Combination immunotherapy of squamous cell carcinoma of the head and neck - A phase 2 trial

Objectives: To test the efficacy of a natural cytokine mixture (IRX-2), cyc lophosphamide, indomethacin, and zinc to-induce immune regression of squamo us cell carcinoma (SCC) of the head and neck (H&N) prior to conventional th erapy and to characterize the responses. Patients and Design: A phase 2 trial was performed in 15 adults with recent ly diagnosed, biopsy-confirmed H&N SCC (3 with stage II disease, 6 with sta ge III disease, and 6 with stage IV disease). The patients were treated wit h 20 days of perilymphatic injections of IRX-2 (administered subcutaneously at the base of the skull) in combination with contrasuppression consisting of a low-dose infusion of cyclophosphamide (300 mg/m(2)), and daily oral i ndomethacin and zinc (StressTabs) in a 21-day cycle before surgery and/or r adiotherapy. Tumor dimensions, toxic effects, and disease-free survival wer e monitored. The tumor sections were histologically examined after surgery, and tumor reduction, fragmentation, and lymphoid infiltration were assesse d. Results: All 15 patients responded clinically to the 21-day IRX-2 protocol: 1 with a complete response, 7 with a partial response, and 7 with a minor response. All 15 patients responded pathologically with tumor reduction (me an, 42%) and fragmentation (mean, 50%) in the histological section and incr eased lymphoid infiltration. The adverse effects of the IRX-2 protocol were negligible except for an allergic skin rash (n = 1) and parotiditis (n = 1 ). Indomethacin caused gastritis in 1 patient. Reduction of pain and ulcera tion and bleeding were observed in 8 and 4 patients, respectively. Four of 5 patients with lymphopenia showed increased CD3, CD4, and CD8 cell counts. After surgery (n = 13) and/or radiotherapy (n = 10) and with a mean follow -up of 17 months, 3 patients have had recurrences, 1 patient has died of di sease, 1 patient has been re-treated with immunotherapy and has no evidence of disease, and 1 patient is alive with disease. Two patients died of othe r causes with no evidence of disease. Conclusions: The IRX-2 immunotherapy induced lymphocyte mobilization and in filtration in H&N SCC associated with clinical and histological tumor respo nses indicative of immune regression in all 15 patients. Minimal toxic effe cts were observed, and overall survival may have been improved. A phase 3 t rial seems warranted.