Discrepancy in calculated and measured glomerular filtration rates in patients treated with PARP inhibitors.

OBJECTIVE: To describe discrepancies in calculated and measured glomerular filtration rate in patients using PARP (poly ADP ribose polymerase) inhibitors who had an elevation in serum creatinine levels. METHODS: Retrospective cohort, single center study. Patients included were those with ovarian or endometrial cancer taking olaparib, rucaparib or niraparib, and in in whom an increased serum creatinine was identified. The study cohort included those who also underwent technetium-99m radioisotope renography (glomerular filtration rate (GFR) scan). The main objective is to describe the discrepancies in calculated glomerular filtration rate using the Cockcroft-Gault method and measured glomerular filtration rate using a GFR scan. RESULTS: 211 patients were included in the study; 64 (30%) had on-treatment elevated serum creatinine, and 23 (36%) underwent a GFR scan. 32 GFR scans were performed (six patients had more than one scan). Using a clinical cut-off ≥50 mL/min as normal renal function, both calculated and estimated glomerular filtration rates were below normal in 6 of 32 GFR scans. In those patients undergoing a GFR scan, serum creatinine had risen a median 49% (IQR 20-66%, range 0-144%) above baseline. Discordance between a calculated low glomerular filtration rate and an estimated normal glomerular filtration rate occurred in 63% (range of glomerular filtration rate discrepancy: -46% to +237%). Despite increases in serum creatinine on therapy and a subsequent significant decline in the per patient calculated creatinine clearance (mean 65.6 mL/min vs 43.4 mL/min; p<0.0001), the estimated glomerular filtration rate from the renal scan was nearly identical to the patient's baseline (65.6 mL/min vs 66.1 mL/min; p=0.89). CONCLUSIONS: Serum creatinine elevation in patients taking PARP inhibitors may not be associated with a true decrease in glomerular filtration rate. A high index of suspicion should be maintained for alternative causes of elevated serum creatinine in patients treated with PARP inhibitors who lack other sources of renal injury.

A practical guide for the safe implementation of early phase drug development and immunotherapy program in gynecologic oncology practice.

The success of targeted and immune therapies in other malignancies has led to an exponential increase in the number of active and pending clinical trials using these therapeutic approaches in patients with gynecologic cancers. These novel investigational agents are associated with unique and potentially life-threatening toxicities and many require special multidisciplinary logistical considerations. The objective of this review is to describe a practical approach for the safe implementation of targeted and immune therapies in academic gynecologic oncology practices based on our experience at M.D. Anderson Cancer Center.

Fighting cancer together: Development and implementation of shared medical appointments to standardize and improve chemotherapy education.

OBJECTIVE: Shared medical appointments offer a novel approach to improve efficiency and quality of care consistent with the goals of the Institute of Medicine. Our objective was to develop and implement a shared medical appointment for gynecologic cancer patients initiating chemotherapy. METHODS: We first assessed the level of interest in shared medical appointments among our patients and providers through qualitative interviews. Both patients and providers identified pre-chemotherapy as an optimal area to pilot shared medical appointments. We subsequently created a multidisciplinary team comprised of physicians, advanced practice providers, nurses, pharmacists, administrators, health education specialists and members of the Quality Improvement Department to establish a Shared Medical Appointment and Readiness Teaching (SMART) program for all gynecologic oncology patients initiating chemotherapy with platinum- and/or taxane-based regimens. We developed a standardized chemotherapy education presentation and provided patients with a tool kit that consisted of chemotherapy drug education, a guide to managing side effects, advance directives, and center contact information. RESULTS: From May 9, 2014 to June 26, 2015, 144 patients participated in 51 SMART visits. The majority of patients had ovarian cancer and were treated with carboplatin/paclitaxel. Surveyed patients reported being highly satisfied with the group visit and would recommend shared medical appointments to other patients. CONCLUSIONS: This model of care provides patient education within a framework of social support that empowers patients. Shared medical appointments for oncology patients initiating chemotherapy are both feasible and well accepted.

Nitrous oxide-antinociception is mediated by opioid receptors and nitric oxide in the periaqueductal gray region of the midbrain.

Previous studies have shown that nitrous oxide (N(2)O)-induced antinociception is sensitive to antagonism by blockade of opioid receptors and also by inhibition of nitric oxide (NO) production. The present study was conducted to determine whether these occur within the same brain site. Mice were stereotaxically implanted with microinjection cannulae in the periaqueductal gray (PAG) area of the midbrain. In saline-pretreated mice, exposure to 70% N(2)O resulted in a concentration-dependent antinociceptive effect in the mouse abdominal constriction test. Pretreatment with an opioid antagonist in the PAG significantly antagonized the antinociceptive effect. Pretreatment with an inhibitor of NO production in the PAG also significantly antagonized the antinociceptive effect. These findings suggest that N(2)O acts in the PAG via an NO-dependent, opioid receptor-mediated mechanism to induce antinociception.

A model to estimate the oestrogen receptor mediated effects from exposure to soy isoflavones in food.

The advantages that regular consumption of a diet containing soy may have on human health have been enshrined in a major health claim that has been approved by the Food and Drug Administration in the USA, regarding potential protection from heart disease by soy. This could have a major influence on the dietary consumption patterns of soy for consumers and lead to the development of soy enriched foods to enable consumers to achieve the benefits thought to be associated with increased soy consumption in a Western diet. If an increase in soy consumption is beneficial to particular disease conditions, there is always the possibility that there will be effects other than those that are desirable. For soy-containing foods there has been concern that the phytoestrogen content of soy, which is composed of several isoflavones, could be a separate health issue, due to the oestrogen-like activity of isoflavones. To address this, a method has been developed to estimate, relative to 17-beta oestradiol, the activity of the common isoflavones present in soy phytoestrogens, based on their binding to and transcriptional activation of the major oestrogen receptor sub-types alpha and beta. Using this approach, the additional oestrogen-like activity that would be expected from inclusion of soy supplemented foodstuffs in a Western diet, can be determined for different sub-populations, who may have different susceptibilities to the potential for the unwanted biological effects occurring with consumption of soy enriched foods. Because of the theoretical nature of this model, and the controversy over the nature of whether some of the oestrogen-like effects of phytoestrogens are adverse, the biological effects of soy isoflavones and their potential for adverse effects in man, is also reviewed. The question that is critical to the long term safe use of foods enriched in soy is, which observed biological effects in animal studies are likely to also occur in man and whether these would have an adverse effect on human health.