Metronomic oral vinorelbine doublet chemotherapy with carboplatin in treatment of advanced lung cancer: a feasibility and safety study

Background: Non-small cell lung cancer (NSCLC) is globally one of the most common forms of cancer. Palliative treatment is a delicate balance against toxicity and survival. Using small frequent doses of chemotherapy, metronomic regimens have been hypothesized to maintain or even improve efficacy while achieving a lower treatment-related toxicity. The mechanism is thought to result from a more continuous exposure of the tumour cells to the drugs. Treating NSCLC, this study addresses the feasibility and tolerability of carboplatin in combination with 12 weeks of daily metronomic vinorelbine. Method: Patients were included over a period of ten months. All patients had biopsy-verified incurable NSCLC and were candidates for first line chemotherapy (PD-L1<50% and no targetable mutations). This open label, non-randomized prospective safety and feasibility study was investigator initiated. Patients received up-to four cycles of standard dose carboplatin AUC 5 every third week in combination with 12 weeks of metronomic oral daily Navelbine ® (20/30 mg). Patients were evaluated by CT scans after end of treatment and then every 8 weeks (+/- 1 week) until progression. Results: A total of 20 patients were included. Male/female-ratio was 4/16. Age ranged from 49-83 with a median of 70.5 years. Majority had adenocarcinoma (95%). Two patients withdrew their consent within a week. 18 patients were included in safety analysis. 13 received all four cycles. Grade 1/2 toxicity was frequently seen and included fatigue 13 (72%), diarrhoea 13 (72%), constipation/congestion 13 (72%). Grade 3 toxicities were dyspnoea 2 (11%), nausea 3 (17%) and fatigue 3 (17%). Two (11%) had grade 4 toxicity with neutropenic fever, both recovered. No grade 5 toxicity was detected. Conclusion: In treatment of NSCLC this study is the first addressing the regimen of carboplatin in combination with daily metronomic vinorelbine. We conclude that doublet chemotherapy with daily vinorelbine is safe and feasible.