein G Jr., Fayette J, Guigay J, Colevas AD, Licitra L, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N. Engl J Med. 2016;375:1856–67.
Cohen EEW, Soulieres D, Le Tourneau C, Dinis J, Licitra L, Ahn MJ, et al. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet 2019;393:156–67.
Burtness B, Rischin D, Greil R, Soulieres D, Tahara M, de Castro G Jr, et al. Pembrolizumab alone or with chemotherapy for recurrent/metastatic head and neck squamous cell carcinoma in KEYNOTE-048: subgroup analysis by programmed death ligand-1 combined positive score. J Clin Oncol. 2022:JCO2102198.
Seiwert TY, Melotek JM, Blair EA, Stenson KM, Salama JK, Witt ME, et al. Final results of a randomized phase 2 trial investigating the addition of cetuximab to induction chemotherapy and accelerated or hyperfractionated chemoradiation for locoregionally advanced head and neck cancer. Int J Radiat Oncol Biol Phys. 2016;96:21–9.
We would like to acknowledge support from Celgene (Bristol Myers Squibb). This trial was supported, in part, by the University of Chicago Medicine Comprehensive Cancer Center Support Grant (#P30 CA14599) and support from the V. and R.W Svendsen Foundation. This study was presented in part at the ESMO Annual Meeting 2021.
This study was funded by Celgene (Bristol Myers, Squibb).
AJR: consulting/advisory: EMD-Serono, Nanobiotix, Galectin Therapeutics, Privo Technologies. NA: stock options: Privo Technologies. ATP: consulting/advisory: Prelude, Abbvie, Elevar, Ayala; stock options: Privo Technologies; research funding: Abbvie, Kura Oncology. AJ: consulting: Isoray. Research funding: AstraZeneca. VMV: Stock: J&J. Research funding: Takeda. TS: research funding: BMS, AstraZeneca, Genentech, Nanobiotix, Merck. Honoraria: Merck, Nanobiotix. Consulting/advisory: Innate, Regeneron, Vir, Merck, Nanobiotix, BostonGene EEV: consulting/advisory: AstraZeneca, BeiGene, BioNTech, Eli Lilly, EMD-Serono, Genentech, GlaxoSmithKline, Novartis. The remaining authors declare no competing interests.
Ethics approval and consent to participate
This study was conducted in accordance with the Declaration of Helsinki and was approved by the University of Chicago institutional review board. Furthermore, written consent was obtained from all participants.
Consent to publish
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Rosenberg, A.J., Agrawal, N., Pearson, A.T. et al. Phase I study of nab-paclitaxel-based induction followed by nab-paclitaxel-based concurrent chemotherapy and re-irradiation in previously treated head and neck squamous cell carcinoma. Br J Cancer (2022). https://doi.org/10.1038/s41416-022-01941-0