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Stathopoulos G.P.,Errikos Dunant Hospital | Armakolas A.,National and Kapodistrian University of Athens | Tranga T.,Bioanalytica Genotype S.A | Marinou H.,Errikos Dunant Hospital | And 2 more authors.
Oncology Reports | Year: 2011

Hematologic paraneoplastic alternations may not be very common, but they have been observed in a small number of patients. Granulocytosis has been described in several malignancies and its common mechanism may be associated with granulocyte colony-stimulating factor (G-CSF) production by the tumor. High neutrophilia (150,000-240,000 white blood cell count) observed in two patients with non-small cell lung cancer led us to run the present trial. The purpose of this study was to compare the white blood cell counts and the G-CSF plasma levels of the patients and classify the results into groups, as well as to determine the survival rates of the patients in each of the groups. The histological specimens and plasma of two patients as well as the plasma of another 87 patients with several malignancies, were examined. The plasma G-CSF levels were determined using a quantitative sandwich immunoassay technique (Quantikine; RYSD Systems) according to the manufacturer's instructions and all samples were tested in triplicate. It was found that 12 patients had a white blood cell count increased beyond normal as well as a high G-CSF plasma level and the survival of these patients was shorter as compared to the rest of the patients. We assume that these findings may indicate that increased G-CSF levels may function as a biomarker of survival. Copyright © 2011 Spandidos Publications Ltd. All rights reserved.


Stathopoulos G.P.,Errikos Dunant Hospital | Stathopoulos J.,Errikos Dunant Hospital | Dimitroulis J.,Hospital of Thoracic Diseases
Oncology Letters | Year: 2012

Liposomal cisplatin (Lipoplatin) is a new agent, a cisplatin formulation that has been investigated in a number of studies and compared with cisplatin with respect to toxicity and effectiveness. It has been administered once weekly and in combination with a second agent, once every two weeks. The main outcome of the studies was that lipoplatin has no renal toxicity and is as equally effective as cisplatin. The present study investigated toxicity and effectiveness when lipoplatin is administered on two consecutive days, repeated every two weeks. Between January 2011 and November 2011, a total of 21 patients with histologically- or cytologically-confirmed non-small cell lung cancer (NSCLC) were enrolled in the study. All but two patients, who had not been pretreated, had received one or two series of chemotherapy and some had undergone radiotherapy. Lipoplatin monotherapy was infused for 8  h the first and second  days and repeated every 2  weeks with the aim of administering 6  cycles. The dose per day was 200  mg/m 2. Eight out of 21 (38.10%) patients had a partial response, 9 (42.86%) had stable disease and 4 (19.05%) had progressive disease. Results showed that there was no renal failure toxicity and no other adverse reactions apart from grade  1 myelotoxicity in only 2  patients who had been heavily pretreated, and grade  1 nausea/vomiting in 4 patients. Liposomal cisplatin is an agent with negligible toxicity and reasonably high effectiveness even when administered to pretreated patients with NSCLC.


Stathopoulos G.P.,Errikos Dunant Hospital | Antoniou D.,Hospital for Thoracic Disorders | Dimitroulis J.,Hospital for Thoracic Disorders | Stathopoulos J.,Errikos Dunant Hospital | And 2 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2011

Purpose: Liposomal cisplatin was developed to reduce the systemic toxicity of cisplatin, particularly the nephrotoxicity, and it has been used in combination with other agents in pancreatic and head and neck cancers and non-small-cell lung cancer (NSCLC). Our objective was to compare the effectiveness of lipoplatin combined with paclitaxel versus cisplatin with paclitaxel in advanced non-squamous NSCLC. Methods: During 2007-2010, 202 patients with non-squamous NSCLC (stage IIIB and IV) were recruited from the two participating institutions and divided into two arms: Arm A was treated with liposomal cisplatin 200 mg/m 2 combined with paclitaxel 135 mg/m 2 and Arm B with cisplatin 75 mg/m 2 in combination with paclitaxel 135 mg/m 2, repeated every 2 weeks. The number of cycles administered was 632 (Arm A) and 640 (Arm B), totaling 1,272. Results: A partial response was achieved by 59.22% of Arm A patients versus 42.42% of Arm B, and the difference was statistically significant (P 0.036). The median survival time in months was 10 for Arm A and 8 for Arm B (P 0.1551). After 18 months, the number of surviving patients was double for Arm A versus Arm B. Conclusion: Liposomal cisplatin in combination with paclitaxel produces a statistically significantly higher response rate than cisplatin combined with paclitaxel in non-squamous NSCLC. © 2011 The Author(s).


Stathopoulos G.P.,Errikos Dunant Hospital | Trafalis D.,Errikos Dunant Hospital | Dimitroulis J.,Hospital for Thoracic Diseases | Kosmas C.,Anticancer Hospital | And 2 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2013

Purpose: The established treatment for small-cell lung cancer has been a cisplatin-etoposide combination, as the most effective chemotherapy regimen. Paclitaxel has also been used in combination with cisplatin and etoposide but this has been unacceptable due to the toxicity. This toxicity could be attributed to the three consequent days of treatment with etoposide plus the doses of each of the three drugs. Our objectives were to determine an equal or longer survival and lower toxicity by administering all 3 drugs with low dosage on day one, compared to the established guideline of 3-day administration. Methods: We tested the aforementioned three-drug combination and avoided the toxicity in the majority of patients by administering all 3 drugs on day one. Fifty-one patients (50 evaluable) were recruited from 4 oncology clinics. All patients had histologically or cytologically confirmed small-cell lung cancer with limited and extensive disease in 40 and 60 % of the patients, respectively. The treatment was: cisplatin 75 mg/m2, etoposide 120 mg/m 2 (maximum 200 mg), and paclitaxel 135 mg/m2. The agents were administered on day one and repeated every 3 weeks for 6 cycles. Results: The median survival was 15 months (95 % CI 13.6-16.4) (mean 16 months). Forty-five (90 %) patients achieved a response: 20 (40 %) patients, a complete response and 25 (50 %), a partial response. Adverse reactions included grade 3 and 4 neutropenia in 12 and 2 % of the patients, respectively. Other side effects were of very low toxicity. Conclusion: The 1-day, three-agent (cisplatin-etoposide-paclitaxel) treatment of small-cell lung cancer is beneficial with respect to response rate and survival, and the toxicity is low and well-tolerated. © 2012 The Author(s).


Stathopoulos G.P.,Errikos Dunant Hospital | Rigatos S.K.,Errikos Dunant Hospital | Stathopoulos J.,Errikos Dunant Hospital
Anticancer Research | Year: 2010

Background: The aim of the present trial was to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of liposomal cisplatin (lipoplatin) using nephrotoxicity, gastrointestinal toxicity and myelotoxicity as the main adverse reactions. Patients and Methods: Lipoplatin, a liposomal formulation of cisplatin was first tested as monotherapy starting at a dose of 125 mg/m2 and escalating up to 350 mg/m2. Lipoplatin was then escalated in combination with paclitacel starting at a dose of 100 mg/m2 escalating up to 250 mg/m2 for the former and 100 mg/m2 escalating up to 175 mg/m2 for the latter. Results and Conclusion: The present trial determined the DLT for lipoplatin monotherapy at 350 mg/m2 and the MTD at 300 mg/m2; for lipoplatin-paclitaxel combination therapy, the DLT was 250 mg/m2 for lipoplatin and 175 mg/m2 for paclitaxel whereas the MTD was 200 mg/m2 for lipoplatin and 175 mg/m2 for paclitaxel.


Stathopoulos G.P.,Errikos Dunant Hospital | Batziou C.,Errikos Dunant Hospital | Trafalis D.,Errikos Dunant Hospital | Koutantos J.,Errikos Dunant Hospital | And 4 more authors.
Oncology | Year: 2010

Objective: The objective of this phase III trial was to compare chemotherapy combined with bevacizumab versus chemotherapy alone in the treatment of patients with advanced colorectal cancer. Methods: From September 2004 till September 2008, 222 treatment-naive patients were enrolled and divided into 2 arms: 114 arm A patients were treated with leucovorin, 5-fluorouracil plus irinotecan in combination with bevacizumab, and 108 arm B patients were treated as above without bevacizumab. All patients were stage IV with histologically confirmed adenocarcinoma. Results: The median overall survival of arm A patients was 22.0 months (95% CI: 18.1-25.9) and 25.0 months (CI: 18.1-31.9) for arm B patients. There was no statistically significant difference between the 2 arms (p = 0.1391). No statistically significant difference between the 2 arms regarding the response ratewas observed: partial response, 42 patients (36.8%) and 38 patients (35.2%) for arms A and B, respectively. Hematologic toxicity did not differ in the comparison of the 2 arms. Nonhematologic toxicity in arm A involved hypertension in 23 (20.2%) of the patients and proteinuria in 7 (6.1%); 3 patients experienced hemorrhage and 1 patient intestinal perforation. None of these side effects was observed in arm B patients. Conclusion: No statistically significant difference in median overall survival in patients with advanced colorectal cancer treated with bevacizumab plus a combination therapy (arm A) and those treated with the combination only, without bevacizumab (arm B), was observed. Copyright © 2010 S. Karger AG, Basel.


Stathopoulos G.P.,Errikos Dunant Hospital
Anti-Cancer Drugs | Year: 2010

Over the last three decades, cisplatin has been one of the most effective cytotoxic agents, but its administration has been hindered by its nephrotoxicity, neurotoxicity and myelo toxicity. Recently, liposomal cisplatin, lipoplatin, has been formulated and tested thoroughly in preclinical (in vitro) and phase I, II and III trials, as documented in the literature. Experiments in animals showed that lipoplatin is less toxic than cisplatin and that it produces tumour reduction. The histological examination of treated tumours from mouse xenografts was consistent with apoptosis in the tumour cells in a mechanism similar to that of cisplatin. Lipoplatin infusion in patients and measurements of platinum levels in tumour specimens showed 10-50 times higher levels in tumours and metastases than in the adjacent normal specimens. A phase I-II study using a combination of lipoplatin and gemcitabine in pretreated patients (with disease progression or stable disease) with advanced pancreatic cancer was conducted. No nephrotoxicity was observed. With lipoplatin monotherapy the dose-limiting toxicity was determined to be 350mg/m and the maximum tolerated dose 300mg/m; when used in combination with paclitaxel the dose-limiting toxicity for lipoplatin was 250mg/m and for paclitaxel 175mg/m, and the maximum tolerated dose was 200 and 175mg/m, respectively. In two phase II randomized studies comparing the lipoplatin combination versus the cisplatin combination, it was found that the former was statistically significantly less toxic than the latter, whereas the response rate and survival were similar. Up to now, the data on lipoplatin treatment in malignant tumours are quite impressive, because of the negligible toxicity and because it is equal if not superior to cisplatin with regard to response rate. This review aims to chronologically document publications relevant to liposomal cisplatin to date. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Stathopoulos G.P.,Errikos Dunant Hospital
Journal of B.U.ON. | Year: 2013

One of the most important anticancer agents is cisplatin (CDDP). Numerous studies with a CDDP-based combination have been reported over the last 30 years. The use of CDDP in the 1980s and 1990s showed responses in advanced stage non-small-cell lung cancer (NSCLC). Over the years it was found that the side effects of this agent (particularly nephrotoxicity) were a common problem. Agents such as carboplatin, taxanes, gemcitabine, irinotecan and pemetrexed proved to be effective in NSCLC with reduced or no nephrotoxicity. The administration of these newer agents improved several side effects, but without improving efficacy. When prophylactic (adjuvant) treatment for NSCLC was introduced, CDDP was the agent selected, which indicated the value of the drug. Recently, a novel formulation of CDDP, liposomal cisplatin, which has shown very low toxicity, no nephrotoxicity and equal effectiveness was produced; its importance is its higher effectiveness than standard CDDP in lung adenocarcinoma.


Stathopoulos G.P.,Errikos Dunant Hospital | Trafalis D.,Errikos Dunant Hospital
Journal of B.U.ON. | Year: 2013

High-dose tamoxifen was used as a treatment for bone metastasis in 16 patients with breast cancer. All of them had been pretreated with hormonal therapy, including lowdose tamoxifen. The results were extremely positive with clinical amelioration and also disappearance of osteolysis in 5 patients.


Stathopoulos G.P.,Errikos Dunant Hospital
Oncology Letters | Year: 2011

Colorectal cancer has specific biological characteristics that distinguish it from other malignancies. One such characteristic is its slow growth in patients in advanced stages. For the past 15 years, no effective systemic treatment has been available in clinical practice. The present study involved a retrospective evaluation of patients with advanced colorectal cancer in order to assess the median and overall survival of patients. Concurrently, the study aimed to describe the biological characteristics of this slow-growing disease and the quality of life of the patients. The key characteristic of this patient group was the lack of any systemic treatment. The study included 40 patients (25 male and 15 female, median age 67 years) who were evaluated between 1993 and 1996. Only supportive treatment was provided. One patient underwent 2 cycles of chemotherapy. Liver surgery was unsuccessfully performed on 3 patients. Two patients underwent radiofrequency once and 2 had intra-arterial treatment, also once. The results showed the median survival of patients to be 24 months (range 16-42). One-year survival was found to be 65% while the 2-year survival was found to be 25%. A satisfactory quality of life was also observed. In conclusion, colorectal cancer is a slow-going malignancy, as indicated by the long-term survival of patients and the biological characteristics of the tumor.

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