Oral Health and Dental Management

A first-in-man phase I study of Photochemical Internalisation (PCI) of bleomycin with TPCS2a in patients with solid malignancies – a dose escalation study showing promising signs of efficacy

4^th Asia Pacific Congress & Expo on Dental and Oral Health

July 27-29, 2015 Brisbane, Australia

Ahmed A Sultan1, 2, Waseem Jerjes2, Kristian Berg5, Anders H�gset6, Charles A Mosse2, Celia Simeon1, Dawn Carnell1, Martin Forster1, 4 and Colin Hopper1, 2, 3

Posters-Accepted Abstracts: Oral Health Dent Manag

Abstract:

Purpose: This article reports on a first-in-man study of TPCS2a-mediated photochemical internalisation (PCI), a new technique for enhancing and directing the effect of anti-cancer drugs by illumination. PCI was performed with bleomycin for treatment of cutaneous or subcutaneous tumours. The primary objective was to assess the safety and tolerability of TPCS2a and determine the maximum tolerated dose (MTD) in PCI with bleomycin. Secondary objectives were to: (i) evaluate toxicity profile; (ii) determine TPCS2a pharmacokinetics; (iii) document anti-tumour activity. Experimental Design: The study was an open-label single centre, non-randomised Phase I dose-escalation study. Patients were administered TPCS2a on day 0, followed by a fixed dose of 15,000 IU/m2 bleomycin on day 4. Three hours later, the surface of the target tumour was illuminated with red laser light (fixed at 60J/cm2). The TPCS2a starting dose was 0.25 mg/kg and was escalated in successive dose groups of 3 patients within a modified accelerated trial design. Results: 22 patients were included, of which 16 had head and neck cancer. The MTD of TPCS2a was determined to be 1.0 mg/kg. Dose limiting toxicities observed included skin photosensitivity (n=1) and wound infection (n=1) at 1.5 mg/kg dose level. Other common adverse events were nausea, pain and tongue oedema. Anti-tumour effects were observed through the dose range of 0.25 ? 1.5 mg/kg with no obvious dose dependency; overall response rates of >80% at 28 days and >60% at the confirmation visit (at least 28 days later) were reported. Conclusion: PCI treatment can be safely delivered to patients and a recommended phase 2 dose was established. Significant anti-tumour effects were seen at all doses tested, warranting further clinical studies with the PCI technology.