Vasilios Karavasilis

Papageorgiou Hospital, Saloníki, Central Macedonia, Greece

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Publications (52)198.81 Total impact

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    ABSTRACT: Background: Intensive chemotherapy confers benefit to patients with high-risk early breast cancer (BC). We characterized the feasibility and toxicity profile of anthracycline-containing adjuvant chemotherapy (ACAC) in older women with early BC. Patients and methods: Available data from women who received ACAC for BC in 3 randomized trials were retrieved. We identified women aged >65 years and we examined differences in tolerability and delivery of chemotherapy, toxicity, and treatment outcome. Results: From a total of 2640 patients, we identified 453 patients (17%) as being >65 years old, 89% of whom had tumors that were node-positive, with 77% who were hormone receptor-positive. At least 90% of the planned doses were delivered in 37% of the elderly, compared with 49% in the younger patients (P < .0001). Grade 3 and 4 hematological toxicity was observed in 32% of elderly patients, compared with 21% of the younger (P < .0001). Febrile neutropenia occurred in 4.5% of the elderly patients, as opposed to 2.0% in the younger patients (P < .002). Elderly patients experienced more frequent Grade 3 and 4 fatigue, mucositis, and sensory neuropathy. Relative dose intensities were significantly lower in elderly patients. Treatment discontinuation was not different in the 2 groups. At a median follow-up of 120 months, competing risks analysis showed a significant benefit in disease-free survival for elderly patients. Conclusion: Elderly BC patients treated with ACAC derive clinical benefit comparable to that in younger patients, mainly at the cost of increased risk of hematological toxicity. This should be taken into account in decision-making and treatment individualization in high-risk BC patients.
    No preview · Article · Dec 2015 · Clinical Breast Cancer
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    ABSTRACT: Background: The CpG island methylator phenotype (CIMP) is a promising biomarker for irinotecan/5-fluorouracil/leucovorin chemotherapy for stage III colon cancer. In the present study, we evaluated whether CIMP is a prognostic biomarker for standard-of-care oxaliplatin-based adjuvant therapy. Materials and methods: The HE6C/05 trial randomized 441 patients with stage II-III colorectal adenocarcinoma to adjuvant XELOX (capecitabine, oxaliplatin) or modified FOLFOX6 (5-fluorouracil, leucovorin, oxaliplatin). The primary and secondary objectives were disease-free and overall survival, respectively. CIMP status was determined using the DNA methylation status of CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS1. Cox models were used to assess the association of CIMP with survival. Results: Of the 293 available tumors, 28 (9.6%) were CIMP(+). On univariate Cox regression analysis, no significant differences in survival were observed between individuals with CIMP(+) versus CIMP(-) tumors. CIMP(+) tumors were more likely to be right-sided and BRAF mutant (χ(2), P < .001). In the multivariate model, TNM stage II (vs. stage III) was associated with a reduced risk of relapse (hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.11-0.55; Wald's P < .001), and a colon primary located on the left side and earlier TNM stage were associated with a reduced risk of death (HR, 0.48; 95% CI, 0.28-0.81; P = .006; and HR, 0.22; 95% CI, 0.10-0.49; P < .001, respectively). Conclusion: In the present exploratory analysis, CIMP did not appear to be a prognostic biomarker in oxaliplatin-treated patients with resected colorectal cancer.
    No preview · Article · Nov 2015 · Clinical Colorectal Cancer
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    ABSTRACT: Purpose: Following the establishment of adjuvant carboplatin in stage I testicular seminoma as a standard, we adopted this treatment for all stage I seminoma patients. We report our 8-year experience and compare these results with our previous adjuvant etoposide/cisplatin (EP) strategy. Patients and methods: Patients with stage I seminoma, treated with adjuvant carboplatin and with a minimum follow-up of 1 year, were included. Two cycles of carboplatin [area under the curve (AUC) 6] were administered. Results: A total of 138 patients with median age of 34 years, treated from September 2003 to December 2011, were selected. There were 5 relapses [5-year relapse-free rate (RFR) 96.8 % (95 % confidence interval 91.6-98.8)]: 3 relapses at retroperitoneal lymph nodes, 1 relapse at the adrenal gland, and 1 isolated brain metastasis. Four patients with relapse were cured with salvage chemotherapy. All patients with relapse had tumor diameter ≥4 cm and/or age ≤34 years. Patients with at least 1 of the above risk factors (n = 111) had a significantly higher relapse rate compared with a similar population (n = 64) treated with 2 cycles of adjuvant EP: 5-year RFR was 95 % (SE 2 %) versus 100 % (SE 0 %), (p = 0.067). Conclusions: Age and tumor diameter were associated with relapse in stage I seminoma treated with adjuvant carboplatin. Although adjuvant carboplatin in patients with age ≤34 and/or tumor diameter ≥4 cm is associated with higher relapse rates than EP, the prognosis of these patients is excellent, and therefore, the use of less toxic treatment is justified.
    No preview · Article · Sep 2015 · World Journal of Urology

  • No preview · Conference Paper · Sep 2015
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    ABSTRACT: Although host immune response is an emerging prognostic factor for colorectal cancer, there is no consensus on the optimal methodology, surrogate markers or tissue for study. Tumour blocks were prospectively collected from 344 patients with stage II/III colorectal cancer (CRC) treated with adjuvant chemotherapy. Whole section lymphocytic infiltration was studied along with mRNA expression of CD3Z, CD8, CD4, CXCL9, CXCL13, IGHM, FOXP3, SNAI2 and ESR1 by qRT-qPCR in tissue microarray (TMA) cores from the centre of tumour, invasive margin and adjacent normal mucosa. Lymphocytic infiltration, deficient MMR (10.9%), KRAS (40.7%) and BRAF (4.9%) mutations or single mRNA gene expression were not prognostic. Tumour ESR1 gene expression (Hazard Ratio [HR] for relapse 2.33, 95% CI 1.35-4.02; HR for death 1.74, 95% CI 1.02-2.97) and absence of necrosis (HR for relapse 1.71, 95% CI 1.05-2.71; HR for death 1.98, 95% CI 1.14-3.43) were adverse prognostic features. We used CD3Z and CD8 expression in order to devise the mRNA-based Immune Score (mIS) and proceeded to partitioning analysis in 267 patients, with age, stage, tumour site (Right vs Left CRC), KRAS mutation and tumour mIS as input factors. Only in patients with stage III right-sided colon cancer, a low immune response was associated with inferior disease-free survival (mIS-low, HR for relapse 2.28, 95% CI 1.05-8.02). No prognostic significance was seen for tumour mIS in any other stage or site of CRC, or for a similar mIS score derived from adjacent normal mucosa. Independent adverse prognostic significance was retained in multivariable analysis for absence of necrosis, tumour ESR1 expression in all patients and low tumour mIS in stage III right-sided CRC. In localised CRC, mRNA-based CD3Z/CD8 profiling of tumour immune response may have stage, site and tissue-specific prognostic significance, along with ESR1 expression. ACTRN12610000509066.
    Full-text · Article · May 2015 · PLoS ONE
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    ABSTRACT: The aim of the trial was to compare two active adjuvant chemotherapy regimens in patients with early stage colorectal cancer (CRC). Patients were assigned to oxaliplatin, leucovorin and 5-FU for 12 cycles (group A, FOLFOX6) or oxaliplatin and capecitabine for eight cycles (group B, CAPOX). Primary endpoint was disease-free survival (DFS). Tumors were classified as mismatch repair proficient (pMMR) or deficient (dMMR) according to MLH1, PMS2, MSH2 and MSH6 protein expression. KRAS exon two and BRAF V600E mutational status were also assessed. Between 2005 and 2008, 441 patients were enrolled, with 408 patients being eligible. After a median follow-up of 74.7 months, 3-year DFS was 79.8 % (95 % CI 76.5-83.4) in the FOLFOX group and 79.5 % (95 % CI 75.9-83.1) in the CAPOX group (p = 0.78). Three-year OS was 87.2 % (95 % CI 84.1-91.1) in the FOLFOX and 86.9 % (95 % CI 83.4-89.9) in the CAPOX group (p = 0.84). Among 306 available tumors, 11.0 % were dMMR, 34.0 % KRAS mutant and 4.9 % BRAF mutant. Multivariate analysis showed that primary site in the left colon, earlier TNM stage and the presence of anemia at diagnosis were associated with better DFS and overall survival (OS), while grade one-two tumors were associated with better OS. Finally, a statistically significant interaction was detected between the primary site and MMR status (p = 0.010), while KRAS mutated tumors were associated with shorter DFS. However, the sample was too small for safe conclusions. No significant differences were observed in the efficacy of FOLFOX versus CAPOX as adjuvant treatment in high-risk stage II or stage III CRC patients, but definitive conclusions cannot be drawn because of the small sample size. ANZCTR 12610000509066 . Date of Registration: June 21, 2010.
    Full-text · Article · May 2015 · BMC Cancer

  • No preview · Article · Jan 2015 · Journal of Clinical Oncology
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    ABSTRACT: Aim: To determine the more effective dosing sequence of intermittent erlotinib and docetaxel for treating chemotherapy-naive patients with advanced Non-Small Cell Lung Cancer (NSCLC). Patients and methods: Patients were randomized to receive daily erlotinib for 12 consecutive days prior to docetaxel (Arm A) or after docetaxel (Arm B). Progression-free survival (PFS) was the primary end-point; secondary end-points were overall survival (OS) and objective response rate (ORR). Results: Fifty eligible patients received a total of 226 treatment cycles (median: 3). Median PFS and OS were 3.6 months and 10.5 months, respectively (differences were not statistically significant between the two arms). Neutropenia grade 3 and 4 occurred in 15 patients, while two patients developed grade 3 diarrhea. There were two treatment-related deaths (pulmonary embolism and non-neutropenic sepsis). Conclusion: Intermittent administration of erlotinib does not appear to improve the clinical outcome of single-agent docetaxel chemotherapy in unselected patients with NSCLC in the first-line setting.
    No preview · Article · Oct 2014 · Anticancer research
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    ABSTRACT: Aims: The aim of this article was to evaluate afatinib (BIBW 2992), an ErbB family blocker, and nintedanib (BIBF 1120), a triple angiokinase inhibitor, in castration-resistant prostate cancer patients. Patients & methods: Patients were randomized to receive nintedanib (250 mg twice daily), afatinib (40 mg once daily [q.d.]), or alternating sequential 7-day nintedanib (250 mg twice daily) and afatinib (70 mg q.d. [Combi70]), which was reduced to 40 mg q.d. (Combi40) due to adverse events. The primary end point was progression-free rate at 12 weeks. Results: Of the 85 patients treated 46, 20, 16 and three received nintedanib, afatinib, Combi40 and Combi70, respectively. At 12 weeks, the progression-free rate was 26% (seven out of 27 patients) for nintedanib, and 0% for afatinib and Combi40 groups. Two patients had a ≥50% decline in PSA (nintedanib and the Combi40 groups). The most common drug-related adverse events were diarrhea, nausea, vomiting and lethargy. Conclusion: Nintedanib and/or afatinib demonstrated limited anti-tumor activity in unselected advanced castration-resistant prostate cancer patients.
    No preview · Article · Feb 2014 · Future Oncology
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    ABSTRACT: Ichthyoses are a heterogeneous group of cutaneous keratinization disorders that can be congenital or acquired. Apart from neoplastic disorders, the acquired form of ichthyosis (AI) has been associated with a variety of diseases including infections, autoimmune/inflammatory and endocrine/metabolic diseases as well as nutritional conditions, medications and others. However, malignancy accounts for half of the reported cases, most commonly including lymphoproliferative disorders. We present a case of AI as a paraneoplastic skin manifestation of a primary, osseous hemangiopericytoma (HP) accompanied by multiple liver metastases. We also review the literature and discuss the necessity of investigating underlying diseases, especially malignancy, when adult-onset ichthyosis arises.
    Full-text · Article · Jan 2014 · Case Reports in Dermatology
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    ABSTRACT: Background: Advanced pancreatic adenocarcinoma (APA) remains a difficult to manage disease with a high mortality rate. Limited data is available from the Greek Cancer Registry on patients with pancreatic cancer. Patients & Methods: The PATHOS multicenter survey aimed at capturing real-world data on pancreatic cancer disease status in Greece. A standardized questionnaire administered to ten interviewed physicians specialized in pancreatic cancer, captured data from patient medical records as well as the physicians' opinion about limitations of the most common treatment modalities for APA and the likelihood of using nab-paclitaxel in the metastatic APA population. Results: During 2011, 187 patients with APA, 63.6% of whom had been diagnosed with metastatic (Stage IV) disease, were treated by the participating physicians. Surgery had been performed in 39.7% of patients with locally advanced and in 8.4% of those with metastatic APA. Overall, 62/68 patients with locally advanced disease received chemotherapy (31 adjuvant/neoadjuvant). Of 119 patients with metastatic disease, 101 received chemotherapy (7 adjuvant; 94 palliative). As part of standard practice, 89% of patients with metastatic APA had received firstline therapy, mainly with gemcitabine, gemcitabine +erlotinib or FOLFIRINOX. However, various limitations were reported for gemcitabine +erlotinib and FOLIFIRINOX, underscoring the need for new treatments. Of the physicians, 80% reported that they were highly likely to use the combination of nab-paclitaxel/gemcitabine for metastatic APA in the future. Conclusions: The survey demonstrated that APA in Greece is mostly diagnosed in the metastatic state and underscored the importance of adding new treatment modalities to the current therapeutic armamentarium.
    No preview · Article · Jun 2013 · Annals of Oncology
  • A Patsatsi · A Kyriakou · V Karavasilis · K Panteliadou · D Sotiriadis
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    ABSTRACT: Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBL-LT) is a primary cutaneous B-cell lymphoma of intermediate behavior. The disease predominantly affects elderly patients. A 76-year old man presented with red to violaceous nodules in the anterior aspect of both tibias. Histology confirmed the diagnosis of PCDLBL-LT. A thorough clinical and laboratory investigation was negative for any systemic involvement. However, computed tomography of the thorax showed mediastinal lymphadenopathy. Both bone marrow aspiration and trephine did not show any evidence of bone marrow infiltration. Initially R-CHOP regimen (rituximab-cyclophosphamide, doxorubicin, vincristine, prednisone) achieved a total clearance of the lesions. Nevertheless, five months later patient presented with a relapse and was managed with palliative radiotherapy. The same treatment modality was applied for the second recurrence, as well. PCDLBL-LT affects mostly elderly patients. The consequent age related comorbidities and the frequent relapses require a strict follow up of the patients.
    No preview · Article · Apr 2013 · Hippokratia
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    ABSTRACT: Although lymphomas involving the prostate gland are rare, they should always be considered in the differential diagnosis. We report a case of primary prostatic NHL in a 70-year-old man presented with hematuria and urinary obstructive symptoms. Routine laboratory tests were within normal limits and prostate-specific antigen (PSA) was 0,01 ng/ml. The patient underwent radical prostatectomy. Histologically, two different coexisting patterns of non-Hodgkin lymphoma, infiltrating the prostatic tissue, were identified. The diagnosis of diffuse large B-cell lymphoma (DLBCL) presenting with an associated low-grade lymphoma of MALT-type was confirmed by immunohistochemistry. The patient received chemotherapy without any complication and has been followed-up for 2 years since surgical resection with no recurrence. The clinicopathologic characteristics of prostatic lymphomas are discussed, while reviewing the current English-language literature. Hippokratia. 2012; 16 (1): 86-89
    Full-text · Article · Jan 2013 · Hippokratia
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    ABSTRACT: We undertook this phase I study to investigate the feasibility of the combination of temozolomide (TMZ) and lapatinib (LP) and to define the maximum tolerated dose (MTD) of LP in patients with relapsed high-grade gliomas. Eligible patients were enrolled in this dose escalation study of LP. TMZ was administered at a fixed dose of 200 mg/m(2) d1-d5 every 28 days. Starting dose of LP was set at 1,000 mg daily continuously, escalated by 250 mg in cohorts of minimum three patients. Translational research investigations were also undertaken in available biopsy material. Between January 2009 and December 2010, 16 patients were entered into the study at three LP levels: 1,000 mg sid (11 patients), 1,250 mg sid (4 patients) and 1,500 mg sid (1 patient). A total of 55 cycles had been delivered. Fourteen patients had stopped treatment because of disease progression, and two because of toxicity. Three patients received 10, 11 and 17 cycles of treatment. Dose-limiting hematological toxicity was observed in 2 patients at the second LP dose level of 1,250 mg sid. MTD was defined at LP 1,000 mg sid. Median progression-free survival (PFS) and survival were 2.4 and 5.9 months, respectively. EGFR amplification and EGFRvIII expression were not related to PFS. Combination of TMZ and LP is feasible with manageable toxicity. The activity of this combination in patients with recurrent glioblastoma multiforme is further investigated in a recently initiated phase II trial.
    No preview · Article · Jan 2013 · Journal of Neurology
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    ABSTRACT: Aim: The association between two polymorphisms of ERCC1 and treatment outcomes after platinum-based chemotherapy in patients with advanced urothelial cancer (UC) was examined. Materials & methods: Genotyping of 19007C>T and 8092C>A polymorphisms was determined by PCR amplification and RFLP in 113 advanced UC patients, treated with platinum-based chemotherapy. Results: Seventy eight patients (69%) were carriers of the 19007T polymorphic allele: 51 (45%) heterozygotes and 27 (24%) homozygotes. Fifty three (47%) patients were carriers of the 8092A polymorphic allele: the frequencies of C/A and A/A genotypes were 37% and 10%, respectively. The T/T genotype was independently associated with prolonged median cancer-specific survival (not-reached vs 14.8 months; p = 0.026). There was no interaction between T/T or any other genotype with the type of platinum derivative (cisplatin/carboplatin). Conclusion: 19007C>T, especially in its homozygotic state, but not 8092C>A polymorphism, could be a useful prognostic marker in advanced UC treated with platinum-based chemotherapy.
    Full-text · Article · Nov 2012 · Pharmacogenomics
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    ABSTRACT: Background–aim: ALK1 (ALK) translocation is a rare event in NSCLC, which more often seem to harbor aberrant ALK gene copies. Herein, we investigated the still undefined impact of ALK gene copies and of ALK mRNA expression on NSCLC patient outcome. Methods: The presence and relative quantity of two ALK exon spanning transcript targets located before (ALK-5’) and after (ALK-3’) the translocation breakpoints of this gene were assessed with qRT-PCR in 198 NSCLC RNA samples from paraffin tissues upon stringent intra- and inter-run assay performance validation. ALK mRNA expression was compared with ALK gene status assessed with FISH. Patients had been treated in the adjuvant and/or 1st line setting. None of them received crizotinib. Results: Four patterns of ALK mRNA expression emerged: tumors negative for both transcripts (85/198, 42.9%) or positive for both (56/198, 28.3%), which were considered as close to normal (ALK-N); and, ALK-5’ positive only (34/198, 17.2%) or ALK-3’ positive only (23/198, 11.6%), which were termed as aberrant (ALK-A). ALK translocation was observed in 9/124 cases (7.3%). ALK copies >2.2 were noticed in 40 cases (32.3%) with >6 copies in 26 cases (21%) and overall complex gene gain patterns. ALK mRNA was unrelated to ALK translocation, but ALK-3’ was associated with increased ALK gene copies (p = 0.017). ALK-A was more common in stage IIIB-IV tumors, while ALK mRNA and gene copy gains were not associated with gender, smoking and histology. ALK gene status was not associated with patient outcome. In comparison to patients with tumors expressing ALK-N, those with ALK-A had a significantly shorter overall survival (OS, median 29.3 vs. 13.1 months, CI95% 19.1-39.6 vs. 5.4-20.9, p = 0.0007). The same unfavorable impact of ALK-N vs. ALK-A was observed on stage IIIB-IV patient OS (median 17.5 vs. 11 months, CI95% 9.1-26.0 vs. 6.6-15.3, p = 0.0050). Conclusions: ALK gene status and mRNA expression seem to suffer a complex pathology in NSCLC. When expressed, ALK mRNA may be fragmented, possibly due to currently unknown genomic alterations. Aberrant ALK mRNA expression appears to have an unfavorable prognostic impact on NSCLC patient outcome; its role on NSCLC biology merits further evaluation.
    No preview · Conference Paper · Sep 2012
  • R Ferraldeschi · C Pezaro · V Karavasilis · JS de Bono
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    ABSTRACT: Suppression of gonadal androgens by medical or surgical castration remains the mainstay of treatment for patients with advanced prostate cancer. However, the response to treatment is not durable, and transition to a "castration-resistant" state is invariable. Recent advances in our understanding of the androgen receptor signaling pathway have led to the development of therapeutic strategies to overcome castration resistance. This article reviews current concepts and challenges behind targeting continued androgen receptor signaling in castration-resistant prostate cancer and provides an overview of recently completed and ongoing clinical trials of novel hormonal agents, with a focus on abiraterone acetate and enzalutamide (MDV3100). Expected final online publication date for the Annual Review of Medicine Volume 64 is January 07, 2013. Please see for revised estimates.
    No preview · Article · Sep 2012 · Annual review of medicine
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    ABSTRACT: Introduction Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have become a treatment option in non-small-cell lung cancer (NSCLC) patients. However, despite their use in this disease, a significant number of patients will eventually develop resistance and relapse. In this study, we aimed to characterize several molecular events involved in potential resistance mechanisms to anti-EGFR treatment and correlate our findings with clinical outcome. Material and methods The medical records of patients with NSCLC who received anti-EGFR TKIs in any line within the participating centers were reviewed and available paraffin embedded tissue was retrieved. Mutational analysis for EGFR, KRAS, BRAF and intron-exon 14 deletions of MET; FISH analysis for chromosomal gain or amplification for EGFR, MET and the deletion marker D7S486 were performed. Furthermore, the expression of EGFR and MET were analysed by immunohistochemistry. All results were correlated with treatment outcomes. Results Between 10/2001 and 12/2009 from an initial cohort of 72 treated patients, 59 cases (28 gefitinib/ 31 erlotinib) were included in the analysis. The majority had adenocarcinoma histology (68%), and received treatment in the second line setting (56%). Disease control rate (DCR) was 25.4% for all patients. EGFR and RAS mutational rates were 33% and 10% respectively, no other mutations were identified. High EGFR expressing tumors were found in 7 of 45 cases and pEGFR positivity (IHC) was found in 56% of the cases; MET expression was found in 48% of tumors. EGFR gene amplification was found in 4 cases, two cases showed high polysomy; overall, 13% cases were FISH positive for EGFR. High polysomy of MET gene was detected in 1/43 cases tested. D7S486 locus deletion was detected in 15/37 (40%) of cases. EGFR mutational status and gene gain were both associated with more favorable DCR. No other associations between examined biomarkers and DCR or survival were noted. Conclusions EGFR mutational status is a predictor for disease control in patients with NSCLC treated with anti-EGFR TKIs. The predictive role of several other molecules involved in potential resistance to anti-EGFR TKIs is worthy of additional investigation.
    Full-text · Article · Sep 2012 · Journal of Experimental & Clinical Cancer Research
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    ABSTRACT: Background TH-302 is a hypoxia targeted prodrug with a hypoxia-triggered 2-nitroimidazole component designed to release the DNA alkylator, bromo-isophosphoramide mustard (Br-IPM), when reduced in severe hypoxia. A randomized Phase 2B study (NCT01144455) was conducted to assess the benefit of G + T to standard dose G as first-line therapy of PAC.
    Full-text · Conference Paper · Sep 2012
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    ABSTRACT: Background BRCA1 (B), ERCC1 (E), RRM1 (R) and TYMS (T) mRNA expression has been extensively studied with respect to NSCLC patient outcome upon various chemotherapy agents. However, these markers have not been introduced into clinical practice yet. One of the reasons seems to be lack of a standard approach for the classification of the reported high/low mRNA expression. The aim of this study was to determine the prognostic/predictive impact of B, E, R, T in routinely-treated NSCLC patients by taking into account the expression of these genes in the normal lung parenchyma. Methods B, E, R, T mRNA expression was examined in 276 NSCLC samples (real-time PCR). The normal range of B, E, R, T transcript levels was first determined in matched tumor – normal pairs and then applied to the entire tumor series. Four main chemotherapy categories were examined: taxanes-without-platinum (Tax); platinum-without-taxanes (Plat); taxanes/platinum doublets (Tax/Plat); and, all-other combinations. Results In comparison to remotely located normal lung parenchyma, B, E, R, T mRNA expression was generally increased in matched tumors, as well as in the entire tumor series. Therefore, tumors were classified as expressing normal or aberrant B, E, R, T mRNA. In general, no marker was associated with overall and progression free survival (OS, PFS). Upon multivariate analysis, aberrant intratumoral TYMS predicted for shorter PFS than normal TYMS in 1st line chemo-naïve treated patients (p = 0.012). In the same setting, specific interactions were observed for aberrant TYMS with Plat and Tax/Plat (p = 0.003 and p = 0.006, respectively). Corresponding patients had longer PFS in comparison to those treated with Tax (Plat: HR = 0.234, 95% CI:0.108-0.506, Wald’s p < 0.0001; Tax/Plat: HR = 0.242, 95% CI:0.131-0.447, Wald’s p < 0.0001). Similar results were obtained for PFS in 1st line chemo-naïve and (neo)adjuvant pre-treated patients. Adenocarcinoma, early disease stage, and treatment with Tax/Plat doublets independently predicted for prolonged OS in patients who received only one line of treatment (adjuvant or 1st line). Conclusion Classifying intratumoral B, E, R, T mRNA expression in comparison to normal lung may facilitate standardization of these parameters for prospective studies. With this approach, NSCLC patients with aberrant intratumoral TYMS expression will probably fare better with platinum-based treatments.
    Full-text · Article · Aug 2012 · BMC Cancer

Publication Stats

800 Citations
198.81 Total Impact Points


  • 2010-2015
    • Papageorgiou Hospital
      Saloníki, Central Macedonia, Greece
  • 2009-2015
    • Aristotle University of Thessaloniki
      Saloníki, Central Macedonia, Greece
  • 2012
    • Alexandra Regional General Hospital
      Athínai, Attica, Greece
  • 2006-2010
    • The Royal Marsden NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2008
    • Institute of Cancer Research
      Londinium, England, United Kingdom
    • Ontario Institute for Cancer Research
      Toronto, Ontario, Canada
  • 2000-2006
    • University of Ioannina
      • • School of Medicine
      • • Division of Internal Medicine II
      Ioánnina, Ipeiros, Greece
  • 1997-2001
    • University Hospital of Ioannina
      Yannina, Epirus, Greece