In patients with prostate cancer (PCa), prostate enlargement may give rise to lower urinary tract symptoms (LUTS); many patients suffer from moderate-to-severe symptoms. We compare the efficacy of degarelix and goserelin plus bicalutamide in improving LUTS in PCa patients.

The potential for an interaction between lapatinib and absorption of the P-glycoprotein (ABCB1) substrate digoxin at a therapeutic dose in breast cancer patients was characterized. Seventeen women with HER2-positive metastatic breast cancer received a single oral 0.5-mg dose of digoxin on days 1 and 9 and oral lapatinib 1500 mg once daily on days 2 through 9. Digoxin pharmacokinetic parameters were determined on day 1 (digoxin administration alone) and on day 9 (coadministration of lapatinib and digoxin), and parameters were compared to determine the effects of lapatinib on digoxin absorption. Concomitant medications that could affect ABCB1 were accounted for. Lapatinib 1500 mg/day increased digoxin absorption approximately 80%, implicating lapatinib inhibition of intestinal ABCB1-mediated efflux. In summary, coadministration of lapatinib with narrow therapeutic index drugs that are substrates of ABCB1 should be undertaken with caution and dose adjustment should be considered.

Tofacitinib is an oral Janus kinase inhibitor. The objective of this phase 1, open-label study was to characterize the single- and multiple-dose pharmacokinetics (PK) of tofacitinib in 12 healthy, adult Chinese volunteers. Eligible subjects received oral tofacitinib 10 mg once daily on days 1 and 6 and twice daily on days 2-5. Blood samples were collected on day 1 predose and over 24 hours postdose (day 2 predose), predose on days 3-6, and over 12 hours postdose on day 6. PK parameters were calculated using noncompartmental analysis. Mean concentration-time profiles for days 1 and 6 were similar, with median time to peak concentration of 0.5 hours on both days. Plasma concentrations declined rapidly following attainment of peak concentrations, with a mean terminal half-life of 3.3 hours on day 1 (single dose) and 2.5 hours on day 6 (multiple dose). No accumulation in plasma occurred with twice-daily administration: accumulation ratio of 1.04. The rapid absorption, elimination, and systemic exposures (peak and area under the concentration-time curve) observed in healthy Chinese volunteers in this study are similar to those previously reported in white subjects.

Ponatinib, an oral tyrosine kinase inhibitor with significant activity in heavily pretreated patients with chronic myeloid leukemia, is a CYP3A4 substrate. This open-label, nonrandomized, fixed-order crossover study evaluated the effect of multiple oral doses of rifampin, a strong CYP3A4 inducer, on the pharmacokinetics of ponatinib (45 mg, single dose). Twenty healthy adults received ponatinib on day 1, rifampin 600 mg alone on days 8-13, 15, and 16, and rifampin 600 mg with ponatinib on day 14. Rifampin decreased maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC) from time zero to time of last measurable concentration (AUC0-t ) and from time zero to infinity (AUC0-∞ ) of ponatinib by 42%, 59%, and 63%, respectively, with no effect on time to Cmax . The limits of the 90% confidence intervals of the estimated geometric mean ratios of ponatinib Cmax , AUC0-t , and AUC0-∞ did not fall within the 80-125% margins for equivalence, suggesting a statistically significant interaction. Coadministration of ponatinib with strong CYP3A4 inducers should be avoided unless the benefit outweighs the possible risk of ponatinib underexposure, because the safety of ponatinib dose increases has not been studied in this context.

Trametinib (Mekinist®) is a selective inhibitor of mitogen-activated protein kinase kinase (MEK) approved in the United States as a single agent and in combination with dabrafenib (Tafinlar®) for treatment of patients with unresectable or metastatic melanoma with a positive BRAF V600E/V600K mutation for which a pediatric oral solution formulation is being developed. This open-label, two-period, two-treatment, randomized, crossover study assessed the relative bioavailability of the trametinib pediatric oral solution compared to the tablet formulation after a single-dose administration to adult patients with solid tumors. Primary pharmacokinetic endpoints derived from standard non-compartmental methods were AUC0-inf , AUC0-t , and Cmax . As expected, Cmax was higher and Tmax earlier for the pediatric oral solution compared to the tablet formulation. Administration of the trametinib pediatric oral solution resulted in a 12%, 10%, 18%, and 71% higher AUC0-inf , AUC0-last , AUC0-24 , and Cmax , respectively, as compared to the tablet formulation. Safety results were aligned with the known safety profile of trametinib. No serious or non-serious adverse events resulted in study drug withdrawal. Palatability of the pediatric oral solution was evaluated and found to be acceptable to most adult patients, but may differ in the pediatric population.

The vascular endothelial growth factor (VEGF) pathway is associated with the promotion of endothelial cell proliferation, migration, and survival necessary for angiogenesis. VEGF and its three receptor isoforms are often overexpressed in many human solid tumors. Tivozanib is a potent, selective inhibitor of VEGF receptors 1, 2, and 3, with a long half-life. The purpose of these studies was to evaluate the effect of ketoconazole, a potent inhibitor of CYP3A4, and rifampin, a potent inducer of CYP3A4, on the pharmacokinetics of tivozanib. Two phase I, open-label, 2-period, single-sequence studies evaluated the effect of steady-state ketoconazole (NCT01363778) or rifampin (NCT01363804) on the pharmacokinetic profile, safety, and tolerability of a single oral 1.5-mg dose of tivozanib. Tivozanib was well tolerated in both studies. Steady-state ketoconazole did not cause a clinically significant change in the pharmacokinetics of a single dose of tivozanib; therefore, dosing of tivozanib with a CYP3A4 pathway inhibitor should not cause a clinically significant change in serum tivozanib levels. However, coadministration of tivozanib with rifampin caused a significant decrease in the area under the curve from 0 to infinity and half-life and an increase in clearance of tivozanib, which suggest increased clearance via the enhanced CYP3A4-mediated metabolism of tivozanib.

Rucaparib is a potent Poly (ADP-ribose) Polymerase (PARP) inhibitor currently under clinical development. The objectives of this analysis were to establish population PK and PK/PD models for rucaparib, and to evaluate the predictability of PARP activity in PBL for PARP activity in tumor tissues.

To determine the maximally tolerated dose of sorafenib delivered before, during, and after stereotactic body radiation therapy (SBRT) in hepatocellular carinoma (HCC).

Therapeutic touch (TT) is independent nursing intervention which is effective on nausea induced by chemotherapy but technique, steps and variables affected by this therapy are not yet well known. The aim of this study was to elicit descriptions of how TT is used with cancer patients, providing a basis for the systematic use and evaluation of TT with patients.

Vitamin E δ-tocotrienol (VEDT), a natural vitamin E from plants, has shown anti-neoplastic and chemoprevention activity in preclinical models of pancreatic cancer. Here, we investigated VEDT in patients with pancreatic ductal neoplasia in a window-of-opportunity preoperative clinical trial to assess its safety, tolerability, pharmacokinetics, and apoptotic activity.

To analyze and evaluate the clinical efficacy of heat-sensitive moxibustion for symptoms of large intestine cancer.

Gemcitabine-based combinations in advanced pancreatic cancer have been reported to have superior activity compared with gemcitabine alone. The results of the commonly used endpoints of clinical trials after chemotherapy or targeted therapy have been poorly reported.

Long-term disease-free survival in adult patients with acute lymphoblastic leukemia (ALL) remains unsatisfactory, and the treatment options are limited for those patients with relapse or a failure to respond after initial therapy. We conducted a dose-escalation/expansion phase II, multicenter, single-arm study to determine the optimal dose of coltuximab ravtansine (SAR3419), an anti-CD19 antibody-drug conjugate, in this setting.

To observe the clinical effect of Huikangling Tablet (HT, extracted from Scabrous Patrinia root) on peripheral blood micrometastasis of differentiated thyroid carcinoma (DTC) patients.

Androgen deprivation therapy (ADT) with luteinizing hormone releasing hormone (LHRH) agonists is an effective initial therapy for men with advanced prostate cancer. LHRH agonists are usually administered indefinitely at a fixed interval.

Sorafenib monotherapy has shown benefits in phase II trials as third-/fourth-line treatment in patients with non-small-cell lung cancer (NSCLC).

To evaluate activity and toxicity of mTOR inhibitor temsirolimus in patients with platinum-refractory/resistant ovarian cancer (OC) or advanced/recurrent endometrial carcinoma (EC).

Macular edema is the main cause of visual loss in patients with branch retinal vein occlusion. Macular edema is initially reversible, but over time, permanent loss ofvision occurs from structural damage to the macula. For this reason, there is a need for more rapid and effective treatments than laser photocoagulation which has been established as a gold standard. There are several pharmacologic agents which have changed the management of macular edema.

To investigate the clinical efficacy of adoptive immunotherapy using dendritic cells (DC) and cytokine-induced killer (CIK) cells combined with chemotherapy in multiple myeloma. The immunomodulatory effect of the therapy was discussed by detecting the levels of peripheral blood T cell subsets and CD4(+)CD25(+) regulatory cells (Treg). Fifty MM patients were randomly divided into two groups: 24 cases in the simple chemotherapy group and 26 cases in the combined therapy group (chemotherapy plus DC/CIK immunotherapy). The therapeutic efficacy and the proportions of peripheral blood T cell subsets and Treg cells were compared between the two groups. The cellular immunity indicators were also compared, including IL-2, IFN-γ, IL-4, IL-10, AgNORs ratio and TGF-β. After 3 weeks of treatment, the life quality and clinical efficacy of the combined therapy group were superior to those of the simple chemotherapy group (P<0.05). CD3(+)CD8(+) ratio, CD4(+)CD25(+) ratio, CD4(+)CD25(+)/CD4(+) ratio, CD4(+)CD25(+)FoxP3(+)/CD4(+)CD25(+) ratio, IL-4, IL-10 and TGF-β levels of the combined therapy group were obviously lower than those of the simple chemotherapy group (P<0.05). The CD3(+)CD4(+)/CD3(+)CD8(+) ratio, AgNOR ratio, IL-2 and IFN-γ level and positive rate of NKG2D in the combined therapy group were significantly higher than those of the simple chemotherapy group (P<0.05). These results indicated better immunomodulatory effect of the combined therapy. DC/CIK immunotherapy combined with chemotherapy has a good clinical efficacy and prospect for MM, reversing the Th1 to Th2 shift and increasing the anti-tumor capacity of the immune system.