Randomized, phase III trial comparing liposomal platin with cisplatin in patients (pts) with advanced squamous cell carcinoma of the head & neck (SCCHN) regarding safety and efficacy profiles

Autor: Diana Lüftner, D. Pollmann, Klaus-Dieter Wernecke, G. Pecher, S. Siepmann, Kurt Possinger, J. Christian
Rok vydání: 2006
Předmět:
Zdroj: Journal of Clinical Oncology. 24:5564-5564
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2006.24.18_suppl.5564
Popis: 5564 Background: Based on a metanalysis of > 16,000 patients (Bourhis, ASCO 2004), cisplatin emerges as the essential agent for the treatment of advanced SCCHN. However, its clinical use is impeded by its severe adverse reactions, as renal toxicity. In a randomized, phase III trial we replaced conventional cisplatin by a liposomal formulation of cisplatin (lipoplatin) and compared the safety and efficacy profiles. Methods: The study was designed for two treatment arms: 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; B: 100 mg/m2/d cisplatin (d 1) plus 1000 mg/m2/d 5-FU (d 1–5) q3w for 6 cycles. Main inclusion criteria selected pts with primary metastatic, relapsed or progressive SCCHN between 18–75 years and creatinin clearance >50ml/min. Main endpoints for this interims analysis were hemato- and nephrotoxicity. First response data were collected. The study was designed for non-inferiority. Results: Out of 41 randomized pts, 30 pts are evaluable for toxicity (15 pts for every arm) and 27 pts (15 pts for lipoplatin, 12 pts for cisplatin) for outcome. In the cisplatin arm hematotoxicity was more frequent (leucopenia grade I/II: 5 pts, grade III/IV: 3 and 1 pts vs 5 pts with grade I/II in the lipoplatin arm). The rate of anemia was similar between the treatment arms. A total of 11 pts in the lipoplatin arm experienced renal toxicity grade I/II as measured by a reduction of the creatinine clearance and 12 pts in the cisplatin arm (grade I/II: 7 pts; grade III: 5 pts). No renal toxicity grade III was developed in the lipoplatin arm until now. Outcome was as follows: lipoplatin arm: PR: 1 pt; SD: 6 pts; PD: 8 pts; cisplatin arm: PR: 7 pts; SD: 3 pts; PD: 2 pts. Thus, the non-PD pts (PR or SD) is 7/15 (47%) in the lipoplatin arm vs 10/12 (83%) cases in the cisplatin arm. Conclusions: Liposomal platin seems to reduce both the hematological and non-hematological toxicity profiles as compared to conventional cisplatin to a clinically relevant extent. As patients with advanced SCCHN have an increased risk of renal toxicity due to poor hydration, the observed 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.
Databáze: OpenAIRE
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