A phase i trial combining oral cisplatin (CP Ethypharm) with radiotherapy in patients with locally advanced head and neck squamous cell carcinoma

Yungan Tao, Keyvan Rezaï, Etienne Brain, Atoussa Etessami, Antoine Lusinchi, Stephane Temam, Saik Urien, Marie Louise Vo Van, Françoise Vauzelle-Kervroedan, François Lokiec, Nicolas Daly-Schveitzer, Jean Bourhis

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    Résumé

    Purpose: To determine the maximum tolerated dose (MTD) of oral cisplatin (CP Ethypharm®) in combination with radiotherapy in head and neck squamous cell carcinoma (HNSCC) and the recommended dose for phase II trials. Patients and methods: Phase I, multicenter, open-labelled, non-comparative and dose escalating trial. CP Ethypharm® was administered on five consecutive days every other week for 7 weeks (4 treatment cycles) in combination with radiotherapy. Eighteen patients with locally advanced HNSCC were allocated to four cisplatin dose levels: 10 mg/m 2/day: 4 patients; 15 mg/m 2/day: 4, 20 mg/m 2/day: 5 and 25 mg/m 2/day: 5. The inclusion of patients was dictated by occurrence of dose limiting toxicities (DLTs) at each dosing level. Results: The most frequently experienced AEs were gastrointestinal (GI) disorders. Five DLTs were observed, including three at 25 mg/m 2 level (two grade 2 renal toxicities, one grade 3 GI and renal toxicities), one at 20 mg/m 2 level (grade 3 GI disorders), one at 10 mg/m 2 level (grade 4 mucositis). PK analysis showed no significant difference of C max values between day 1 and day 5 of treatment at each dose level (total & ultrafilterable platinum). Conclusion: Due to 3 DLTs experienced at 25 mg/m 2/day, MTD was reached and the recommended dose for phase II studies was determined as 20 mg/m 2/day.

    langue originaleAnglais
    Pages (de - à)42-47
    Nombre de pages6
    journalRadiotherapy and Oncology
    Volume98
    Numéro de publication1
    Les DOIs
    étatPublié - 1 janv. 2011

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