Probable drug-drug interaction between erlotinib and amiodarone causes severe neurotoxicity in a patient with advanced lung cancer.

Drug-drug interactions (DDIs) are of great concern in the treatment of cancer, especially when target therapies, such as tyrosine kinase inhibitors, are being used. Here, we report a case of probable DDI between erlotinib and amiodarone leading to severe neurotoxicity. Amiodarone inhibits P-glycoprotein (P-gp), for which erlotinib is a substrate. P-gp is an important drug transporter that is involved in limiting the blood-brain barrier penetration of erlotinib. Clinicians should be aware of emerging data characterizing the effect of the P-gp transport system on drug exposure and its potential for DDI.

Is ranitidine necessary as premedication for regimens containing paclitaxel? A non-inferiority study.

BACKGROUND: Histamine type-2-receptor antagonist drugs (H2-antagonists) have been used as standard treatment to prevent hypersensitivity reactions (HRs) in paclitaxel-containing regimens, however, their use has been strongly questioned. Ranitidine has been the most widely used H2-antagonist. Therefore, especially after its withdrawal from the market, the objective of this study is to determine the impact of its elimination from premedication on HR incidence. METHODS: A cohort, multicenter, observational, prospective, and non-inferiority study, including paclitaxel-naïve cancer patients, designed to determine the incidence of HRs of any grade associated with paclitaxel administration and analyze non-inferiority against the incidence estimated in the literature (20%), with 5% as the maximum difference (Δ). Patients with a solid neoplasm of any type/stage, who initiated treatment with paclitaxel without H2-antagonists in the premedication regimen were enrolled. RESULTS: A total of 441 patients were included, of whom 50 presented 54 HRs of any grade. The cumulative incidence was 11.3% (95%CI 8.5-14.7), thus fulfilling the hypothesis of non-inferiority. Of the overall HRs detected, 15 were grade ≥ 3 with a cumulative incidence of 3.4% (95%CI 1.9-5.5). CONCLUSIONS: This study demonstrates that the elimination of ranitidine from paclitaxel premedication schedules is non-inferior in the development of HRs of any grade compared to the administration of H2-antagonists.

Population-based survival analyses of central nervous system tumors from 1994 to 2008. An up-dated study in the temozolomide-era.

The present population-based study describes the survival of malignant central nervous system (CNS) tumors diagnosed during 15 years. Also, we obtained individual data regarding the use of temozolomide to analyze the impact of this drug on the survival of patients diagnosed with glioblastoma. From 1994 to 2008, a total of 679 incident cases of primary CNS tumors were reported by the Girona Cancer Registry after excluding 39 cases diagnosed by death certificate only. Number of cases and the corresponding proportion for each CNS histological subtype in the study population were: 25 oligodendroglial and oligoastrocytics (3.7%), 22 ependymal tumors (3.2%), 24 embryonal (3.5%), 372 astrocytic (54.8%), 1 choroid plexus (0.1%) and 235 without histological confirmation (34.6%). Observed survival after 5 years since diagnosis for the histological subtype were: 58.8%; 47.5%; 37.0%; 14.5% and 6.5%, respectively (p<0.001). Survival of patients diagnosed with glioblastoma according to temozolomide treatment (yes/no) was 60.8% vs. 13.6% and 5.9% vs. 2.5% after 1 and 5 years since diagnosis, respectively. Short-term survival was higher for patients diagnosed with glioblastoma and treated with temozolomide than patients not treated with temozolomide.