Phase 1 study of nab-paclitaxel, cisplatin and 5-fluorouracil as induction chemotherapy followed by concurrent chemoradiotherapy in locoregionally advanced squamous cell carcinoma of the oropharynx.

Abstract

BACKGROUND:

Induction chemotherapy followed by concurrent chemoradiation (CRT) (sequential therapy) has been evaluated in the treatment of locoregionally-advanced squamous cell cancer of the head and neck (LA-SCCHN), with docetaxel, cisplatin (P) and 5-flurouracil (F) shown to be superior to PF doublet. Nab-paclitaxel (A) is a novel albumin-bound paclitaxel with a superior therapeutic index to docetaxel.

METHODS:

A phase I trial [Clinical trials.gov identifier NCT00731380] to assess the safety and efficacy of nab-paclitaxel+cisplatin+5-fluorouracil (APF) as induction chemotherapy for three cycles, followed by concurrent carboplatin (area-under-curve (AUC) 1.5 weekly) with radiation therapy (RT) (70 Gy/35 fractions), was conducted using a 3+3 design in patients with previously untreated LA-SCCHN. Dose-limiting toxicities (DLTs) included: standard haematologic and non-haematologic toxicities, treatment delays, inability to complete ⩾95% of RT and skin/mucosal toxicity related to RT assessed from day 1 of treatment to 8 weeks after completion of CRT.

RESULTS:

17 patients with oropharyngeal cancer were enrolled in three dose levels, with 15 patients evaluable for DLT. The median age was 54 years (range, 44-65 years), 14 patients were male, and 11 patients' tumours were p16 positive and four negative. Grade 3/4 adverse events during APF (%total number of cycles) were hyponatraemia (14%) neutropenia (10%), lymphopaenia (4%) and thrombocytopenia (2%) during 49 evaluable APF cycles. Febrile neutropenia occurred during one cycle of treatment.

CONCLUSION:

The recommended phase 2 dose of APF is nab-paclitaxel 100mg/m(2) days 1 and 8, cisplatin 75 mg/mg(2) day 1 and 5-fluorouracil 1000 mg/m(2)/day×96 h days 1-4, every 3 weeks, for three cycles prior to CRT.

• Authors: H H Loong, E Winquist, J Waldron, E X Chen, J Kim, D Palma, N Read, A R A Razak, I Diaz-Padilla, K Chan, A Bayley, M Hossain, L Wang, S Chin, L L Siu, A Hope
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 50 Issue 13 Pg. 2263-70 (Sep 2014) ISSN: 1879-0852 [Electronic] England
• PMID: 24953566 (Publication Type: Clinical Trial, Phase I, Journal Article)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Paclitaxel
• Cisplatin
• Fluorouracil

Topics

• Adult
• Aged
• Animals
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma, Squamous Cell (drug therapy, pathology, radiotherapy)
• Chemoradiotherapy
• Cisplatin (administration & dosage)
• Female
• Fluorouracil (administration & dosage)
• Head and Neck Neoplasms (drug therapy, pathology, radiotherapy)
• Humans
• Induction Chemotherapy
• Male
• Middle Aged
• Oropharyngeal Neoplasms (drug therapy, pathology, radiotherapy)
• Paclitaxel (administration & dosage)
• Squamous Cell Carcinoma of Head and Neck