The Gap of Health Inequalities Amongst Lung Cancer Patients of Different Socioeconomic Status: A Brief Reference to the Greek Reality.

Lung cancer treatment and patient care are constantly improving, but it remains doubtful whether this applies equally to all socioeconomic groups. It is nowadays well established that there are socioeconomic inequalities regarding lung cancer incidence, screening, effective treatment, overall survival, and prognosis. One of the key contributing factors to low socioeconomic status is low education. Low educational level is correlated with several factors, such as smoking habits, bad lifestyle behaviors, lower paid and unhealthier occupations, polluted neighborhoods, and genetic-familial risk, that lead to increased lung cancer incidence. The disparities regarding lung cancer care are further enhanced by stigma. On this basis and inspired by the gap in health equality among the Greek population, the Greek Society of Lung Cancer initiated a campaign, "MIND THE GAP", to help increase awareness and minimize the gap associated with lung cancer, both in Greece and across Europe. The aim of this review is to explore the gap of health inequalities regarding lung cancer incidence and prognosis between patients of different SES and its root of causality. Key pivotal actions towards bridging this gap are reviewed as well.

Clinical Outcomes Beyond 1L EGFR-TKI Progression in mNSCLC: Final Results of the Real-World Study 'LUNGFUL'.

BACKGROUND/AIM: Real-world data on the EGFR mutational profile upon progression after first/second-generation EGFR-TKI treatment in patients with advanced non-small-cell lung cancer (NSCLC) and treatment strategies employed thereon are needed. PATIENTS AND METHODS: This observational study was conducted in 23 hospital-based lung cancer Centers in Greece (protocol code: D133FR00126). Ninety-six eligible patients were consecutively enrolled between July-2017 and September-2019. Re-biopsy was performed in 18 of 79 patients who tested T790M-negative in liquid biopsy after progression in the first-line (1L) setting. RESULTS: Of the study population, 21.9% tested T790M-positive, while 72.9% proceeded to 2L treatment, mainly comprising of a third-generation EGFR-TKI (48.6%), a switch to chemotherapy (30.0%), or chemo-immunotherapy (17.1%). The objective response rate (ORR) in 2L was 27.9% in T790M-negative and 50.0% in T790M-positive patients. Of evaluable patients, 67.2% experienced disease progression; median progression-free survival (PFS) was 5.7 and 10.0 months among T790M-negative and positive patients, respectively. Among T790M-negative patients, longer median PFS and post-progression survival were observed with third-generation EGFR-TKI treatment. CONCLUSION: Mutational status and treatment strategy were identified as critical determinants of clinical outcomes in the 2L-setting of EGFR-mutated NSCLC patients in real-world settings in Greece, with early diagnosis, appropriate molecular testing and high-efficacy treatments at first lines positively affecting ORR and PFS.

The Role of Dietary Lipids in Cognitive Health: Implications for Neurodegenerative Disease.

Neurodegenerative diseases are a group of disorders characterised by progressive loss of brain function. The most common of these is Alzheimer's disease, a form of dementia. Intake of macro- and micro-nutrients impacts brain function, including memory, learning, mood, and behaviour. Lipids, particularly phospholipids and sphingolipids, are crucial structural components of neural tissues and significantly affect cognitive function. The importance of functional foods in preventing cardiovascular disease is well-documented in the current literature. However, the significance of such foods for central nervous system health and neurodegenerative diseases is less recognized. Gut microbiome composition affects cognitive health and function, and dietary lipids are known to influence gut health. Thus, this review will discuss different sources of dietary lipids and their effect on cognitive functioning and their interaction with the gut microbiome in the context of neurodegenerative disease.

Molecular subtypes of clear cell renal cell carcinoma are associated with sunitinib response in the metastatic setting.

PURPOSE: Selecting patients with metastatic clear-cell renal cell carcinoma (m-ccRCC) who might benefit from treatment with targeted tyrosine kinase inhibitors (TKI) is a challenge. Our aim was to identify molecular markers associated with outcome in patients with m-ccRCC treated with sunitinib. EXPERIMENTAL DESIGN: We performed global transcriptome analyses on 53 primary resected ccRCC tumors from patients who developed metastatic disease and were treated with first-line sunitinib. We also determined chromosome copy-number aberrations, methylation status, and gene mutations in von Hippel-Lindau and PBRM1. Molecular data were analyzed in relation with response rate (RR), progression-free survival (PFS), and overall survival (OS). Validation was performed in 47 additional ccRCC samples treated in first-line metastatic setting with sunitinib. RESULTS: Unsupervised transcriptome analysis identified 4 robust ccRCC subtypes (ccrcc1 to 4) related to previous molecular classifications that were associated with different responses to sunitinib treatment. ccrcc1/ccrcc4 tumors had a lower RR (P = 0.005) and a shorter PFS and OS than ccrcc2/ccrcc3 tumors (P = 0.001 and 0.0003, respectively). These subtypes were the only significant covariate in the multivariate Cox model for PFS and OS (P = 0.017 and 0.006, respectively). ccrcc1/ccrcc4 tumors were characterized by a stem-cell polycomb signature and CpG hypermethylation, whereas ccrcc3 tumors, sensitive to sunitinib, did not exhibit cellular response to hypoxia. Moreover, ccrcc4 tumors exhibited sarcomatoid differentiation with a strong inflammatory, Th1-oriented but suppressive immune microenvironment, with high expression of PDCD1 (PD-1) and its ligands. CONCLUSIONS: ccRCC molecular subtypes are predictive of sunitinib response in metastatic patients, and could be used for personalized mRCC treatment with TKIs, demethylating or immunomodulatory drugs.

Efflux pump ABCB1 single nucleotide polymorphisms and dose reductions in patients with metastatic renal cell carcinoma treated with sunitinib.

UNLABELLED: There is growing evidence that sunitinib plasma levels have an impact on treatment outcome in patients with metastatic renal cell carcinoma (mRCC). We studied the impact of single nucleotide polymorphisms (SNPs) in genes involved in sunitinib pharmacokinetics, and additionally, sunitinib pharmacodynamics on dose reductions of the tyrosine kinase inhibitor. METHODS: We retrospectively analyzed germ-line DNA retrieved from mRCC patients receiving sunitinib as first-line therapy. We genotyped 11 key SNPs, respectively, in ABCB1, NR1/2, NR1/3 and CYP3A5, involved in sunitinib pharmacokinetics as well as VEGFR1 and VEGFR3, which have been suggested as regulators of sunitinib pharmacodynamics. Association between these SNPs and time-to-dose-reduction (TTDR) was studied by Cox regression. RESULTS: We identified 96 patients who were treated with sunitinib and from whom germ-line DNA and data on dose reductions were available. We observed an increased TTDR in patients carrying the TT-genotype in ABCB1 rs1125803 compared to patients with CC- or CT-genotypes (19 vs. 7 cycles; p = 0.031 on univariate analysis and p = 0.012 on multivariate analysis) and an increased TTDR in patients carrying the TT/TA-variant in ABCB1 rs2032582 compared to patients with the GG- or GT/GA-variant (19 vs. 7 cycles; p = 0.046 on univariate analysis and p = 0.024 on multivariate analysis). CONCLUSION: mRCC patients carrying the rs1128503 TT-variant or the TT/TA-variant in rs2032582 in ABCB1, which encodes for an efflux pump, do require less dose reductions due to adverse events compared to patients with the wild type or heterozygote variants in these genes.

The role of CXC-chemokine receptor CXCR2 and suppressor of cytokine signaling-3 (SOCS-3) in renal cell carcinoma.

BACKGROUND: Chemokine receptor signaling pathways are implicated in the pathobiology of renal cell carcinoma (RCC). However, the clinical relevance of CXCR2 receptor, mediating the effects of all angiogenic chemokines, remains unclear. SOCS (suppressor of cytokine signaling)-3 is a negative regulator of cytokine-driven responses, contributing to interferon-α resistance commonly used to treat advanced RCC with limited information regarding its expression in RCC. METHODS: In this study, CXCR2 and SOCS-3 were immunohistochemically investigated in 118 RCC cases in relation to interleukin (IL)-6 and (IL)-8, their downstream transducer phosphorylated (p-)STAT-3, and VEGF expression, being further correlated with microvascular characteristics, clinicopathological features and survival. In 30 cases relationships with hypoxia-inducible factors, i.e. HIF-1a, p53 and NF-κΒ (p65/RelA) were also examined. Validation of immunohistochemistry and further investigation of downstream transducers, p-JAK2 and p-c-Jun were evaluated by Western immunoblotting in 5 cases. RESULTS: Both CXCR2 and IL-8 were expressed by the neoplastic cells their levels being interrelated. CXCR2 strongly correlated with the levels of HIF-1a, p53 and p65/RelA in the neoplastic cells. Although SOCS-3 was simultaneously expressed with p-STAT-3, its levels tended to show an inverse relationship with p-JAK-2 and p-c-Jun in Western blots and were positively correlated with HIF-1a, p53 and p65/p65/RelA expression. Neither CXCR2 nor SOCS-3 correlated with the extent of microvascular network. IL-8 and CXCR2 expression was associated with high grade, advanced stage and the presence/number of metastases but only CXCR2 adversely affected survival in univariate analysis. Elevated SOCS-3 expression was associated with progression, the presence/number of metastasis and shortened survival in both univariate and multivariate analysis. CONCLUSIONS: Our findings implicate SOCS-3 overexpression in RCC metastasis and biologic aggressiveness advocating its therapeutic targeting. IL-8/CXCR2 signaling also contributes to the metastatic phenotype of RCC cells but appears of lesser prognostic utility. Both CXCR2 and SOCS-3 appear to be related to transcription factors induced under hypoxia.

Prognostic impact of baseline serum C-reactive protein in patients with metastatic renal cell carcinoma (RCC) treated with sunitinib.

OBJECTIVE: To evaluate the impact of baseline serum C-reactive protein (CRP) level on outcome in patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib. PATIENTS AND METHODS: We reviewed the charts of patients with mRCC who started sunitinib as a first targeted treatment between 2005 and 2012 in three hospitals in Belgium and France. Collected data included known prognostic factors for mRCC, anatomical location of metastatic sites, response rate (RR), progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 200 eligible patients were identified by retrospective chart review. The median PFS and OS were 12 and 20 months, respectively. We observed a clear impact of baseline CRP levels on outcome: the median PFS was 25 months in the group with baseline CRP ≤5 mg/L and 8 months in the group with baseline CRP >5 mg/L (hazard ratio [HR] 2.48, 95% CI 1.74-3.59). The median OS in each group was 50 vs 12 months, respectively (HR 3.17, 2.20-4.68). In the group with baseline CRP ≤5 mg/L, 61% of patients experienced a partial response compared with 32% of patients in the group with baseline CRP >5 mg/L (difference = 29%, 95% CI 15-42). When adding baseline CRP (with a log transformation) to the six variables of the International Metastatic RCC Database Consortium (IMDC) model in a multivariable Cox regression model, baseline CRP was independently associated with poor PFS (HR for each doubling in CRP level: 1.14, 95% CI 1.03-1.26; P = 0.01) and OS (HR: 1.29, 95% CI 1.16-1.43; P < 0.001). Adding baseline CRP to the model increased the c-statistic of PFS at 5 years from 0.63 (0.59-0.68) to 0.69 (0.65-0.73), and the c-statistic of OS at 5 years from 0.65 (0.60-0.69) to 0.70 (0.66-0.74). Patients with elevated baseline CRP levels had a poor prognosis independent of the IMDC risk group, whereas patients with a low baseline CRP in the IMDC favourable risk group had a very good outcome. CONCLUSION: Baseline serum CRP level is a strong independent variable linked with RR, PFS and OS in patients with mRCC treated with sunitinib.

VEGFR1 single nucleotide polymorphisms associated with outcome in patients with metastatic renal cell carcinoma treated with sunitinib - a multicentric retrospective analysis.

BACKGROUND: There are no validated markers that predict outcome in metastatic renal cell cancer (mRCC) patients treated with sunitinib. Recently, single nucleotide polymorphism (SNP) rs9582036 in VEGFR1 has been proposed as a predictor of progression-free survival (PFS) and overall survival (OS) to bevacizumab in patients with pancreatic cancer and rs7993418 in VEGFR1 as predictor for PFS in mRCC-patients treated with bevacizumab. Here, we aim to study the impact of these SNPs in mRCC patients treated with sunitinib. METHODS: We included patients with mRCC treated in 15 institutions in France and Belgium. Patients received sunitinib as first-line targeted therapy. We assessed response, time-to-tumor progression (TTP), OS, and clinical and biochemical parameters associated with outcome. We genotyped rs9582036 and rs7993418 as well as three other surrounding SNPs in VEGFR1: rs9554320, rs9554316 and rs9513070. Association between SNPs and treatment outcome were studied by univariate analysis and by multivariate Cox regression using relevant clinical factors associated with TTP and OS as covariates. FINDINGS: Ninety-one patients were included. We found that mRCC patients with the CC-variant in rs9582036 in VEGFR1 have a poorer response rate (RR) (0% vs. 46%, p = 0.028), a poorer PFS (10 vs. 18 months, p = 0.033 on univariate and 0.06 on multivariate analysis) and a poorer OS (14 vs. 31 months, p = 0.019 on univariate and 0.008 on multivariate analysis) compared to patients with the AC- and AA-genotypes. mRCC patients with the AA-variant in rs9554320 in VEGFR1 have a poorer PFS (12 vs. 21 months, p = 0.0066 on univariate and 0.005 on multivariate analysis) and a poorer OS (22 vs. 34 months, p = 0.019 on univariate and 0.067 on multivariate analysis) compared to patients with the AC- and CC-genotypes. Interpretation. mRCC patients with the CC-genotype in VEGFR1 SNP rs9582036 have a poorer response rate, PFS and OS when treated with sunitinib. These findings are in agreement with the association of rs9582036 and outcome observed in bevacizumab treated pancreatic cancer patients. Prospective validation of this SNP is warranted.

Association of ERCC1 SNPs with outcome in platinum-treated patients with advanced urothelial cancer: a Hellenic Cooperative Oncology Group study.

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.

Sequential treatment with sorafenib and sunitinib in metastatic renal cell carcinoma: clinical outcomes from a retrospective clinical study.

Sorafenib and sunitinib are inhibitors of receptor protein tyrosine kinases (TKIs) and are approved for the treatment of metastatic renal cell carcinoma (mRCC). Although the mTOR inhibitor everolimus is effective for the treatment of patients who have failed TKI therapy, it is important to consider all available treatment options before switching therapy mode of action. Herein, we report outcomes in patients with mRCC switched to sorafenib following disease progression on sunitinib treatment. The medical records of 35 patients treated between November 2006 and November 2009 at two large referral centers in Greece were retrospectively analyzed for time-to-progression (TTP), overall survival (OS), and tolerability of sorafenib after sunitinib. Median TTP and OS on sorafenib were 4.9 and 11.5 months, respectively. Among 33 patients evaluable for tumor response, three had a partial response and 17 achieved disease stabilization (objective response rate 8.5%; total clinical benefit rate 57%). Sorafenib was well tolerated, with mostly grade 1/2 adverse events and no treatment-related deaths. Sorafenib was effective and well tolerated in this group of patients. The TTP with sorafenib following sunitinib was comparable to outcomes reported previously, providing further support that TKIs should be used in sequence before switching to an mTOR inhibitor.

Leukocytoclastic vasculitis after long-term treatment with sunitinib: a case report.

We report on a 63-year-old woman, previously in good health, who had undergone nephrectomy for clear cell renal cell carcinoma in 2002. Because of systemic relapse with multiple lung metastases in 2006, the patient was treated with sunitinib 50 mg daily on a 4-weeks on-/2-weeks off-schedule. After 3 years of treatment, she developed a purpuric rash on her feet and trunk. Biopsy revealed leukocytoclastic vasculitis. No other organ involvement was diagnosed. She was started on oral prednisone 30 mg daily with rapid resolution of the vasculitic skin lesions. Sunitinib was temporally discontinued and reintroduced at the same dose level. Reappearance of a less serious vasculitis after 2 cycles of re-treatment was resolved in the weeks off-treatment and by reducing the dose of sunitinib along with 5 mg of prednisone daily. One year after the diagnosis, the patient is still on this therapy. Oncology providers should be aware of this rare but potentially serious, possible adverse effect of sunitinib.

Intermittent docetaxel chemotherapy in patients with castrate-resistant prostate cancer.

OBJECTIVES: To determine whether intermittent docetaxel might control disease while limiting the toxicity and improving the quality-of-life parameters in patients with advanced, castrate-resistant prostate cancer. Intermittent docetaxel represents an appealing therapeutic approach. METHODS: We reviewed the records of 35 patients with chemotherapy-naive castrate-resistant prostate cancer who had received docetaxel 45 mg/m(2) every 2 weeks, with oral prednisone 5 mg twice daily. Treatment was held when the patients had reached a >50% prostate-specific antigen reduction from baseline that was confirmed by a second measurement 4 weeks later, in the absence of disease progression. Docetaxel was resumed at a >25% prostate-specific antigen increase from the nadir level, also confirmed by a second measurement 4 weeks later, or in cases of documented disease progression. RESULTS: Of the 35 patients, 18 (51.42%) had entered the first chemotherapy-free interval (CFI) after a median of 6 infusions (range 2-12), 6 patients had entered a second CFI after a median of 4 months (range 2-12), and 1 patient, a third CFI at the last follow-up point. The median interval "off chemotherapy" was 4.5 months (range 1-16) for the first CFI. Two patients discontinued docetaxel because of Grade 4 nonhematologic toxicity. The median interval to treatment failure was 8.1 months (95% confidence interval 5.1-12.2) for the entire cohort and 12.2 months (95% confidence interval 8.3-25+) for the patients who had entered the first CFI. CONCLUSIONS: The results of our study have shown that intermittent docetaxel is a clinically active and likely more tolerable and less costly therapeutic strategy for patients with castrate-resistant prostate cancer than continuous administration. Additional validation of this approach is warranted.

A risk-adapted strategy of adjuvant paclitaxel/carboplatin in early-stage ovarian cancer: time-dependent effect of 4 versus 6 cycles on outcome.

OBJECTIVE: We investigated the efficacy of risk-adapted adjuvant paclitaxel/carboplatin chemotherapy in early-stage ovarian carcinoma. METHODS: Fifty-three patients were treated according to the risk of relapse: patients with stages IA or IB or with grade 1 (low risk) received 4 cycles of paclitaxel and carboplatin; patients with IC/IIA and grade 2 or 3 (high risk) received 6 cycles of chemotherapy. The outcome was compared with that of 95 patients who were all treated with 4 cycles. RESULTS: Median follow-up was 88, 113 and 42 months for the whole cohort, non-risk-adapted and risk-adapted treatment, respectively. Five-year relapse-free and disease-specific survival was 86 and 93% for the whole population, 96 and 97% for low-risk and 81 and 91% for high-risk patients. Risk classification was the only significant prognostic factor for relapse-free (p = 0.011) and disease-specific survival (p = 0.039). Among high-risk patients, the administration of 6 cycles was associated with a significantly lower relapse rate after censoring events, which occurred beyond 2 years (3 vs. 18%; p = 0.013), but this difference was diminished at 5 years (23 vs. 25%; p = 0.797). CONCLUSIONS: Six cycles of chemotherapy reduced the risk of relapse within 2 years, but the benefit from two additional cycles beyond this time is questionable.

Prognostic stratification of patients with advanced renal cell carcinoma treated with sunitinib: comparison with the Memorial Sloan-Kettering prognostic factors model.

BACKGROUND: The treatment paradigm in advanced renal cell carcinoma (RCC) has changed in the recent years. Sunitinib has been established as a new standard for first-line therapy. We studied the prognostic significance of baseline characteristics and we compared the risk stratification with the established Memorial Sloan Kettering Cancer Center (MSKCC) model. METHODS: This is a retrospective analysis of patients treated in six Greek Oncology Units of HECOG. Inclusion criteria were: advanced renal cell carcinoma not amenable to surgery and treatment with Sunitinib. Previous cytokine therapy but no targeted agents were allowed. Overall survival (OS) was the major end point. Significance of prognostic factors was evaluated with multivariate cox regression analysis. A model was developed to stratify patients according to risk. RESULTS: One hundred and nine patients were included. Median follow up has been 15.8 months and median OS 17.1 months (95% CI: 13.7-20.6). Time from diagnosis to the start of Sunitinib (12 months, p = 0.001), number of metastatic sites (1 vs. >1, p = 0.003) and performance status (PS) (1, p = 0.001) were independently associated with OS. Stratification in two risk groups ("low" risk: 0 or 1 risk factors; "high" risk: 2 or 3 risk factors) resulted in distinctly different OS (median not reached [NR] vs. 10.8 [95% confidence interval (CI): 8.3-13.3], p < 0.001). The application of the MSKCC risk criteria resulted in stratification into 3 groups (low and intermediate and poor risk) with distinctly different prognosis underlying its validity. Nevertheless, MSKCC model did not show an improved prognostic performance over the model developed by this analysis. CONCLUSIONS: Studies on risk stratification of patients with advanced RCC treated with targeted therapies are warranted. Our results suggest that a simpler than the MSKCC model can be developed. Such models should be further validated.

Prechemotherapy serum levels of CD105, transforming growth factor beta2, and vascular endothelial growth factor are associated with prognosis in patients with advanced epithelial ovarian cancer treated with cytoreductive surgery and platinum-based chemotherapy.

BACKGROUND: Serum CD105 has been associated with angiogenic activity in cancer, and low CD105 expression has been associated with improved prognosis. The present study evaluated the prognostic significance of serum levels of CD105 and related factors in patients with epithelial ovarian cancer (EOC) after cytoreductive surgery and chemotherapy. PATIENTS AND METHODS: Eighty-six patients with stages IIC to IV EOC treated postoperatively with platinum-based chemotherapy were included. The enzyme-linked immunosorbent assay was used to measure prechemotherapy serum levels of CD105, transforming growth factor beta1/2 (TGF-beta1/2), angiopoietin 2, vascular endothelial growth factor, and tumor necrosis factor-alpha. RESULTS: High levels of TGF-beta2 (>8908.86 pg/mL) and CD105 (>4.25 ng/mL) were independently associated with improved overall survival (not reached vs 39 months, P = 0.009 and 75 vs 39 months, P = 0.029, respectively), whereas a high level of TGF-beta2 and a low level of vascular endothelial growth factor (<219.04 pg/mL) were independently associated with improved progression-free survival (49 vs 17 months, P = 0.022 and 57 vs 16 months, P = 0.023, respectively). Among patients with favorable (>4.25 ng/mL) CD105 levels, only patients with low TGF-beta1 levels (<177.1 ng/mL) had superior survival than patients with low CD105 levels. CONCLUSIONS: Our study confirms the prognostic significance of angiogenesis in EOC and supports a biological interaction between CD105 and TGF-beta1. High angiogenic activity may be associated by increased efficacy of postoperative chemotherapy.

The role of high-dose chemotherapy in the treatment of testicular cancer.

Testicular cancer is a highly curable neoplasm, even in the case of extragonadal disease. Nevertheless, patients with adverse prognostic features or relapsing after first-line cisplatin-based chemotherapy have a worse prognosis with a death rate greater than 50%. High-dose chemotherapy (HDC) has long been used in this group of patients. The introduction of stem cells, instead of bone marrow, as the source of hemopoietic cells and the use of leukocyte growth factors have substantially reduced the mortality and morbidity of this procedure although the role of HDC is not well defined. This review summarizes the available data, focusing on published randomized studies. The problems associated with the design of these studies and the interpretation of data are discussed. Currently this HDC approach is mainly used in patients who relapse after first-line chemotherapy. Nevertheless, selection of patients likely to benefit from this treatment remains an issue of intense clinical research.

Efficacy of methotrexate/vinblastine/doxorubicin cisplatin combination in gemcitabine-pretreated patients with advanced urothelial cancer: a retrospective analysis.

OBJECTIVE: Second-line treatment options in advanced urothelial cancer are limited. We investigated the efficacy of a methotrexate/vinblastine/doxorubicin/cisplatin (MVAC) combination after failure of gemcitabine/platinum chemotherapy. PATIENTS AND METHODS: Twenty-five patients with advanced urothelial cancer, who received second-line MVAC after first-line gemcitabine/cisplatin (n = 9) or gemcitabine/carboplatin (n = 16), were included in this retrospective analysis. RESULTS: Twenty-two patients (88%) relapsed within 6 months after first-line treatment. Following MVAC, there were 5 (20%) objective responses. Median follow-up was 20.2 months. Median progression-free survival (PFS) was 3.8 months (95% CI: 2.3-5.2), and median overall survival (OS) was 9 months (95% CI: 6.6-11.4). Eastern Cooperative Oncology Group performance status 0.1 versus 2 was associated with longer PFS (5 months versus 3.3 months, P = 0.049). Response or stabilization of disease during second-line chemotherapy predicted for a significantly longer PFS and OS (7.4 versus 3.5, P = 0.005; 15.5 versus 7, P = 0.046). CONCLUSIONS: Second-line MVAC chemotherapy may result in prolonged survival in some patients with refractory disease. Further research in this field is necessary.

Immune response in ovarian cancer: how is the immune system involved in prognosis and therapy: potential for treatment utilization.

Ovarian cancer is one of the leading causes of cancer-related death among women. Resistance to the disease occurs in more than 70% of the cases even after treated with chemotherapy agents such as paclitaxel- and platinum-based agents. The immune system is increasingly becoming a target for intense research in order to study the host's immune response against ovarian cancer. T cell populations, including NK T cells and Tregs, and cytokines have been associated with disease outcome, indicating their increasing clinical significance, having been associated with prognosis and as markers of disease progress, respectively. Harnessing the immune system capacity in order to induce antitumor response remains a major challenge. This paper examines the recent developments in our understanding of the mechanisms of development of the immune response in ovarian cancer as well as its prognostic significance and the existing experience in clinical studies.