Results of a phase I / II and pharmacokinetic study of vinflunine (VFL) in combination with cisplatin (CDDP) for primary treatment of advanced non-small cell lung cancer (NSCLC)

Abstract

7110 Background: VFL (Javlor) is a new semi-synthetic vinca alkaloid which has shown synergistic effects in vitro againts A549 human NSCLC line when combined with CDDP. Platinum-based doublets are the standard treatment in advanced NSCLC. Methods: The phase I part of this trial was designed to determine the recommended dose (RD) and to study the possible pharmacokinetic (PK) interaction of the combination VFL and CDDP. The RD was established at of VFL 320 mg/m2 plus CDDP 80 mg/m2 on day 1 every 3 weeks; no PK interaction was observed. We describe the results of the phase II part of the study, which was designed to to determine the response rate (WHO) and safety (NCI-CTC) of the combination. Results: At the RD 53 patients (41 males, 12 females), median age 57, initial stages IIB 2 pts, IIIB 15 pts and IV 36 pts were treated. Karnofsky performance status was: 100 % 11 pts, 90 % 32 pts, 80 % 10 pts. The median number of cycles administered was 6 [1–8] and the median dose intensities of both drugs are > 97 %. Disease control was achieved in 77 % of the 49 evaluable pts: there were 16 confirmed responses (after external radiological review) (33 %) (95 % CI [20–48]) and 22 stabilizations. In terms of tolerance, among 237 cycles analyzed grades 3/4 neutropenia and anemia were reported in 43 % and 7 % of cycles respectively; 5 patients experienced febrile neutropenia and there were 2 neutropenic infections. Grades 3/4 non-hematological toxicities observed were: fatigue 3.8 % cycles (15.1 % pts), abdominal pain 3 % cycles (9.4 % pts), nausea 1.7 % cycles (3.8 % pts), vomiting 1.2 % cycles (3.8 % pts) constipation: 1.3 % cycles (5.7 % pts), diarrhea and dehydration 0.4 % cycles (1.4 % pts). No peripheral neuropathy grades 3/4 has been observed.Conclusions: Very good results were achieved in terms of dose intensities and toxicity profile. In first line treatment of advanced NSCLC patient, the combination of VFL 320 mg/m2 plus CDDP 80 mg/m2 both given once every 3 weeks is an highly active combination in terms of response rate. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Institut de Recherche Pierre Fabre (IRPF), France