Phase I study of weekly albumin-bound paclitaxel (ab-P) plus weekly cetuximab (Cet) plus intensity-modulated radiation therapy (IMRT) in patients with stage III/IVb head and neck squamous cell carcinoma (HNSCC).

Abstract

6034 Background: There is a clinical need to improve the efficacy of standard Cet + concurrent RT for pts with stage III/IVB HNSCC. Taxanes have potent activity against HNSCC, and ab-P may offer therapeutic advantages in comparison with other drugs of this class. Methods: This was a single institution phase I study with a modified 3 + 3 design. 4 dose levels (DLs) of weekly ab-P were explored (30, 45, 60, and 80 mg/m2) during IMRT. Standard Cet (450 mg/m2 loading dose followed by 250 mg/m2 weekly) concurrent with IMRT (total dose, 70 Gy) was prescribed for all pts. The maximum-tolerated dose (MTD) would be exceeded if >2/6 pts experienced DLTs at a given dose level. NCI CTCAE v.3 was used, and DLT monitoring extended until 2 wks after IMRT. Results: 25 eligible pts (20M, 5F) enrolled, with median age 58 years (range, 46-84) and median KPS 90 (range 80-100). Primary tumor sites were oropharynx, 20 (10 HPV pos, 5 HPV neg, 5 not done); neck node with unknown primary, 2; and larynx, oral cavity, and maxillary sinus, 1 each. Two pts never received ab-P and were deemed inevaluable. At DL 1 (ab-P, 30 mg/m2), there was one DLT (g.4 pneumonia) among 6 pts. At DL2 (ab-P, 45 mg/m2), there were 2 DLTs (g.4 cerebrovascular accident; g.3 decrease in L. ventricle ejection fraction/CHF exacerbation) among 6 pts. At DL3 (ab-P, 60 mg/m2), there was 1 DLT (g.3 supraventricular tachycardia) among 6 pts. MTD was exceeded at DL4 (ab-P, 80 mg/m2) with 3 DLTS (g.3 neuropathy, g.3 dehydration, g.3 anemia) among 5 evaluable pts. For the entire study population, most common ≥ g3 AEs were: lymphopenia 100%, functional mucositis, 56%, and pain in throat/oral cavity, 52%. There were no treatment-related deaths. Among 23 evaluable pts at a median follow up of 29 months, 2y PFS rate is 64% (95% CI: 41-80%) and 2y OS rate is 90% (95% CI: 66-97). Conclusions: The recommended phase II dose is ab-P 60 mg/m2 weekly when given concurrently with IMRT and standard weekly Cet. This regimen merits further study as an alternative to IMRT + Cet alone for pts who require a non-platinum regimen. This study was approved and funded by the NCCN from general research support provided by Celgene, Inc. Clinical trial information: NCT00736619.