EORTC Early Clinical Studies Group early phase II trial of S-1 in patients with advanced or metastatic colorectal cancer

Cancer of the colon and rectum is one of the most frequent malignancies both in the US and Europe. Standard palliative therapy is based on 5-fluorouracil/folinic acid combinations, with or without oxaliplatin or irinotecan, given intravenously. Oral medication has the advantage of greater patient convenience and acceptance and potential cost savings. S-1 is a new oral fluorinated pyrimidine derivative. In a nonrandomized phase II study, patients with advanced/metastatic colorectal cancer were treated with S-1 at 40 mg m-2 b.i.d. for 28 consecutive days, repeated every 5 weeks, but by amendment the dose was reduced to 35 mg m-2 during the study because of a higher than expected number of severe adverse drug reactions. In total 47 patients with colorectal cancer were included. In the 37 evaluable patients there were nine partial responses (24%), 17 stable diseases (46%) and 11 patients had progressive disease (30%). Diarrhoea occurred frequently and was often severe: in the 40 and 35 mg m-2 group, respectively, 38 and 35% of the patients experienced grade 3-4 diarrhoea. The other toxicities were limited and manageable. S-1 is active in advanced colorectal cancer, but in order to establish a safer dose the drug should be subject to further investigations

Comparative cost efficiency across the European G5 countries of originators and a biosimilar erythropoiesis-stimulating agent to manage chemotherapy-induced anemia in patients with cancer

Objectives: To evaluate the comparative cost efficiency across the European Union G5 countries of the erythropoiesis-stimulating agents (ESAs) epoetin α (originator [Eprex®] and biosimilar [Binocrit®]; once weekly), epoetin β (NeoRecormon®; once weekly), and darbepoetin α (Aranesp®; once weekly or once every 3 weeks) under different scenarios of fixed and weight-based dosing in the management of chemotherapy-induced anemia. Methods: Direct costs of ESA treatment were calculated for one patient with cancer undergoing chemotherapy (six cycles at 3-week intervals) with ESA initiated at week 4 and continued for 15 weeks. Five scenarios were developed under fixed and weight-based dosing: continuous standard dose for 15 weeks; sustained dose escalation to 1.5× or double the standard dose at week 7, continued for 12 weeks; and discontinued dose escalation to 1.5× or double the standard dose at week 7 for a 3-week period, then 9 weeks of standard dose. Results: Under fixed dosing, the average cost of biosimilar epoetin α treatment across scenarios was €4643 (30,000 IU) or €6178 (40,000 IU). Corresponding estimates were €7168 for originator epoetin α, €7389 for epoetin β, €8299 for darbepoetin α once weekly, and €9221 for darbepoetin α once every 3 weeks. Under weight-based dosing, the average cost of biosimilar epoetin α treatment across scenarios was €4726. Corresponding estimates were €5484 for originator epoetin α, €5652 for epoetin β, and €8465 for both darbepoetin α once weekly and once every three weeks. Conclusion: Managing chemotherapy-induced anemia with biosimilar epoetin α is consistently cost efficient over treatment with originator epoetin α, epoetin β, and darbepoetin α under both fixed and weight-based dosing scenarios