Dose and dose-intensity of chemotherapy, studies in small cell lung cancer

Contains fulltext : 19175_doseandoi.pdf (publisher's version ) (Open Access)Without treatment, survival of patients with small cell lung cancer (SCLC) is less than 3 months. Although combination chemotherapy has improved the prognosis, long-term survival remains poor. To assess the impact of chemotherapy dose intensification on survival, 244 SCLC patients were randomised to standard CDE (cyclophosphamide 1000mg/m2, doxorubicin 45mg/m2, etoposide 100mg/m2 x3, every 3 weeks for 5 cycles) or intensified CDE (125% dose with G-CSF 5 g/kg/day days 4-13, every 2 weeks for 4 cycles). After a median follow-up of 4u years there was no survival difference: median survival was 54 weeks versus 52 weeks, with 2-year survival rates of 15% and 18%, respectively (P=0.885). The first 163 pts in the aforementioned trial were also randomised (2x2 factorial design) to prophylactic antibiotics or placebo to assess their impact on febrile leukopenia (FL). Prophylactic ciprofloxacin plus roxithromycin reduced the incidence of FL, the number of infections, the use of therapeutic antibiotics and hospitalisations due to FL by approximately 50%, with reduced number of infectious deaths. It was shown that giving prophylactic antibiotics to SCLC patients undergoing chemotherapy produces cost-savings. Sensitivity analyses indicate that, with an efficacy of prophylaxis of 50%, and with expected costs of antibiotic prophylaxis of 500 Euro or less, cost-savings will incur over a broad range of baseline risks for FL, that is a risk above 10% to 20% for FL per cycle. Further it was demonstrated in a small pilot study, that G-CSF administration until 48 hours before the next chemotherapy cycle increased chemotherapy-associated leukopenia and thrombocytopenia. Finally, 20 randomised studies, in which the dose or DI of chemotherapy for SCLC were the only variables tested, were analysed. From this analysis, it appears that the number of cycles, dose level, dose-density and cumulative dose are all important factors for improving survival.224 p