Pharmacokinetics and pharmacodynamics of topotecan administered daily for 5 days every 3 weeks

Topotecan is a novel semisynthetic derivative of the anticancer agent camptothecin and inhibits the intranuclear enzyme topoisomerase I. The lactone structure of topotecan, which is in equilibrium with the inactive ringopened hydroxy acid, is essential for this activity. The open form predominates at physiological pH. We performed a pharmacokinetic, study as part of a phase I study in patients with various types of soli

Ultrasound is at least as good as magnetic resonance imaging in predicting tumour size post-neoadjuvant chemotherapy in breast cancer

Background: The aim of this study was to evaluate the accuracy of clinical imaging of the primary breast tumour post-neoadjuvant chemotherapy (NAC) related to the post-neoadjuvant histological tumour size (gold standard) and whether this varies with breast cancer subtype. In this study, results of both magnetic resonance imaging (MRI) and ultrasound (US) were reported. Methods: Patients with invasive breast cancer were enrolled in the INTENS study between 2006 and 2009. We included 182 patients, of whom data were available for post-NAC MRI (n = 155), US (n = 123), and histopathological tumour size. Results: MRI estimated residual tumour size with <10-mm discordance in 54% of patients, overestimated size in 28% and underestimated size in 18% of patients. With US, this was 63%, 20% and 17%, respectively. The negative predictive value in hormone receptor-positive tumours for both MRI and US was low, 26% and 33%, respectively. The median deviation in clinical tumour size as percentage of pathological tumour was 63% (P25 = 26, P75 = 100) and 49% (P25 = 22, P75 = 100) for MRI and US, respectively (P = 0.06). Conclusions: In this study, US was at least as good as breast MRI in providing information on residual tumour size post-neoadjuvant chemotherapy. However, both modalities suffered from a substantial percentage of over- and underestimation of tumour size and in addition both showed a low negative predictive value of pathologic complete remission (Gov nr: NCT00314977)

Ultrasound is at least as good as magnetic resonance imaging in predicting tumour size post-neoadjuvant chemotherapy in breast cancer

Item does not contain fulltextBACKGROUND: The aim of this study was to evaluate the accuracy of clinical imaging of the primary breast tumour post-neoadjuvant chemotherapy (NAC) related to the post-neoadjuvant histological tumour size (gold standard) and whether this varies with breast cancer subtype. In this study, results of both magnetic resonance imaging (MRI) and ultrasound (US) were reported. METHODS: Patients with invasive breast cancer were enrolled in the INTENS study between 2006 and 2009. We included 182 patients, of whom data were available for post-NAC MRI (n=155), US (n=123), and histopathological tumour size. RESULTS: MRI estimated residual tumour size with <10-mm discordance in 54% of patients, overestimated size in 28% and underestimated size in 18% of patients. With US, this was 63%, 20% and 17%, respectively. The negative predictive value in hormone receptor-positive tumours for both MRI and US was low, 26% and 33%, respectively. The median deviation in clinical tumour size as percentage of pathological tumour was 63% (P25=26, P75=100) and 49% (P25=22, P75=100) for MRI and US, respectively (P=0.06). CONCLUSIONS: In this study, US was at least as good as breast MRI in providing information on residual tumour size post-neoadjuvant chemotherapy. However, both modalities suffered from a substantial percentage of over- and underestimation of tumour size and in addition both showed a low negative predictive value of pathologic complete remission (Gov nr: NCT00314977)

Primary Granulocyte Colony-Stimulating Factor Prophylaxis During the First Two Cycles Only or Throughout All Chemotherapy Cycles in Patients With Breast Cancer at Risk for Febrile Neutropenia

Purpose Early breast cancer is commonly treated with anthracyclines and taxanes. However, combining these drugs increases the risk of myelotoxicity and may require granulocyte colony-stimulating factor (G-CSF) support. The highest incidence of febrile neutropenia (FN) and largest benefit of G-CSF during the first cycles of chemotherapy lead to questions about the effectiveness of continued use of G-CSF throughout later cycles of chemotherapy. Patients and Methods In a multicenter study, patients with breast cancer who were considered fit enough to receive 3-weekly polychemotherapy, but also had > 20% risk for FN, were randomly assigned to primary G-CSF prophylaxis during the first two chemotherapy cycles only (experimental arm) or to primary G-CSF prophylaxis throughout all chemotherapy cycles (standard arm). The noninferiority hypothesis was that the incidence of FN would be maximally 7.5% higher in the experimental compared with the standard arm. Results After inclusion of 167 eligible patients, the independent data monitoring committee advised premature study closure. Of 84 patients randomly assigned to G-CSF throughout all chemotherapy cycles, eight (10%) experienced an episode of FN. In contrast, of 83 patients randomly assigned to G-CSF during the first two cycles only, 30 (36%) had an FN episode (95% CI, 0.13 to 0.54), with a peak incidence of 24% in the third cycle (ie, first cycle without G-CSF prophylaxis). Conclusion In patients with early breast cancer at high risk for FN, continued use of primary G-CSF prophylaxis during all chemotherapy cycles is of clinical relevance and thus cannot be abandoned