title: Phase Ib trial of radiotherapy in combination with combretastatin-A4-phosphate in patients with non-small-cell lung cancer, prostate adenocarcinoma, and squamous cell carcinoma of the head and neck.
abstract: BACKGROUND
  The vascular disrupting agent combretastatin-A4-phosphate (CA4P) demonstrated antitumour activity in preclinical studies when combined with radiation.
  
  
  METHODS
  Patients with non-small-cell lung cancer (NSCLC), prostate adenocarcinoma, and squamous cell carcinoma of the head and neck (SCCHN) received 27 Gy in 6 fractions treating twice weekly over 3 weeks, 55 Gy in 20 fractions over 4 weeks, and 66 Gy in 33 fractions over 6 weeks respectively. CA4P was escalated from 50 mg/m2 to 63 mg/m2. CA4P exposure was further increased from one to three to six doses. Patients with SCCHN received cetuximab in addition.
  
  
  RESULTS
  Thirty-nine patients received 121 doses of CA4P. Dose-limiting toxic effects (DLTs) of reversible ataxia and oculomotor nerve palsy occurred in two patients with prostate cancer receiving weekly CA4P at 63 mg/m2. DLT of cardiac ischaemia occurred in two patients with SCCHN at a weekly dose of 50 mg/m2 in combination with cetuximab. Three patients developed grade 3 hypertension. Responses were seen in 7 of 18 patients with NSCLC. At 3 years, 3 of 18 patients with prostate cancer had prostate-specific antigen relapse.
  
  
  CONCLUSIONS
  Radiotherapy with CA4P appears well tolerated in most patients. The combination of CA4P, cetuximab, and radiotherapy needs further scrutiny before it can be recommended for clinical studies.
authors.affiliation: Mount Vernon Cancer Centre, Northwood, Middlesex, UK; Department of Medical Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Q-S
authors.initials: QS
authors.lastname: Ng
authors.affiliation: Mount Vernon Cancer Centre, Northwood, Middlesex, UK.
authors.forename: H
authors.initials: H
authors.lastname: Mandeville
authors.affiliation: Paul Strickland Scanner Centre, Mount Vernon Hospital, Northwood, Middlesex, UK.
authors.forename: V
authors.initials: V
authors.lastname: Goh
authors.affiliation: Mount Vernon Cancer Centre, Northwood, Middlesex, UK.
authors.forename: R
authors.initials: R
authors.lastname: Alonzi
authors.affiliation: Mount Vernon Cancer Centre, Northwood, Middlesex, UK.
authors.forename: J
authors.initials: J
authors.lastname: Milner
authors.affiliation: Mount Vernon Cancer Centre, Northwood, Middlesex, UK.
authors.forename: D
authors.initials: D
authors.lastname: Carnell
authors.affiliation: Mount Vernon Cancer Centre, Northwood, Middlesex, UK.
authors.forename: K
authors.initials: K
authors.lastname: Meer
authors.affiliation: Paul Strickland Scanner Centre, Mount Vernon Hospital, Northwood, Middlesex, UK.
authors.forename: A R
authors.initials: AR
authors.lastname: Padhani
authors.affiliation: Mount Vernon Cancer Centre, Northwood, Middlesex, UK.
authors.forename: M I
authors.initials: MI
authors.lastname: Saunders
authors.affiliation: Mount Vernon Cancer Centre, Northwood, Middlesex, UK. Electronic address: peterhoskin@nhs.net.
authors.forename: P J
authors.initials: PJ
authors.lastname: Hoskin
mesh_terms: D000230:Adenocarcinoma / Q000628:therapy; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000628:therapy*; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006258:Head and Neck Neoplasms / Q000628:therapy*; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000628:therapy*; D000077195:Squamous Cell Carcinoma of Head and Neck; D013267:Stilbenes / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; C058728:fosbretabulin