Intratumoral cisplatin/epinephrine gel in advanced head and neck cancer: A multicenter, randomized, double‐blind, phase III study in North America

Abstract Background. The objective was to evaluate the efficacy and safety of a novel intratumoral cisplatin/epinephrine injectable gel (CDDP/epi gel) for local control and palliation of tumor‐related symptoms in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Patients and Methods. Eighty‐seven patients were randomly assigned to either CDDP/epi or placebo gel in this phase III, double‐blind study. Tumors were ≤20 cm 3 ; most recurrences (88%) were in a previously irradiated field. The most symptomatic or threatening tumor was designated as the target tumor. Dose: 0.25 mL CDDP/epi gel/cm 3 tumor volume. Treatments: ≤6 weekly intratumoral injections in an 8‐week period. Primary outcomes: target tumor response and symptom relief. Results. During the blinded phase, 34% (21 of 62) of patients achieved an objective response (CR or PR) in the target tumor treated with CDDP/epi gel vs 0% (0 of 24) treated with placebo gel ( p < .001). Responses occurred within a median of four treatments (range, 2–6) and were durable (median, 95 days; range, 34–168+ days). More patients treated with CDDP/epi gel achieved palliative benefit than did those treated with placebo gel (37% vs 12%, p = .036). Most frequent side effects were local pain and local cutaneous reactions, which resolved over 3–12 weeks. Renal and hematologic toxicities were rare. Conclusions. This phase III trial showed that CDDP/epi gel significantly reduces tumor burden, palliates tumor‐related symptoms, and is an effective local treatment for recurrent tumors. © 2003 Wiley Periodicals, Inc. Head Neck 25: 717–731, 2003