G. Tartarelli

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)

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).

Phase II trial of single-agent oral vinorelbine in elderly (≥70 years) patients with advanced non-small-cell lung cancer and poor performance status

BACKGROUND Elderly patients with advanced non-small-cell lung cancer (NSCLC) with poor performance status (PS) are a special population requiring particular attention. Single-agent oral vinorelbine could be an attractive option. PATIENTS AND METHODS A total of 43 patients with stage IIIB-IV NSCLC and Eastern Cooperative Oncology Group (ECOG) PS of two or more with good functional status were prospectively recruited. Oral vinorelbine was administered at the dose of 60 mg/m(2) on days 1-8 every 3 weeks. Primary end points were response rate and safety. RESULTS Overall response rate was 18.6% with 8 partial responses; 18 of 43 (41.8%) experienced stable disease lasting >12 weeks and 17 of 43 (39.6%) disease progression for an overall clinical benefit of 60.4%. Median time to progression was 4.0 (range 2-22) months and median overall survival 8.0 (range 3-35) months. Treatment was well tolerated. Of 187 cycles, we did not observe any grade 3/4 toxicity with the exception of a single not-febrile G3 neutropenia. Regardless of severity, main toxic effects observed were nausea in 48.1% and vomiting in 22.9% of patients, anemia in 43.2%, fatigue in 32.6% and leukopenia in 23.2%. CONCLUSION Single-agent oral vinorelbine is extremely safe in elderly patients with advanced NSCLC and ECOG PS of two or more and may represent a valid option in this very special population.

Long-term monitoring of cell-mediated immunity in disease-free breast cancer patients: a preliminary retrospective study

In 102 N- and 44 N+ disease-free breast cancer patients, lymphocytic populations and skin reaction of delayed hypersensitivity (SRDH) were monitored up to 266 months after mastectomy to find out whether they were similar or different from control values. In two selected groups of 34 N- and 11 N+ breast cancer patients, the whole 10 year follow-up was divided into three subintervals, each of them lasting 40 months and the time course of lymphocytic populations was evaluated. In the 102 N- patients, mean CD4+, CD8+, CD3+ values were lower (P < 0.01, P < 0.001, P < 0.01, respectively) while CD4+/CD8+ ratio was higher (P < 0.05) than in controls. Fifteen N- breast cancer patients (16%) were anergic compared to 30(32%) of controls (P < 0.05). In the 34 selected N- breast cancer patients soon after mastectomy the mean value of CD4+, CD8+, CD3+ T subpopulations was lower (P < 0.01, P < 0.001, P < 0.01, respectively) than in controls. Successively their mean value increased so that in the last subinterval they were not or were only slightly lower (P n.s., P < 0.05, P < 0.05, respectively) than in controls. In the 44 N+ patients, mean CD4+, CD8+, CD3+ values were lower (P < 0.001, v < 0.05, P < 0.01, respectively) and CD19+ lymphocytes higher (P < 0.001) than in controls. Five N+ breast cancer patients (13%) were anergic compared to 32% of controls (P < 0.05). In the 11 selected N+ breast cancer patients soon after mastectomy, the mean value of CD4+, CD8+ T subpopulations and CD16+56+ cells was significantly lower (P < 0.001, P < 0.001, P < 0.01, respectively) than in controls. Successively their mean value constantly increased so that in the last subinterval, no or slight (P n.s., P < 0.05, P n.s., respectively) significant difference compared to controls occurred. The mean CD4+/CD8+ ratio value of N- patients was significantly higher than in controls. However in the last subinterval, the significance was lower than in the first one (P < 0.05 and P < 0.01, respectively). In the N+ patients, the mean value of CD4+/CD8+ ratio was constant, although not significantly, lower than in controls; however it progressively increased from the first to the last subinterval. Therefore the significance of the difference of the mean CD4+/CD8+ ratio between N- and N+ patients strongly decreased from the first to the last subinterval (P < 0.001 and P < 0.05, respectively). These data indicate that in breast cancer patients, following mastectomy, a significant activation of memory and CD4+ T cells and long-term decrease of the circulating immunocompetent CD4+, CD8+ and CD16+56+ cells occurs. The prolonged disease-free interval observed in the 34 N- and 11 N+ breast cancer patients can be correlated with the restoration of the normal state of cell-mediated immunity.

First-line treatment of NSCLC with bevacizumab: real world data from an Italian regional based survey

Background: We aimed to explore the use of platinum plus bevacizumab in a real world NSCLC population. Patients and methods: We retrospectively collected data from patients affected by NS-NSCLC treated with platinum plus bevacizumab across Tuscany. Results: We evaluated 62 (median age: 63.5 [30–77] years) pts. All but one presented with adenocarcinoma and the majority had ECOG PS of 0/1. 17.7% presented with central lesion, 11.3% with brain metastasis, 38.7% with hypertension and 4.8% with mild haemoptysis. We observed a median time to progression (TTP) of 6.5 [2–37] and a median overall survival (OS) of 10.5 [2–39] months. Overall response rate (ORR) was 59.6% with a disease control rate (DCR) of 80.6%. Safety profile was acceptable. We observed five cardiovascular events and two major bleedings with no toxic deaths. Conclusion: Safety and efficacy real world data are consistent with those from clinical trials even in a less selected population.

1259PPHASE II TRIAL OF METRONOMIC ORAL VINORELBINE AS FIRST-LINE TREATMENT IN ELDERLY PATIENTS WITH ADVANCED NON-SMALL CELL LUNG CANCER (MOVE TRIAL)

ABSTRACT Aim: Metronomic oral vinorelbine could be a safe option for elderly patient 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. Methods: 43 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. Primary endpoints were overall response rate (ORR), clinical benefit (CB – disease response + stabilization >12 weeks) and safety. Health-related QoL (HRQoL) was also assessed. We conducted an exploratory time-course analysis of VEGF and thrombospondin-1 (TSP1) serum levels in a subgroup of patients. Results: Patients 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 G3/4 toxicity. Regardless of severity main toxicities observed were anemia in 44%, fatigue in 32.4%, and diarrhoea 10.5%. HRQoL scores did not significantly vary. Baseline VEGF levels were lower and showed a rapid increase during treatment in non-responders pts only while TSP1 levels did not change. Conclusions: Metronomic 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. Disclosure: All authors have declared no conflicts of interest.