Showing papers by "Cezary Szczylik published in 2011"

Sunitinib in metastatic renal cell carcinoma patients with brain metastases

Abstract: BACKGROUND: In a broad patient population with metastatic renal cell carcinoma (RCC), enrolled in an open-label, expanded access program (EAP), the safety profile of sunitinib was manageable, and efficacy results were encouraging. Here, the authors report results for patients with baseline brain metastases participating in this global EAP. METHODS: Previously treated and treatment-naive metastatic RCC patients >= 18 years received sunitinib 50 mg orally, once daily, on Schedule 4/2. Safety was assessed regularly, tumor measurements done per local practice, and survival data collected where possible. Analyses were done in the modified intention-to-treat (ITT) population, consisting of all patients who received >= 1 dose of sunitinib. RESULTS: As of December 2007, 4564 patients had enrolled in 52 countries. Of these enrollees, 4371 were included in the modified ITT population, of whom 321 (7%) had baseline brain metastases and had received a median of 3 treatment cycles (range 1-25). Reasons for their discontinuation included lack of efficacy (32%) and adverse events (8%). The most common grade 3-4 treatment-related adverse events were fatigue and asthenia (both 7%), thrombocytopenia (6%), and neutropenia (5%), the incidence of which were comparable to that for the overall EAP population. Of 213 evaluable patients, 26 (12%) had an objective response. Median progression-free survival and overall survival were 5.6 months (95% CI, 5.2-6.1) and 9.2 months (95% CI, 7.8-10.9), respectively. CONCLUSIONS: In patients with brain metastases from RCC, the safety profile of sunitinib was comparable to that in the general metastatic RCC population, and sunitinib showed evidence of antitumor activity. Cancer 2011;117:501-9. (C) 2010 American Cancer Society.

Prognostic significance of Wnt-1, β-catenin and E-cadherin expression in advanced colorectal carcinoma.

Abstract: Wnt/β-catenin pathway plays an important role in initiation and progression of colorectal oncogenesis. The aim of this study was to determine expression and localization of E-cadherin, β-catenin and Wnt-1 proteins in colorectal tumors. Expression of β-catenin, E-cadherin and Wnt-1 was determined by immunohistochemistry on advanced colorectal cancers. Abnormal expression of E-cadherin, β-catenin, Wnt-1 was observed. Additionally, we revealed correlations between levels of studied proteins and histoclinical data. In multivariate analysis nuclear β-catenin, higher carcinoembryonic antigen serum level before treatment, female sex and tumor localized in colon or rectum were independent unfavorable prognostic factors. These findings support the hypothesis that Wnt/β-catenin pathway plays an important role in advanced colorectal carcinoma.

The role of Tau protein in resistance to paclitaxel

Abstract: Resistance to taxanes, related to limited efficacy of systemic therapy in cancer patients, is multifactorial. Among mechanisms of resistance to taxanes, those related to microtubule-associated proteins (MAP), including protein Tau, are of great importance. Protein Tau (50–64 kD) binds to beta-tubulin in the same place as paclitaxel. In preclinical studies, low expression of Tau in cancer cells was associated with increased sensitivity to paclitaxel. High expression of Tau protein in ER-positive breast cancers indicates resistance to taxane-containing chemotherapy and sensitivity to hormonal treatment. This article reviews current knowledge on predictive value of protein Tau in response to taxanes. Better understanding of its role may facilitate patients selection to this sort of treatment and lead to treatment optimization.

Efficiency of Supersaturated Calcium Phosphate Mouth Rinse Treatment in Patients Receiving High-Dose Melphalan or BEAM Prior to Autologous Blood Stem Cell Transplantation: A Single-Center Experience

Abstract: Objective Oral mucositis (OM) is an unresolved problem among patients treated with a high-dose therapy supported by hematopoietic stem cell transplantation (HSCT). We tested the ability of supersaturated calcium phosphate mouth rinse (Caphosol) to ameliorate oral mucosal injury induced by a conditioning regimen. Patients and methods Thirty-two patients with hematologic malignancies were treated with Caphosol to prevent OM during HSCT procedures. The conditioning regimens for 16 patients were BGNU 300 mg/m2, day 6; ARA-C 200 mg/m2 daily, days 5, 4, 3, 2; VP-16 200 mg/m2 daily, days 5, 4, 3, 2; L-PAM 140 mg/m2, day 1 (BEAM) and for 16 patients, MEL 200 (non-Hodgkin's lymphoma). A control group was composed of 24 consecutive patients, who had been treated with HSCT before Caphosol was available. The source of the graft was autologous peripheral blood. Results Among patients treated with Caphosol no one had to receive total parenteral nutrition. Among the BEAM group no one experienced III to IV degree OM compared with 40% of the control group. The median OM duration was 2.25 days versus controls of 8.6, (P Conclusion Caphosol may reduce the incidence, severity, and duration of oral mucositis and decrease the number of days with painkillers among patients treated with a BEAM but not a Mel 200 regimen.

A new patient-focused approach to the treatment of metastatic renal cell carcinoma: establishing customized treatment options

Abstract: What's known on the subject? and What does the study add? • Six targeted agents--sorafenib, sunitinib, pazopanib, bevacizumab, temsirolimus and everolimus--have been approved for the treatment of advanced renal cell carcinoma (RCC) based on evidence from large randomized controlled trials (RCTs). However, no head-to-head trials have been conducted to evaluate the relative efficacy of these agents in this setting. • Patient populations included in clinical trials do not accurately reflect the wider population of patients with RCC, as certain subgroups, such as the elderly or those with co-morbidities, are typically under-represented. • The optimum choice of therapy should be based on patient characteristics, nature of disease, and history and aims of therapy; however, there is currently no clear guidance for physicians in this decision-making process. • A patient-focussed schema has been developed that acknowledges nine different patient-, disease-, and treatment-related factors relevant to clinical decision-making, and provides a visual indication of the strength of evidence with which a particular agent can be recommended for use in specific subgroups. • To demonstrate the applicability of this tool, a review of all available evidence (published articles, congress presentations and personal communications) for sorafenib in RCC was conducted by a panel of experts, findings from which showed that sorafenib can be recommended for use in various subgroups of differing age, prognosis, performance status, tumour burden and distribution, treatment history and co-morbidity. • This patient-focussed approach has broad application and can be used to assess other agents and tumour types. Randomized controlled trials (RCTs) show that six targeted agents--sorafenib, sunitinib, temsirolimus, everolimus, bevacizumab and pazopanib--improve outcome in advanced renal cell carcinoma (RCC). The populations enrolled in the pivotal phase III studies differed, and, to date, no head-to-head comparisons allow us to judge relative efficacy and tolerability. Populations recruited to RCTs under-represent certain patient subtypes, notably the elderly and those with comorbidities. Choosing the agent most appropriate in a specific case requires that we take into account the characteristics of the patient, the nature of their disease, and the history and aims of therapy. Data from expanded access programmes and clinical experience may be as relevant as the results of RCTs when making this difficult decision. To show how different sources of data can be integrated, we propose a schema that acknowledges nine patient-, disease-, and treatment-related factors relevant to clinical decision-making and provides an easily understood visual indication of the strength with which a particular agent can be recommended for use in specific subgroups of patients. As an example, we show how this tool shows the suitability of sorafenib in RCC subpopulations of differing age, prognosis, performance status, tumour burden and distribution, treatment history, and comorbidity. This patient-focused approach has broad application to other agents and tumour types.

Metastatic colorectal cancer in the elderly: An overview of the systemic treatment modalities (Review)

Abstract: Colorectal cancer (CRC) is one of the most frequently occurring types of cancer. Worldwide, more than 800,000 new cases of CRC are diagnosed each year. The median ages at CRC diagnosis and death are 71 and 75 years, respectively. The majority ot patients (50–60%) with colorectal cancer are diagnosed at stage IV disease. Patients aged 65 or older are characterized by a higher incidence of significant co-morbidities, decreased regenerative capacity of bone marrow and worse general performance. Anti-neoplastic therapies used for the treatment of colorectal cancer include irinotecan, oxaliplatin, 5-fluorouracil, leucovorin, capecitabine and monoclonal antibodies. Analysis of the efficacy of the presented chemotherapeutic and chemoimmunotherapeutic regimens in the treatment of metastatic CRC in patients older than 65 and 70 years compared to ‘younger’ patients, generally demonstrated comparable efficacy, time to disease progression and overall survival. Age criterion should not be considered when assessing the eligibility of patients with metastatic CRC for treatment of the above-mentioned chemotherapeutic and chemoimmunotherapeutic regimens. Treatment should be individualized based on the potential risks and benefits anticipated for each patient.

Optimal chemotherapy treatment for patients with advanced colorectal cancer

Abstract: most common malignancies in the world. Each year one million new cases are diagnosed and about 500 000 people die of this disease. Due to the development of research in clinical oncology, many new antineoplastic agents are registered and available in the treatment of CRC, for example irinotecan, oxaliplatin, 5-fluorouracil, capecitabine, and the monoclonal antibodies bevacizumab, panitumumab and cetuximab. Introduction of molecularly targeted therapies caused prolongation of median time to progression of the disease as well as median overall survival. The best sequence of the therapeutic options for the achievement of the patients’ benefits and good tolerance of the treatment has not been established. This article contains a review of randomized phase II/III studies and registration trials regarding systemic treatment of CRC. The authors have attempted to translate the results of the studies into treatment optimization.

Serum TRAIL levels in patients with epithelial ovarian cancer or primary peritoneal cancer treated with neoadjuvant chemotherapy. A pilot study.

Abstract: AIMS The study attempted to evaluate the kinetics of changes in serum TRAIL levels as a potential predictive and prognostic factor in patients with epithelial ovarian cancer (EOC) or primary peritoneal carcinoma (PPC), eligible for an interval debulking surgery (IDS). MATERIAL AND METHODS 17 patients with primary inoperable EOC or PPC in FIGO Stage IIIC or IV who underwent an exploratory operation were enrolled to the study. Serum TRAIL levels were determined by ELISA method (DIACLONE, Besancon Cedex, France) before and after two courses of neoadjuvant chemotherapy (NAC) based on paclitaxel and platinum analogue (cisplatin or carboplatin). The control group consisted of six healthy volunteers. The median difference in concentration of TRAIL (dTRAIL) between the initial marking and after two courses of NAC in each patient was 192 pg/ml and it was used for dichotomization of the test group. RESULTS Suboptimal interval debulking surgery (IDS) was performed in 23.5% (4/17) and optimal IDS in 76.5% (13/17) patients. TRAIL concentration before chemotherapy did not differ significantly between patients with EOC or PPC [1426.96 +/- 321.06 pg/ml (mean +/- SD) (U = 26, p = 0.08)] and the control group [1160.40 +/- 256.39 pg/ml (mean +/- SD. After two courses of NAC serum TRAIL concentration level was 1247.49 +/- 378.46 pg/ml (mean +/- SD). The difference was significant (Z = 2.44, p = 0.0147). Statistical analysis showed that dTRAIL did not significantly influence either extent of IDS (U = 35, p = 0.0962) or time to progression (log-rank test, p = 0.1185), overall survival (log-rank test, p = 0.1973) and response to treatment according to RECIST criteria (U = 35.5, p = 0.9616). CONCLUSIONS Serum TRAIL concentration levels changed significantly during NAC. However, it seems that the concentration of this protein has no critical value as a predictive or prognostic factor in patients with EOC or PPC.

Inhibition of molecular signaling of epidermal growth factor receptor (EGFR) and its clinical potential for treating renal cell cancer

Abstract: Rak nerki stanowi okolo 3% wszystkich rozpoznawanych nowotworow zlośliwych. W okresie ostatnich 10 lat stale obserwuje sie postep w zakresie leczenia zaawansowanego i przerzutowego raka nerki. Nowe formy terapii pojawily sie w wyniku prowadzonych prac z zakresu poznania patofizjologii raka nerki na poziomie molekularnym. Wśrod potencjalnych celow molekularnych, ktore mogą miec znacznie kliniczne w postaci pojawienia sie nowego sposobu leczenia, jest receptor naskorkowego czynnika wzrostu (EGFR). Szlak sygnalowy EGFR jest istotnym elementem w powstawaniu i progresji wielu chorob nowotworowych. W przypadku raka nerki wiedza w zakresie znaczenia tego szlaku molekularnego jest niewielka i cześciowo ma związek z niepowodzeniem leczenia chorych na te chorobe nowotworową z zastosowaniem substancji blokujących EGFR, a ktore juz stosuje sie w codziennej praktyce lekarskiej, np. podczas leczenia raka jelita grubego, nowotworow glowy i szyi czy tez raka piersi. W tym artykule autorzy omowili role szlaku sygnalowego EGFR w odniesieniu do komorek raka nerki oraz opisali wyniki prob klinicznych blokowania szlaku EGFR u chorych na raka nerki. Onkol. Prak. Klin. 2011; 7, 4: 197–207

M-TOR inhibitors in the treatment of advanced renal cell carcinoma

Abstract: Renal cell cancer (RCC) accounts for ap proximately 3% of all registered malig nancies in Poland. According to the most recent National Cancer Register, 2283 men and 1483 women were diag nosed with renal cancer in 2006. Up to 30% of patients with RCC present with metastatic disease. M-TOR inhibitors became a new therapeutic option for patients with metastatic RCC. Two of them, temsirolimus and everolimus, are currently approved for clinical use for pa tients with advanced renal cancer. An ticancer activity of m-TOR inhibitors is re lated to cellular cycle regulation and inhibition of uncontrolled angiogenesis. Based on clinical trials, temsirolimus is indicated as the first line of chemother apy for patients with at least three poor prognostic factors. Everolimus should be administered as the second line of treatment, for patients who re lapsed after antiangiogenic therapy.