Oral vinorelbine (NVBo) at 3-weekly flat-dose intakes (FDI) as single agent or with cisplatin (CDDP) concomitantly with thoracic radiotherapy (RT) in stage III NSCLC: Escalation-dose phase I trial results.

Abstract

7045 Background: In vitro, vinorelbine (NVB) has shown to be a powerful radiosensitizer. Based on the bioavailability of NVBo, a dose-determination study was implemented in patients (pts) with untreated locally advanced or inoperable stage III NSCLC assessing continuous exposure to NVBo through 3 times a week (w) FDI during the RT period, either alone (1st part of the trial) or in combination with CDDP (2nd part). Methods: 3 pts with stage IIIAN2/IIIB NSCLC were expected at each dose-level (L) with 3 additional pts in case of a dose-limiting toxicity (DLT): age 18-70 years, adequate bone marrow, hepatic and renal function, KPS ≥80%. NVBo was given concomitantly with 60 Gy RT (2 Gy/day; 5 days/w) from 60 mg up to 180 mg total-dose/w splited on days (D) 1, 3 and 5 during 6 w. Based on the maximal tolerated dose (MTD) defined as 2 DLT in a L and the recommended dose (RD) of NVBo alone, the trial assessed its RD in combination with CDDP 80 mg/m2 D1 every 3 w (q3w) in a 2nd cohort. Results: In the 1st cohort, ...