Metronomic oral vinorelbine as first-line treatment in elderly patients with advanced non-small cell lung cancer: results of a phase II trial (MOVE trial)

Abstract

BackgroundMetronomic oral vinorelbine could be a safe option for elderly patients with advanced non small cell lung cancer (NSCLC). Metronomic administration of chemotherapy leads to a cytostatic action shifting treatment target from cancer cell to tumor angiogenesis.Methods43 chemotherapy naive elderly (≥70 yrs) PS 0-2 patients with stage IIIB-IV NSCLC were prospectively recruited. Median age was 80 yrs (M/F 36/7) with predominantly squamous histology. PS distribution was 0-1(16)/2(27) with a median of 3 serious co-morbid illnesses. Study treatment consisted of oral vinorelbine 50mg three times weekly (Monday-Wednesday-Friday) continuously until disease progression, unacceptable toxicity or patient refusal. Primary endpoints were overall response rate (ORR), clinical benefit (CB – disease response plus disease stabilization >12 weeks) and safety. Health-related QoL (HRQoL) was also assessed with FACT-L V4 scoring questionnaire. We conducted an exploratory time-course analysis of VEGF and thrombospondin-1 (TSP1) serum levels in a subgroup of patients.ResultsPatients received a median of 5 (range 1-21) cycles with a total of 272 cycles delivered. ORR was 18.6% with 7 partial and 1 complete responses; 17/43 experienced stable disease lasting more than 12 weeks leading to an overall CB of 58.1%. Median time to progression was 5 (range 2-21) and median overall survival 9 (range 3-29) months. Treatment was well tolerated with rare serious toxicity. Regardless of severity main toxicities observed were anemia in 44%, fatigue in 32.4%, and diarrhoea 10.5%. FACT-L v4 scores did not significantly vary during treatment. Baseline VEGF levels were lower and showed a rapid increase during treatment in non-responders pts only while TSP1 levels did not change.ConclusionsMetronomic oral vinorelbine is safe in elderly patients with advanced NSCLC with an interesting activity mainly consisting in long-term disease stabilization coupled with an optimal patient compliance (Eudra-CT 2010-018762-23, AIFA OSS on 26 February 2010).

Efficacy of Metronomic Vinorelbine in Elderly Patients with Advanced Non-Small-Cell Lung Cancer and Poor Performance Status

“…Our study population included only patients with an ecog ps of 2 and multiple comorbidities; however, we found survival and efficacy rates comparable to those in the Camerini et al trials 14,21 . The lower toxicity and improved safety profile were also similar.…”

“…The median pfs in the study was 5 months (range: 2-21 months), and the median os was 9 months (range: 3-29 months). In addition, the 1-and 2-year survival rates were 37.2% and 9.3% respectively 14 .…”

“…Those patients should therefore be evaluated in terms of the risk-benefit ratio of treatment. Many prefer oral rather than intravenous treatment 5,13,14 . Chemotherapy with a single agent is an acceptable option for a significant percentage of patients with stage iii or iv nsclc 15 .…”

“…Two of those studies used (non-metronomic) oral vinorelbine, and one applied metronomic oral vinorelbine 14,21,22 . Kosmidis et al 22 compared two single agents, paclitaxel (intravenous) and vinorelbine (oral), in nsclc patients with an ecog ps of 2.…”

“…In that study, 46% of patients had previously received chemotherapy; thus, grades 1 and 2 and nonhematologic toxicities were especially common (range: 10%-48%). The more recent study 14 investigated the role of oral metronomic vinorelbine as a single agent in the first-line treatment of elderly patients with advanced nsclc. That study included 43 chemotherapynaïve elderly patients (70 or more years of age), with a ps of 0-2 in stages iiib-iv nsclc.…”