title: 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.
  
  
  CONCLUSIONS
  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: Princess Margaret Cancer Centre, Toronto, ON, Canada. Electronic address: herbertloong@gmail.com.
authors: H H
authors: HH
authors: Loong
authors: London Health Sciences Centre, London, ON, Canada.
authors: E
authors: E
authors: Winquist
authors: Princess Margaret Cancer Centre, Toronto, ON, Canada.
authors: J
authors: J
authors: Waldron
authors: Princess Margaret Cancer Centre, Toronto, ON, Canada.
authors: E X
authors: EX
authors: Chen
authors: Princess Margaret Cancer Centre, Toronto, ON, Canada.
authors: J
authors: J
authors: Kim
authors: London Health Sciences Centre, London, ON, Canada.
authors: D
authors: D
authors: Palma
authors: London Health Sciences Centre, London, ON, Canada.
authors: N
authors: N
authors: Read
authors: Princess Margaret Cancer Centre, Toronto, ON, Canada.
authors: A R A
authors: AR
authors: Razak
authors: Princess Margaret Cancer Centre, Toronto, ON, Canada.
authors: I
authors: I
authors: Diaz-Padilla
authors: Princess Margaret Cancer Centre, Toronto, ON, Canada.
authors: K
authors: K
authors: Chan
authors: Princess Margaret Cancer Centre, Toronto, ON, Canada.
authors: A
authors: A
authors: Bayley
authors: Princess Margaret Cancer Centre, Toronto, ON, Canada.
authors: M
authors: M
authors: Hossain
authors: Princess Margaret Cancer Centre, Toronto, ON, Canada.
authors: L
authors: L
authors: Wang
authors: Princess Margaret Cancer Centre, Toronto, ON, Canada.
authors: S
authors: S
authors: Chin
authors: Princess Margaret Cancer Centre, Toronto, ON, Canada. Electronic address: lillian.siu@uhn.ca.
authors: L L
authors: LL
authors: Siu
authors: Princess Margaret Cancer Centre, Toronto, ON, Canada.
authors: A
authors: A
authors: Hope
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D060828:Induction Chemotherapy; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D017239:Paclitaxel / Q000008:administration & dosage; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil
keywords: Head & neck cancer; Induction chemotherapy; Nab-paclitaxel; Sequential therapy; Squamous cell carcinoma