Acute effect of palonosetron on electrocardiographic parameters in cancer patients: a prospective study.

OBJECTIVES: Palonosetron is a novel 5-hydroxytryptamine(3) (5 HT(3)) receptor antagonist, which has been shown to be superior to first generation 5 HT(3) receptor antagonists regarding the prevention of acute, delayed and overall chemotherapy-induced nausea and vomiting. First generation 5 HT(3) receptor antagonists may induce electrocardiographic changes of heart rate and repolarization. The acute cardiac effect of palonosteron is unknown. The purpose of this study is to determine acute effects of palonosetron on electrocardiographic (ECG) parameters in cancer patients. MATERIALS AND METHODS: The study had a prospective design. Seventy-six cancer patients with normal cardiac function who received palonosetron for prevention of chemotherapy-induced nausea and vomiting were enrolled. Standard 12-lead ECG recordings were performed at baseline and 30 min after palonosetron administration. P wave durations and corrected QT intervals were measured; P wave dispersion (Pd) and QTc dispersion were calculated. RESULTS: Median heart rate did not differ among 76 patients enrolled before and after palonosetron administration (p: 0.6). Systolic and diastolic blood pressures were not significantly different before and after palonosteron (p values 0.9 and 0.3, respectively). Although median QT min value was higher after palonosetron administration than before palonosetron administration, the difference was not statistically significant (p: 0.6). CONCLUSION: Palonosetron seems to have no acute arrhythmogenic potential.

Evaluation of the acute effect of palonosetron on transmural dispersion of myocardial repolarization.

BACKGROUND: 5-hydroxytryptamine receptor type-3 (5-HT3) antagonists are widely used for prophylaxis of chemotherapy-induced nausea and vomiting (CINV) and regarded to have a high safety profile. However, several electrocardiographic changes and cardiac arrhythmias have been reported due to administration of 5-HT3 antagonists. Only prolongation of QT interval has been investigated as an index of potential for life-threatening arrhythmias in adult patients using 5-HT3 antagonists. Recently, increase in transmural dispersion of repolarization (TDR) has been proposed as a more reliable determinant of arrhythmogenic potential. AIM: To assess the effects of palonosetron, a second-generation 5-HT3 antagonist, on the T-wave peak to T-wave end (TpTe) interval which has been proposed as a reliable index of spatial TDR. PATIENTS AND METHODS: A total of 50 consecutive cancer patients (aged: 57 +/- 12 years) who were scheduled to receive emetogenic chemotherapy were included to the study. Baseline12-lead electrocardiography (ECG) recordings were obtained. Then, all patients received 8 mg intravenous dexamethasone followed by a single dose of 0.25 mg intravenous palonosetron administered over 30 seconds. A second ECG was performed 30 minutes after the administration of palonosetron. Indices of cardiac repolarization and TDR before and after the administration of palonosetron were compared. RESULTS: In comparison with baseline there was no statistically significant change in any of the heart rate-corrected parameters, including QT(c) (lead V5), QT(maxc), QT(minc), QT(cd), TpTe (V5), TpTe(max), TpTe(min), TpTe(d) and TpTe/QT (V5). CONCLUSIONS: Palonosetron does not have any significant effect on QT(c) and TpTe intervals. It might be the drug of choice for prophylaxis of CINV in cancer patients receiving chemotherapy with known cardiotoxic potential or who have pre-existing cardiac disease that predispose them to drug-induced arrhythmias.

Correlation between osteopontin protein expression and histological grade of astrocytomas.

Osteopontin is a ligand for the integrin proteins, which are cell surface receptors that mediate the physical and functional interactions between a cell and the extracellular matrix. The expression of osteopontin is reportedly increased in a number of transformed cell lines and tumor tissues. Furthermore, increased expression of osteopontin results in some infiltrative features of tumors. The aim of the study is to demonstrate that expression of osteopontin in human astrocytomas correlates with histological tumor grade. The expression of osteopontin in human astrocytomas was determined with immunohistochemistry. Median osteopontin expression levels were 1%, 7.5%, 60%, and 50% in grade I, II, III, and IV tumors, respectively. Osteopontin staining was significantly higher in high grade (grade III-IV) than low grade (grade I-II) tumors. These findings indicate that osteopontin immunoreactivity in human astrocytomas may correlate with the grade of a tumor.

The use of concurrent hormonotherapy and radiotherapy does not deteriorate radiation-induced cardiac toxicity.

Postmenopausal patients with breast cancer have two options for adjuvant endocrine therapy, tamoxifen and aromatase inhibitors (AIs) as well as radiotherapy (RT) and chemotherapy. However, there is limited data regarding the optimal sequencing of RT and tamoxifen/AIs. Thus, we aimed to evaluate the effects of tamoxifen and AIs on radiation-induced cardiotoxicity. Eighty ovariectomized rats were divided into eight groups (G). G1 was defined as a control group; G2, G3, G4, and G5 were RT, tamoxifen, anastrozle, and letrozole groups, respectively; G6, G7, and G8 were RT plus tamoxifen, anastrozle, and letrozole groups, respectively. Drugs were started 1 week before RT and continued until the animals were killed 16 weeks after RT. The heart tissues were then dissected and examined with light microscopy to determine endocardial thickness and cardiac fibrosis. The endocardial thickness scores of both RT alone and the tamoxifen groups as well as the cardiac fibrosis score of RT alone were higher than that the control group ( p < 0.05 for all). There was no difference in the endocardial thickness and cardiac fibrosis scores of the RT-only group and the RT plus hormonotherapy groups ( p > 0.05 for all). Concurrent administration of RT and hormonal therapy with either tamoxifen or AIs did not further amplify radiation-induced cardiac toxicity. This issue warrants further study.

Amelioration of radiation-induced lung injury by halofuginone: An experimental study in Wistar-Albino rats.

To evaluate effects of halofuginone (H) on radiation-induced lung injury (RILI), 60 rats were divided into six groups: Group (G) 1 control, G2 radiotherapy (RT) only, G3 and G4 2. 5 and 5 µg H and G5 and G6 RT + 2.5 and 5 µg H groups, respectively. A single dose of 12 Gy RT was given to both lungs. H was applied intraperitoneally with daily doses, until animals were killed at 6 and 16 weeks after RT. At 6th and 16th weeks of RT, five rats from each group were killed. Lung tissues were dissected for light and electron microscopy. Chronic inflammation, fibrosis and transforming growth factor-beta (TGF)-ß scores of all study groups were significantly different at 6th and 16th week ( p < 0.001). Chronic inflammation, fibrosis and TGF-ß scores of G2 were higher than G5 and G6 at 6th and 16th weeks of RT. At 16th week, fibrosis and TGF-ß scores of G5 were higher than G6 ( p = 0.040 and 0.028, respectively). Electron microscopical findings also supported these results. Therefore, H may ameliorate RILI. The effect of the H was more prominent at higher dose and after long-term follow-up. These findings should be clarified with further studies.

Postmastectomy radiation therapy in locally advanced breast cancer.

Despite wide efforts for early detection of breast cancer using screening mammography, locally advanced breast carcinomas account for a remarkable proportion of all breast carcinomas, particularly in developing countries. Locally advanced breast cancer may have widely different clinical and biological features. Radiotherapy plays an important role in the management of locally advanced breast cancer. Postmastectomy radiotherapy has been shown to significantly reduce the risk of loco-regional failure and to improve disease free survival as well as overall survival in high-risk women with breast cancer. This review article summarizes the data from randomized trials revealing a significant benefit from postmastectomy radiation therapy in patients with locally advanced disease.