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: Q-S Ng, H Mandeville, V Goh, R Alonzi, J Milner, D Carnell, K Meer, A R Padhani, M I Saunders, P J Hoskin
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 23 Issue 1 Pg. 231-237 (Jan 2012) ISSN: 1569-8041 [Electronic] England
• PMID: 21765046 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Stilbenes
• fosbretabulin

Topics

• Adenocarcinoma (therapy)
• Aged
• Aged, 80 and over
• Antineoplastic Agents, Phytogenic (administration & dosage, adverse effects)
• Carcinoma, Non-Small-Cell Lung (therapy)
• Carcinoma, Squamous Cell (therapy)
• Chemoradiotherapy (methods)
• Dose-Response Relationship, Drug
• Female
• Head and Neck Neoplasms (therapy)
• Humans
• Lung Neoplasms (therapy)
• Male
• Middle Aged
• Prostatic Neoplasms (therapy)
• Squamous Cell Carcinoma of Head and Neck
• Stilbenes (administration & dosage, adverse effects)