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

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/m²/day: 4 patients; 15 mg/m²/day: 4, 20 mg/m²/day: 5 and 25 mg/m²/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/m² level (two grade 2 renal toxicities, one grade 3 GI and renal toxicities), one at 20 mg/m² level (grade 3 GI disorders), one at 10 mg/m² 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/m²/day, MTD was reached and the recommended dose for phase II studies was determined as 20 mg/m²/day.