Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer: a systematic review and meta-analysis.

Background: The role of platinum-based neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients is highly controversial and it is not endorsed by current guidelines. Our meta-analysis aimed to better elucidate its activity, efficacy and safety. Material and methods: A systematic search of Medline, Web of Science and conferences proceedings up to 30 October 2017 was carried out to identify randomized controlled trials (RCTs) investigating platinum-based versus platinum-free neoadjuvant chemotherapy in TNBC patients. Using the fixed and random effects models, pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CI) were calculated for pathological complete response (pCR, defined as ypT0/is pN0), event-free survival (EFS), overall survival (OS) and grade 3 and 4 adverse events (AEs: neutropenia, anemia, thrombocytopenia and neuropathy). Results: Nine RCTs (N = 2109) were included. Overall, platinum-based neoadjuvant chemotherapy significantly increased pCR rate from 37.0% to 52.1% (OR 1.96, 95% CI 1.46-2.62, P < 0.001). Platinum-based neoadjuvant chemotherapy remained significantly associated with increased pCR rate also after restricting the analysis to the three RCTs (N = 611) that used the same standard regimen in both groups of weekly paclitaxel (with or without carboplatin) followed by anthracycline and cyclophosphamide (OR 2.53, 95% CI 1.37-4.66, P = 0.003). Conversely, among the 96 BRCA-mutated patients included in two RCTs, the addition of carboplatin was not associated with significantly increased pCR rate (OR 1.17, 95% CI 0.51-2.67, P = 0.711). Two RCTs (N = 748) reported survival outcomes: no significant difference in EFS (HR 0.72, 95% CI 0.49-1.06, P = 0.094) and OS (HR 0.86, 95% CI 0.46-1.63, P = 0.651) was observed. A significant higher risk of grade 3 and 4 hematological AEs, with no increased risk of grade 3 and 4 neuropathy was observed with platinum-based neoadjuvant chemotherapy. Conclusion: In TNBC patients, platinum-based neoadjuvant chemotherapy is associated with significantly increased pCR rates at the cost of worse hematological toxicities. Platinum-based neoadjuvant chemotherapy may be considered an option in TNBC patients. PROSPERO registration number: CRD42018080042.

Ovarian suppression using luteinizing hormone-releasing hormone agonists during chemotherapy to preserve ovarian function and fertility of breast cancer patients: a meta-analysis of randomized studies.

BACKGROUND: The role of temporary ovarian suppression with luteinizing hormone-releasing hormone agonists (LHRHa) in the prevention of chemotherapy-induced premature ovarian failure (POF) is still controversial. Our meta-analysis of randomized, controlled trials (RCTs) investigates whether the use of LHRHa during chemotherapy in premenopausal breast cancer patients reduces treatment-related POF rate, increases pregnancy rate, and impacts disease-free survival (DFS). METHODS: A literature search using PubMed, Embase, and the Cochrane Library, and the proceedings of major conferences, was conducted up to 30 April 2015. Odds ratios (ORs) and 95% confidence intervals (CIs) for POF (i.e. POF by study definition, and POF defined as amenorrhea 1 year after chemotherapy completion) and for patients with pregnancy, as well hazard ratios (HRs) and 95% CI for DFS, were calculated for each trial. Pooled analysis was carried out using the fixed- and random-effects models. RESULTS: A total of 12 RCTs were eligible including 1231 breast cancer patients. The use of LHRHa was associated with a significant reduced risk of POF (OR 0.36, 95% CI 0.23-0.57; P < 0.001), yet with significant heterogeneity (I(2) = 47.1%, Pheterogeneity = 0.026). In eight studies reporting amenorrhea rates 1 year after chemotherapy completion, the addition of LHRHa reduced the risk of POF (OR 0.55, 95% CI 0.41-0.73, P < 0.001) without heterogeneity (I(2) = 0.0%, Pheterogeneity = 0.936). In five studies reporting pregnancies, more patients treated with LHRHa achieved pregnancy (33 versus 19 women; OR 1.83, 95% CI 1.02-3.28, P = 0.041; I(2) = 0.0%, Pheterogeneity = 0.629). In three studies reporting DFS, no difference was observed (HR 1.00, 95% CI 0.49-2.04, P = 0.939; I(2) = 68.0%, Pheterogeneity = 0.044). CONCLUSION: Temporary ovarian suppression with LHRHa in young breast cancer patients is associated with a reduced risk of chemotherapy-induced POF and seems to increase the pregnancy rate, without an apparent negative consequence on prognosis.

Eribulin in combination with bevacizumab as second-line treatment for HER2-negative metastatic breast cancer progressing after first-line therapy with paclitaxel and bevacizumab: a multicenter, phase II, single arm trial (GIM11-BERGI).

BACKGROUND: We evaluated the efficacy and safety of the nontaxane microtubule dynamics inhibitor eribulin plus the humanized anti-VEGF monoclonal antibody bevacizumab in a novel second-line chemotherapy scheme in HER2-negative metastatic breast cancer (MBC) patients progressing after first-line paclitaxel and bevacizumab. PATIENTS AND METHODS: This is a multicenter, single-arm, Simon's two-stage, phase II study. The primary endpoint was the overall response rate, considered as the sum of partial and complete response based on the best overall response rate (BORR). The secondary endpoints were progression-free survival (PFS), overall survival (OS), and clinical benefit rate. RESULTS: A total of 58 of the 61 patients enrolled in the study were evaluable for efficacy. The BORR was 24.6% (95% CI 14.5-37.3). The clinical benefit rate was 32.8% (95% CI 21.3-46.0). The median PFS was 6.2 months (95% CI 4.0-7.8), and median OS was 14.8 months (95% CI 12.6-22.8). Overall, adverse events (AEs) were clinically manageable and the most common AEs were fatigue, paresthesia, and neutropenia. Quality of life was well preserved in most patients. CONCLUSIONS: The results of this study suggest that second-line therapy with bevacizumab in combination with eribulin has a meaningful clinical activity and may represent a potential therapeutic option for patients with HER2-negative MBC.

Concurrent versus sequential adjuvant chemo-endocrine therapy in hormone-receptor positive early stage breast cancer patients: a systematic review and meta-analysis.

BACKGROUND: Although in clinical practice adjuvant chemotherapy (CT) and endocrine therapy (ET) are administered sequentially in patients with hormone-receptor positive breast cancer, the optimal timing, i.e. concurrent or sequential administration, of these treatments has been scarcely investigated. To better clarify this issue we conducted a systematic review and meta-analysis of randomized studies comparing these two modalities of administrations in terms of disease-free survival (DFS) and overall survival (OS). METHODS: Relevant studies were identified by searching PubMed, Web of Knowledge and the proceedings of the major conferences with no date restriction up to March 2016. The summary risk estimates (pooled hazard ratio [HR] and 95% confidence intervals [CI]) for DFS and OS were calculated using random effect models (DerSimonian and Laird method). RESULTS: A total of three randomized studies were eligible including 2021 breast cancer patients. Overall, 755 DFS events were observed, 365 in the sequential arm and 390 in the concomitant arm, with a pooled HR of 0.95 (95% CI = 0.76 to 1.18, P = 0.643). No association between timing of treatment and OS was observed (HR = 0.95; 95% CI = 0.80 to 1.12, P = 0.529). CONCLUSION: Our pooled analysis showed no association between the timing of administration of adjuvant CT and ET and DFS and OS in breast cancer patients candidates for both adjuvant treatments. Because of the small number of published trials, the lack of data on the timing with modern adjuvant treatments, i.e. taxane-containing CT and aromatase inhibitors, this topic remain still controversial and requires further studies to be clarified.

Acid-base balance and respiratory response during biofiltration with polyacrylonitrile membrane.

To further elucidate the mechanisms responsible for the hypoxemia we studied ventilation, pulmonary gas exchanges, blood gas pressures and exchanges of CO2-T, CO2-D and HCO-3 in six patients during AD and BD on 1 m2 cuprophan filter and during BF on 1.2 m2 polyacrylonitrile filter. Blood passing through the dialyzer lost 172.8 mM/h of CO2-T in AD, 149.2 mM/h in BF and gained 25.6 mM/h in BD. In AD VE, VA and PaO2 decreased significantly after 30 and 60 min., in BF for the whole duration of dialysis. PoO2 showed a significant decrease both in AD and BF after 60 min. In AD PaCO2 was significantly reduced after 120 and 180 min. All the above parameters remained unchanged in BD. VCO2 remained unchanged in all. VCO2 and R decreased both in AD and BF. However, when VCO2 was corrected for CO2 loss across the dialyzer, overall CO2 loss (ventilated plus filtered) and R returned to basal values. In AD, HCO-3 and pH fell in the first 120 min., while in BD and BF they increased from the beginning of dialysis. In AD hypoventilation, hypoxemia and inadequate correction of acid-base balance were due to the loss of HCO-3 across the filter. In BF also hypoventilation and hypoxemia were due to the loss of HCO-3 across the filter but the acid-base balance was adequately corrected by HCO-3 reinfusion. In BD, there was HCO-3 gain across the filter which induced a gradual correction of acid-base balance without impairment of ventilation.

Physician recruitment: the role of the hospital information system.

Hospital information systems can support physician recruitment activities by helping identify the type of physician the institution needs, describe the type of medical practice a physician can expect, support the institution's strategic plan for the future, and demonstrate the institution's ability to assist a physician with his or her office billing and other administrative functions.

Will sophisticated MIS lead to increased legislation of medicine?

If the healthcare industry automates clinical practices and links them along critical care pathways, will it be providing Federal regulators with data they may use to legislate how hospital care should be delivered? This article examines the implications of expanded use of increasingly sophisticated information systems in health care.

Agile and cost-conscious, HMDS (Health Micro Data Systems) uses new technologies to succeed. Interview by Bill W. Childs.

Health Micro Data Systems (HMDS), headed by Frank Poggio, president, is headquartered in Madison WI, with more than 40 employees in the home office in Madison and the sales and support office in San Francisco. The firm generates approximately $2.6 million a year strictly with microcomputer based systems for healthcare facilities. Recently, HC&C Editor/Publisher Bill W. Childs had the opportunity to speak with Poggio about HMDS, the firm's role in the industry and some challenges for the present and the future.

Little packages with big power. A micro-network to meet nursing information needs.

Installation and use of microcomputer LANs is on the rise in health care facilities. The microprocessor is becoming more powerful each day. The microcomputer is quite adept at handling textual and graphic information, which is a major requirement of any nursing patient information system. Microcomputer technology has now advanced to a level where a handful of hospitals have installed, and many hospitals actively plan to install, a complete nursing system based entirely upon a network of microcomputers. This paper discusses components of an order entry/results reporting/care management system based on a distributed, micro network architecture; the benefits of such a design; and the future technology to aid in system use and growth.

Efficacy and safety of long-term treatment with calcium carbonate as a phosphate binder.

The efficacy and safety of calcium carbonate as a phosphate binder was evaluated in 20 patients on chronic hemodialysis who had previously received aluminum hydroxide. During the control period the patients were on aluminum hydroxide and calcitriol therapy and had plasma phosphorus levels less than 6 mg/dL (4.95 +/- 0.8 mg/dL). Aluminum hydroxide was then discontinued and no phosphate binder was prescribed for 1 month. Every patient developed hyperphosphatemia so that calcium carbonate treatment was begun and calcitriol dose was adjusted in relation to plasma calcium changes. After 24 months of calcium carbonate therapy, plasma phosphorus was 4.85 +/- 0.7 mg/dL, using a daily dose of calcium carbonate of 2.57 +/- 1.3 g (range, 1 to 6 g). The daily dose per patient of calcitriol was not different from that prescribed during the control period, but in five patients calcitriol was permanently withdrawn for hypercalcemia. At the end of the study plasma calcium, magnesium, bicarbonate, alkaline phosphatase, and parathyroid hormone values were unchanged in comparison with the control period, whereas a significant reduction in plasma aluminum and plasma aluminum increase induced by deferoxamine infusion was observed. The frequency of hypercalcemic and hyperphosphatemic episodes during the last 12 months of calcium carbonate therapy (6.2% and 16.6%, respectively) was not different from that observed during the 12 months on aluminum hydroxide therapy preceding the control period (4.5% and 14.7%, respectively). It was concluded that calcium carbonate is effective in the control of hyperphosphatemia and secondary hyperparathyroidism in patients on chronic hemodialysis and that the incidence of hypercalcemia is low when the daily dosage is less than 6 g.

Recombinant human erythropoietin reduces free erythrocyte protoporphyrin levels in patients on chronic dialysis.

We studied the significance of free erythrocyte protoporphyrin (FEP) in relation to iron status, aluminum levels and anemia in uremic patients on chronic dialysis. All but 1 patient showed high FEP values closely related to the degree of anemia. Increased FEP levels are due to a defective heme synthesis, not related to iron deficiency or aluminum overload. Treatment of anemia with recombinant human erythropoietin reduced FEP values. We therefore hypothesize that recombinant human erythropoietin ameliorates an enzymatic defect in heme synthesis.

[Respiratory response and acid-base equilibrium in acetate dialysis and bicarbonate dialysis]. / Réponse respiratoire et équilibre acido-basique au cours de la dialyse à l'acétate et au cours de la dialyse au bicarbonate.

In order to elucidate the mechanisms responsible for the hypoxemia observed during acetate dialysis, but not found during bicarbonate dialysis, the authors studied ventilation, blood gases and their exchanges in the lungs and across the dialyzer on 9 patients. Oxygen consumption was similar both in acetate and bicarbonate dialysis. At the beginning of acetate dialysis, hypocapnia, due to CO2 losses through the dialyzer, causes hypoventilation and hypoxemia; afterwards, the worsening of acidosis (due to bicarbonate losses) stimulates ventilation, thus correcting the initial imbalance. Authors also hypothesize a pulmonary mechanism for CO2 "sparing" contributing to compensate CO2 losses through the dialyzer. The absence of hypoxemia during bicarbonate dialysis would be due to the absence of CO2 losses through the dialyzer.