1061TiP - First-in-man phase I study of TPCS2a-based photochemical internalisation (PCI) of bleomycin in locally recurrent or advanced/metastatic, cutaneous o...

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Drug Development
Head and Neck Cancers
Presenter Martin Forster
Authors M.D. Forster1, A. Sultan2, W. Jerjes2, C. Simeon2, S. Morley2, D. Carnell2, C. Hopper2
  • 1Cancer Institute, University College London Hospital, London/UK
  • 2Head And Neck, University College London Hospital, London/UK

Abstract

Objective

PCI is a novel technique in which chemotherapeutic cytotoxicity is enhanced with a photosensitiser and light exposure. This dose-escalation study assessed the safety and tolerance of TPCS2a (tetraphenyl chlorin disulphonic acid, Amphinex®) in bleomycin PCI, pharmacokinetic profiles, and determined the maximum tolerated dose (MTD).

Method

Cohorts of 3 to 6 patients were enrolled and the TPCS2a dose escalated by a pre-specified amount until dose-limiting toxicity (DLT) occurred in at least two patients (≥33%). Patients received TPCS2a at a starting dose of 0.25mg/kg. Four days later they received bleomycin (15,000IU/m2 IV) and after 3 hours red light laser (652nm) was applied to target lesions for 600 seconds to initiate a therapeutic response. Patients were followed for 3 months.

Results

Nineteen patients were enrolled: 4 with cutaneous breast cancer, 13 squamous cell carcinoma (SCC) of head and neck and other regions, 2 other cancers. 17/19 patients experienced 94 AEs, most commonly pain, photosensitivity and nausea. Most (83%) were mild or moderate. Fourteen episodes of pain (3 severe) were treatment-related. Mean patient-reported pain using a VAS scale declined from 4.9 to 1.3 24 hours after treatment. Four patients experienced skin photosensitivity reactions; 3 were in the highest dose cohort. 10/19 patients experienced 15 serious adverse events: 3 (swelling, and blistering of hands, tongue oedema) were probably related to treatment. The MTD of TPCS2a was found to be 1.5mg/kg. At day 28, 11/16 patients had a complete response (CR) in target lesions, 2 had a partial response (PR), 2 had stable disease (SD) and 1 had progressive disease (PD). At last visit there were 8 CRs, 2 PRs, 2 SDs and 2 PDs. During the course of the study four patients died (no relation to treatment) and six were withdrawn prematurely.

Conclusion

With appropriate analgesia and anaesthesia TPCS2a-based PCI of bleomycin was well tolerated in these patients with locally advanced cancer. Treatment-related AEs were as expected and can be managed. Preliminary efficacy data are very encouraging and a phase II study in HNSCC has just begun.

Disclosure

All authors have declared no conflicts of interest.