Determination of copper and other trace elements in serum samples from patients with biliary tract cancers: prospective noninterventional nonrandomized clinical study protocol.

BACKGROUND: Biliary tract cancers (BTCs) are usually diagnosed at an advanced stage, when the disease is incurable. Currently used tumor biomarkers have limited diagnostic value for BTCs, so there is an urgent need for sensitive and specific biomarkers for their earlier diagnosis. Deregulation of the homeostasis of trace elements is involved in the carcinogenesis of different cancers, including BTCs. The objective of the study is to determine/compare the total concentrations of copper (Cu), zinc (Zn) and iron (Fe) and the proportions of free Cu and Cu bound to ceruloplasmin (Cp) and the isotopic ratio of 65Cu/63Cu in serum samples from healthy volunteers and cancer patients using inductively coupled plasma-mass spectrometry-based methods (ICP-MS). PATIENTS AND METHODS: In this prospective, noninterventional, nonrandomized study 20 patients and 20 healthy volunteers will be enrolled to identify serum Cu, Zn and Fe levels, Cu isotopic fractionation as a predictive biomarker of response to systemic therapy of BTCs, which will be evaluated by computed tomography. Newly developed analytical methods based on ICP-MS will be applied to metal-based biomarker research in oncology. CONCLUSIONS: In the study the comparison of the total concentration of selected trace elements, the proportion of free Cu and Cu bound to Cp and the isotopic ratio of 65Cu/63Cu in serum samples from healthy volunteers and cancer patients will be conducted to provide the foundation for the development of a BTC cancer screening methodology and the data on their usability as a potential predictive biomarker for BTCs of response to systemic therapy.

The five-year KRAS, NRAS and BRAF analysis results and treatment patterns in daily clinical practice in Slovenia in 1st line treatment of metastatic colorectal (mCRC) patients with RAS wild-type tumour (wtRAS) - a real- life data report 2013-2018.

BACKGROUND: We preformed a Phase IV non-interventional study to assess KRAS, NRAS and BRAF status in metastatic colorectal cancer (mCRC) patients suitable for 1st line treatment and to evaluate the decisions for 1st line treatment considering the treatment goals in the RAS wild type (wt) patients. The aim of our study was also to evaluate the influence of a waiting period for biomarkers analysis on the start of first-line treatment. PATIENTS AND METHODS: Patients with histologically confirmed mCRC adenocarcinoma suitable for first-line treatment fulfilling all inclusion criteria were included in the study. The KRAS, NRAS and BRAF analysis was performed from tissue samples of primary tumor site or metastatic site. All included patients have given consent to participate in the study by signing the informed consent form. RESULTS: From April 2013 to March 2018 at the Institute of Oncology Ljubljana 650 patients were included, 637 of them were treated with first- line systemic treatment according to RAS and BRAF status. Remaining 13 patients with mCRC did not receive systemic first-line treatment. The distribution of patients with KRAS mutated and wild-type tumors, was almost equal, 48.8% and 47.9% respectively, 89 % of the patients had wt NRAS tumours and 86.1% had wt BRAF tumours. The most frequently prescribed treatment was bevacizumab-based therapy (53.1%), either in combination with doublet chemotherapy or with mono-chemotherapy. EGFR inhibitors cetuximab and panitumumab were prescribed in wt RAS mCRC patients (30.9%). The waiting period for biomarkers analysis was two weeks. CONCLUSIONS: Our real-world data, single centre 5-year analysis showed that the distribution between wild type and mutated type tumors of the patients with mCRC was approximately the same, as worldwide, so the Slovenian population with mCRC has the same ratio distribution of KRAS, NRAS and BRAF wild and mutated genes. We concluded that a two-week waiting period for biomarkers analysis did not influence the first line treatment decision, so it was in the accordance with the worldwide treatment guidelines based on evidence-based medicine.

Quantitative imaging biomarkers of immune-related adverse events in immune-checkpoint blockade-treated metastatic melanoma patients: a pilot study.

PURPOSE: To develop quantitative molecular imaging biomarkers of immune-related adverse event (irAE) development in malignant melanoma (MM) patients receiving immune-checkpoint inhibitors (ICI) imaged with 18F-FDG PET/CT. METHODS: 18F-FDG PET/CT images of 58 MM patients treated with anti-PD-1 or anti-CTLA-4 ICI were retrospectively analyzed for indication of irAE. Three target organs, most commonly affected by irAE, were considered: bowel, lung, and thyroid. Patient charts were reviewed to identify which patients experienced irAE, irAE grade, and time to irAE diagnosis. Target organs were segmented using a convolutional neural network (CNN), and novel quantitative imaging biomarkers - SUV percentiles (SUVX%) of 18F-FDG uptake within the target organs - were correlated with the clinical irAE status. Area under the receiver-operating characteristic curve (AUROC) was used to quantify irAE detection performance. Patients who did not experience irAE were used to establish normal ranges for target organ 18F-FDG uptake. RESULTS: A total of 31% (18/58) patients experienced irAE in the three target organs: bowel (n=6), lung (n=5), and thyroid (n=9). Optimal percentiles for identifying irAE were bowel (SUV95%, AUROC=0.79), lung (SUV95%, AUROC=0.98), and thyroid (SUV75%, AUROC=0.88). Optimal cut-offs for irAE detection were bowel (SUV95%>2.7 g/mL), lung (SUV95%>1.7 g/mL), and thyroid (SUV75%>2.1 g/mL). Normal ranges (95% confidence interval) for the SUV percentiles in patients without irAE were bowel [1.74, 2.86 g/mL], lung [0.73, 1.46 g/mL], and thyroid [0.86, 1.99 g/mL]. CONCLUSIONS: Increased 18F-FDG uptake within irAE-affected organs provides predictive information about the development of irAE in MM patients receiving ICI and represents a potential quantitative imaging biomarker for irAE. Some irAE can be detected on 18F-FDG PET/CT well before clinical symptoms appear.

Gut microbiome and its role in colorectal cancer.

Colorectal cancer (CRC) is still one of the most common types of cancer in the world, and the gut microbiome plays an important role in its development. The microbiome is involved in the carcinogenesis, formation and progression of CRC as well as its response to different systemic therapies. The composition of bacterial strains and the influence of geography, race, sex, and diet on the composition of the microbiome serve as important information for screening, early detection and prediction of the treatment outcome of CRC.Microbiome modulation is one of the most prospective new strategies in medicine to improve the health of individuals. Therefore, future research and clinical trials on the gut microbiome in oncology as well as in the treatment of CRC patients are warranted to determine the efficacy of systemic treatments for CRC, minimize adverse effects and increase survival rates.

Consensus molecular subtypes (CMS) in metastatic colorectal cancer - personalized medicine decision.

Background Colorectal cancer (CRC) is one of the most common types of cancer in the world. Metastatic disease is still incurable in most of these patients, but the survival rate has improved by treatment with novel systemic chemotherapy and targeted therapy in combination with surgery. New knowledge of its complex heterogeneity in terms of genetics, epigenetics, transcriptomics and microenvironment, including prognostic and clinical characteristics, led to its classification into various molecular subtypes of metastatic CRC, called consensus molecular subtypes (CMS). The CMS classification thus enables the medical oncologists to adjust the treatment from case to case. They can determine which type of systemic chemotherapy or targeted therapy is best suited to a specific patient, what dosages are needed and in what order. Conclusions CMS in metastatic CRC are the new tool to include the knowledge of molecular factors, tumour stroma and signalling pathways for personalized, patient-orientated systemic treatment in precision medicine.

Retrospective analysis of treatment-naive Slovenian patients with metastatic melanoma treated with pembrolizumab - real-world experience.

Background Based on recent data from clinical trials, the immune checkpoint inhibitor pembrolizumab prolongs survival and has a good toxicity profile in patients with advanced or metastatic melanoma. However, the question remains whether these results are transmitted into daily clinical practice. The aim of this study was to assess the efficacy and toxicity of pembrolizumab in treatment-naive patients with metastatic melanoma in everyday clinical practice in Slovenia and compare it to the results from clinical trials. Patients and methods This observational retrospective cohort study included 138 consecutive metastatic treatment-naive melanoma patients treated with pembrolizumab at the Institute of Oncology Ljubljana in Slovenia, from January 2016 to December 2018. Patient and treatment characteristics were retrospectively collected from hospital data base. Statistical data was obtained using the SPSS software version 22. Survival rate was calculated with the Kaplan-Meier method. Observation period took place between January 2016 and the end of June 2019. Results The estimated median overall survival (OS) was 25.1 months (95% CI, 14.6-35.6) and the median progression-free survival (PFS) was 10.7 months (95% CI, 5.9-15.4). Among all patients, 29 (21.0%) achieved complete response, 31 (22.5%) partial response and 23 (16.7%) reached stable disease. The number of organs with metastatic involvement and the level of baseline lactate dehydrogenase (LDH) concentration had significant influence on survival rates. Immune-related adverse events (irAE) were reported in 88 (63%) patients, while grade 3-4 irAE occurred in 12 (8.7%). Due to toxicity, 16 (11.6%) patients discontinued the treatment. Conclusions Our real-world data from single centre retrospective analysis of treatment-naive metastatic melanoma patients treated with pembrolizumab showed inferior median OS and similar median PFS, compared to the results from clinical trials. However, patients with normal serum levels of LDH and a small number of organs with metastatic involvement had comparable survival outcomes. Toxicity rates of pembrolizumab were quite similar. These results further support the use of pembrolizumab for metastatic treatment-naive melanoma patients.

Molecular biomarkers and histological parameters impact on survival and response to first- line systemic therapy of metastatic colorectal cancer patients.

Background Histological parameters of primary tumour and nodal metastases are prognostic factors for survival of operable colorectal (CRC) patients, but not predictive for response rate of systemic therapy. KRAS mutations in codons 12 and 13 were first recognized as a predictive factor for resistance to anti-EGFR monoclonal antibodies. Not all patients with wild-type KRAS (wtKRAS) respond to anti-EGFR antibody treatment. Additional mechanisms of resistance may activate mutations of the other main EGFR effectors pathway, such as other mutations in RAS gene, mutations in P13K and PTEN expression. Patients and methods In the prospective study prognostic and predictive impact of histological parameters of primary tumour, KRAS and BRAF mutations on overall survival (OS) and objective response (OR) rate of metastatic CRC (mCRC) patients treated with 1st line systemic therapy were analysed. We additionally retrospectively analysed other mutations in RAS genes and their impact on survival and time to progression. Results From November 2010 to December 2012, we enrolled 154 patients in the study, 95 men and 59 women. Mutations in KRAS gene and V600E BRAF gene were found in 42% and in 3% of patients, respectively. Median OS of the patients with T1, T2 and T3 tumour was 65.4 months (95% CI, 55.7-75.6) while in patients with T4 tumour, lymphangiosis, vascular and perineural invasion it has not been reached yet. Median OS of the patients with G1, G2 and G3 of tumour differentiation was 65.6 (95% CI, 53.7-77.5) and 25.3 months (95% CI, 16.6-34.1), respectively. Median OS of the patients with stage N0, N1 and N2 was 65.6 (95% CI, 56.4-74.8) and 58.0 months (95% CI, 21.9-94.2), respectively. Median OS of wtKRAS and mutated KRAS patients was 56.5 (95% CI, 48.2-64.9) and 58 months (95% CI, 52.6-63.4), respectively. Median OS of mutated codon 12 and codon 13 patients was 57 (95% CI, 50.9-64.4) and 44 months (95% CI, 40.1-48.4), respectively. Median OS of wtBRAF and of mutated BRAF patients was 59.2 (95% CI, 52.5-65.9) and 27.6 months (95% CI, 12.6-42.5), respectively. wtKRAS significantly affected the response to the first systemic therapy (p = 0.028), while other parameters did not affected it, p= 0.07. In 14 patients (17%), additional mutations in NRAS gene, codon 61 and codon 146 were found. Median OS of wtNRAS, codon 61 and 146 patients was 67.1 months (50.3-67.6) while median OS of mutated NRAS patients has not been reached yet (p = 0.072). Median time to progression of wtNRAS, codon 61 and 146 patients was 11.7 months (10.4-14.5) while median time to progression of mutated NRAS patients was 7.9 months (6.1-11.0), (p = 0.025). Conclusions Mutated BRAF, N2 and G3 of primary tumour were poor prognostic factors for OS in mCRC patients. wtKRAS significantly affected the response to the first line systemic therapy. Histological parameters included in the analysis and mutated BRAF did not affect significantly the efficacy of 1st line systemic therapy in mCRC patients.

Prevalence of BRAF, NRAS and c-KIT mutations in Slovenian patients with advanced melanoma.

Background BRAF, NRAS and c-KIT mutations are characteristics of tumour tissues that influence on treatment decisions in metastatic melanoma patients. Mutation frequency and their correlation with histological characteristics in Slovenian population have not been investigated yet. Patients and methods In our retrospective analysis we analysed mutational status of BRAF, NRAS and c-KIT in 230 pathological samples of patients who were intended to be treated with systemic therapy due to metastatic disease at the Institute of Oncology Ljubljana between 2013 and 2016. We collected also histological characteristics of primary tumours and clinical data of patients and correlated them with mutational status of tumour samples. Results The study population consisted of 230 patients with a mean age 59 years (range 25-85). 141 (61.3%) were males and 89 (38.7%) females. BRAF mutations were identified in 129 (56.1%), NRAS in 31 (13.5%) and c-KIT in 3 (1.3%) tissue samples. Among the 129 patients with BRAF mutations, 114 (88.4%) patients had V600E mutation and 15 (11.6%) had V600K mutation. Patients with BRAF mutations tended to be younger at diagnosis (52 vs. 59 years, p < 0.05), patients with NRAS mutations older (61 vs. 55 years, p < 0.05). Number of c-KIT mutations were too low for any statistical correlation, but there was one out of 3 melanoma located in mucus membranes. Conclusions The analysis detected high rate of BRAF mutations, low NRAS mutations and low c-KIT mutations compared to previously published studies in Europe and North America. One of the main reasons for this observation is specific characteristics of study population.

Bevacizumab plus chemotherapy in elderly patients with previously untreated metastatic colorectal cancer: single center experience.

BACKGROUND: Metastatic colorectal cancer (mCRC) is mainly a disease of elderly, however, geriatric population is underrepresented in clinical trials. Patient registries represent a tool to assess and follow treatment outcomes in this patient population. The aim of the study was with the help of the patients' register to determine the safety and efficacy of bevacizumab plus chemotherapy in elderly patients who had previously untreated metastatic colorectal cancer. PATIENTS AND METHODS: The registry of patients with mCRC was designed to prospectively evaluate the safety and efficacy of bevacizumab-containing chemotherapy as well as selection of patients in routine clinical practice. Patient baseline clinical characteristics, pre-specified bevacizumab-related adverse events, and efficacy data were collected, evaluated and compared according to the age categories. RESULTS: Between January 2008 and December 2010, 210 patients with mCRC (median age 63, male 61.4%) started bevacizumab-containing therapy in the 1(st) line setting. Majority of the 210 patients received irinotecan-based chemotherapy (68%) as 1(st) line treatment and 105 patients (50%) received bevacizumab maintenance therapy. Elderly (≥ 70 years) patients presented 22.9% of all patients and they had worse performance status (PS 1/2, 62.4%) than patients in < 70 years group (PS 1/2, 35.8%). Difference in disease control rate was mainly due to inability to assess response in elderly group (64.6% in elderly and 77.8% in < 70 years group, p = 0.066). The median progression free survival was 10.2 (95% CI, 6.7-16.2) and 11.3 (95% CI, 10.2-12.6) months in elderly and < 70 years group, respectively (p = 0.58). The median overall survival was 18.5 (95% CI, 12.4-28.9) and 27.4 (95% CI, 22.7-31.9) months for elderly and < 70 years group, respectively (p = 0.03). Three-year survival rate was 26% and 37.6% in elderly vs. < 70 years group (p = 0.03). Overall rates of bevacizumab-related adverse events were similar in both groups: proteinuria 21/22 %, hypertension 25/19 %, haemorrhage 2/4 % and thromboembolic events 10/6 %, for elderly and < 70 years group, respectively. CONCLUSIONS: In routine clinical practice, the combination of bevacizumab and chemotherapy is effective and well-tolerated regimen in elderly patients with metastatic colorectal cancer.

Bevacizumab and irinotecan in recurrent malignant glioma, a single institution experience.

BACKGROUND: Treatment options of recurrent malignant gliomas are very limited and with a poor survival benefit. The results from phase II trials suggest that the combination of bevacizumab and irinotecan is beneficial. PATIENTS AND METHODS: The medical documentation of 19 adult patients with recurrent malignant gliomas was retrospectively reviewed. All patients received bevacizumab (10 mg/kg) and irinotecan (340 mg/m(2) or 125 mg/m(2)) every two weeks. Patient clinical characteristics, drug toxicities, response rate, progression free survival (PFS) and overall survival (OS) were evaluated. RESULTS: Between August 2008 and November 2011, 19 patients with recurrent malignant gliomas (median age 44.7, male 73.7%, WHO performance status 0-2) were treated with bevacizumab/irinotecan regimen. Thirteen patients had glioblastoma, 5 anaplastic astrocytoma and 1 anaplastic oligoastrocytoma. With exception of one patient, all patients had initially a standard therapy with primary resection followed by postoperative chemoradiotherapy. Radiological response was confirmed after 3 months in 9 patients (1 complete response, 8 partial responses), seven patients had stable disease and three patients have progressed. The median PFS was 6.8 months (95% confidence interval [CI]: 5.3-8.3) with six-month PFS rate 52.6%. The median OS was 7.7 months (95% CI: 6.6-8.7), while six-month and twelve-month survival rates were 68.4% and 31.6%, respectively. There were 16 cases of hematopoietic toxicity grade (G) 1-2. Non-hematopoietic toxicity was present in 14 cases, all G1-2, except for one patient with proteinuria G3. No grade 4 toxicities, no thromboembolic event and no intracranial hemorrhage were observed. CONCLUSIONS: In recurrent malignant gliomas combination of bevacizumab and irinotecan might be an active regimen with acceptable toxicity.

Randomized prospective phase II study to compare the combination chemotherapy regimen epirubicin, cisplatin, and 5-fluorouracil with epirubicin, cisplatin, and capecitabine in patients with advanced or metastatic gastric cancer.

OBJECTIVES: The aim of this study was to compare the efficacy and safety of the epirubicin, cisplatin, and continuous infusion of 5-fluorouracil (ECF) regimen with that of the epirubicin, cisplatin, and capecitabine (ECX) regimen in patients with advanced or metastatic gastric cancer. METHODS: Patients were randomized to receive either the ECF or ECX regimen. The primary end point was the response rate. The secondary end points were time to progression (TTP), overall survival (OS), and safety. RESULTS: Eighty-five patients were enrolled in the study from January 2003 to March 2007. Forty-five patients received the ECF regimen and 40 patients received the ECX regimen. The objective response rate was 31% [9% complete response (CR) and 22% partial response (PR)] for ECF and 30% (10% CR and 20% PR) for ECX. The disease control rate was 51% and 73%, respectively (P<0.05). Median OS and TTP were 6.8 and 5.5 months, respectively, in the ECF group and 8.3 and 6.0 months, respectively, in the ECX group. The majority of adverse events were grade 1/2. The most frequent grade 3/4 adverse events in both groups were fatigue (ECF 15%, ECX 21%), neutropenia (ECF 16%, ECX 16%), vomiting (ECF 11%, ECX 8%), nausea (ECF 9%, ECX 3%), and anemia (ECF 7%, ECX 5%). CONCLUSIONS: The ECX regimen was at least as effective as the ECF regimen with a similar tolerability profile, and could therefore replace the ECF regimen for the first-line treatment of patients with advanced gastric cancer.

Bevacizumab in first-line therapy of metastatic colorectal cancer: a retrospective comparison of FOLFIRI and XELIRI.

BACKGROUND: The antivascular endothelial growth factor monoclonal antibody bevacizumab with infusional 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) is a standard first-line treatment option for metastatic colorectal cancer. However, clinical data for capecitabine and irinotecan (XELIRI) with bevacizumab are limited. PATIENTS AND METHODS: A retrospective study was conducted on 139 patients with metastatic colorectal cancer to assess the efficacy and safety of first-line bevacizumab in combination with XELIRI or FOLFIRI. Primary endpoints were overall response rate (ORR), disease control rate and radical resection rate. Secondary endpoints included overall survival (OS), progression-free survival (PFS) and safety. RESULTS: No significant differences in efficacy were observed between patients administered XELIRI or FOLFIRI with bevacizumab. The ORR, median OS and PFS and recorded adverse events (AEs) were comparable to those previously reported, with no new or unexpected AEs observed. CONCLUSION: Bevacizumab is similarly efficacious and well tolerated when administered with XELIRI or FOLFIRI.

Efficacy of first-line systemic treatment in correlation with BRAF V600E and different KRAS mutations in metastatic colorectal cancer - a single institution retrospective analysis.

BACKGROUND: KRAS mutation status in codons 12 and 13 is recognized as a predictive factor for resistance to anti-EGFR monoclonal antibodies. Despite having a wild type KRAS (wt-KRAS), not all patients with wt-KRAS respond to anti-EGFR antibody treatment. Additional mechanisms of resistance may activate mutations of the other main EGFR effectors pathway. Consequently, other molecular markers in colorectal cancer are needed to be evaluated to predict the response to therapy. PATIENTS AND METHODS: In this retrospective study, objective responses (OR), time to progression (TTP), overall survival (OS) were analyzed in 176 metastatic colorectal cancer (mCRC) patients treated with first-line chemotherapy in combination with monoclonal antibodies in respect of KRAS status in codons 12 and 13 and BRAF mutational status. RESULTS: The KRAS mutations were found in 63 patients (35.8 %), the KRAS mutation in codon 12 in 53 patients (30.1%) and the KRAS mutation in codon 13 in 10 patients (5.7%). The BRAF V600E mutation was detected in 13 of 176 patients (7.4%). In the subgroup of mCRC patients having wt-KRAS and wild type BRAF (wt-BRAF), the objective response rates were higher (OR 54.0% ,CR 14.7%, PR 39.3%) than in the patients with wt-KRAS and mt-BRAF (OR 38.5%,CR 15.4%, PR 23.1%), the difference was not statistically significant (p= 0.378). Median OS in patients with wt-KRAS wt-BRAF, and in patients with wt-KRAS mt-BRAF, was 107.4 months and 45 months, respectively. The difference was statistically significant (p= 0.042). TTP in patients with wt-KRAS wt-BRAF, and in patients with wt-KRAS mt-BRAF, was 16 months and 12 months, respectively. The difference was not statistically significant (p= 0.558). CONCLUSIONS: Patients with BRAF V600E mutation have statistically significantly worse prognosis than the patients with wt-BRAF and progress earlier during treatment. The definitive role of the BRAF V600E mutation as a prognostic and predictive factor for the response to anti-EGFR monoclonal antibodies needs to be analyzed in large prospective clinical studies.

Capecitabine plus Irinotecan (XELIRI regimen) compared to 5-FU/LV plus Irinotecan (FOLFIRI regimen) as neoadjuvant treatment for patients with unresectable liver-only metastases of metastatic colorectal cancer: a randomised prospective phase II trial.

BACKGROUND: Phase II studies have shown that the combination of capecitabine and irinotecan (the XELIRI regimen) is active in metastatic colorectal cancer (MCRC). There are, however, no data about the use of the XELIRI regimen in the neoadjuvant treatment. METHODS: Patients with unresectable liver-only metastases of MCRC with < or = 75 years of age were randomised to either the XELIRI (irinotecan 250 mg/m(2) given on day one and capecitabine 1000 mg/m(2) twice daily from day 2-15, every 21 days) or the FOLFIRI arm (irinotecan 180 mg/m(2), 5-FU 400 mg/m(2), LV 200 mg/m(2), 5-FU 2400 mg/m(2) (46-h infusion)--all given on day one, every 14 days). Primary end points were objective response rate (ORR) and rate of radical (R0) surgical resection. Secondary end points were progression-free survival (PFS), overall survival (OS) and safety. RESULTS: Altogether 87 patients were enrolled (41 pts in the XELIRI and 46 pts in the FOLFIRI arm). The median age was 63 years (63 years in the XELIRI and 62 years in the FOLFIRI arm) (p = 0.33). ORR was 49% in the XELIRI and 48% in the FOLFIRI arm (p = 0.76). The rate of radical R0 resection was 24% in both arms of patients. At the end of treatment, 37% of patients in the XELIRI and 26% of patients in the FOLFIRI arm were without evidence of the disease (CR+R0 resection) (p = 0.56). There were no statistical differences in grade 3 or 4 adverse events between both arms: diarrhoea 7% vs. 6%, neutropenia 5% vs. 13%, ischemic stroke 0 vs. 2%, acute coronary syndrome 2% vs. 4%, respectively. At the median follow up of 17 (range 1-39) months, the median PFS was 10.3 months in the XELIRI and 9.3 months in the FOLFIRI arm (p = 0.78), the median OS was 30.7 months in the XELIRI arm and 16.6 months in the FOLFIRI arm (p = 0.16). CONCLUSION: The XELIRI regimen showed similar ORR as the FOLFIRI regimen in the neoadjuvant treatment of patients with MCRC. In addition, the XELIRI regimen showed similar PFS and OS with acceptable toxicity compared to the FOLFIRI regimen. TRIAL REGISTRATION: Current Controlled Trials ISRCTN19912492.

Electrochemotherapy with cisplatin of cutaneous tumor lesions in breast cancer.

We have evaluated the efficiency of electrochemotherapy with cisplatin on cutaneous tumor lesions of breast cancer and have compared its efficiency with the efficiency of intratumoral (i.t.) administration of cisplatin alone. The study was performed on six breast cancer patients with 26 cutaneous lesions in whom all standard treatment modalities were exhausted. Of 26 lesions, 12 were treated by electrochemotherapy, six by i.t. cisplatin application, while eight were controls. In all 12 lesions treated by electrochemotherapy and followed-up for up to 26 weeks at the most, the objective response was obtained [complete response in 33% with mean duration of 10 weeks and partial response (PR) in 67% with a mean duration of 5 weeks]. In six lesions treated with i.t. application of cisplatin and followed-up for up to 12 weeks at the most, objective response was obtained in 83% of lesions; none of these responses were complete, the mean duration of PR was 5 weeks. During electrochemotherapy, only minimal local side-effects were observed, whereas no systemic side-effects of the treatment were noticed. We conclude that electrochemotherapy with i.t. cisplatin application is effective in local treatment of cutaneous tumor lesions of breast cancer.