Hellenic Oncology Research Group

Athens, Greece

Hellenic Oncology Research Group

Athens, Greece

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Koinis F.,University of Crete | Koinis F.,Hellenic Oncology Research Group | Vetsika E.K.,University of Crete | Aggouraki D.,University of Crete | And 7 more authors.
Journal of Thoracic Oncology | Year: 2016

Introduction: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature cells of myeloid origin whose expression is induced by, among others things, vascular endothelial growth factor. We have previously identified two monocytic and one granulocytic MDSC subpopulations associated with the clinical outcome in patients with non-small cell lung cancer (NSCLC). The aim of the present study was to evaluate the effect of chemotherapy on these MDSC subpopulations. Methods: Circulating immune cells from 46 patients with unresectable NSCLC were analyzed by flow cytometry before the initiation of chemotherapy and after three cycles. Changes in the frequencies of the MDSC subpopulations were correlated with clinical outcome. Results: Chemotherapy had no uniform effect on either the number or the functionality of monocytic and granulocytic MDSCs. However, three cycles of bevacizumab-containing regimens significantly reduced the percentage of the granulocytic-MDSCs compared with non-bevacizumabbased regimens (p = 0.0086). At the time of evaluation of response, disease progression was associated with significantly higher levels of all three MDSC subpopulations compared with in patients with disease control. In patients with disease progression after three cycles of chemotherapy, the percentage of CD15-positive monocytic MDSCs was significantly increased compared with baseline. Conclusions: In the peripheral blood of patients with NSCLC, bevacizumab-based chemotherapy significantly reduced the levels of granulocytic MDSCs. An increase in the levels of CD15-positive monocytic MDSCs was associated with poor response to treatment and disease progression, providing evidence of their clinical relevance in patients with NSCLC. © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.


Karachaliou N.,Hellenic Oncology Research Group | Polyzos A.,Hellenic Oncology Research Group | Kentepozidis N.,Hellenic Oncology Research Group | Kakolyris S.,Hellenic Oncology Research Group | And 6 more authors.
Oncology | Year: 2010

Purpose: To evaluate the efficacy and tolerability of oxaliplatin (L-OHP) in combination with irinotecan (CPT-11) as first-line treatment of advanced biliary tract cancer. Patients and Methods: Patients with histologically confirmed nonresectable biliary adenocarcinoma were treated with oxaliplatin (85 mg/m2) and irinotecan (200 mg/m2) every 3 weeks.Results: Twenty-eight patients were enrolled between May 2005 and March 2009. The overall objective response rate was 17.9% with an additional 21.4% of patients with stable disease (disease control rate 39.3%). The median overall survival time was 9.2 months (95% CI 5.8-12.5) and the median progression-free survival time 2.7 months (95% CI 2.2-3.2). Grades 3 and 4 neutropenia occurred in 1 (3.6%) and 4 (14.3%) patients, respectively, and febrile neutropenia in 3 (10.7%). Grade 3-4 diarrhea was observed in 2 (7.1%) patients and grade 3 asthenia in 1 (6%). There were no treatment-related deaths. Conclusion: The combination of oxaliplatin and irinotecan has a modest antitumor activity with manageable toxicity as first-line treatment in metastatic cancer of the biliary tract and therefore it cannot be recommended as front-line treatment for unresectable biliary tract cancer. Copyright © 2010 S. Karger AG, Basel.


Tryfonidis K.,Hellenic Oncology Research Group | Boukovinas I.,Hellenic Oncology Research Group | Xenidis N.,Hellenic Oncology Research Group | Christophyllakis C.,Hellenic Oncology Research Group | And 7 more authors.
Breast | Year: 2013

Purpose: To assess the efficacy and toxicity of docetaxel (D) plus epirubicin (E) in combination with bevacizumab (B) [DEB regimen] as front-line treatment in patients with metastatic breast cancer (MBC). Patients and methods: Women with previously untreated HER2-negative MBC received B (15mg/kg), E (75mg/m2) and D (75mg/m2) with prophylactic G-CSF support every 3 weeks (q3w) for up to 9 cycles followed by B (15mg/kg q3w) until disease progression. Primary endpoint was the overall response rate (ORR). Circulating tumor cells (CTCs) were evaluated using the CellSearch system at different time points during therapy. Results: Eighty-three women were enrolled with median age 62 years, performance status 0-1 in 93%, triple negative disease in 12% and liver metastases in 47%. In an intention to treat analysis, complete response was achieved in 13 (15.7%) and partial response in 42 (50.6%) (overall response rate 66.3%; 95% CI 56.09-76.44%). The median time to progression was 20.1 months and the 1-year overall survival rate 82.3%. Grade 3-4 neutropenia occurred in 37%, febrile neutropenia in 10%, anemia in 4%, thrombocytopenia in 2% and diarrhea in 2% of patients. There were two deaths possibly related to study treatment (sigmoid perforation n=1; sudden death n=1). Moreover, one patient developed pulmonary embolism and another one myocardial infarction while on treatment. Although DEB administration significantly reduced the proportion of patients presenting CTCs, the detection of ≥5 or ≥1 CTCs before treatment initiation was significantly associated with worse progression-free survival (. p=0.001 and p=0.004) and overall survival (. p=0.001 and p=0.027), respectively. Conclusions: The DEB regimen is a very active but also potentially toxic combination in MBC. Detection of CTCs before treatment is associated with worse outcome. Clinicaltrials.gov: NCT00705315. © 2013 Elsevier Ltd.


PubMed | Hellenic Oncology Research Group
Type: Clinical Trial, Phase II | Journal: Cancer chemotherapy and pharmacology | Year: 2013

The docetaxel/cisplatin (DC) combination is an active regimen against advanced/metastatic non-small-cell lung cancer (NSCLC), and bevacizumab (B) improves the efficacy of frontline chemotherapy. This phase II study was designed in order to explore the efficacy and safety of DCB regiment in this setting.Chemotherapy-nave patients (n = 48) with measurable, histologically confirmed non-squamous, IIIB (wet)/IV NSCLC, and PS 0-2 were eligible. Patients received D (75 mg/m(2) IV), C (80 mg/m(2) IV), and B (15 mg/kg IV) every 3 weeks. Maintenance of bevacizumab was not mandatory.Complete and partial responses were achieved in two (4.2%) and 14 (29.2%) patients, respectively [overall response rate: 33.3%; 95% CI = 20.0-46.7%], whereas stable disease was documented in 14 [disease control rate = 62.5%; 95% CI = 48.8-76.2%]. The median progression-free survival was 4.4 months and the median overall survival 13.3 months. Treatment-related grade 3 or 4 hematologic adverse events were leukopenia, neutropenia, and anemia in 8.4, 18.7, and 2.1% of the patients, respectively. Febrile neutropenia occurred in three (6.3%) patients. Bleeding was documented in 4% of the patients, thrombotic episodes in 8%, and proteinuria in 3%. There was one treatment-related death.Frontline DCB in patients with advanced non-squamous NSCLC is an active regimen with manageable toxicity and merits to be further investigated.


PubMed | Hellenic Oncology Research Group
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

15008 Background: CAPIRI has been reported to be associated with significant toxicity. Therefore, an unplanned interim analysis for safety of a randomized trial evaluating CAPIRI + Bevacizumab vs FOLFIRI + Bevacizumab regimens for the treatment of mCRC was performed.Assuming time to tumor progression (TTP) of 7.5 months for Arm B and 5.5 months for Arm B, 280 patients should be enrolled in the study (two-tailed log-rank test; a=0.05, b=0.8).Patients were randomized to receive either (Arm A) CPT-11 (250 mg/mAmong the 156 enrolled patients (Arm A = 74; Arm B = 82), were evaluable for toxicity (administered cycles: 1061). Treatment delays were observed in 4% and 2% Arm A and B patients, respectively (p=0.09). Dose reduction was required in 9.5% and 4.5% Arm A and B patients, respectively (p=0.002). Treatment discontinuation due to treatment related toxicity occurred in 13% and 4.5% Arm A and B patients, respectively. Sixty days mortality rate was low in both arms (Arm A: 1.5%, Arm B: 1.2%). There was no difference between the two regimens in terms of objective response rate, TTP and OS (n = 142 patients).These preliminary results show that CAPIRI + Bevacizumab regimen could safely administered in patients with mCRC. No significant financial relationships to disclose.


PubMed | Hellenic Oncology Research Group
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

658 Background: Both Vinorelbine plus Gemcitabine (VG) regimen and Capecitabine (C) monotherapy are active salvage treatments in patients (pts) with advanced breast cancer (ABC). In this multicenter study we compared the efficacy and tolerability of the two regimens as salvage treatment in pts with ABC pretreated with taxane and anthracycline chemotherapy.Pts were randomized to receive either vinorelbine 25 mg/mA total of 114 pts were randomized to VG (n=60) and C (n=54). All pts were evaluable for toxicity and 58 VG and 54 C pts for response. Seven (VG) vs 9 (C) pts had stage IIIB disease and 6 vs 5 pts had PS 2. We observed one complete response on each arm and 14(24%) vs 12(22%) partial responses for an overall response rate of 25.8% vs 24.1% (p=0.8) in VG vs C pts, respectively. The median duration of response was 5 vs 12 months (p=0.02) and the median TTP 3.7 vs 5.8 months (p=0.4) for VG and C pts, respectively. A total of 339 VG and 270 C cycles were administered with no toxic deaths. Both regimens were overall well tolerated; grade 3-4 neutropenia 17% vs 4% (p=0.02), anemia 4% vs 2% (p=0.6), grade 3 thrombocytopenia 2% vs 2%, neurotoxicity 3% vs 2%, grade 2-4 hand-foot syndrome 2% vs 15% (p=0.009) for VG and C pts, respectively.In this preliminary analysis the VG and C regimens showed similar activity but different although rarely severe toxicity. Updated results will be presented at the meeting. No significant financial relationships to disclose.


PubMed | Hellenic Oncology Research Group
Type: Journal Article | Journal: Annals of oncology : official journal of the European Society for Medical Oncology | Year: 2011

Approximately 50% of newly diagnosed cases of non-small-cell lung cancer (NSCLC) are observed in patients >65 years, while 30%-40% of cases occur in patients >70 years.The objective of the current study was to determine (i) the number of elderly (>70 years) patients with advanced/metastatic NSCLC enrolled in phase III trials of the Hellenic Oncology Research Group, (ii) the treatment-related toxicity observed in these patients compared with their younger counterparts, and (iii) the differences in terms of response rate, time to tumor progression (TTP), and overall survival (OS) between younger and older patients.Pooled data from five clinical trials including 1845 patients were analyzed; 1421 (77%) and 424 (23%) were <70 years and 70 years, respectively. No difference was observed in terms of the overall response rate and TTP. There was an OS difference between young and older patients, with higher risk for death in older patients. However, when the analysis was carried out after omitting a trial that showed a different trend, no difference was observed. Older patients experienced higher toxicity.This report supports the feasibility of chemotherapy treatment for older NSCLC patients. Optimization of treatment of older NSCLC patients requires the design of prospective older-specific phase III trials for these patients.


PubMed | Hellenic Oncology Research Group
Type: Clinical Trial, Phase II | Journal: Oncology | Year: 2010

To evaluate the efficacy and tolerability of oxaliplatin (L-OHP) in combination with irinotecan (CPT-11) as first-line treatment of advanced biliary tract cancer.Patients with histologically confirmed nonresectable biliary adenocarcinoma were treated with oxaliplatin (85 mg/m(2)) and irinotecan (200 mg/m(2)) every 3 weeks.Twenty-eight patients were enrolled between May 2005 and March 2009. The overall objective response rate was 17.9% with an additional 21.4% of patients with stable disease (disease control rate 39.3%). The median overall survival time was 9.2 months (95% CI 5.8-12.5) and the median progression-free survival time 2.7 months (95% CI 2.2-3.2). Grades 3 and 4 neutropenia occurred in 1 (3.6%) and 4 (14.3%) patients, respectively, and febrile neutropenia in 3 (10.7%). Grade 3-4 diarrhea was observed in 2 (7.1%) patients and grade 3 asthenia in 1 (6%). There were no treatment-related deaths.The combination of oxaliplatin and irinotecan has a modest antitumor activity with manageable toxicity as first-line treatment in metastatic cancer of the biliary tract and therefore it cannot be recommended as front-line treatment for unresectable biliary tract cancer.


To compare the activity and toxicity of docetaxel/carboplatin (DC) doublet vs single agent docetaxel (D) as second-line treatment in patients with advanced non-small cell lung cancer (NSCLC).Patients pre-treated with front-line platinum-free regimens, were randomized to receive either docetaxel/carboplatin (DC), (docetaxel 50 mg/m2; carboplatin AUC4; both drugs administered on days 1 and 15) or docetaxel single-agent (D), (docetaxel 50 mg/m2 on days 1 and 15).Response rate was similar between the two arms (DC vs D: 10.4% vs 7.7%; p = 0.764). After a median follow-up time of 28.0 months for DC arm and 34.5 months for D arm, progression free survival (PFS) was significantly higher in the DC arm (DC vs D:3.33 months vs 2.60 months; p-value = 0.012), while no significant difference was observed in terms of overall survival (OS) (DC vs D: 10.3 months vs 7.70 months; p-value = 0.550). Chemotherapy was well-tolerated and grade III/IV toxicities were relatively infrequent. No toxic deaths were observed.This study has not achieved its primary objective of significant OS prolongation with docetaxel/carboplatin combination over single-agent docetaxel in patients who had not received front-line docetaxel; however, the docetaxel/carboplatin combination was associated with a significant clinical benefit in terms of PFS.


PubMed | Hellenic Oncology Research Group
Type: Clinical Trial, Phase I | Journal: Breast (Edinburgh, Scotland) | Year: 2013

To assess the efficacy and toxicity of docetaxel (D) plus epirubicin (E) in combination with bevacizumab (B) [DEB regimen] as front-line treatment in patients with metastatic breast cancer (MBC).Women with previously untreated HER2-negative MBC received B (15 mg/kg), E (75 mg/m2) and D (75 mg/m2) with prophylactic G-CSF support every 3 weeks (q3w) for up to 9 cycles followed by B (15 mg/kg q3w) until disease progression. Primary endpoint was the overall response rate (ORR). Circulating tumor cells (CTCs) were evaluated using the CellSearch system at different time points during therapy.Eighty-three women were enrolled with median age 62 years, performance status 0-1 in 93%, triple negative disease in 12% and liver metastases in 47%. In an intention to treat analysis, complete response was achieved in 13 (15.7%) and partial response in 42 (50.6%) (overall response rate 66.3%; 95% CI 56.09-76.44%). The median time to progression was 20.1 months and the 1-year overall survival rate 82.3%. Grade 3-4 neutropenia occurred in 37%, febrile neutropenia in 10%, anemia in 4%, thrombocytopenia in 2% and diarrhea in 2% of patients. There were two deaths possibly related to study treatment (sigmoid perforation n = 1; sudden death n = 1). Moreover, one patient developed pulmonary embolism and another one myocardial infarction while on treatment. Although DEB administration significantly reduced the proportion of patients presenting CTCs, the detection of 5 or 1 CTCs before treatment initiation was significantly associated with worse progression-free survival (p = 0.001 and p = 0.004) and overall survival (p = 0.001 and p = 0.027), respectively.The DEB regimen is a very active but also potentially toxic combination in MBC. Detection of CTCs before treatment is associated with worse outcome.NCT00705315.

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