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/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.

• Authors: M G Fury, E J Sherman, S S 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
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 25 Issue 3 Pg. 689-694 (Mar 2014) ISSN: 1569-8041 [Electronic] England
• PMID: 24496920 (Publication Type: Clinical Trial, Phase I, Journal Article)

Chemical References

• 130-nm albumin-bound paclitaxel
• Albumins
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents, Phytogenic
• ErbB Receptors
• Paclitaxel
• Cetuximab

Topics

• Aged
• Aged, 80 and over
• Albumins (adverse effects, therapeutic use)
• Antibodies, Monoclonal, Humanized (adverse effects, therapeutic use)
• Antineoplastic Agents, Phytogenic (adverse effects, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Carcinoma, Squamous Cell (drug therapy, mortality, radiotherapy)
• Cetuximab
• Chemoradiotherapy
• Combined Modality Therapy (adverse effects)
• ErbB Receptors (antagonists & inhibitors)
• Female
• Head and Neck Neoplasms (drug therapy, mortality, radiotherapy)
• Humans
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasm Staging
• Paclitaxel (adverse effects, therapeutic use)
• Radiotherapy, Intensity-Modulated
• Squamous Cell Carcinoma of Head and Neck