| General information |
| Database: | DB00276 |
| Objective: | There is a clinical need to improve the efficacy of standard cetuximab + concurrent intensitymodulated radiation therapy (IMRT) for patients with locally and/or regionally advanced HNSCC. Taxanes have radiosensitizing activity against HNSCC, and nabpaclitaxel may offer therapeutic advantage in comparison with other taxanes. |
| Authors: | Fury MG, et al |
| Title: | Phase I study of weekly nabpaclitaxel + weekly cetuximab + intensitymodulated radiation therapy (IMRT) in patients with stage IIIIVB head and neck squamous cell carcinoma (HNSCC). |
| Journal: | Ann Oncol. |
| Year: | 2014 |
| PMID: | 24496920 |
| Trial Design |
| Clinical Trial Id: | NCT00736619 |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced head and neck squamous cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 3 |
| Therapeutic Combination Content: | nabpaclitaxel + weekly cetuximab + intensitymodulated radiation therapy |
| Study Type: | a singleinstitutionphase I study |
| Key Patients Feature: | Eligible patients were more than and equal to 18 years of age with histologically or cytologically confirmed stage IIII/IVB HNSCC, Karnofsky performance status (KPS) of at least 70%, and adequate organ function with median age 58 years (range, 4684 years). |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | a modified 3 + 3 design. Four dose levels (DLs) of weekly nabpaclitaxel 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). |
| Primary End Point: | MTD, DLT, ORR, toxicity |
| Secondary End Point: | NA |
| Patients Number: | 25 |
| Trial Results |
| DLT_MTD: | Maximum tolerated dose (MTD) was exceeded at DL4 (nabpaclitaxel, 80 mg/m(2)) with three doselimiting 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 (nabpaclitaxel, 60 mg/m(2)), and this was deemed the MTD. |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 2year failurefree survival (FFS) is 65% [95% confidence interval (CI) 42% to 81%] |
| Median OS A vs. C: | 2year overall survival (OS) is 91% (95% CI 6997) |
| Adverse Event(agent arm): | Among 23 assessable patients, the most common more than and equal to g3 AEs were lymphopenia 100%, functional mucositis 65%, and pain in throat/oral cavity 52%. |
| Conclusions: | The recommendedphase II dose for nabpaclitaxel 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. |