Luboš Petruželka

Gemcitabine plus cisplatin vs. gemcitabine plus carboplatin in stage IIIb and IV non-small cell lung cancer: a phase III randomized trial

PURPOSE This randomized, multicenter, phase III trial was conducted to compare the tolerability of gemcitabine plus cisplatin (GP) vs. gemcitabine plus carboplatin (GC) in chemonaive patients with stage IIIb and IV non-small cell lung carcinoma (NSCLC). Secondary objectives were to evaluate response, duration of response, time to progressive disease (TTPD), and survival. PATIENTS AND METHODS Eligible patients were required to have stage IIIb or IV NSCLC, no previous chemotherapy, Karnofsky performance status of at least 70, bidimensionally measurable disease, and age 18-75 years. Randomized patients in both arms were given gemcitabine 1200 mg/m(2) on days 1 and 8, followed on day 1 by cisplatin 80 mg/m(2) (GP) or carboplatin AUC=5 (GC). Treatment cycles were repeated every 21 days for a maximum of six cycles, or until disease progression or unacceptable toxicity occurred. RESULTS Enrolled patients in both arms, 87 in GP and 89 in GC, were well balanced for demographics and disease characteristics. Dose intensity was 93.8 and 92.7% for gemcitabine in GP/GC arms, respectively; 97.7% for cisplatin and 99.9% for carboplatin. Patients with at least one grade 3/4 toxicity excluding nausea, vomiting or alopecia, were 44% in GP arm and 54% in GC arm. The only significantly different toxicities were, nausea and vomiting in GP and thrombocytopenia in GC group. The overall response rates, median TTPD, response duration and survival were, 41/29%, 5.87/4.75 months, 7.48/5.15 months, and 8.75/7.97 months for GP and GC arms, respectively. CONCLUSION GP and GC are effective and feasible regimens for advanced NSCLC, and are comparable in efficacy and toxicity. GC may offer acceptable option to patients with advanced NSCLC, especially those who are unable to receive cisplatin.

Plasma Fatty Acid Composition in Patients with Pancreatic Cancer: Correlations to Clinical Parameters

Pancreatic cancer (PC) ranks as the fourth cause of cancer-related deaths in the Czech Republic. Evidence exists that deregulation of fatty acid (FA) metabolism is connected with some malignancies; therefore, we decided to analyze FA profile in plasma lipid classes in patients with PC with relation to tumor staging, nutritional status, and survival. The study included 84 patients (47 males, 37 females) with PC and 68 controls (36 males, 32 females). FA patterns were analyzed in plasma lipid classes by gas-chromatography. We observed increased proportion of total monounsaturated FA (MUFA) in PC group in all plasma lipid classes. These changes were connected with increased Δ9-desaturase (SCD1) and Δ5-desaturase indices. Correlations of dihomo-γ-linolenic acid (DHGLA) with these variables were opposite. Longer survival of patients was connected with higher content of EPA, DHA, and with lower SCD1 index, respectively. Plasma phospholipid proportions of α-linolenic acid, DHGLA, EPA, and n-3 polyunsaturated fatty acids displayed negative trend with tumor staging. Plasma lipid FA pattern in PC patients resulted from decreased dietary fat intake and increased de novo synthesis of FA with transformation into MUFA. Changes in FA profile implicated some pathophysiological mechanisms responsible for disturbed FA metabolism in PC and importance of appropriate nutritional support.

Analysis of human blood plasma and hen egg white by chiroptical spectroscopic methods (ECD, VCD, ROA)

AbstractChiroptical methods are widely used in structural and conformational analyses of biopolymers. The application of these methods to investigations of biofluids would provide new avenues for the molecular diagnosis of protein-misfolding diseases. In this work, samples of human blood plasma and hen egg white were analyzed using a combination of conventional and chiroptical methods: ultraviolet absorption/electronic circular dichroism (UV/ECD), Fourier transform infrared absorption/vibrational circular dichroism (FTIR/VCD), and Raman scattering/Raman optical activity (Raman/ROA). For comparison, the main components of these substances—human serum albumin (HSA) and ovalbumin (Ova)—were also analyzed by these methods. The ultraviolet region of the ECD spectrum was analyzed using the CDNN CD software package to evaluate the secondary structures of the proteins. The UV/ECD, FTIR/VCD, and Raman/ROA spectra of the substances were quite similar to those of the corresponding major proteins, while some differences were also detected and explained. The conclusions drawn from the FTIR/VCD and Raman/ROA data were in good agreement with the secondary structures calculated from ECD. The results obtained in this work demonstrate that the chiroptical methods used here can be applied to analyze not only pure protein solutions but also more complex systems, such as biological fluids. FigureAnalysis of human blood plasma and hen egg white by ECD, VCD and ROA.

Optimizing treatment for patients with metastatic renal cell carcinoma in the central and Eastern European region

Introduction: Belarus, Bulgaria, Croatia, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Republic of Moldova, Romania, Russian Federation, Serbia, Slovakia, Slovenia and the Ukraine represent a collection of Central and Eastern European (CEE) countries in which the epidemiology and treatment of cancer varies greatly between and within countries. Current challenges include non-adherence to current treatment guidelines, restrictions in access and reimbursement for new therapies, and a lack of basic oncology programs. Metastatic renal cell carcinoma (mRCC) is a malignancy with historically poor prognosis. In CEE countries, the incidence and mortality rates of mRCC are among the highest in the world. Fortunately, mRCC represents a cancer for which a number of new targeted therapies have recently demonstrated benefit, resulting in new evidence-based treatment guidelines. Incorporating these mRCC treatment recommendations into the routine care of patients with mRCC in CEE countries would represent a major step forward for cancer care in this region. Areas covered: This review discusses the unique challenges faced by the aforementioned Eastern European countries in the treatment of metastatic renal cell cancer, in an attempt to assist health-care providers in providing the best care possible for their European patients. Expert opinion: Despite a wealth of clinical trial data supporting the use of targeted therapies for first-line treatment of mRCC, cytokine-based immunotherapy is still used in some of these European countries. With implementation and adherence to existing guidelines, treatment can be clinically and economically optimized in patients with mRCC from this region.

Apoptosis – associated genes and their role in predicting responses to neoadjuvant breast cancer treatment

Summary Background Neoadjuvant chemotherapy is used in the treatment of breast carcinoma because it substantially reduces the size of the primary tumor and lymph node metastases. The present study investigated biomarkers that can predict a pathologic response to the therapy. Material/Methods The role of apoptosis in regression of the tumors after neoadjuvant chemotherapy was determined by TUNEL and anti-active caspase 3 assay. The transcriptional profile of 84 key apoptosis genes was evaluated in both pre-therapeutically obtained tumor tissue by core needle biopsy and in specimens removed by final surgery, using a pathway-specific real-time PCR assay. Obtained data were analyzed by hierarchical cluster analysis and correlation analysis. The immunohistochemical profile of each tumor was determined using the standard ABC method. Results On the basis of a hierarchical cluster analysis of 13 significantly changed genes, we divided patients into good and poor prognosis groups, which correlate well with progression-free survival. In the good prognosis group, we found a statistically significant down-regulation of the expression of MCL1 and IGF1R genes after neoadjuvant treatment. We also found a statistically significant overexpression of BCL2L10, BCL2AF1, CASP8, CASP10, CASP14, CIDEB, FADD, HRK, TNFRSF25, TNFSF8 and CD70 genes. In contrast, we found up-regulation of IGF1R after the treatment in the group with poor prognosis. Conclusions Gene expression profiling using real-time PCR assay is a valuable research tool for the investigation of molecular markers, which reflect tumor biology and treatment response.

Serum Adiponectin Relates to Shortened Overall Survival in Men with Squamous Cell Esophageal Cancer Treated with Preoperative Concurrent Chemoradiotherapy: A Pilot Study

Background The convergence of nutritional, genetic, and inflammatory factors plays a significant role in the pathophysiology of squamous cell esophageal cancer (SCEC). The parameters of inflammation, indices of nutritional status, and adipocyte-derived hormones such as leptin, adiponectin, and resistin have been shown to be prognostic factors in some gastrointestinal and pancreatic cancers. Material/Methods Forty-two patients with SCEC were subjected to a multimodal regimen of concurrent neoadjuvant chemoradiotherapy (CRT) followed by surgery. We retrospectively analyzed the impact of pretreatment values of serum leptin, adiponectin, resistin, soluble leptin receptor, C-reactive protein, TNF alpha, leukocytes, and indices of nutritional status (BMI, plasma total protein, albumin, cholesterol, and triacylglycerols) on overall survival (OS). Results Univariate analysis revealed significant a negative correlation between OS and serum adiponectin (p=0.027), and a positive relationship was found between serum albumin (p=0.002), cholesterol (p=0.049) level, and OS. In multivariate analysis, only the trend (p=0.086) for negative serum adiponectin association with the OS was observed. Conclusions In men with SCEC treated by neoadjuvant concurrent CRT and esophagectomy, high pretreatment level of serum adiponectin was associated with shorter OS while the serum albumin and cholesterol were associated with longer OS.

The Inclusion of a Gemcitabine + Nab-paclitaxel Regimen as a 2nd Line Treatment for Advanced Pancreatic Cancer – First Experience

INTRODUCTION Pancreatic cancer is the fourth leading cause of cancer-related death worldwide. The outcomes at all stages of the disease are the worst among patients with solid tumors. PATIENTS AND METHODS Analyses were conducted on 19 patients treated with gamcitabine + nab-paclitaxel for locally advanced or metastatic pancreatic cancer as a second line treatment between October, 2014, and December, 2016, at Department of Oncology of First Faculty of Medicine and General University Hospital in Prague. Patients were treated with gemcitabine (1,000 mg/sqm) + nab-paclitaxel (125 mg/sqm) at days 1, 8 and 15 of each 28-day cycle. Antitumor efficacy (disease control rate (DCR), time to progression (TTP), and overall survival (OS)) and adverse events were monitored. RESULTS Disease control according to RECIST criteria was achieved in nine cases (56.3%, two partial regressions were observed). The median TTP was 5.5 months and median OS was 10.1 months. CONCLUSION In patients with advanced or metastatic pancreatic cancer with good performance statuses (0-1) gemcitabine + nab-paclitaxel as a second line treatment led to a prolongation in time to progression and higher overall survival with good quality of life.Key words: pancreatic cancer - gemcitabine - nab-paclitaxel - efficiency - toxicity This project was supported by grant PROGRES-Q-25/LF1, The League Against Cancer a AZV CR 15-28188A. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 11. 7. 2017Accepted: 20. 9. 2017.

Plasma Phosphatidylcholines Fatty Acids in Men with Squamous Cell Esophageal Cancer: Chemoradiotherapy Improves Abnormal Profile

Background Abnormal metabolism of fatty acids (FA) is considered to play a role in human cancers, including esophageal cancer (EC). Nevertheless, there have been only a few studies dealing with the influence of the chemotherapy or radiotherapy on the plasma FA profiles. In this work we compared FA in plasma phosphatidylcholine (PC) of the patients with squamous EC and healthy subjects and investigated changes in the FA spectrum during neoadjuvant chemoradiotherapy (CRT). Material/Methods Forty-two men with squamous EC were compared with age-matched healthy controls. The EC group was subjected to concurrent neoadjuvant CRT. We analyzed FA in plasma PC before and after CRT. Results The EC group was characterized by increased levels of both saturated and monounsaturated FA, associated with an increased index of SCD1 (stearoyl-CoA desaturase-1). Moreover, decreased levels of linoleic acid and total polyunsaturated FA (PUFA) n-6 were found in EC patients. The CRT was accompanied by increased docosahexaenoic acid and total PUFA n-3 content in plasma PC, concurrently with the decrease of estimated activity of SCD1. Conclusions We found that patients with EC had altered FA profile in plasma PC, which could be related to abnormal FA metabolism in cancer (e.g., altered synthesis de novo, β-oxidation, desaturation, and elongation). The described changes in FA profiles during CRT could be involved in favorable functioning of CRT. Further studies investigating the plasma FA compositions and their changes due to CRT in EC patients are warranted.

173 Symptomatic benefit of palliative radiotherapy for patient with advanced non-small cell lung cancer

The efficacy of palliative radiotherapy of NSCLC was evaluated. Seventy patients with histologically and cytologically confirmed advanced NSCLC were palliatively irradiated in the Department of Oncology I Medical Faculty, Charles University, Prague, in the period 1/93–12/94. Forty-six patients were evaluable for response (32 men, 14 women, median age 66.1, range 46−82). Median survival was 24.5 weeks. The most frequent intrathoracal symptoms were: cough 54%, chest pain 41%, dyspnoe 54%, hemoptysis 13%, VCS sy 7%. Palliation of the main symptoms have been achieved in 68% for cough, in 83% for hemoptysis, in 89% for chest pain, in 60% for dyspnoe and in 100% for VCS sy (in combination with chemotherapy). The median duration of palliation was 14.7 weeks for all the main symptoms. Two fractionations schedules for the chest radiotherapy were used: 30 Gy/l0 fr/2 wks (67%) or short regimens 8–20 Gy/1–2 fr/1–2wks (33%). The results of palliation and survival are similar for both treatment schedules. Side effects have been infrequent, only 6 patients (13%) had dysphagia during the treatment. Radiation myelopathy has been not observed in any case.