| Title |
|
|
|
Phase I dose-escalation study of vinflunine hard capsules administered twice a day for 2 consecutive days every week in patients with advanced/metastatic solid tumors
| |
| Author |
|
|
|
| |
| Abstract |
|
|
|
| Vinflunine is a new microtubule inhibitor of the vinca-alkaloid family. It is marketed in transitional cell carcinoma of urothelial tract as a 20 min infusion given every 3 weeks in Europe. In this phase I study, vinflunine was administered to patients with advanced malignancies as hard capsules given twice a day on days 1-2 every week, with 3 weeks cycles. Serial blood samples were collected during the first cycle for pharmacokinetic investigations. Thirty-six patients (pts) were treated at 6 dose levels 150 (3 pts), 190 (3 pts), 230 (8 pts), 300 mg/day (6 pts) and then 250 (3 pts) and 270 mg/day (13 pts). The Maximal Tolerated Dose (MTD) was reached at 300 mg/day where 2 patients out of 6 experienced a dose limiting toxicity (febrile neutropenia with diarrhea). The lower dose level of 270 mg/day was the recommended dose (RD), the toxicity profile being mainly anaemia, neutropenia, fatigue and constipation. The pharmacokinetic analysis demonstrated the adequacy of the flat-fixed dosing regimen, as no correlation between clearance of vinflunine and body surface area was evidenced. Blood concentrations and exposure increased with dose, and a pharmacokinetic accumulation was observed, which is consistent with the terminal half-life of the compounds. The inter-individual exposure variability at the RD was 35%. Repeated weekly administration of oral vinflunine is feasible and exhibits a moderate inter-individual PK variability. The MTD was achieved at 300 mg/day given for 2 consecutive days. According to the protocol rules, the RD was established at 270 mg/day. | | |
| Language |
|
|
|
English
| |
| Source (journal) |
|
|
|
Cancer chemotherapy and pharmacology. - Berlin | |
| Publication |
|
|
|
Berlin : 2012
| |
| ISSN |
|
|
|
0344-5704
| |
| Volume/pages |
|
|
|
69:6(2012), p. 1467-1475
| |
| ISI |
|
|
|
000304622600009
| |
| Full text (Publisher's DOI) |
|
|
| | |
| Full text (publisher's version - intranet only) |
|
|
| | |
|