A Canadian single-centre retrospective study of patients treated topically with diphencyprone (DPCP) for in-transit or unresectable melanoma lesions has found that the immunotherapy is a feasible option for lesions where surgery is not an option, and may delay the need for systemic therapy
Some 15 consecutive patients at the Sunnybrook Health Sciences Centre in Toronto (median age 78 years, range 43 to 92) were identified between Dec. 1, 2014 and Dec. 31, 2015. Of those, 73% had prior treatments for their lesions.
At the time of the study, the centre’s primary treatment for melanoma lesions ineligible for surgery (lesions were too numerous, lesions recurring too quickly after resection, patient declines surgery) injected leukin (IL)-2 or systemic therapy. However, the high cost to the patient of IL-2—not covered by Canadian or was inter drug plans or the government at the time—led the team to explore DPCP as an alternative, senior author Dr. Nicole Look Hong said. She is an associate scientist in the Odette Cancer Research Program, Sunnybrook Research Institute, and a staff physician, division of surgical oncology, Sunnybrook Health Sciences Centre, Toronto.
The findings were published in Expert Review of Clinical Immunology (Apr. 2017; 13(4):383–388).
“This is a treatment that had been used fairly extensively, especially in Australia, and been published on and seemed to have a good success rate,” said Dr. Look Hong regarding the rationale for trialling DPCP for this indication. She communicated with a treatment team in Australia to adapt their protocol.
Dr. Nicole Look Hong
Disease improved or stabilized
On the DPCP treatment, two patients (13%) had a complete response after 25 and 32 weeks. Another four patients (27%) had partial response with a mean treatment time of 30 weeks, ranging from six to 51 weeks. Another six patients (40%) had stable disease, and three patients (20%) discontinued treatment due to systemic progression of their disease.
These efficacy rates are similar to what has been seen from IL-2 therapy, said Dr. Look Hong, although she emphasized these are non-randomized studies with highly selected patients treated at cancer centres.
At the time of the study, the cost-to-patient difference was favourable for DPCP, Dr. Look Hong said, with a course of treatment for IL-2 comprising approximetly six to eight treatments at $600 each, compared to a vial of DPCP costing less than $100 and lasting several months. Since then, she said, IL-2 has been covered by the Ontario provincial government for this indication, so the cost is no longer as important a factor. However, there are still good reasons for having DPCP as an available option.
The clinic has more experience with IL-2, she said, so in their protocol they would likely still start with that.
However, she said that for some patients one medication works better than another, or a patient will simply not respond to one of the two therapies.
“So the way that we have it in an algorithm now, is we give the patients the pros and cons of using both options,” she said.
As an injected therapy, the IL-2 has to be administered professional, which requires the patient to travel to clinic regularly, she said. In contrast, topical DPCP can be administered by the patient or a family member, which some patients prefer. Some patients simply do not want injections, she said. Additionally, IL-2 tends to work a little faster, so there are disease-related factors to consider as well.
“The other interesting thing is that we tend to see that DPCP tends to work better for head and neck patients [compared to other body sites],” said Dr. Look Hong. “For some reason, the face, head, and neck patients respond really well, and for durable durations.”
The DPCP also had safety comparable to the IL-2 treatment, she said. Three patients (20%) stopped DPCP due to toxicity, with the most common toxicity observed being local blisters. One patient’s significant skin ulceration resolved after stopping DPCP.
“Because it is a local therapy, most of the side effects are local in terms of irritation to the local site,” said Dr. Look Hong. “At the time of administration of the drug, there is very little systemic absorption. So nausea, vomiting, feeling unwell, time away from work, all that is really quite minimized.” As well, the blistering observed typically occurs early in therapy when dosages are being adjusted for the patient. “[DPCP therapy] requires a little bit more of a period of adjustment [than IL-2]—the physician changing either duration of application or changing the dosage in order to get the perfect response where the blistering [is not occurring].”
Dr. Look Hong emphasizes that this is a small case series, and further data will need to be examined. She and her colleagues have an ongoing project to more formally compare DPCP and IL-2 therapy in this indication, but have no clinical trials scheduled at this time. The physicians at the Sunnybrook Health Sciences Centre mentor academic and smaller centres, as well as individual physicians on how to use these agents effectively and safely, noted Dr. Look Hong. The goal is to disseminate information so that patients are treated properly, she said.