Prognostic factors for survival in patients with advanced oesophageal cancer treated with cisplatin-based combination chemotherapy

The objective of this study was to identify prognostic factors for survival in patients with advanced oesophageal cancer, who are treated with cisplatin-based combination chemotherapy. We analysed the baseline characteristics of 350 patients who were treated in six consecutive prospective trials with one of the following regimens: cisplatin/etoposide, cisplatin/etoposide/5-fluorouracil, cisplatin/paclitaxel (weekly) and cisplatin/paclitaxel (biweekly). Predictive factors in univariate analyses were further evaluated using multivariate analysis (Cox regression). The median survival of all patients was 9 months. The 1, 2 and 5-year survival rates were 33, 12 and 4%, respectively. The main prognostic factors were found to be WHO performance status (0 or 1 vs 2), lactate dehydrogenase (normal vs elevated), extent of disease (limited disease defined as locoregional irresectable disease or lymph node metastases confined to either the supraclavicular or celiac region vs extensively disseminated disease) in addition to the type of treatment (weekly or biweekly cisplatin/paclitaxel regimen vs 4-weekly cisplatin/etoposide with or without 5-fluorouracil). Although weight loss, liver metastases and alkaline phosphatase were significant prognostic factors in univariate analyses, these factors lost their significance in multivariate analyses. The median survival for patients without any risk factors was 12 months, compared to only 4 months in patients with WHO 2 plus elevated LDH and extensive disease. The performance status, extent of disease, LDH and the addition of paclitaxel to cisplatin are independent prognostic factors in patients with advanced oesophageal cancer, who are treated with cisplatin-based combination chemotherapy

Real-world Outcomes of Sequential Androgen-receptor Targeting Therapies with or Without Interposed Life-prolonging Drugs in Metastatic Castration-resistant Prostate Cancer:Results from the Dutch Castration-resistant Prostate Cancer Registry

BACKGROUND: Cross resistance between androgen-receptor targeting therapies (ARTs) (abiraterone acetate plus prednisone [ABI+P] or enzalutamide [ENZ]) for treatment of metastatic castration-resistant prostate cancer (mCRPC) may affect responses to second ART (ART2). OBJECTIVE: To establish treatment duration and prostate-specific antigen (PSA) response of ART2 in real-world mCRPC patients treated with or without other life-prolonging drugs (LPDs; ie, docetaxel, cabazitaxel, or radium-223) between ART1 and ART2. DESIGN, SETTING, AND PARTICIPANTS: Castration-resistant prostate cancer patients, diagnosed between 2010 and 2016 were retrospectively registered in Castration-resistant Prostate Cancer Registry (CAPRI). Patients treated with both ARTs were clustered into two subgroups: ART1>ART2 or ART1>LPD>ART2. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes were ≥50% PSA response and treatment duration of ART2. Descriptive statistics and binary logistic regression after multiple imputations were performed. RESULTS AND LIMITATIONS: A total of 273 patients were included with a median follow-up of 8.4 mo from ART2. Patients with ART1>ART2 were older and had favourable prognostic characteristics at ART2 baseline compared with patients with ART1>LPD>ART2. No differences between ART1>ART2 and ART1>LPD>ART2 were found in PSA response and treatment duration. Multivariate analysis suggested that PSA response of ART2 was less likely in patients with visceral metastases (odds ratio [OR] 0.143, p=0.04) and more likely in patients with a relatively longer duration of androgen-deprivation treatment (OR 1.028, p=0.01) and with ABI + P before ENZ (OR 3.192, p=0.02). A major limitation of this study was missing data, a common problem in retrospective observational research. CONCLUSIONS: The effect of ART2 seems to be low, with a low PSA response rate and a short treatment duration irrespective of interposed chemotherapy or radium-223, especially in patients with short time on castration, visceral disease, and ENZ before ABI+P. PATIENT SUMMARY: We observed no differences in outcomes of patients treated with sequential abiraterone acetate plus prednisone (ABI+P) and enzalutamide (ENZ) with or without interposed chemotherapy or radium-223. In general, outcomes were lower than those in randomised trials, questioning the additional effect of second treatment with ABI+P or ENZ in daily practice

Аксіологічні виміри душпастирства у творах Іоана Золотоустого

Стаття Світлани Білоус "Аксіологічні виміри душпастирства у творах Іоана Золотоустого" присвячена пошуку джерел духовної опіки над людиною, витоки яких автор бачить у християнському середньовіччі. Життя і творча спадщина Іоана Золотоустого – яскравий приклад пояснення сутності й визначення ціннісної природи душпастирювання крізь призму поняття священства.Статья Светланы Билоус "Аксиологические измерения душпастирства в произведениях Іоана Золотоустого" посвящена поиску источников духовной опеки над человеком, истоки которіх автор видит в христианском средневековье. Жизнь и творческое наследство Иоанна Золотоустого – яркий пример объяснения сущности и определение ценностной природы душпастирства сквозь призму понятия священства.The article by Svitlana Bilous "Axiological dimensions of priesthood in the Ioan Zolotoustyi’s works" is dedicated to finding sources of spiritual care over a human, the origin of which the author sees in the Christian Middle Ages. The life and literary heredity of Ioan Zolotoustyi is a brilliant pattern of explaining the essence and definition of valuable ​​nature of pastoral care through the prism of the concept of the priesthood

Real-world Data of Nivolumab for Patients With Advanced Renal Cell Carcinoma in the Netherlands:An Analysis of Toxicity, Efficacy, and Predictive Markers

Background: Nivolumab, a programmed death 1 inhibitor, has been approved as second-line treatment for advanced renal cell carcinoma (RCC) in Europe since 2016. We investigated the toxicity and efficacy of nivolumab as well as potential predictive biomarkers in the Dutch population. Patients and Methods: This was a retrospective, multicenter study of the Dutch national registry of nivolumab for the treatment of advanced RCC. The main outcome parameters included toxicity, objective response rate (ORR), overall survival (OS), progression-free survival (PFS), time to progression (TTP), and time to treatment failure (TTF). In addition, potential predictive and prognostic biomarkers for outcomes were evaluated. Results: Data on 264 patients were available, of whom 42% were International Metastatic RCC Database Consortium (IMDC) poor risk at start of nivolumab, 16% had ≥ 3 lines of previous therapy, 7% had non–clear-cell RCC, 11% had brain metastases, and 20% were previously treated with everolimus. Grade 3/4 immune-related adverse events occurred in 15% of patients. The median OS was 18.7 months (95% confidence interval, 13.7-23.7 months). Progression occurred in 170 (64.4%) of 264 patients, with a 6-and 12-months TTP of 49.8% and 31.1%, respectively. The ORR was 18.6% (49 of 264; 95% confidence interval, 14%-23%). Elevated baseline lymphocytes were associated with improved PFS (P =.038) and elevated baseline lactate dehydrogenase with poor OS, PFS, and TTF (P =.000). On-treatment increase in eosinophils by week 8 predicted improved OS (P =.003), PFS (P =.000), and TTF (P =.014), whereas a decrease of neutrophils was associated with significantly better TTF (P =.023). Conclusions: The toxicity and efficacy of nivolumab for metastatic RCC after previous lines of therapy are comparable with the results in the pivotal phase III trial and other real-world data. On-treatment increase in eosinophil count is a potential biomarker for efficacy and warrants further investigation

Phase II study of bi-weekly administration of paclitaxel and cisplatin in patients with advanced oesophageal cancer

In a phase I study we demonstrated the feasibility of a bi-weekly combination of paclitaxel 180 mg m−2 with cisplatin 60 mg m−2. In this study we further assessed toxicity and efficacy of this schedule in the treatment of advanced cancer of the oesophagus or the gastro-oesophageal junction. Patients received paclitaxel 180 mg m−2 administered over 3 h followed by a 3-h infusion of cisplatin 60 mg m−2. Patients were retreated every 2 weeks unless granulocytes were <0.75×109 or platelets <75×109. Patients were evaluated after three and six cycles and responding patients received a maximum of eight cycles. Fifty-one patients were enrolled into the study. The median age was 56 years (range 32–78). WHO performance status were: 0 (19 patients); 1 (29 patients); 2 (three patients). All patients received at least three cycles of chemotherapy and all were evaluable for toxicity and response. Haematological toxicity consisted of uncomplicated neutropenia grade 3 in 39% and grade 4 in 31% of patients. Five patients (10%) were hospitalised, three patients because of treatment related complications and two patients because of infections without neutropenia. Sensory neurotoxicity was the predominant non-haematological toxicity; grade 1 and 2 neurotoxicity was observed in 43 and 20% of patients, respectively. Response evaluation in 51 patients with measurable disease: complete response 4%, partial response 39%, stable disease 43% and progressive disease in 14% of the patients. The median duration of response was 8 months. The median survival for all patients was 9 (range 2–29+) months and the one-year survival rate was 43%. Four patients who received additional local treatment (two patients surgery and two patients radiotherapy) are still disease free after a follow-up of 20–29 months. This bi-weekly treatment of paclitaxel and cisplatin is well tolerated by patients with advanced oesophageal cancer. The toxicity profile of this regimen compares favourable to that of previously used cisplatin- and paclitaxel-based regimens. Trials are underway evaluating this bi-weekly regimen in a neo-adjuvant setting

First-line treatment with oxaliplatin and capecitabine in patients with advanced or metastatic oesophageal cancer: a phase II study

This phase II study assessed the safety and efficacy of oxaliplatin and capecitabine in patients with advanced oesophageal cancer. Fifty-one eligible patients received oxaliplatin 130 mg m−2 intravenously on day 1 and capecitabine 1000 mg m−2 orally twice daily on days 1 to 14 in a 21-day treatment cycle as first-line treatment for advanced oesophageal cancer. Grade 3 neutropenia was seen in one patient and anaemia in another patient. No grade 4 haematological toxicities were observed. Grade 4 non-haematological toxicity (lethargy) occurred in one patient (2%). Grade 3 non-haematological toxicity was seen in 14 (27%) patients (vomiting and polyneuropathy (8%); nausea (6%); lethargy and hand–foot syndrome (4%); and anorexia, diarrhoea, and hyperbilirubinaemia (each in one patient)). In 22% of the patients, toxicity was the reason for stopping the treatment. The overall response rate was 39%. The median overall survival was 8 months; the 1-year survival rate was 26%. In the quality of life (QoL) analysis, the emotional well-being improved during treatment, but the physical functioning scores declined. The fatigue score on the symptom scales increased. Overall, the global QoL score did not change during treatment. In conclusion, the activity of oxaliplatin and capecitabine is comparable with other chemotherapy regimens in advanced oesophageal cancer with a low frequency of grade 3/4 toxicity. Because this treatment can be given on an outpatient basis, it is probably less toxic than cisplatin-based therapy and preserves QoL during treatment, it is a viable treatment option in patients with advanced oesophageal cancer

Phase II study of weekly paclitaxel and capecitabine in patients with metastatic or recurrent esophageal squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>This phase II study assessed the response rate and toxicity profile of weekly paclitaxel and capecitabine in patients with metastatic or recurrent squamous cell carcinoma of the esophagus (SCCE)</p> <p>Methods</p> <p>Patients with histologically confirmed SCCE were treated with paclitaxel 80 mg/m²intravenously on days 1 and 8 plus capecitabine 900 mg/m²orally twice a day on days 1-14. Treatment cycles were repeated every 3 weeks until disease progression or unacceptable toxicity.</p> <p>Results</p> <p>Between 2006 and 2009, 32 patients were enrolled. Twelve patients were chemotherapy-naïve. Twenty patients had received prior chemotherapy including platinum-based regimens. Patients received a median of 5 cycles of treatment (range, 1-12). The response rate was 75% (95%CI; 50.5~99.5%) in the first-line and 45% (95%CI; 26.9~73.1%) in the second-line. With a median follow-up of 20.7 months, median progression-free survival was 5.2 months (95% CI, 4.0 to 6.4) for all patients and median overall survival (OS) was 11.7 months (95% CI, 5.5 to 18.0) for all patients. The median OS was 14.3 months (95% CI, 10.6 to 18.0) for patients receiving therapy as 1^stline and 8.4 months (95% CI, 6.6 to 10.1) for those receiving as 2^nd-line therapy. Grade 3/4 neutropenia was observed in 53.3% of the patients, which was the most common cause of dose reduction. G3 non-hematologic toxicity included stomatitis (9.4%), asthenia (6.3%), and hand-foot skin reaction (3.1%).</p> <p>Conclusions</p> <p>Weekly paclitaxel and capecitabine is a highly active and well-tolerated regimen in patients with metastatic or recurrent SCCE in the first-line as well as second-line setting.</p

Radiofrequency ablation and chemotherapy versus chemotherapy alone for locally advanced pancreatic cancer (PELICAN):study protocol for a randomized controlled trial

Contains fulltext : 239066.pdf (Publisher’s version ) (Open Access)BACKGROUND: Approximately 80% of patients with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy, of whom approximately 10% undergo a resection. Cohort studies investigating local tumor ablation with radiofrequency ablation (RFA) have reported a promising overall survival of 26-34 months when given in a multimodal setting. However, randomized controlled trials (RCTs) investigating the effect of RFA in combination with chemotherapy in patients with LAPC are lacking. METHODS: The "Pancreatic Locally Advanced Unresectable Cancer Ablation" (PELICAN) trial is an international multicenter superiority RCT, initiated by the Dutch Pancreatic Cancer Group (DPCG). All patients with LAPC according to DPCG criteria, who start with FOLFIRINOX or (nab-paclitaxel/)gemcitabine, are screened for eligibility. Restaging is performed after completion of four cycles of FOLFIRINOX or two cycles of (nab-paclitaxel/)gemcitabine (i.e., 2 months of treatment), and the results are assessed within a nationwide online expert panel. Eligible patients with RECIST stable disease or objective response, in whom resection is not feasible, are randomized to RFA followed by chemotherapy or chemotherapy alone. In total, 228 patients will be included in 16 centers in The Netherlands and four other European centers. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, RECIST response, CA 19.9 and CEA response, toxicity, quality of life, pain, costs, and immunomodulatory effects of RFA. DISCUSSION: The PELICAN RCT aims to assess whether the combination of chemotherapy and RFA improves the overall survival when compared to chemotherapy alone, in patients with LAPC with no progression of disease following 2 months of systemic treatment. TRIAL REGISTRATION: Dutch Trial Registry NL4997 . Registered on December 29, 2015. ClinicalTrials.gov NCT03690323 . Retrospectively registered on October 1, 2018

Validation of a new prognostic index score for disseminated nasopharyngeal carcinoma

Patients with metastatic nasopharyngeal carcinoma have variable survival outcomes. We previously designed a scoring system to better prognosticate these patients. Here, we report results on validation of this new prognostic index score in a separate cohort of patients. Clinical features and laboratory parameters were examined in 172 patients with univariate and multivariate analyses and a numerical score was derived for each independent prognostic variable. Significant independent prognostic variables and their scores assigned included poor performance status (score 5), haemoglobin <12 g dl−1 (score 4) and disease-free interval (DFI) (DFI⩽6 months (score 10) or metastases at initial diagnosis (score 1)). Maximum score was 19 and patients stratified into three prognostic groups: good, 0–3; intermediate, 4–8; poor, ⩾9. When applied to a separate cohort of 120 patients, 59 patients were good, 43 intermediate and 18 poor prognosis, with median survivals of 19.6 (95% CI 16.1, 23.1), 14.3 (95% CI 12.3, 16.2) and 7.9 (95% CI 6.6, 9.2) months, respectively. (logrank test: P=0.003). We have validated a new prognostic score with factors readily available in the clinics. This simple score will prove useful as a method to prognosticate and stratify patients as well as to promote consistent reporting among clinical trials

Continuous ambulatory peritoneal dialysis: pharmacokinetics and clinical outcome of paclitaxel and carboplatin treatment

Purpose: Administration of chemotherapy in patients with renal failure, treated with hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) is still a challenge and literature data is scarce. Here we present a case study of a patient on CAPD, treated with weekly and three-weekly paclitaxel/ carboplatin for recurrent ovarian cancer. Experimental: During the first, second and ninth cycle of treatment, blood, urine and CAPD samples were collected for pharmacokinetic analysis of paclitaxel and total and unbound carboplatin-derived platinum. Results: Treatment was well tolerated by the patient. No excessive toxicity was observed and at the e