Photoimmunotherapy: a winning combination?
My final stint at this year’s BiOS meeting was a session on biophotonics and immune responses. I went along specifically to hear how laser therapies can trigger secondary host immune responses, a double-headed combination that shows real promise in controlling difficult-to-treat local tumours and metastatic disease at distant sites.
A case in point is advanced cutaneous melanoma, the sixth leading cause of cancer death in the US and one of the top three cancers worldwide in terms of recent rises in incidence. “Fundamentally, we don’t have good ways to treat this,” explained Mark Naylor, professor of dermatology at the University of Oklahoma (Norman, OK), citing less than 50% two-year survival for current FDA-approved chemotherapy regimes.
Naylor and his colleagues at Oklahoma are pioneering an alternative treatment for advanced melanoma called in-situ photoimmunotherapy (ISPI). The trick here is to combine local photothermal destruction of existing solid tumours (using fibre-optic delivery of 806 nm laser light) with the topical administration of an immune-response modifier (a drug called imiquimod) to trigger an anti-tumour response.
In early 2006, the Oklahoma team began enrolling patients in a phase I clinical trial of ISPI. The results so far, admittedly limited to a small study group, indicate that photoimmunotherapy is an effective treatment for stage III and some stage IV melanoma subjects.
Of the first 10 patients treated, all four stage III subjects are still alive. Of those, two are tumour-free, and two have had partial responses and are expected to achieve tumour-free status with further treatment. Of the six stage IV subjects, two are still alive and the majority survived beyond the expected median survival of 6-8 months. One stage IV subject is currently tumour-free and has survived for over three years.
Naylor’s conclusion is unequivocal: the trial data show that ISPI yields the highest response rate of any therapy for advanced melanoma as well as greatly enhanced quality of survival versus traditional chemotherapy. “Over the next five to 10 years, ISPI will probably become the treatment of choice for unresectable stage III [cutaneous melanoma] disease,” he added.
In a related presentation, Zheng Huang, a clinical oncologist at the University of Colorado (Denver, CO), discussed the evolving role for PDT:immunotherapy combination treatments in dermatology. Huang and his co-workers in China have been carrying out a number of early-stage clinical studies to evaluate what role PDT-induced local and systemic antitumour immune response might play in the control of malignant diseases.
Their studies to date have concentrated on the combination of ALA-PDT and topical application of imiquimod for conditions such as genital bowenoid papulosis, Bowen’s disease and actinic keratosis. Initial results indicate that “improved clinical outcomes can be obtained by a combination of PDT and immunomodulation therapy”, Huang told delegates.