Phase I study of nab-paclitaxel-based induction followed by nab-paclitaxel-based concurrent chemotherapy and re-irradiation in previously treated head and neck squamous cell carcinoma

Br J Cancer. 2022 Nov;127(8):1497-1506. doi: 10.1038/s41416-022-01941-0. Epub 2022 Aug 9.

Abstract

Background: Recurrent head and neck squamous cell carcinoma (HNSCC) is associated with poor overall survival (OS). Prior studies suggested incorporation of nab-paclitaxel (A) may improve outcomes in recurrent HNSCC.

Methods: This Phase I study evaluated induction with carboplatin and A followed by concomitant FHX (infusional 5-fluorouracil, hydroxyurea and twice-daily radiation therapy administered every other week) plus A with cohort dose escalation ranging from 10-100 mg/m2 in recurrent HNSCC. The primary endpoint was maximally tolerated dose (MTD) and dose-limiting toxicity (DLT) of A when given in combination with FHX (AFHX).

Results: Forty-eight eligible pts started induction; 28 pts started AFHX and were evaluable for toxicity. Two DLTs occurred (both Grade 4 mucositis) at a dose level 20 mg/m2. No further DLTs were observed with subsequent dose escalation. The MTD and recommended Phase II dose (RP2D) of A was 100 mg/m2.

Conclusions: In this Phase I study, the RP2D of A with FHX is 100 mg/m2 (AFHX). The role of re-irradiation with immunotherapy warrants further investigation.

Clinical trial information: This clinical trial was registered with ClinicalTrials.gov identifier: NCT01847326.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Carboplatin / adverse effects
  • Carcinoma* / drug therapy
  • Fluorouracil / adverse effects
  • Head and Neck Neoplasms* / drug therapy
  • Head and Neck Neoplasms* / radiotherapy
  • Humans
  • Hydroxyurea
  • Maximum Tolerated Dose
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / radiotherapy
  • Paclitaxel
  • Re-Irradiation*
  • Squamous Cell Carcinoma of Head and Neck / drug therapy
  • Squamous Cell Carcinoma of Head and Neck / radiotherapy

Substances

  • 130-nm albumin-bound paclitaxel
  • Albumins
  • Carboplatin
  • Paclitaxel
  • Fluorouracil
  • Hydroxyurea

Associated data

  • ClinicalTrials.gov/NCT01847326