Hellenic Oncology Research Group HORG

Athens, Greece

Hellenic Oncology Research Group HORG

Athens, Greece
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Matikas A.,Karolinska Institutet | Matikas A.,Hellenic Oncology Research Group HORG | Foukakis T.,Karolinska Institutet | Michalakis I.,General Hospital of Serres | And 2 more authors.
Expert Review of Anticancer Therapy | Year: 2017

Introduction: Although neoadjuvant chemotherapy has been widely adopted as it increases breast conservation rates, permits the in vivo testing of the activity of chemotherapeutics and offers the opportunity to conduct translational research based on longitudinal assessments of tumor tissue, neoadjuvant endocrine therapy has been met with skepticism owing to slow regression rates and a low chance for pathologic remission. Areas covered: Herein, the results of clinical trials comparing different endocrine agents as neoadjuvant treatment, endocrine therapy with chemotherapy, treatment duration, novel combinations and putative biomarkers are reviewed, with the aim to better understand the current and future role of this modality in clinical practice. Expert commentary: Available evidence clearly indicates that, in properly selected patients, short-term outcomes do not differ compared to chemotherapy. In addition, the realization that its effects at the cellular level occur shortly after its initiation and have important prognostic implications, could serve as a tool for the early identification of non-responders. Ongoing trials which integrate novel agents in addition to endocrine therapies will help guide treatment decisions and may establish neoadjuvant endocrine therapy as a standard of care for well-defined patient subgroups. © 2017 Informa UK Limited, trading as Taylor & Francis Group.

Mavroudis D.,University Hospital of Heraklion | Saloustros E.,General Hospital of Heraklion Venizelio | Boukovinas I.,Bioclinic | Papakotoulas P.,Theageneio Cancer Center | And 11 more authors.
British Journal of Cancer | Year: 2017

Background:Sequential anthracyclines and taxanes are standard adjuvant chemotherapy for patients with high-risk axillary node-positive breast cancer. We compared a sequential to a concurrent regimen in high-risk node-negative early breast cancer.Methods:Patients were eligible if they had tumours >2 cm or T1c with two of the following characteristics: no oestrogen receptor (ER) and progesterone receptor (PR) expression, histological grade III, Ki67 >40% and vascular, lymphovascular or perineural invasion. They were randomised to receive four cycles of epirubicin 90 mg m '2 followed by four cycles of docetaxel 75 mg m '2 (sequential regimen) or six cycles of epirubicin 75 mg m '2 plus docetaxel 75 mg m '2 (concurrent regimen). All chemotherapy cycles were administered every 21 days with G-CSF prophylaxis only for the concurrent arm. The primary endpoint was disease-free survival (DFS).Results:Between 2001 and 2013, 658 women received the sequential (n=329) or the concurrent (n=329) regimen. The median age was 53 years, 43.9% of the patients were premenopausal and of the tumours 44.2% were 1/22 cm, 52.7% histological grade 3 and 35.3% hormone receptor-negative. After a median follow-up of 70.5 months, there were 29 (8.8%) vs 42 (12.8%) disease relapses (P=0.102) and 11 (3.3%) vs 19 (5.8%) deaths (P=0.135), in the sequential and concurrent arm, respectively. The 5-year DFS rates were 92.6% vs 88.2% for sequential and concurrent arm, respectively (hazard ratio (HR): 1.591; 95% confidence interval (CI): 0.990-2.556; P=0.055). Toxicity included grade 2-4 neutropenia in 54% vs 41% (P=0.001), febrile neutropenia 2.7% vs 6.1% (P=0.06), nausea/vomiting 18.5% vs 12.4% (P=0.03) of patients in the sequential and concurrent arm. There were no toxic deaths.Conclusions:Sequential compared with the concurrent administration of anthracyclines and taxanes is associated with a non-significant but possibly clinically meaningful improvement in DFS. In the era of molecular selection of patients for adjuvant chemotherapy, this study offers valuable information for the optimal administration of anthracyclines and taxanes in patients with node-negative disease. © 2017 Cancer Research UK. All rights reserved.

Syrios J.,St Savvas Cancer Hospital | Nintos G.,University of Crete | Georgoulias V.,Hellenic Oncology Research Group HORG
Expert Review of Anticancer Therapy | Year: 2015

Non-small lung cancer (NSCLC) is a lethal malignancy when diagnosed in advanced stage. The evolution of chemotherapy and the development of agents targeting certain molecular pathways involved in tumor progression improved the prognosis. Nintedanib is a new tyrosine kinase inhibitor, which exerts its activity by blocking VEGF, FGF and PDGF receptors and inhibits the angiogenic signaling by preventing receptor dimerization. Several Phase I and II studies proved its safety and efficacy in diverse solid tumors. In patients with advanced NSCLC, the administration of nintedanib may offer an additional chemotherapy benefit in terms of response rate, progression-free survival and overall survival particularly in patients with adenocarcinoma histology, with manageable toxicity. Here, we present an analytical review of literature regarding nintedanib and we focus on its particular importance in NSCLC treatment. © Informa UK, Ltd.

Matikas A.,University of Crete | Mistriotis D.,University of Ioannina | Georgoulias V.,Hellenic Oncology Research Group HORG | Kotsakis A.,University of Crete
Clinical Lung Cancer | Year: 2015

Metastatic non-small-cell lung cancer carries a dismal prognosis. However, the recognition of the predictive value of activating epidermal growth factor receptor (EGFR) mutations and the availability of tyrosine kinase inhibitors has markedly improved the prognosis of these patients, because treatment with these inhibitors induces rapid and robust responses. Unfortunately, the responses are not durable and resistance inevitably occurrs after a median of 9 to 14 months. Although the management of resistant patients who harbor EGFR mutations is rapidly evolving, there are no conclusive guidelines regarding this issue. However, palliative cytotoxic chemotherapy is considered the standard of care for these patients. The elucidation of the mechanisms of acquired resistance has led to efforts to personalize the treatment approach. Promising results from early clinical trials using the third-generation inhibitors that specifically target the most common mechanism of resistance, the gatekeeper T790M mutation, provide the basis to look to the future with cautious optimism. Moreover, it has been shown that in some cases of oligoprogressive disease, aggressively treating all metastatic sites while continuing the targeted treatment could improve outcomes. Herein, we review the treatment strategies being evaluated that will shape the future management of these patients. © 2015 Elsevier Inc. All rights reserved.

Mavroudis D.,Hellenic Oncology Research Group HORG | Mavroudis D.,University of Crete
Cancer Chemotherapy and Pharmacology | Year: 2015

Purpose: To evaluate the activity and safety of the doc-etaxel, gemcitabine and bevacizumab combination, administered biweekly, in pretreated patients with HER-2-negative metastatic breast cancer (MBC). Patients and methods: Women with HER-2-negative MBC, and disease progression after at least one prior line of chemotherapy, were treated with docetaxel 50 mg/m2, gemcitabine 1, 500 mg/m2 and bevacizumab 10 mg/kg every 2 weeks. Bevacizumab was continued until disease progression. Results: Forty-eight patients have been enrolled. Their median age was 61 years, 95.8 % had a performance status 0-1, 83.3 % had hormone receptor-positive disease, and 47.9 % had received one prior line of chemotherapy. All patients were evaluable for toxicity and 45 for response. Partial response was achieved in 20 patients [PR = 44.4 %, 95 % confidence interval (CI) 29.9-59 %] and disease stabilization in 15 (33.3 %). The median progression-free survival was 7.1 months (95 % CI 4.7-9.5 months) and the median overall survival 21.1 months (95 % CI 10.3-31.9 months). Grade 3-4 neutropenia occurred in 19 patients (39.6 %) and febrile neutropenia in 2 (4.2 %). Most common grade 2-3 non-hematologic adverse events included nausea (10.4 %), diarrhea (10.5 %), neurotoxic-ity (12.5 %) and fatigue (31.3 %), whereas grade 2 hemorrhage and hypertension occurred in 6.3 and 10.4 %, respectively. There were no grade 4 non-hematologic toxicities or toxic deaths. Conclusion: The combination of docetaxel, gemcitabine and bevacizumab has promising activity and manageable toxicity as salvage chemotherapy for HER-2-negative MBC patients. © Springer-Verlag Berlin Heidelberg 2014.

Matikas A.,Hellenic Oncology Research Group HORG | Georgoulias V.,Hellenic Oncology Research Group HORG | Kotsakis A.,Hellenic Oncology Research Group HORG
Expert Review of Respiratory Medicine | Year: 2016

Introduction: Non-small cell lung cancer lung cancer (NSCLC) is a devastating disease, with poor prognosis for patients with metastatic disease. The management of these patients has evolved during the past decade, challenging the role of cytotoxic chemotherapy as the only available treatment option. Nevertheless, chemotherapy still retains a dominant position for the majority of both treatment naïve and pretreated patients. Among the chemotherapeutic agents, docetaxel is one of the most commonly used in 1st and subsequent treatment lines, even in the current era of precision medicine. Areas covered: We searched Medline, Embase, Scopus and Cochrane Library for randomized phase III trials that evaluated docetaxel in various clinical settings of NSCLC and for meta-analyses of such trials and we present all relevant data regarding the pharmacology and clinical use of docetaxel in NSCLC. Expert commentary: Despite its diminishing role, docetaxel in combination with novel targeted agents remains an important option of the therapeutic armamentarium in advanced NSCLC. © 2016 Informa UK Limited, trading as Taylor & Francis Group.

Souglakos J.,Hellenic Oncology Research Group HORG | Ziras N.,Hellenic Oncology Research Group HORG | Kakolyris S.,Hellenic Oncology Research Group HORG | Boukovinas I.,Hellenic Oncology Research Group HORG | And 8 more authors.
British Journal of Cancer | Year: 2012

BACKGROUND: To compare the efficacy and safety of CAPIRI+bevacizumab (Bev) in comparison with FOLFIRI+Bev as first-line treatment for patients with metastatic colorectal cancer (mCRC). METHODS: Patients were randomised to receive either FOLFIRI plus Bev 5mg kg -1 every 2 weeks (Arm-A) or CAPIRI plus Bev 7.5 mg kg -1 every 3 weeks (Arm-B). RESULTS: Three hundred thirty-three patients (Arm-A=167; Arm-B=166) were enrolled into the study. No difference was observed in median progression-free survival (PFS) (10.0 and 8.9 months; P=0.64), overall survival (25.7 and 27.5 months; P=0.55) or response rates (45.5 and 39.8.7%; P=0.32) for FOLFIRI-Bev and CAPIRI-Bev, respectively. Patients treated with CAPIRI-Bev presented significantly higher incidence of diarrhoea (P=0.005), febrile neutropenia (P=0.003) and hand-foot skin reactions (P=0.02) compared with patients treated with FOLFIRI-Bev. Treatment delays (P=0.05), dose reduction (Po0.001) and treatment discontinuation owing to toxicity (P=0.01) occurred more frequently in the CAPIRI-Bev arm. CONCLUSION: The PFS of FOLFIRI-BEV is not superior to that observed with the CAPIRI-Bev regimen. CAPIRI-Bev has a less favourable toxicity profile, requiring dose reductions, in order to be considered as an option in first-line treatment of patients with mCRC. © 2012 Cancer Research UK.

Pallis A.G.,Hellenic Oncology Research Group HORG | Karampeazis A.,Hellenic Oncology Research Group HORG | Vamvakas L.,Hellenic Oncology Research Group HORG | Vardakis N.,Hellenic Oncology Research Group HORG | And 6 more authors.
Annals of Oncology | Year: 2011

Background: 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. Patients and methods: 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. Results: 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. Conclusions: 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. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

PubMed | Hellenic Oncology Research Group HORG
Type: Journal Article | Journal: Cancer chemotherapy and pharmacology | Year: 2016

Bortezomib is a selective reversible proteasome inhibitor with proapoptotic effects. Preclinical and phase I clinical data suggest activity of bortezomib in NSCLC, either as monotherapy or in combination with chemotherapeutic agents including gemcitabine and cisplatin.Chemotherapy-nave patients with inoperable stage IIIB or IV NSCLC were administered bortezomib 1mg/m(2) i.v. on days 1 and 8, and starting on day 21 (cycle 2), bortezomib (days 1 and 8) in combination with gemcitabine 1000mg/m(2), (days 1 and 8), and cisplatin 70mg/m(2) (day 1) in cycles of 21 days. Up to 8 cycles of combination therapy could be administered; single-agent bortezomib was continued until disease progression or unacceptable toxicity.Fifty-three patients [median age 66years; 79.2% male; 96.2% stage IV; performance status (ECOG) 0/1 73.6/26.4%; adenocarcinoma 45.3%, squamous cell carcinoma 41.5%] were enrolled. All patients were evaluable for toxicity and 43 for efficacy. Grade 3-4 hematologic toxicity consisted of neutropenia (22.6%) and thrombocytopenia (17%). Grade 2-4 non-hematologic adverse events were fever (9.4%), fatigue (20.8%), infection (18.9%), and dyspnea (15.1%). There was no >grade 2 neurotoxicity. Febrile neutropenia occurred in two (1.9%) patients, and there were three possibly treatment-related deaths (5.4%). In the intention-to-treat population, the objective response rate was 17% (95% CI 6.9-27.1%). No difference in response rate was observed for squamous versus other histology (18.2 vs. 16.1%, p=0.845). The median progression-free survival was 2.5months, the median overall survival 10.6months and the 1-year survival rate 38.1%.The incorporation of bortezomib into the gemcitabine/cisplatin regimen, in the dose and schedule used in this study, could not improve the efficacy of the chemotherapy regimen and has not to be further investigated.

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

7052 Background: To compare the efficacy and toxicity of the DG combination versus D monotherapy in chemotherapy-nave patients with advanced/metastatic NSCLC.Patients with histologically or cytologically confirmed NSCLC were randomized to receive either the DG (gemcitabine; 1000mg/mA total of 925 (DG=475 and D=450) chemotherapy cycles were administered with a median of 3 cycles/pt in each group. The incidence of grade 2-4 anemia and grade 3-4 thrombocytopenia were higher (p=0.011 and 0.028, respectively) in the DG than the D group; there was no difference between the two groups concerning grade 3-4 neutropenia or febrile neutropenia. Other severe toxicities were rare. There were 3 (2.6%) CRs and 26 (22.4%) PRs (ORR=25%; 95% CI: 17.12-32.88%) in the DG arm and 1 (0.8%) CR and 12 (10.2%) PRs (ORR=11%; 95% C.I: 5.37-16.67%) in the D arm (p=0.005). The median response duration was 5 months in each arm (p=0.798) while the median time to tumor progression was 5.7 months in each arm (p=0.609). The overall survival time was 9.1 and 8.3 months in the DG and D arm, respectively (p=0.0305); The 1- and 2-year survival rate was 38.6% and 16.5%, respectively for the DG arm and 32.19% and 7.3%, respectively, for the D arm.The docetaxel/gemcitabine combination is more active in terms of response rate and overall survival than single agent docetaxel and further patients accrual was stopped for ethical reasons. No significant financial relationships to disclose.

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