OBJECTIVES: Cost of management of toxicity associated with chemotherapy can be considerable. We estimated costs of treating drug-related adverse events associated with pemetrexed or docetaxel as second-line therapy for non-small cell lung cancer (NSCLC). METHODS: Resource utilisation (RU) data (hospital admissions, concomitant medications, transfusions) were collected prospectively during a multinational, randomised phase III trial comparing pemetrexed 500 mg/m2 and docetaxel 75 mg/m2, both administered every 21 days. Clinic visits were estimated from grade four toxicities not requiring hospitalisation. Using the perspective of the national health care system, Spanish costs were applied to RU data from patients who received treatment (N=541). Unit costs were obtained from published sources. Mean cost per patient was calculated. RESULTS: Baseline characteristics were well-balanced (72% male, 88% performance status 0/1, 75% Stage IV). Patients received a median of four cycles in both treatment arms. Survival was similar between arms (HR=0.99), with a median of about eight months. Grade 3/4 neutropenia and neutropenic fever occurred more frequently with docetaxel (40% vs. 5%, 13% vs. 2%, respectively; p<0.001). Most other grade 3/4 toxicities occurred at low rates (£5%) and were similar between arms. Patients receiving docetaxel were hospitalised more frequently and received more granulocyte colony-stimulating factors, erythropoietin, antibiotics and antifungals. Patients receiving docetaxel were more likely to incur extra clinic visits to manage grade four toxicity. Patients treated with pemetrexed received more transfusions. Total mean cost per patient was 309€ for pemetrexed and 1036€ for docetaxel. Hospitalisation and outpatient medications accounted for majority of costs (67% and 25% in the pemetrexed group, respectively, and 77% and 21% in the docetaxel group, respectively). CONCLUSIONS: Pemetrexed demonstrated similar efficacy to docetaxel in second-line treatment of NSCLC, but with a superior toxicity profile. The differences in toxicity are expected to translate to considerable cost savings to the Spanish health care system.