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).
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.


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).


CONCLUSIONS
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.


BACKGROUND
NCT00736619.
Departments of Medicine. Electronic address: furym@mskcc.org.
M G
MG
Fury
Departments of Medicine.
E J
EJ
Sherman
Radiation Oncology.
S S
SS
Rao
Radiation Oncology.
S
S
Wolden
Departments of Medicine.
S
S
Smith-Marrone
Radiation Oncology, MSKCC Regional Network Affiliate, Sleepy Hollow.
B
B
Mueller
Departments of Medicine.
K K
KK
Ng
Radiation Oncology, MSKCC Regional Network Affiliate, Rockville Center.
P R
PR
Dutta
Departments of Medicine.
D Y
DY
Gelblum
Radiation Oncology, MSKCC Regional Network Affiliate, Commack, USA.
J L
JL
Lee
Epidemiology and Biostatistics.
R
R
Shen
Departments of Medicine.
S
S
Kurz
Pathology.
N
N
Katabi
Radiology, Memorial Sloan-Kettering Cancer Center (MSKCC), New York.
S
S
Haque
Radiation Oncology.
N Y
NY
Lee
Departments of Medicine.
D G
DG
Pfister
D000368:Aged; D000369:Aged, 80 and over; D000418:Albumins / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D000068818:Cetuximab; D059248:Chemoradiotherapy; D003131:Combined Modality Therapy / Q000009:adverse effects*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000009:adverse effects / Q000627:therapeutic use; D050397:Radiotherapy, Intensity-Modulated; D000077195:Squamous Cell Carcinoma of Head and Neck
C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D061067:Antibodies, Monoclonal, Humanized; D000972:Antineoplastic Agents, Phytogenic; D066246:ErbB Receptors; D017239:Paclitaxel; D000068818:Cetuximab
cetuximab; head and neck; nab-paclitaxel; radiation; squamous