Transient elevation of international normalized ratio during cisplatin-based chemotherapy in patients who are taking warfarin.

OBJECTIVE: To report 2 cases of a probable interaction between cisplatin and warfarin. CASE SUMMARY: Two cases of transient elevation of international normalized ratio (INR) during irinotecan (60 mg/m2 on days 1, 8, and 15) plus cisplatin (60 mg/m2 on day 1) chemotherapy with concomitant warfarin are presented. In both cases, warfarin dosages were stable at the therapeutic target range prior to initiation of chemotherapy. Granisetron hydrochloride (3 mg on days 1, 8, and 15) and dexamethasone (13.2 mg on day 1 and 6.6 mg on days 2, 3, 8, and 15) were used prior to irinotecan administration in both patients. In addition, aprepitant was administered to both patients for 3-5 days with cisplatin. One of these patients also received aprepitant with irinotecan on days 8 and 15. During chemotherapy, INR was transiently elevated almost 1.5-fold over baseline level on day 3. This variation did not occur in subsequent irinotecan cycles on days 8 and 15. The timing of these increases was similar in each of the cycles. DISCUSSION: Cisplatin was the common drug in the cases presented and therefore could be related to the INR elevations. To our knowledge, these are the first reports of an interaction between warfarin and irinotecan-cisplatin chemotherapy, but reports of a similar interaction with chemotherapy including platinum derivatives exist. Use of the Horn Drug Interaction Probability Scale indicated a probable interaction between warfarin and cisplatin. CONCLUSIONS: Cisplatin might affect the anticoagulation function of warfarin. Careful INR monitoring is necessary during antineoplastic chemotherapy with cisplatin in patients taking warfarin.

Comparison of 18F-FDG PET and MRI in assessment of uterine smooth muscle tumors.

UNLABELLED: The purpose of this study was to prospectively determine whether combined MRI and (18)F-FDG PET is more accurate than MRI in assessing nonbenign uterine smooth muscle tumors (USMTs). METHODS: Seventy patients (mean age, 49+/-10 y; range, 28-77 y) suspected of having nonbenign USMTs underwent both MRI and (18)F-FDG PET before surgery. Results were evaluated using receiver-operating-characteristic (ROC) analyses and the Cochran Q test. RESULTS: The area under the ROC curve for MRI with (18)F-FDG PET was significantly higher than that for MRI (0.97 vs. 0.89, P<0.05). Although multiple comparisons using the Cochran Q test were not significant, the sensitivity, specificity, and accuracy for MRI with (18)F-FDG PET with probable nonbenign USMT cases considered to be positive were higher than those for MRI (93.3% vs. 73.3%; 92.7% vs. 85.5%; and 92.9% vs. 82.9%, respectively). CONCLUSION: MRI with (18)F-FDG PET is useful in assessing nonbenign USMTs, as compared with MRI.

The potent peptide antagonist to angiogenesis, C16Y, and cisplatin act synergistically in the down-regulation of the Bcl-2/Bax ratio and the induction of apoptosis in human ovarian cancer cells.

Cisplatin is one of the most potent antitumor agents for ovarian cancer, but has also been implicated in normal tissue cytotoxicity. We examined the effect of cisplatin alone and in combination with C16Y, a newly-identified anti-angiogenic peptide from the NH2-terminal domains of the γ-chain of laminin-1, on the modulation of Bcl-2/Bax expression and induction of apoptosis in ovarian cancer cells (OVACAR3). C16Y did not elicit cell death of human umbilical vein endothelial cells (HUVECs). Cisplatin exerted a lethal effect with an EC50 of 10 µM in OVACAR3s. In the presence of 25 or 50 µg/ml of C16Y (a range which has no effect against HUVECs), the EC50 for cisplatin in OVACAR3s decreased to 3.5 and 2.0 µM, respectively. Using fluorescence-activated cell sorting (FACS) analysis of DNA stained OVACAR3s and terminal deoxynucleotide tranferase-mediated dUTP nick end-labeling (TUNEL), we found that even at concentrations of 1 and 3 µM cisplatin, C16Y at 10 and 25 µg/ml increased the incidence of apoptosis in OVACAR3s by 3-5-fold. Each drug had some measurable effect on Bax protein expression. Furthermore, Bcl-2 protein expression levels were markedly reduced by C16Y alone and cisplatin alone in a dose-dependent manner. The combination of C16Y and cisplatin resulted in a further dramatic reduction in Bcl-2, underscoring the pronounced synergy produced by cisplatin and C16Y together. On the other hand, C16Y did not activate any other signal transduction pathways that usually culminate in the activation of apoptosis, such as the p53, p21waf1, p73, ERK1/2 or PI3-AKT pathways. These observations suggest that the suppression of the Bcl-2/Bax ratio may play an important role in mediating the synergistic effect of cisplatin and C16Y on the induction of apoptosis in OVACAR3 cells.

Localisation of phosphorylated mTOR expression is critical to tumour progression and outcomes in patients with endometrial cancer.

Correlations between mammalian target of rapamycin (mTOR) expression, and clinicopathological features, outcome and Akt expression in endometrial endometrioid adenocarcinoma (EEC) were investigated. Tumour samples were obtained from 82 patients with EEC who had undergone hysterectomy, and phosphorylated mTOR (p-mTOR) and Akt (p-Akt) expression in the cytoplasm and nucleus was analysed by immunohistochemical staining. Nuclear p-mTOR was significantly elevated in poorly differentiated tumours and positively correlated with lymph node involvement (P = 0.05). Nuclear p-mTOR expression was associated with significantly shorter relapse-free survival (RFS) (P<0.01) and slightly shorter overall survival (OS) (P = 0.08). Cytoplasmic expression of p-mTOR was not correlated with any clinicopathological factors. Although not significant, cytoplasmic p-mTOR expression was associated with shorter PFS and OS (P = 0.09, P = 0.283, respectively). Neither cytoplasmic nor nuclear p-Akt expression was associated with clinicopathological factors or with survival. Localisation of p-mTOR may be critical for tumour progression and outcomes in patients with EEC.

The positron emission tomography with F18 17beta-estradiol has the potential to benefit diagnosis and treatment of endometrial cancer.

BACKGROUND: The positron emission tomography (PET) with F18 17beta-estradiol (FES) has good imaging for assessment of estrogen receptor in breast cancer. CASE: We report on a 30-year-old woman who desired to preserve her fertility with well-differentiated endometrial adenocarcinoma. Before hormone treatment was started, FES-PET showed increased uptake of endometrium, magnetic resonance imaging (MRI) showed thickness and F-18 fluorodeoxyglucose (FDG)-PET showed increased uptake. FES-PET after 3 months showed remaining FES uptake, but there were no abnormal findings on MRI and FDG-PET. Hysteroscopy showed remaining adenocarcinoma. After additional treatment, FES-PET showed a therapeutic response, and hysteroscopy showed no abnormal finding. CONCLUSIONS: To our knowledge, this is the first report that FES-PET has the potential to provide more useful information than did FDG-PET about the hormone therapy.