A novel combination treatment approach may be a promising new avenue for managing cutaneous lymphoma, researchers from University Hospitals (UH) Case Medical Center and Case Western Reserve University School of Medicine report.

According to the research team, which was led by Kevin Cooper, MD, Chairman of the Department of Dermatology at UH Case Medical Center and Case Western Reserve University School of Medicine, cutaneous lymphoma often relapses and increasingly becomes more difficult to treat. The new combination approach uses O6-benzylguanine and carmustine.

When used alone, carmustine attaches to a cancer cell’s DNA during the replication process, causing the cells to die, but problems can occur when an enzyme clips off the treatment from the DNA, which allows the cancer cells to replicate. In this combination approach, the researchers added O6-benzylguanine, which inhibits the enzyme from clipping off the carmustine from the DNA, so the drug can complete its mission and kill the cancer cells.

The open-label, dose-escalation Phase I trial included 21 adult patients (11 male, 10 female) with early-stage (IA-IIA) refractory cutaneous T-cell lymphoma (CTCL), mycosis fungoides type, treated with topical carmustine following intravenous O6-benzylguanine, according to the results of the study that were published in Archives of Dermatology. While the team reported that they did observe some minimal toxic effects, “mean baseline O6-alkylguanine-DNA alkyltransferase activity in CTCL lesions was 3 times greater than in normal controls and was diminished by a median of 100% at 6 and 24 hours following O6-benzylguanine with recovery at 1 week.” In addition, clinical disease reduction correlated positively with “O6-alkylguanine-DNA alkyltransferase activity at 168 hours (P = .02) and inversely with area under the curve of O6-alkylguanine-DNA alkyltransferase over 1 week (P = .01).”

Five patients discontinued therapy due to adverse events with a possible, probable or definite relationship to the study drug. Four complete responses and 12 partial responses were observed, the researchers reported.

“This treatment essentially weakens the cancer cells to make the lymphoma more vulnerable to topical chemotherapy,” Dr. Cooper explained. “By adding O6-benzylguanine, we can effectively lower the dosage of the topical treatment, carmustine, and render it less toxic on healthy cells but more effective at killing cancer cells. This combination treatment has had excellent initial clinical results and we are following it up with additional ongoing studies.”