Fatal pulmonary fibrosis associated with induction chemotherapy with carboplatin and vinorelbine followed by CHART radiotherapy for locally advanced non-small cell lung cancer

In an attempt to evaluate the safety and efficacy of chemotherapy and continuous hyperfractionated radiotherapy (CHART) for non small cell lung cancer (NSCLC), a dose-escalation study was initiated, in which patients were treated with a combination of Vinorelbine and Carboplatin chemotherapy and CHART radiotherapy. The first cohort of 3 patients were treated with induction chemotherapy (Vinorelbine 30mg/m2 weeks 1,2,4 and 5, and Carboplatin, AUC = 5mg/ml/min weeks 1 and 4) followed by CHART radiotherapy (5400cGy in 36 fractions in 12 days on weeks 7 and 8). It was intended to then treat subsequent cohorts of patients with increasing doses of chemotherapy concomitantly with CHART, but unfortunately 2 of the first 3 patients both developed respiratory failure due to widespread pulmonary fibrosis, and died 7 and 9 weeks after completing treatment. At this point the study was closed. The combination of chemotherapy and CHART for NSCLC may have significant pulmonary toxicity and this potentially serious adverse effect needs to be carefully considered when planning future research studies is this area.