OBJECTIVE: To estimate costs associated with management of chemotherapy-induced toxicity with pemetrexed compared with docetaxel as second-line chemotherapy for advanced non-small cell lung cancer (NSCLC). METHODS: Resource utilization data were analysed from a multinational phase III randomised trial comparing pemetrexed (ALIMTA(r)) with docetaxel (N = 571). Costs included in this initial analysis were hospitalisations, transfusions, erythropoietin, granulocyte colony-stimulating factors (GCSFs) and parenteral antibiotics. Unit costs were sourced from UK National Health Service (NHS) case mix data (2002) and national drug prices. RESULTS: Efficacy was shown to be similar with median survival times of approximately 8 months for both arms, although toxicity-related events and need for medical management were lower for pemetrexed. CTC grade 3/4 neutropenia and neutropenic fever were significantly higher for docetaxel (40% vs 5%, 13% vs 2%, respectively). Most other grade 3/4 toxicities, including nausea/vomiting, diarrhoea, thrombocytopenia and anaemia, occurred at low rates (<5%) and were similar between treatment arms. The most common reasons for drug-related hospitalisation for both arms were febrile neutropenia and neutropenia (4 admissions on the pemetrexed arm [£4,730] vs 42 on the docetaxel arm [£48,554]). Admissions for other drug-related toxicities were lower for pemetrexed (17 admissions [£15,020]) vs docetaxel (31 admissions [£27,091]). Average cost of these hospitalisations was £75 and £274 for pemetrexed and docetaxel, respectively. More patients on the pemetrexed arm received red blood cell transfusions (17% vs 12%), however, more patients on the docetaxel arm received erythropoietin (10% vs 7%). Patients on the pemetrexed arm received fewer courses of parenteral antibiotics and GCSF and required fewer hospital admissions and days. Total average costs were £159 and £484 for the pemetrexed and docetaxel arms, respectively. CONCLUSIONS: In the second-line treatment of NSCLC, pemetrexed offers similar efficacy to docetaxel but better tolerability. This results in less expensive management of chemotherapy-related adverse events, primarily through reduced hospitalisation.