Photochemical Internalisation Potential For Solid Malignancies

An intravenous photosensitiser for bleomycin is tested in patients for the first time

medwireNews: First-in-man study findings suggest a possible role for photochemical internalisation in patients with recurrent or advanced solid malignancies, say researchers who tested a new photosensitiser for bleomycin.

The phase I dose-escalation trial included 22 patients with local recurrent, advanced or metastatic cutaneous or subcutaneous tumours who were considered suitable for bleomycin chemotherapy, say Colin Hopper, from University College London Hospitals in the UK, and co-workers.

“The effects of treatment on target lesion response were not confined to squamous cell carcinomas but were also seen in other tumour types such as sarcoma and chemoresistant ductal breast carcinoma, which have traditionally been very resistant to most treatment modalities”, the researchers report in The Lancet Oncology.

The patients were given a slow intravenous dose of disulfonated tetraphenyl chlorin (TPCS2a) on the first day, with the initial dose of 0.25 mg/kg escalated in patient cohorts up to 1.5 mg/kg. On day 4 patients were then given a bleomycin infusion (15,000 IU/m2) and after 3 hours the surface of the target tumour was illuminated by laser light (652 nm, fixed at 60 J/cm2).

TPCS2a 1.5 mg/kg was associated with dose-limiting skin photosensitivity and wound infection toxicity in two of the three patients given this dosage and the maximum tolerated dose was therefore fixed at 1.0 mg/kg.

The researchers describe the treatment as “safe and tolerable” with no adverse events within 96 hours of TPCS2a administration. Mild adverse events were reported by 15 patients and moderate events by 10 patients; severe side effects (grade 3 or above) occurred in 14 patients and included unexpected localised pain, severe localised infection, severe photosensitivity skin pruritus, respiratory failure and death.

RECIST analysis for target lesions in 16 patients at day 28 showed a complete response in 58%, a partial response and stable disease in 11% each, and progressive disease in one patient. Three patients had missing information.

And clinical review of 12 patients after 3 months demonstrated a complete response in six, with partial response, stable disease and progressive disease each reported in two patients.

The author of an accompanying comment says that complete response for tumours 35 mm thick is “somewhat surprising in view of the limited penetration depth of 652 nm light”.

“The investigators postulate that this might be a result of photochemical internalisation-induced immune responses akin to those seen with photodynamic therapy; however, this theory is somewhat speculative and will certainly require more thorough investigation in future studies”, he notes.

Nevertheless, Steen Madsen, from the University of Nevada in Las Vegas, USA, says that the results are “intriguing because they suggest that photochemical internalisation might have a role in the treatment of early lesions and palliation of advanced disease, especially in the head and neck region.”

But he observes that the modality may be limited for head and neck cancer “as unlike surgery and radiotherapy, it is unlikely to result in successful control of multiple lymphatic metastases and, as such, it is ill suited as a primary treatment modality in most patients with head and neck cancer.”

“Even so, photochemical internalisation could have a role as a primary palliative treatment and in the treatment of patients with early cancers who are at fairly low risk of nodal metastases.”

References

Sultan AA, Jerjes W, Berg K, et al. Disulfonated tetraphenyl chlorin (TPCS2a)-induced photochemical internalisation of bleomycin in patients with solid malignancies: a phase 1, dose-escalation, first-in-man trial. Lancet Oncol 2016; Advance online publication 27 July. DOI: http://dx.doi.org/10.1016/S1470-2045(16)30224-8

Madsen S. Photochemical internalisation for solid malignancies. Lancet Oncol 2016; Advance online publication 27 July. DOI: http://dx.doi.org/10.1016/S1470-2045(16)30274-1

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2016