Phase I study of weekly nab-paclitaxel + weekly cetuximab + intensity-modulated radiation therapy (IMRT) in patients with stage III-IVB head and neck squamous cell carcinoma (HNSCC)

M. G. Fury, E. J. Sherman, Shyam Rao, S. Wolden, S. Smith-Marrone, B. Mueller, K. K. Ng, P. R. Dutta, D. Y. Gelblum, J. L. Lee, R. Shen, S. Kurz, N. Katabi, S. Haque, N. Y. Lee, D. G. Pfister

Research output: Contribution to journalArticle

11 Scopus citations

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/m2), given with standard weekly cetuximab (450 mg/m2 loading dose followed by 250 mg/m2 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/m2) 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/m2), 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/m2 weekly when given standard weekly cetuximab and concurrent IMRT. This regimen merits further study as a nonplatinum alternative to IMRT + cetuximab alone.

Original languageEnglish (US)
Article numbermdt579
Pages (from-to)689-694
Number of pages6
JournalAnnals of Oncology
Volume25
Issue number3
DOIs
StatePublished - Mar 1 2014
Externally publishedYes

Keywords

  • Cetuximab
  • Head and neck
  • Nab-paclitaxel
  • Radiation
  • Squamous

ASJC Scopus subject areas

  • Hematology
  • Oncology

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    Fury, M. G., Sherman, E. J., Rao, S., Wolden, S., Smith-Marrone, S., Mueller, B., Ng, K. K., Dutta, P. R., Gelblum, D. Y., Lee, J. L., Shen, R., Kurz, S., Katabi, N., Haque, S., Lee, N. Y., & Pfister, D. G. (2014). Phase I study of weekly nab-paclitaxel + weekly cetuximab + intensity-modulated radiation therapy (IMRT) in patients with stage III-IVB head and neck squamous cell carcinoma (HNSCC). Annals of Oncology, 25(3), 689-694. [mdt579]. https://doi.org/10.1093/annonc/mdt579