First safety and response results of a randomized phase III study with liposomal platin in the treatment of advanced squamous cell carcinoma of the head and neck (SCCHN)

Abstract

6040 Background: Cisplatin is one of the most active chemotherapeutic agents used in the treatment of advanced squamous cell carcinoma of the head and neck (SCCHN). However, its clinical efficacy is limited by its renal- and hematotoxicity profile. In a randomized, multicenter phase III trial, we replaced conventional cisplatin by a liposomal formulation of cisplatin (lipoplatin), and compared the safety and efficacy profiles of patients (pts) in the two treatment arms. Methods: Arm A: 100 mg/m2/d lipoplatin (d 1,8,15) plus 1,000 mg/m2/d 5-FU (d 1–5) q3w for 6 cycles; arm B: 100 mg/m2/d cisplatin (d 1) plus 1,000 mg/m2/d 5-FU (day 1–5) q3w for 6 cycles. Inclusion criteria: histologically confirmed SCCHN, age 18–75, renal function (creatinine clearance >50 ml/min) and primary metastatic disease or progressive SCCHN. Results: 62 pts were randomized, from which 43 pts (39 m; 4 w) were evaluable for outcome and toxicity. In the cisplatin arm hematotoxicity was more frequent (grades I/II: 28 pts, grades III/IV: 2 pts) than in the lipoplatin arm (grades I/II: 15 pts, grades III/IV: 3 pts). The rate of anemia was similar between the treatment arms. 13 pts in the lipoplatin arm experienced renal toxicity with (grade I: 3pts) and (grade II: 10 pts), as measured by a reduction of the creatinine clearance (grade I: 99–75 ml/min; grade II: 74–50 ml/min; grade III: <50 ml/min). Renal toxicity occurred in 8 patients in the cisplatin arm with 1 pt (grade I) and 3 pts (grade II), however 5 pts developed grade III. No renal toxicity grade III was developed in the lipoplatin arm until now. Outcome was as follows: lipoplatin arm: PR: 3 pts; SD: 13 pts; PD: 9 pts; cisplatin arm: PR: 8 pts; SD: 9 pts; PD: 1 pts. Thus, the non-PD pts (PR or SD) was 16/25 (64 %) in the lipoplatin arm vs 17/18 (94%) cases in the cisplatin arm. Conclusions: Liposomal platin seems to reduce both the renal and hematological toxicity as compared to conventional cisplatin to a clinically relevant extent. This reduction of side effects will influence the chance to preserve the dose density of chemotherapy, and thereby, the efficacy of treatment. No significant financial relationships to disclose.