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

Mount Vernon Cancer Centre, Northwood, Middlesex, UK.


The vascular disrupting agent combretastatin-A4-phosphate (CA4P) demonstrated antitumour activity in preclinical studies when combined with radiation.

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/m(2) to 63 mg/m(2). CA4P exposure was further increased from one to three to six doses. Patients with SCCHN received cetuximab in addition.

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/m(2). DLT of cardiac ischaemia occurred in two patients with SCCHN at a weekly dose of 50 mg/m(2) 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.

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.

Written by:
Ng QS, Mandeville H, Goh V, Alonzi R, Milner J, Carnell D, Meer K, Padhani AR, Saunders MI, Hoskin PJ.   Are you the author?

Reference: Ann Oncol. 2011 Jul 15. Epub ahead of print.
doi: 10.1093/annonc/mdr332

PubMed Abstract
PMID: 21765046 Prostate Cancer Section