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) Journal Article


Authors: Fury, M. G.; Sherman, E. J.; Rao, S. 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.
Article Title: 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)
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. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Keywords: adult; clinical article; aged; middle aged; constipation; fatigue; neutropenia; intensity modulated radiation therapy; cisplatin; fluorouracil; diarrhea; dose response; drug efficacy; drug safety; paclitaxel; radiation dose; cancer staging; carboplatin; infection; sensory neuropathy; anemia; radiation; mucosa inflammation; nausea; neuropathy; thrombocytopenia; vomiting; dehydration; cetuximab; docetaxel; coughing; drug dose escalation; fever; loading drug dose; lymphocytopenia; pneumonia; rash; confusion; drug fatality; dysphagia; karnofsky performance status; acne; dermatitis; headache; maximum tolerated dose; phase 1 clinical trial; taxane derivative; anaphylaxis; larynx; head and neck; congestive heart failure; supraventricular tachycardia; cerebrovascular accident; mouth pain; dysgeusia; sore throat; neck pain; head and neck squamous cell carcinoma; squamous; nab-paclitaxel; very elderly; human; male; female; priority journal; article
Journal Title: Annals of Oncology
Volume: 25
Issue: 3
ISSN: 0923-7534
Publisher: Oxford University Press  
Date Published: 2014-03-01
Start Page: 689
End Page: 694
Language: English
DOI: 10.1093/annonc/mdt579
PROVIDER: scopus
PUBMED: 24496920
PMCID: PMC4433511
DOI/URL:
Notes: James Lee's middle initial is incorrect on original publication -- Export Date: 2 April 2014 -- Art. No.: mdt579 -- CODEN: ANONE -- Source: Scopus
Altmetric Score
MSK Authors
  1. Pinaki R Dutta
    15 Dutta
  2. Daphna Y Gelblum
    79 Gelblum
  3. Kenneth K Ng
    36 Ng
  4. Suzanne L Wolden
    424 Wolden
  5. James Lee
    8 Lee
  6. Boris A Mueller
    43 Mueller
  7. Eric J Sherman
    152 Sherman
  8. Ronglai Shen
    129 Shen
  9. Nancy Y. Lee
    550 Lee
  10. Sofia S Haque
    77 Haque
  11. Nora Katabi
    157 Katabi
  12. David G Pfister
    251 Pfister
  13. Matthew G Fury
    93 Fury
  14. Shyam S Rao
    81 Rao
  15. Sarah Tybie Kurz
    3 Kurz