Serum Hyaluronic Acid Levels Are Altered in Acute Leukemia Patients: Potential Prognostic Implications.

BACKGROUND: Studies on the serum concentration of hyaluronic acid (HA) in newly diagnosed patients with acute myeloid leukemia (AML), B-acute lymphoblastic leukemia (B-ALL), and mantle-cell lymphoma (MCL) are scarce. In this study, we focused on investigating whether HA could serve as a possible prognostic marker in patients with AML, B-ALL, and MCL. METHODS: The serum concentration of HA was measured in a total of 51 patients with newly diagnosed AML, B-ALL, and MCL. Venous blood was collected 1 day before the initiation of chemotherapy (D0), on day 16 of the first cycle of chemotherapy (D16), and on D30. RESULTS: The serum HA concentration on D0 in patients with AML, B-ALL, and MCL was higher than in the control group. For all types of hematological malignancy, on D0, serum HA values of nonsurvivors were higher than in survivors. Moreover, patients in relapse had higher levels of serum HA than patients in remission. A strong positive correlation between serum HA and ferritin, ß2-microglobulin, and lactate dehydrogenase was found. CONCLUSION: Serum HA may serve as a possible prognostic marker for AML, B-ALL, and MCL patients, especially on D0. Prospective case-control studies on larger populations may provide further information.

Cardiovascular Risk and Serum Hyaluronic Acid: A Preliminary Study in a Healthy Population of Low/Intermediate Risk.

BACKGROUND: Hyaluronic acid (HA) has been found to be an important trigger of atherosclerosis. In this study, we investigate the possible association of serum HA with cardiovascular disease risk in a population of low/intermediate risk for cardiovascular events. METHODS: We enrolled 200 subjects with low/intermediate risk for developing cardiovascular disease. High specific C-reactive protein (hsCRP) was used as an indicator of preclinical atherosclerosis. The Framingham score was used to calculate the cardiovascular risk. RESULTS: Participants with dyslipidemia had significantly higher levels of serum HA than those without dyslipidemia (t-test, P = 0.05), higher levels of hsCRP (Kruskal-Wallis test, P = 0.04), and higher cardiovascular risk according to the Framingham score (Kruskal-Wallis test, P = 0.05). Serum HA concentration correlated significantly with the Framingham score for risk for coronary heart disease over the next 10 years (Spearman r = 0.152, P = 0.02). Diabetic volunteers had significantly higher HA than those without diabetes (t-test, P = 0.02). Participants with metabolic syndrome had higher serum HA levels and higher hsCRP (Kruskal-Wallis test, P = 0.01) compared to volunteers without metabolic syndrome (t-test, P = 0.03). CONCLUSIONS: Serum HA should be explored as an early marker of atheromatosis and cardiovascular risk.

Indications for an alternative effective treatment of head and neck squamous cell carcinoma with temsirolimus plus bevacizumab: from bench to bedside?

Head and neck squamous cell carcinoma (HNSCC) is a group of tumors known to be sensitive to chemotherapy and radiotherapy in patients who are treatment naive. However, when recurrences do occur, these tumors generally become resistant and objective responses to therapy at that point tend to be less effective. There has been an increasing interest in developing novel molecular-targeted agents that specifically modulate growth factor and signaling pathways that are unregulated in HNSCC tumor cells. Combinations of vascular endothelial growth factor and mammalian target of rapamycin inhibitors have been used in some types of neoplasms, but no such efforts have been made in HNSCC. In this study, we investigated the in vitro, in vivo, and clinical effects of the temsirolimus (mammalian target of rapamycin inhibitor, Tem) and bevacizumab (antivascular endothelial growth factor antibody, Bev) combination. In-vitro studies were carried out on the A431 human squamous epidermoid carcinoma cell line and in-vivo studies were carried out on A431 tumor cells implanted on female Nu/Nu*nuBR (athymic nude) mice. Also, the effectiveness of the Tem and Bev combination was tested clinically in two separate clinical cases of chemoresistant HNSCC. The in-vitro, in-vivo, and clinical results showed that this combination can be significantly effective. In conclusion, we discuss the theoretical basis of the molecular pharmacological interactions between Bev and Tem that could explain these good results. If the therapeutic index is ultimately well determined, the antitumor effect of Bev and Tem is very likely to yield fruitful results.

Topotecan and pegylated liposomal doxorubicin combination as palliative treatment in patients with pretreated advanced malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive disease with poor or modest responses to chemotherapy and dismal prognosis. In most of the cases the scope of the treatment is only palliative. In the current study, the combination of i.v. topotecan and pegylated liposomal doxorubicin (PLD) in advanced multi-treated MPM was tested. Primary objective was palliation of the symptoms, with the secondary ones being the establishment of the regimen's safety and efficacy. PATIENTS AND METHODS: Nine patients were enrolled (7 males/2 females, median age 57.5 years, ECOG performance status ≤ 2), having progressed after 2 or 3 lines of chemotherapy including pemetrexed and cisplatin. Main symptoms were dyspnea, cough, chest pain, fatigue, and anorexia. The treatment included topotecan 1.2 mg/m2 i.v. on Days 1 - 3 and PLD 40 mg/m2 on Day 4, every 28 days. The patients received 4 - 8 chemotherapy cycles (median 5.8). RESULTS: In all cases, symptoms were significantly improved after the 2nd treatment cycle. Respiratory function tests showed considerable enhancement, while cough and pain were drastically reduced. All patients had objective clinical benefit, 1 patient achieving partial response and 8 stable disease. Median time to progression and overall survival was 7 and 9 months, respectively. The chosen dose of the topotecan/ PLD combination was well-tolerated with no Grade 3/4 toxicities. Quality of life, as it was evaluated by the QLQ-C30 and QLQLC13 questionnaires, had improved scores especially the ones referring symptomatology. CONCLUSION: The current study shows a significant palliative effect of the topotecan/ PLD combination in pretreated patients with advanced MPM.

Can statin therapy reduce the risk of melanoma? A meta-analysis of randomized controlled trials.

A growing body of literature suggests that statins may have a chemopreventive potential against melanoma through pleiotropic anti-inflammatory, immunomodulatory, and antiangiogenesis mechanisms. Our aim was to examine this association through a detailed meta-analysis of randomized controlled trials (RCTs). A comprehensive search for trials published up to June 2009 was performed, reviews of each study were conducted and data were abstracted. Prior to meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk estimates (RR) and 95% confidence intervals (CIs) were calculated using the fixed- and the random-effects models. Subgroup and sensitivity analyses were also conducted. Sixteen RCTs of statins for cardiovascular outcomes, involving 62,568 individuals with a mean age of 60 years and an average follow-up of nearly 4.7 years, contributed to the analysis. We found no evidence of publication bias (P = 0.47) or heterogeneity among the studies (P = 0.25). Statin use did not significantly affect the risk of developing melanoma assuming either a fixed- (RR = 0.92, 95% CI: 0.67-1.26), or a random-effects model (RR = 0.92, 95% CI: 0.62-1.36). This neutral effect was further supported by the results of subgroup and sensitivity analyses. Our findings do not support a protective effect of statins against melanoma.

HIV/AIDS: recent advances in antiretroviral agents.

Despite the considerable progress in antiretroviral therapy, the eradication of HIV-1 remains unfeasible. Therefore, novel agents are under investigation. The aim of this review is to summarize the conventional compounds, to describe the recently approved agents, and to take a comprehensive look at the clinically relevant findings of current research.

The diagnostic role of glycosaminoglycans in pleural effusions: a pilot study.

BACKGROUND: Pleural effusions are classified into transudates and exudates. Various criteria have been used with Light's et al being the most accepted ones. Glycosaminoglycans (GAGs) have been detected during pleural fluids (PF) analysis in various causes. In this pilot study, we investigated: (a) the usefulness of GAGs in the assessment of pleural effusions, and (b) whether and in what way GAGs correlate with established criteria used to indicate an exudate. METHODS: LDH, total protein, cholesterol and GAG levels were measured in pleural fluid and serum from 50 patients with pleural effusion. GAG levels were defined by the photometric method of Hata. The discriminative properties of pleural GAGs (pGAG), pleural fluid/serum GAG ratio (GAGR), serum GAGs (sGAG) and serum LDH (sLDH) were explored with ROC analysis. RESULTS: According to ROC analysis, pGAG and GAGR exhibited satisfactory discriminative properties in the separation of pleural effusions. For GAGR, at a 1.1 cut off point, sensitivity and specificity reached 75.6%; 95%CI: 60.5-87.1 and 100%; 95%CI: 47.8-100, respectively. For pGAG at a cut off value of 8.4 microg/ml, these percentages changed to 86.7%; 95%CI: 73.2-94.9 and 100%; 95%CI: 47.8-100. The study also revealed the differential role of sGAG between malignancies and benign cases, scoring 68.8%; 95%CI: 50.0-83.9 for sensitivity, and 84.6%; 95%CI: 54.5-97.6 for specificity at a 7.8 microg/ml cut off. CONCLUSION: Our results suggest that glycosaminoglycan measurement of both serum and pleural effusions could be useful for simultaneous differentiation of exudates from transudates, and of malignant from benign exudates.

Statin use and the risk of prostate cancer: A metaanalysis of 6 randomized clinical trials and 13 observational studies.

Statins have been suggested to prevent prostate cancer. Our aim was to examine statin use in relation to both total prostate cancer and the more clinically important advanced prostate cancer, through a detailed metaanalysis of the epidemiologic studies published on the subject in peer-reviewed literature. A comprehensive search for articles published up to November 2007 was performed, reviews of each study were conducted and data were abstracted. Prior to metaanalysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using the random-effects model. Subgroup and sensitivity analyses were also performed. Nineteen studies [6 randomized clinical trials (RCTs), 6 cohort and 7 case-control studies] contributed to the analysis. There was no evidence of an association between statin use and total prostate cancer among either RCTs (RR = 1.06, 95% CI: 0.93-1.20) or the observational studies (RR = 0.89, 95% CI: 0.65-1.24). However, high heterogeneity was detected among the observational studies. Moreover, long-term statin use did not significantly affect the risk of total prostate cancer (RR = 0.93, 95% CI: 0.77-1.13). In contrast, synthesis of the available reports that had specifically examined statin use in relation to advanced prostate cancer indicated a protective association (RR = 0.77, 95% CI: 0.64-0.93). Our results do not support the hypothesis that statins reduce the risk of total prostate cancer. However, further research is required to investigate whether the particular association of statin use with lower risk of advanced prostate cancer is indeed causal.

Statins are not associated with a reduced risk of pancreatic cancer at the population level, when taken at low doses for managing hypercholesterolemia: evidence from a meta-analysis of 12 studies.

OBJECTIVES: Recent experimental research on a class of pharmacological agents that reduce plasma cholesterol, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins), has shown promise in pancreatic cancer chemoprevention. While the mechanism remains unclear, several epidemiological studies have also evaluated the relationship between statin use and pancreatic cancer. Our aim was to examine the strength of this association through a detailed meta-analysis of the studies published on the subject in peer-reviewed literature. METHODS: A comprehensive search for articles published up to December 2007 was performed, reviews of each study were conducted, and data were abstracted. Prior to meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using the random-effects model. RESULTS: Twelve studies (3 randomized placebo-controlled trials [RCTs], 4 cohort, and 5 case-control studies) contributed to the analysis. The studies were grouped on the basis of study design, and separate meta-analyses were conducted. There was no evidence of an association between statin use and pancreatic cancer among either the RCTs (RR 0.99, 95% CI 0.44-2.21) or the observational studies (RR 0.86, 95% CI 0.60-1.24). Similarly, we found no evidence of publication bias. However, a high heterogeneity was detected among the observational studies. CONCLUSION: Despite the chemopreventive potential of statins demonstrated in experimental studies, our results do not support the hypothesis that these agents reduce the risk of pancreatic cancer at the population level, when taken at low doses for managing hypercholesterolemia.

Monitoring aspirin treatment in patients with thrombocytosis: comparison of the platelet function analyzer (PFA)-100 with optical aggregometry.

Aspirin provides satisfactory protection against thrombotic episodes in essential thrombocythemia (ET), but at higher platelet counts has been less effective. Our aim was to compare the platelet function analyzer (PFA)-100 with optical aggregometry in order to determine a reliable method in monitoring aspirin's influence on platelet function in patients with thrombocytosis. We studied 36 patients with thrombocytosis. Sixteen of them, receiving aspirin, composed group A, while group B consisted of 20 patients not taking aspirin. In all patients, we compared the platelet function measured by classic optical aggregation tests with closure times (CT) obtained by the PFA-100. The definition of platelet responses as normal or pathological showed that PFA-100 collagen and/or epinephrine (CEPI) CTs and epinephrine-induced aggregometry is the pair of methods with the higher agreement in monitoring of platelet dysfunction due to ASA treatment (a=94%). Satisfactory results were also obtained for group B (a=81%). The comparison between PFA-100 CEPI CTs and arachidonic acid-induced aggregometry exhibited moderate agreement both in the total number of patients and in group A (a=79% and 94%, respectively). PFA-100 collagen and/or ADP (CADP) CTs and ADP-induced aggregometry were not concordant. The PFA-100 system appears to be a reliable and rapid method in the assessment of aspirin's antiplatelet effect in patients with thrombocytosis. Regarding aggregometry, the selection of the inducer, its concentration and cut-off points is crucial in defining the response to antiaggregating agents. It still remains to determine whether there is any relevance between the measurements obtained by these methods and clinical outcome in thrombocythemic patients.

Cancer chemoprevention: a summary of the current evidence.

Cancer chemoprevention is defined as the use of natural, synthetic, or biological chemical agents to reverse, suppress, or prevent either the initial phase of carcinogenesis or the progression of neoplastic cells to cancer. At present, the circle of agents with an established chemopreventive effect is restricted to tamoxifen and raloxifene in breast cancer, finasteride in prostate cancer, and celecoxib in colon polyp prevention. However, in recent years, there has been an exponential increase in the study of agents that have a chemopreventive potential against cancer. In this review, the current evidence regarding cancer chemoprevention in major target organs is summarised, discussing the epidemiological as well as the experimental data.

Hyaluronic acid and hyaluronidase as possible novel urine biomarkers for the diagnosis of prostate cancer.

The goal of the study is to examine the possible use of HA (hyaluronic acid) and HAase (hyaluronidase) as novel urine biomarkers for the early diagnosis for prostate cancer (Pca). After a prostatic massage, the urine of 118 high-risk patients for Pca was collected, and the patients were submitted to ultrasound-guided transrectal biopsy. HA and HAase were detected and analyzed with Enzyme-Linked Immunosorbent Assay, and a statistical analysis of the urine levels of the two biomarkers according to the histology results was performed. HAase and HA were independently associated with Pca, and both HAase and HA showed significant predictive ability for prostate cancer. With an optimal cut-off point of 183.71 HAase had 70% sensitivity maintaining at the same time a 55.2% specificity, while the optimal cut-off point for HA was 50.13 with 65% sensitivity and 53.9% specificity. Patients with HAase more than 183.71 ng/ml had 3.67 times greater likelihood for prostate cancer and Patients with HA more than 50.13 ng/ml had 2.31 times greater likelihood for prostate cancer. The need of novel biomarkers that will improve the efficacy of PSA is urgent. HAase and HA showed significant predictive ability for prostate cancer and were independently associated with Pca, and greater levels were associated with greater odds for prostate cancer. To Our Knowledge, this is the first study referring to the detection of HAase and HA as potential urine biomarkers for the early diagnosis of Pca.

Detecting Novel Urine Biomarkers for the Early Diagnosis of Prostate Cancer: Platelet Derived Growth Factor-BB as a Possible New Target.

INTRODUCTION: Although the prostate specific antigen revolutionized the diagnosis of prostate cancer (PCa), it has its limitations. We prospectively examined the potential use of the platelet-derived growth factor-BB (PDGF-BB) as a urine biomarker for the early diagnosis of PCa. MATERIALS AND METHODS: The urine samples of 118 patients were collected after a prostatic massage and all the patients subsequently underwent ultrasound-guided transrectal biopsy. PDGF-BB was detected in the urine by enzyme-linked immunosorbent assay. RESULTS: Patients with PCa had greater levels of prostate specific antigen and PDGF-BB. Receiver operating characteristic curve analysis showed that the optimal cut-of of PDGF-BB for the prediction of PCa was 1,504.9 with a sensitivity of 60% and a specificity of 51.3%. For a 100 unit increase in PDGF-BB, the likelihood for PCa increased about 4%. CONCLUSION: PDGF-BB showed a significant predictive ability for PCa. Detection of PDGF-BB in urine with Elisa was easy and improved our diagnostic accuracy in the diagnosis of PCa.

Does pravastatin promote cancer in elderly patients? A meta-analysis.

BACKGROUND: An increase in the incidence of cancer among elderly people assigned to pravastatin therapy has been reported in a randomized controlled trial; however, this finding has been attributed to chance. Our aim was to assess the effect of pravastatin therapy on cancer risk and to examine whether the effect varies according to age by performing a detailed meta-analysis and meta-regression analysis of randomized controlled trials. METHODS: We performed a comprehensive literature search for relevant studies published before February 2006. Before analysis, the selected studies were evaluated for publication bias and heterogeneity. Pooled relative risk estimates with 95% confidence intervals (CIs) were calculated using fixed-and random-effects models. Meta-regression analysis was performed to examine the impact of age on the study estimates of the relative risk of cancer due to pravastatin therapy. RESULTS: Twelve trials that investigated the use of pravastatin therapy for cardiovascular outcomes were included in the analysis (n = 42 902). Although the overall association between pravastatin use and cancer was not statistically significant in the fixed-effects (risk ratio [RR] 1.06, 95% CI 0.99 - 1.13) or random-effects model (RR 1.06, 95% CI 0.97 - 1.14), the meta-regression analysis showed that the age of study participants significantly modified the effect of pravastatin therapy on cancer risk (p = 0.006). Specifically, this analysis showed that pravastatin therapy was associated with an increasing risk of cancer as age increased. This finding was remarkably robust in the sensitivity analysis. INTERPRETATION: Our findings suggest an association between pravastatin therapy and cancer in elderly patients. However, given the importance of this potential association, further verification is warranted.

A retrospective open-label uncontrolled study of Epoetin zeta on the treatment of chemotherapy-induced anemia in solid tumors.

PURPOSE: This is a single-center uncontrolled retrospective study to evaluate the efficacy and safety of the biosimilar epoetin zeta after approval in chemotherapy-induced anemia (CIA). METHODS: Patients screened were >18 years old suffering from solid malignancies and CIA with Hg ≤10 or <11 g/dl if symptomatic anemia. Patients had measurable disease by TNM and Eastern Cooperative Oncology Group (ECOG). Patients were treated for at least 12 weeks and the primary endpoint was to determine the incidence of blood transfusions, and secondarily, the overall safety and efficacy defined as ≥1 g/dl rise in Hb concentration or ≥40,000 cells/µl rise in reticulocyte count. Quality of life was assessed with ECOG performance status (PS) and functional assessment of cancer therapy-anemia (FACT-An) score. RESULTS: 1287 patients with median Hb 9.3 g/dl (range 8.3-10.6) were enrolled and included in the evaluation. Median age was 63 years (range 33-78). 74% of patients were stage III/IV. Patients received epoetin zeta subcutaneously at fixed 40,000-IU once weekly. Blood transfusions were given in 178 patients (13.8%; 95% CI 11.9-15.6%). Appropriate response was observed in 79% patients by week 4, 87% by week 8, and 91% by week 12. A mean Hb increase of 2.5 g/dl was observed by week 12 which correlated with an improvement in PS and Fact-An score. Thrombotic events occurred in 5.2% (95% CI 3.4-7.1%) of patients. CONCLUSIONS: Epoetin zeta is effective in palliation and treatment of CIA in patients with solid tumors. Overall, it is well tolerated and safe even in patients with increased disease burden.

Use of statins and breast cancer: a meta-analysis of seven randomized clinical trials and nine observational studies.

PURPOSE: A growing body of evidence suggests that statins may have chemopreventive potential against breast cancer. Laboratory studies demonstrate that statins induce apoptosis and reduce cell invasiveness in various cell lines, including breast carcinoma cells. However, the clinical relevance of these data remains unclear. The nonconclusive nature of the epidemiologic data prompted us to conduct a detailed meta-analysis of the studies published on the subject in peer-reviewed literature. PATIENTS AND METHODS: A comprehensive search for articles published up until 2005 was performed; reviews of each study were conducted; and data were abstracted. Before meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% CIs were calculated using the random and the fixed-effects models. Subgroup and sensitivity analyses were also performed. RESULTS: Seven large randomized trials and nine observational studies (five case-control and four cohort studies) contributed to the analysis. We found no evidence of publication bias or heterogeneity among the studies. Statin use did not significantly affect breast cancer risk (fixed effects model: RR = 1.03; 95% CI, 0.93 to 1.14; random effects model: RR = 1.02; 95% CI, 0.89 to 1.18). When the analyses were stratified into subgroups, there was no evidence that study design substantially influenced the estimate of effects. Furthermore, the sensitivity analysis confirmed the stability of our results. CONCLUSION: Our meta-analysis findings do not support a protective effect of statins against breast cancer. However, this conclusion is limited by the relatively short follow-up times of the studies analyzed. Further studies are required to investigate the potential decrease in breast cancer risk among long-term statin users.

Redox imbalance, macrocytosis, and RBC homeostasis.

The erythrocyte represents a major component of the antioxidant capacity of the blood through the enzymes contained in the cell, the glutathione system, and the low-molecular-weight antioxidants of the erythrocyte membrane. A further major red blood cell contribution is in regenerating consumed redox equivalents via the oxidative pentose phosphate pathway and glutathione reductase. Moreover, its extracellular antioxidant capacity, its mobility, and the existence of reducing equivalents far in excess of its normal requirements make erythrocytes function as an effective oxidative sink in the organism. That is why red blood cell metabolism and homeostasis strongly affect the antioxidant properties of the whole body. Conversely, the relation between macrocytosis and oxidative stress has not been fully delineated. Reviewing the mechanisms involved in red blood cell homeostasis in cases of redox imbalance is crucial in identification of factors that could potentially improve erythrocyte survival and defense against oxidant damage.

Isolation and Quantification of Glycosaminoglycans from Human Hair Shaft.

BACKGROUND: There is evidence that glycosaminoglycans (GAGs) are present in the hair shaft within the follicle but there are no studies regarding GAGs isolation and measurement in the human hair shaft over the scalp surface, it means, in the free hair shaft. OBJECTIVE: The purpose of our research was to isolate and measure the total GAGs from human free hair shaft. METHODS: Seventy-five healthy individuals participated in the study, 58 adults, men and women over the age of 50 and 17 children (aged 4~9). GAGs in hair samples, received from the parietal and the occipital areas, were isolated with 4 M guanidine HCl and measured by the uronic acid-carbazole reaction assay. RESULTS: GAGs concentration was significantly higher in the occipital area than in the parietal area, in all study groups. GAG levels from both areas were significantly higher in children than in adults. GAG levels were not associated with gender, hair color or type. CONCLUSION: We report the presence of GAGs in the human free hair shaft and the correlation of hair GAG levels with the scalp area and participants' age.

Phase II study of bevacizumab plus irinotecan on the treatment of relapsed resistant small cell lung cancer.

PURPOSE: This phase II study investigates the efficacy and safety of DNA topoisomerase I inhibitor irinotecan plus bevacizumab a monoclonal antibody against VEGF (BEVIRI) in patients with relapsed chemo-resistant SCLC. METHODS: Patients who previously completed treatment with cisplatin-etoposide who relapsed within 3 months, had measurable extensive-stage SCLC, ECOG performance status 0-2 and adequate hematologic, renal and hepatic function, were given intravenous irinotecan 175 mg/m(2) plus intravenous bevacizumab 7.5 mg/kg on day 1 and 15 in 30 day cycles for a target of at least four cycles. No patients had received prophylactic intracranial irradiation. Treatment response was assessed with computer tomography scans with the completion of two consecutive cycles. Primary endpoint was overall response rate (ORR). RESULTS: Thirty-two patients were enrolled and 28 of them were eligible for evaluation of response, toxicity and survival. The median age was 63.5 years (range 48-73). The ORR (CR and PR) was 25 % (95 % CI 8.9-41.0) and including patients with stable disease overall disease control rate at 2 months was 89 % (95 % CI 77.41-100). The median duration of response was 6 months, median progression-free survival was 3 months (mean PFS: 3.2, 95 % CI 2.7-3.7), and median overall survival was 6 months (mean OS: 6.3, 95 % CI 5.4-7.1). The PFS rate at 6 months was 3.6 %, and 1-year OS rate was 3.6 %. The median number of cycles received was 4.5 (range 1-6). There were two (7.1 %) hematologic (neutropenia) and one (3.5 %) non-hematologic (proteinuria) serious grades 3-4 adverse reactions without necessitating treatment discontinuation. CONCLUSION: BEVIRI combination in relapsed chemo-resistant SCLC patients demonstrates promising efficacy and low toxicity compared to historical controls. Further investigation is warranted.