Showing papers by "Cezary Szczylik published in 2010"
TL;DR: Pazopanib demonstrated significant improvement in PFS and tumor response compared with placebo in treatment-naive and cytokine-pretreated patients with advanced and/or metastatic RCC.
Abstract: Purpose Pazopanib is an oral angiogenesis inhibitor targeting vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit. This randomized, double-blind, placebo-controlled phase III study evaluated efficacy and safety of pazopanib monotherapy in treatment-naive and cytokine-pretreated patients with advanced renal cell carcinoma (RCC). Patients and Methods Adult patients with measurable, locally advanced, and/or metastatic RCC were randomly assigned 2:1 to receive oral pazopanib or placebo. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, tumor response rate (Response Evaluation Criteria in Solid Tumors), and safety. Radiographic assessments of tumors were independently reviewed. Results Of 435 patients enrolled, 233 were treatment naive (54%) and 202 were cytokine pretreated (46%). PFS was significantly prolonged with pazopanib compared with placebo in the overall study population (median, PFS 9.2 v 4.2 months; hazard ratio [HR], 0.46; 95% CI, 0.34 to 0.62; P .0001), the treatment-naive subpopulation (median PFS 11.1 v 2.8 months; HR, 0.40; 95% CI, 0.27 to 0.60; P .0001), and the cytokine-pretreated subpopulation (median PFS, 7.4 v 4.2 months; HR, 0.54; 95% CI, 0.35 to 0.84; P .001). The objective response rate was 30% with pazopanib compared with 3% with placebo (P .001). The median duration of response was longer than 1 year. The most common adverse events were diarrhea, hypertension, hair color changes, nausea, anorexia, and vomiting. There was no evidence of clinically important differences in quality of life for pazopanib versus placebo. Conclusion Pazopanib demonstrated significant improvement in PFS and tumor response compared with placebo in treatment-naive and cytokine-pretreated patients with advanced and/or metastatic RCC. J Clin Oncol 28:1061-1068. © 2010 by American Society of Clinical Oncology
2,260 citations
TL;DR: MVA-5T4 in combination with SOC was well tolerated, but no difference in survival was observed in the overall study population, and exploratory analyses suggested a number of pretreatment hematologic factors that could identify patients who derive significant benefit from this vaccine.
Abstract: Purpose: The TroVax Renal Immunotherapy Survival Trial was a randomized, placebo-controlled phase III study that investigated whether modified vaccinia Ankara encoding the tumor antigen 5T4 (MVA-5T4) prolonged survival of patients receiving first-line standard-of-care (SOC) treatment for metastatic renal cell cancer. Experimental Design: Patients with metastatic clear cell renal cancer, prior nephrectomy, and good or intermediate prognosis were randomized 1:1 to receive up to 13 immunizations of MVA-5T4/placebo in combination with either sunitinib, interleukin-2 or interferon-α. The primary end point was overall survival. Secondary end points included progression-free survival, overall response rate, and safety. Results: Seven hundred thirty-three patients were recruited (365 MVA-5T4 and 368 placebo). Treatment arms were well balanced for SOC and prognosis. No significant difference in the incidence of adverse events or serious adverse events was observed. No significant difference in overall survival was evident in the two treatment arms (median 20.1 months MVA-5T4 versus 19.2 months placebo; P = 0.55). The magnitude of the 5T4-specific antibody response induced by vaccination with MVA-5T4 was associated with enhanced patient survival. Furthermore, exploratory analyses suggested a number of pretreatment hematologic factors that could identify patients who derive significant benefit from this vaccine. Conclusion: MVA-5T4 in combination with SOC was well tolerated, but no difference in survival was observed in the overall study population. Exploratory analyses indicate that there may be subsets of patients who could gain significant benefit from MVA-5T4, but such results would need to be confirmed in future randomized clinical studies. Clin Cancer Res; 16(22); 5539–47. ©2010 AACR.
192 citations
TL;DR: In this subpopulation of patients with metastatic renal cell carcinoma, antiangiogenic therapy, such as sorafenib, could be an effective preventive therapy for brain metastases in advanced RCC.
96 citations
TL;DR: The modulation by rhEPO of tumor cell response to anticancer agents is coincident with modulation of multiple signaling pathways, BCL-2 family proteins, caspases and NFkB.
87 citations
TL;DR: Results of this subgroup analysis of patients enrolled in TARGET who received treatment for >1 year indicate that long-term treatment with sorafenib is associated with continued efficacy and a well-tolerated safety profile.
73 citations
TL;DR: A large number of patients with clear-cell RCC and documented progression during or after first-line cytokine- or TKI-based therapy were randomized 1:1 to receive up to 17 intradermal vaccinations of IMA901 together with a single infusion of low-dose cyclophosphamide before the first vaccination.
Abstract: 4529 Background: IMA901 is a therapeutic cancer vaccine based on the selection of naturally presented tumor-associated peptides (9 HLA-class I- and 1 HLA class II-binding peptides). A previous phas...
46 citations
TL;DR: The sunitinib tolerability profile in mRCC is reviewed and practical strategies to manage adverse events in order to maximize clinical benefit are described, thereby optimizing the available clinical efficacy.
Abstract: Sunitinib is a reference standard of care for the treatment of metastatic renal cell carcinoma (mRCC). While the tolerability of sunitinib is consistent across clinical studies, the impact of tolerability on clinical benefit necessitates effective therapy management, focusing on optimization of dosing, treatment duration, and management of adverse events. Managing individual tolerability concerns in clinical practice should include patient education and practical management strategies. We review the sunitinib tolerability profile in mRCC and describe practical strategies to manage adverse events in order to maximize clinical benefit. These strategies may allow long-term sunitinib treatment, thereby optimizing the available clinical efficacy.
39 citations
TL;DR: The need for an individualised patient-focused approach to the management of advanced renal cell carcinoma in clinical practice is identified and a schema providing guidance on the wide range of parameters that should be considered when making treatment decisions is presented.
35 citations
TL;DR: The results of this study suggest that cystatin C is not a reliable marker of the GFR in ovarian cancer patients, probably due to its nature as a cysteine protease inhibitor.
Abstract: Aims: To evaluate the potential role of serum cystatin C as a marker of renal function in patients with ovarian cancer. Methods: Treatment of consecutive ovarian cancer patients who were eligible for chemotherapy with paclitaxel (135 mg/m2/24 h) and cisplatin (75 mg/m2) every 3 weeks in 6 cycles. Glomerular filtration rate (GFR) markers, i.e. serum levels of creatinine and cystatin C, estimated by the Cockcroft-Gault and Modification of Diet in Renal Disease formulas, were recorded before each cycle and 3 weeks after the 6th course. Results: The median age of 34 patients was 54 years. In the initial stage of treatment, we did not observe any correlation between cystatin C and other GFR markers. We noted a significant association between cystatin C and tumor extent on spiral CT scans (diameter: >1 cm) performed at baseline (p = 0.004), and after the 1st (p = 0.03) and 2nd cycle (p = 0.026). We observed a correlation between cystatin C and CA-125 level before chemotherapy (R = 0.4; p = 0.02) and after the 1st cycle (R = 0.43; p = 0.04). Conclusion: The results of our study suggest that cystatin C is not a reliable marker of the GFR in ovarian cancer patients, probably due to its nature as a cysteine protease inhibitor.
31 citations
TL;DR: Sunitinib appeared slightly more effective than sorafenib or IFN-alfa at extending mean time to progression of pre-existing bone lesions (P = 0057) Compared with SORA, sunitinsib significantly decreased formation and prolonged time to occurrence of new bone lesions as mentioned in this paper.
Abstract: Introduction This single-centre retrospective analysis of data from three randomised studies and two expanded-access studies compared the effect of interferon (IFN)-alfa, sunitinib, and sorafenib on the occurrence and progression of metastatic bone lesions in patients with renal cell carcinoma (RCC) Methods The analysis included 292 patients: 107 received sunitinib 50 mg/day in 6-week cycles (Schedule 4/2), 147 received sorafenib 800 mg/day, and 38 received placebo or IFN-alfa 9 MU tiw Results Pre-existing metastatic bone lesions were reported in 82 patients, of which 30 experienced progression Twenty-three of 210 patients developed new bone lesions Overall, sunitinib appeared slightly more effective than sorafenib or IFN-alfa at extending mean time to progression of pre-existing bone lesions (P = 0057) Compared with sorafenib, sunitinib significantly decreased formation (P = 0034) and prolonged time to occurrence of new bone lesions (P = 0047) Conclusion Further evaluation of the effect of these therapies on bone metastases in RCC is warranted
29 citations
TL;DR: It is suggested that most patients prefer oral chemotherapy because of the convenience and possibility of staying at home during treatment, and capecitabine provides a very effective treatment for MBC and additionally addresses patients' desire to receive treatment at home.
Abstract: The importance of selecting treatment for metastatic breast cancer (MBC) that best suits the needs of the patient while offering a good clinical outcome is becoming more prominent in the decision-making process. We designed a questionnaire-based study to identify factors influencing treatment choice. We prospectively surveyed 218 female MBC patients scheduled to receive chemotherapy who were eligible for capecitabine monotherapy. All 215 patients who answered the questionnaire preferred oral capecitabine to intravenous chemotherapy. The most frequently cited reason for this preference was convenience (72%). The possibility of staying at home during treatment was considered important by 67% of patients overall, 42% of the 71 patients giving only one reason for their preference, 65% of those receiving first-line therapy and 74% treated in the second-line setting. Our study suggests that most patients prefer oral chemotherapy because of the convenience and possibility of staying at home during treatment. The study did not explore patient perceptions of efficacy or tolerability, which play a pivotal role in treatment selection from both the patient and physician perspectives. Capecitabine provides a very effective treatment for MBC and additionally addresses patients' desire to receive treatment at home.
TL;DR: An atypical case of CRC is reported in a patient with FAP caused by 2797-2800delAACA mutation of the APC gene, which is the most effective method of CRC prevention.
Abstract: Colorectal cancer (CRC) is one of the most common malignant tumours in Poland. Annually approximately 11 000 new cases of CRC are diagnosed, while the number of deaths caused by CRC approaches 8 000. Five-year survival does not exceed 20%. Familial adenomatous polyposis (FAP) is responsible for about 1% of new cases of CRC. The risk of CRC in FAP syndrome is 100%, and the average age of CRC development is 39 years. Early colectomy is the most effective method of CRC prevention. We report an atypical case of CRC in a patient with FAP caused by 2797-2800delAACA mutation of the APC gene.
TL;DR: This case study is the first to demonstrate the manageability and reversibility of trastuzumab-related cardiac complications in a patient who had developed severe heart failure complicated with left ventricular thrombosis during sequential anthracycline and trastzumab therapy for breast cancer.
Abstract: Trastuzumab-related cardiac dysfunction may be manageable and completely reversible with suitable cardiac medication, allowing optimal breast cancer treatment to continue. We present the case of a 42-year-old woman who developed severe systolic left ventricular failure with impaired contractility of the right ventricle, pulmonary hypertension, and clots in the left ventricular cavity during adjuvant treatment for breast cancer. The patient was initially diagnosed with early breast cancer and underwent surgery on her left breast. She received 6 cycles of anthracycline chemotherapy followed by radiation therapy in the left breast area, then 5 cycles of trastuzumab. After the fifth cycle of trastuzumab, she experienced dyspnoea and leg edema. Fluid was detected in the pleural cavities but no lung metastases were identified. Echocardiography was performed, revealing a severely reduced left ventricular ejection fraction (10%) with impaired contractility of the right ventricle and pulmonary hypertension. Standard medication for heart failure resulted in complete recovery of normal systolic and diastolic function of the left and right ventricles. The combination of low molecular weight heparin and acetylsalicylic acid completely resolved the thrombotic complications. The patient regained her full range of social, occupational, and family activities. This case study is the first to demonstrate the manageability and reversibility of trastuzumab-related cardiac complications in a patient who had developed severe heart failure complicated with left ventricular thrombosis during sequential anthracycline and trastuzumab therapy for breast cancer. The findings contradict other opinions that trastuzumab-related acute heart failure is analogous to stunning or hibernation and recovers without specific cardiac treatment.
TL;DR: Single-agent capecitabine and FOLFIRI are effective first-line regimens in patients aged ≥65 years with mCRC, and the main non-haematological toxicity was hand-foot syndrome found only in the cape citabine group.
Abstract: A retrospective analysis was conducted to compare the tolerability and efficacy of single-agent capecitabine and 5-fluorouracil/leucovorin/irinotecan (FOLFIRI) in the first-line treatment of patients aged ≥65 years with metastatic colorectal cancer (mCRC). Consecutive patients with mCRC treated at the Military Medical Institute, Warsaw, between January 2003 and June 2008 were eligible. A total of 123 patients were identified (FOLFIRI, n = 67; capecitabine, n = 56). The overall response rate with FOLFIRI was 28.1 versus 16.4% with capecitabine (P = 0.1398). Median time to disease progression with FOLFIRI was 8.8 versus 7.5 months with capecitabine (P = 0.20), and median overall survival was 19.0 versus 15.4 months (P = 0.93). In the FOLFIRI group, neutropenia and anaemia were significantly more frequent than in the capecitabine group. The main non-haematological toxicity was hand-foot syndrome found only in the capecitabine group. Single-agent capecitabine and FOLFIRI are effective first-line regimens in patients aged ≥65 years with mCRC.
TL;DR: Ryzyko zachorowania na raka jajnika u nosicielek mutacji genu BRCA1 wynosi ok. 16–60%, aby można było zastosować u nich odpowiednią pro filaktykę zabezpieczającą przed zACHorowaniem na nowotwory zło�
Abstract: nę zgonów z powodu nowotworów narządu rodnego kobiet. Pomimo stosowania zabiegów cytoredukcyjnych i chemioterapii z użyciem pochodnych platyny i taksanów, odsetek przeżyć 5-letnich wśród chorych na zaawanso wa ną postać tego nowotworu wynosi 10–30%. Spośród wszystkich przypadków raka jajnika, ok. 5–10% jest związanych z rodzinną lub dziedziczną postacią, za którą są odpowiedzialne w ok. 80–90% mutacje genów BRCA. Ryzyko zachorowania na raka jajnika u nosicielek mutacji genu BRCA1 wynosi ok. 16–60%. Tak wysokie ryzyko zachorowania wskazuje na potrzebę wykonywania testów genetycznych zarówno wśród chorych, jak i ich krewnych, aby można było zastosować u nich odpowiednią pro filaktykę zabezpieczającą przed zachorowaniem na nowotwory złośliwe. Obecnie wprowadza się strategię direct-to-consumer (DTC), mającą na celu wykorzystywanie testów molekularnych w codziennej praktyce klinicznej.
TL;DR: Thecell carcinoma – RCC (RCC) stanowi ok. 3% litych guzów u dorosłych w chwili rozpoznania RCC stwierdza się przerzuty, które najczęściej dotyczą płuc.
Abstract: cell carcinoma – RCC) stanowi ok. 3% litych guzów u dorosłych. U ok. 30% chorych w chwili rozpoznania RCC stwierdza się przerzuty, które najczęściej dotyczą płuc. Cel pracy: Ocena remisji przerzutów płucnych zaawansowanego raka nerki po nefrektomii i chemioimmunoterapii. Materiał i metody: Analizą objęto dane kliniczne 54 chorych na raka nerki z przerzutami płucnymi. Wszystkich chorych przed leczeniem systemowym poddano nefrektomii (bez metastazektomii), a stadium przerzutowe choroby dokumentowano za pomocą tomografii komputerowej. Terapię oparto na IL-2 s.c., IFN-α s.c., 5-FU i.v. Stan ogólny oceniany był na podstawie skali ECOG, a odpowiedź zmian docelowych wg kryteriów RECIST. Wyniki: Ocena 54 chorych wg skali ECOG: 0 – u 5 chorych, 1 – u 43, 2 – u 6. Po zastosowaniu chemioimmunoterapii zaobserwowano 5 odpowiedzi całkowitych (CR – 9%) oraz 12 odpowiedzi częściowych (PR – 22%). Obiektywne odpowiedzi zanotowano w 17 przypadkach. Średni czas trwania CR wynosił 24 miesiące (znacząco wpływał na wydłużenie przeżycia chorych). Ocena grupy wg skali ECOG: 0 u nikogo, 1 – u 4 chorych, 2 – u 1 chorego. Odpowiedź częściowa trwała średnio 12 miesięcy (zazwyczaj progresja choroby nowotworowej). Toksyczność zastosowanego schematu była przemijająca, z dobrą tolerancją leczenia przez chorych. Wnioski: 1. Skojarzenie nefrektomii i następowej chemioimmunoterapii jest bezpieczną i skuteczną metodą leczenia chorych z przerzutami raka nerki do płuc. 2. Dzięki zastosowanej immunochemioterapii uzyskano u 5 osób CR, co znamiennie wydłużyło przeżycie chorych. 3. Leczenie chorych z przerzutowym RCC powinno być prowadzone w wyspecjalizowanych ośrodkach i mieć charakter interdyscyplinarny.