The incidence and relative risk of cardiovascular toxicity in patients treated with new hormonal agents for castration-resistant prostate cancer

AimNew hormonal agents are available for treating metastatic castration-resistant prostate cancer (mCRPC). We aim to define the incidence and relative risk (RR) of cardiovascular events in mCRPC patients treated with these agents.MethodsProspective studies were identified by searching the MEDLINE/PubMed, Cochrane Library and ASCO Meeting abstracts. Combined relative risks (RRs) and 95% confidence intervals (CIs) were calculated using fixed- or random-effects methods.ResultsWe included six articles in this meta-analysis covering a total of 6735 patients who were used to evaluate cardiac toxicity. The use of new hormonal agents was associated with an increased risk of all grades of such toxicity (RR = 1.32, 95% CI, 1.08–1.60; p = 0.006) compared to a placebo, even if the absolute difference in terms of incidence was small at 14.8% versus 11.5%, respectively. No increased risk of grade 3–4 events (RR = 1.35, 95% CI, 0.90–2.03; p = 0.15) was observed.A total of 7830 patients were used to evaluate hypertension, and it was found that the use of new hormonal agents compared to a placebo was associated with an increased risk of all-grades (RR = 1.84, 95% CI, 1.37–2.46; p < 0.001) and grade 3–4 events (RR = 1.77, 95% CI, 1.13–2.77; p = 0.01). The absolute incidence was 12.5% versus 7.5% for all-grades and 3.7% versus 2.4% for grade 3–4.ConclusionsThis analysis revealed a significant increase in the incidence and RR of cardiovascular toxicity in mCRPC treated with new hormonal agents as opposed to a placebo, even though the occurrence of all- and grade 3–4 events rose only 14% and 4%, respectively. Follow-ups for the onset of treatment-related cardiovascular events should therefore be considered in these patients.     

Role of cardioprotective therapy for prevention of cardiotoxicity with chemotherapy: A systematic review and meta-analysis

BackgroundCardiotoxicity is a well-recognised complication of chemotherapy with anthracycline and/or trastuzumab, and its prevention remains an important challenge in cancer survivorship. Several successful preventative strategies have been identified in animal trials. We sought to assemble the clinical evidence that prophylactic pharmacological interventions could prevent left ventricular (LV) dysfunction and heart failure in patients undergoing chemotherapy.MethodsWe undertook a systemic review of the evidence from randomised trials and observational studies where a prophylactic intervention was compared with a control arm in patients with a normal ejection fraction and no past history of heart failure. The primary outcome was development of heart failure (HF), a drop in ejection fraction (EF) or both. A random-effects model was used to combine relative risks (RR) and 95% confidence intervals (CIs), and a meta-regression was undertaken to assess the impact of potential covariates.FindingsData were collated from 14 published articles (n = 2015 paediatric and adult patients) comprising 12 randomised controlled trials and two observational studies. The most studied chemotherapeutic agents were anthracyclines, and prophylactic agents included dexrazoxane, statins, beta-blocker and angiotensin antagonists. There were 304 cardiac events in the control arm compared to 83 in the prophylaxis arm (RR = 0.31 [95% CI: 0.25–0.39], p < 0.00001). Cardiac events were reduced with dexrazoxane (RR = 0.35 [95% CI 0.27–0.45], p < 0.00001), beta-blockade (RR = 0.31 [95% CI 0.16–0.63], p = 0.001), statin (RR = 0.31 [95% CI 0.13–0.77], p = 0.01) and angiotensin antagonists (RR = 0.11 [95% CI 0.04–0.29], p < 0.0001).InterpretationProphylactic treatment with dexrazoxane, beta-blocker, statin or angiotensin antagonists appear to have similar efficacy for reducing cardiotoxicity.     

The effect of cytotoxic chemotherapy on the risk of high-grade acneiform rash to cetuximab in cancer patients: a meta-analysis

BackgroundThe effect of chemotherapy on the risk of cetuximab-induced acneiform rash is unknown. We carried out a systematic review and meta-analysis of published studies to quantify the incidence and risk of high-grade acneiform rash with combination therapy.MethodsRelevant studies were identified from PubMed database, abstracts presented at the American Society of Clinical Oncology conferences, and Web of Science. Incidence of acneiform rash to cetuximab monotherapy was estimated based on updated data from our previously published meta-analysis. Incidence, relative risk (RR), and 95% confidence intervals (CIs) were calculated based on the heterogeneity of included studies.ResultsA total of 5333 patients from nine trials were included in the analysis. The incidence of high-grade acneiform rash was significantly increased in patients receiving combination treatment (12.8%, 95% CI 9.1% to 17.7%) as compared with cetuximab monotherapy (6.3%, 95% CI 3.7% to 10.5%), with a risk ratio of 2.03 (95% CI 1.52–2.71, P < 0.01). Cetuximab significantly increased the risk of high-grade rash in patients receiving combination therapy (RR = 37.7, 95% CI 17.8–80.0, P < 0.001).ConclusionsAddition of cytotoxic chemotherapy to cetuximab significantly increases the risk of high-grade acneiform rash compared with cetuximab monotherapy. This emphasizes the need for effective management strategies.     

Physical activity in relation to risk of prostate cancer: a systematic review and meta-analysis

BackgroundProstate cancer (PCa) is one of the most common cancers among men, yet little is known about its modifiable risk and protective factors. This study aims to quantitatively summarize observational studies relating physical activity (PA) to PCa incidence and mortality.Materials and methodsPublished articles pertaining to PA and PCa incidence and mortality were retrieved in July 2017 using the Medline and EMBASE databases. The literature review yielded 48 cohort studies and 24 case–control studies with a total of 151 748 PCa cases. The mean age of the study participants at baseline was 61 years.ResultsIn random-effects models, comparing the highest versus the lowest level of overall PA showed a summary relative risk (RR) estimate for total PCa incidence close to the null [RR = 0.99, 95% confidence interval (CI) = 0.94–1.04]. The corresponding RRs for advanced and non-advanced PCa were 0.92 (95% CI = 0.80–1.06) and 0.95 (95% CI = 0.85–1.07), respectively. We noted a statistically significant inverse association between long-term occupational activity and total PCa (RR = 0.83, 95% CI = 0.71–0.98, n studies = 13), although that finding became statistically non-significant when individual studies were removed from the analysis. When evaluated by cancer subtype, an inverse association with long-term occupational activity was noted for non-advanced/non-aggressive PCa (RR = 0.51, 95% CI = 0.37–0.71, n studies = 2) and regular recreational activity was inversely related to advanced/aggressive PCa (RR = 0.75, 95% CI = 0.60–0.95, n studies = 2), although these observations are based on a low number of studies. Moreover, PA after diagnosis was related to reduced risk of PCa mortality among survivors of PCa (summary RR based on four studies = 0.69, 95% CI = 0.55–0.85).ConclusionsWhether PA protects against PCa remains elusive. Further investigation taking into account the complex clinical and pathologic nature of PCa is needed to clarify the PA and PCa incidence relation. Moreover, future studies are needed to confirm whether PA after diagnosis reduces risk of PCa mortality.     

Infectious complications in cancer patients treated with anti-EGFR monoclonal antibodies cetuximab and panitumumab: A systematic review and meta-analysis

BackgroundClinical trials have reported a substantial variation in the risk of infection related to anti-EGFR monoclonal antibodies (mAbs) cetuximab and panitumumab. We performed a systematic review and meta-analysis to assess the infection risk in cancer patients treated with anti-EGFR mAbs.Patients and methodsWe searched PubMed and the ASCO online database of meeting abstracts up to January 2014 for relevant clinical trials. Eligible studies included randomized controlled trials (RCTs) of cetuximab and panitumumab that reported adequate safety data for grade 3–4 infection or febrile neutropenia (FN). The summary incidence, relative risk (RR) and 95% confidence intervals (CIs) were calculated.ResultsA total of 14,957 patients from 28 trials were included. Treatment with anti-EGFR mAbs was associated with an increased risk of high-grade infection (RR, 1.49; 95% CI, 1.33–1.66; P < 0.001) and FN (RR, 1.27; 95% CI, 1.09–1.48; P = 0.002). The incidence of high-grade infection and FN due to anti-EGFR mAbs was 9.3% (95% CI, 7.2–12.0%) and 5.3% (95% CI, 3.3–8.3%), respectively. A significantly increased risk of high-grade infection was observed in all subgroups analyses (type of anti-EGFR mAb, therapy of control arm and duration of treatment) except for tumor type (only colorectal cancer and non-small cell lung cancer (NSCLC) groups had the increased risk). Subgroup analyses revealed a significantly increased risk of FN in the following subgroups: cetuximab, NSCLC and treatment duration longer than the median of all trials (3.1 months).ConclusionsThe use of anti-EGFR mAbs is associated with a significantly higher risk of high-grade infection and febrile neutropenia.     

Risk of suicide in men with low-risk prostate cancer

PurposeRisk of suicide is increased among men with prostate cancer. We investigated this association among men with low-risk cancer, usually detected by prostate specific antigen (PSA)-testing.Patients and MethodsRelative risk (RR) of suicide was calculated by use of Poisson regression analysis within the Prostate Cancer data Base Sweden (PCBaSe) 2.0, a nation-wide, population-based database, comparing 105,736 men diagnosed with prostate cancer between 1997–2009 to 528,658 matched prostate cancer-free men.ResultsDuring the first 6 months after diagnosis, there were 38 suicides among men with prostate cancer; incidence rate 0.73 per 1000 person-years (PY) and 30 suicides in the comparison cohort; 0.11 per 1000 PY, corresponding to a RR of suicide of 6.5 (95% confidence interval (CI) 4.0–10). Risk was highest among men with distant metastases, incidence rate 1.25 per 1000 PY, RR 10 (95% CI 5.1–21) but risk was also increased for men with low-risk tumours, incidence rate difference 0.45 per 1000 PY and RR 5.2 (95% CI 2.3–12) and across categories of socioeconomic status and comorbidity. Eighteen months after diagnosis, risk of suicide had decreased to 0.27 per 1000 PY, RR 1.0 (95% CI 0.68–1.5) for low-risk prostate cancer but remained increased among men with metastases, 0.57 per 1000 PY, RR 1.8 (95% CI 1.1–2.9).ConclusionAlthough the increase in absolute risk of suicide was modest, our findings reflect the severe psychological stress that prostate cancer patients may experience after diagnosis. The increased risk of suicide observed in men with prostate cancer, including low-risk, calls for increased awareness.     

The risk of skin rash and stomatitis with the mammalian target of rapamycin inhibitor temsirolimus: a systematic review of the literature and meta-analysis

ObjectiveWe conducted a systematic review of the literature and performed a meta-analysis to determine the risk of developing skin rash and stomatitis among patients receiving temsirolimus.MethodsDatabases from PubMed and Web of Science from January, 1998 until June, 2011 and abstracts presented at the American Society of Clinical Oncology annual meetings from 2004 through 2011 were searched to identify relevant studies. The incidence and relative risk (RR) of skin rash and stomatitis were calculated using random-effects or fixed-effects model depending on the heterogeneity of included studies.ResultsA total of 779 patients from 10 clinical trials were included in this analysis. The overall incidence of all-grade rash was 45.8% (95% confidence interval (CI): 35.6–56.3%), with a RR of 7.6 (95% CI: 4.4–13.3; p < 0.001). The overall incidence of high-grade rash was 3.3% (95% CI: 1.9–5.6%), with a RR of 13.70 (95% CI: 0.82–227.50, p = 0.07). The overall incidence of all-grade stomatitis was 44.3% (CI: 32.1–57.1%), with a RR of 11.10, 95% CI: 5.60–22.00; p < 0.001). The overall incidence of high-grade stomatitis was 3.2% (95% CI: 1.9–5.4%), with a RR of 13.2 (95% CI: 0.80–218.50, p = 0.07).ConclusionThere is a significant risk of developing skin rash and stomatitis in cancer patients receiving temsirolimus. The risk is independent of underlying tumour. Adequate monitoring and early intervention are recommended to prevent debilitating toxicity and suboptimal dosing.     

Single circulating tumor cell detection and overall survival in nonmetastatic breast cancer

BackgroundCirculation of cancer cells in the blood is a mandatory step for metastasis, but circulating tumor cells (CTC) have a low metastatic efficiency in preclinical animal models. In this prospective study, we reported the clinical outcome of nonmetastatic breast cancer patients according to CTC detection.Patients and methodsIn 115 nonmetastatic patients diagnosed with large operable or locally advanced breast cancer, we prospectively detected CTC using the CellSearch system before and after neoadjuvant chemotherapy in a phase II trial (REMAGUS02).ResultsAt baseline, 23% of patients were CTC positive, but only 10% had >1 CTC/7.5 ml of blood. After a median follow-up of 36 months, CTC detection before chemotherapy was an independent prognostic factor for both distant metastasis-free survival [DMFS; P = 0.01, relative risk (RR) = 5.0, 95% confidence interval (CI) 1.4–17] and overall survival (OS; P = 0.007, RR = 9, 95% CI 1.8–45). CTC detection after chemotherapy was of less significance (P = 0.07 and 0.09, respectively). Moreover, CTC detection showed interesting characteristics as an individual predictive test for metastatic relapses (sensibility 55%, specificity 81%, and global accuracy 77%).ConclusionsDetection of ≥1 CTC/7.5 ml before neoadjuvant chemotherapy can accurately predict OS. Our findings may change the clinical management of nonmetastatic breast cancer and indicate that the metastatic efficiency of CTC could be higher than previously reported.     

Prior long response to androgen deprivation predicts response to next-generation androgen receptor axis targeted drugs in castration resistant prostate cancer

BackgroundThere is an urgent need for qualified predictive biomarkers of sensitivity for the treatments used in patients with castration-resistant prostate cancer (CRPC). We attempted to identify ready-to-use clinical predictors of improved outcome in metastatic CRPC (mCRPC) patients treated with next generation androgen receptor (AR) axis targeted drugs.Patients and methodsWe reviewed a cohort of patients who received AR axis targeted drugs for CRPC at two major French cancer centres. The predictive role of several clinical, biological and radiological parameters on progression-free survival (PFS) was studied.ResultsThe study cohort consisted of 173 patients. Median duration of response to initial androgen deprivation therapy (ADT) (time to castration resistance, TTCRPC) was 17.8 months. The 50% prostate-specific antigen (PSA) response rate to AR axis targeted drugs was 16% (95% confidence interval (CI): 6–27) and 41% (95% CI: 30–47) in patients with TTCRPC of under and over 12 months respectively (p = 0.005). Median PFS was 2.8 months (95% CI: 2.1–3.9) and 5.8 (95% CI: 4.6–7.8; HR: 0.58, p = 0.002). In patients treated with post-docetaxel enzalutamide (n = 57), median PFS was 2.8 months and 8.6 months, (Hazard ratio (HR) = 3.1; 95% CI: 1.6–5.8, p = 0.0016) according to TTCRPC, whereas no difference was observed in placebo-treated patients (n = 27). The 50% PSA response rate to enzalutamide was 8% (95% CI: 0–38) and 58% (95% CI: 42–73) in patients with a TTCRPC of under and over 12 months respectively (p < 0.001).ConclusionThe previous duration of response to ADT is a predictor of sensitivity to next generation AR axis targeted drugs in patients with mCRPC.     

Has the association between hysterectomy and ovarian cancer changed over time? A systematic review and meta-analysis

Until recently most studies suggested that hysterectomy with ovarian conservation was associated with a decreased risk of ovarian cancer. However, several recent studies have reported modestly increased risks of ovarian cancer following hysterectomy. Given that as many as 35% of women will have a hysterectomy, the nature of the association requires clarification. We conducted a systematic review and meta-analysis of the published literature on the relationship between hysterectomy and ovarian cancer to investigate whether there has been a temporal change in the association. Twenty observational studies that have reported a quantitative assessment of the association between hysterectomy and risk of histologically-confirmed ovarian cancer were included in the meta-analysis. The overall relative risk (RR) estimate was 0.81 (95% confidence interval (CI) 0.72–0.92) suggesting hysterectomy decreases the risk of ovarian cancer. However, there was significant heterogeneity in the results (I² = 74%). Our exploration of sources of heterogeneity and metaregression showed that median year of cancer diagnosis of included cases explained most of the heterogeneity relative risk (RR = 0.70 (95% CI 0.65–0.76) for median year diagnosis pre 2000; RR = 1.18 (95% CI 1.06–1.31) for post 2000). This study shows that there has been a temporal shift in the association between hysterectomy and risk of ovarian cancer. One explanation may be the trend away from hysterectomy in younger women. Other speculative possibilities include the decline in oophorectomy rates and the use of oestrogen-only hormone replacement therapy in hysterectomised women. Until further evidence becomes available, clinicians should not advise women that a hysterectomy without salpingo-oophorectomy will favourably influence their future risk of ovarian cancer.     

Bevacizumab combined with chemotherapy for patients with advanced colorectal cancer: a systematic review

BackgroundFluoropyrimidine-based chemotherapy is considered standard treatment of advanced colorectal cancer. Recent studies indicate benefit to the addition of bevacizumab, a recombinant monoclonal antibody targeting vascular endothelial growth factor.MethodsMedline, EMBASE, Cochrane Library, and conference proceedings were searched to identify randomized trials in advanced colorectal cancer comparing chemotherapy plus bevacizumab with chemotherapy alone. A meta-analysis of published data was carried out.ResultsFive trials comparing chemotherapy plus bevacizumab with chemotherapy alone as first- or second-line treatment were identified. Our meta-analysis indicates an advantage in favor of the addition of bevacizumab to chemotherapy in terms of overall survival (OS) [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.69–0.90; P = 0.0005], progression-free survival (PFS) (HR 0.63; 95% CI 0.49–0.81, P = 0.0004), and response rate (RR 1.50; 95% CI 1.06–2.10, P = 0.02). The most commonly observed adverse effects related to bevacizumab included hypertension, proteinuria, bleeding, and thrombosis. Gastrointestinal perforation and poor wound healing were also observed; however, their incidence was rare.ConclusionsFor patients with advanced colorectal cancer receiving first- or second-line fluoropyrimidine-based chemotherapy, the addition of bevacizumab improves PFS and OS at the expense of increased incidence of toxicity. The magnitude of benefit may differ based on the chemotherapy regimen with which bevacizumab is partnered.     

Active and passive cigarette smoking and the risk of endometrial cancer in Poland

BackgroundEpidemiological studies have consistently reported that active cigarette smoking is inversely associated with endometrial cancer risk. However, dose-response relationships with quantitative measures of active smoking or passive smoking remain less clear.MethodsData on lifetime active and passive smoking were collected for 551 endometrial cancer cases and 1925 controls in a population-based case-control study conducted during 2001–2003 in Poland (Warsaw and ?ódz).ResultsCompared with never active smokers, active current (Odds Ratio (OR) = 0.51, 95% Confidence Interval (CI): 0.39, 0.68) and former smokers (OR = 0.60, 95% CI: 0.45, 0.80) were at a statistically significantly decreased risk. We did not observe statistically significant inverse dose-response relationships with increasing exposure with duration and cumulative measures. However, there was some indication that the highest category of number of years (OR = 0.35, 95% CI: 0.23–0.55), intensity (OR = 0.41, 95% CI: 0.24–0.69), and dose (OR = 0.38, 95% CI: 0.24–0.60) of smoking among current smokers had the greatest inverse association compared to never smokers. Our data did not support the presence of an inverse association with passive smoking among never active smokers (OR = 0.92; 95% CI: 0.65, 1.29).ConclusionOur results support that long-term and heavy smoking among current smokers strongly influence endometrial cancer risk.     

Relative mortality rates from incident chronic diseases among breast cancer survivors – A 14 year follow-up of five-year survivors diagnosed in Denmark between 1994 and 2007

BackgroundIt remains unknown whether incident chronic diseases are more often fatal among breast cancer survivors than among women free of breast cancer.MethodsWe conducted a nationwide matched cohort study of all Danish breast cancer patients diagnosed between 1994 and 2007, who survived for five years. We compared their long-term mortality with five times as many women from the general population without breast cancer, matched on age. We used time-varying methods to compute mortality rate ratios (MRRs) for incident diseases included in the Charlson Comorbidity Index (CCI).ResultsOne third of five-year breast cancer survivors developed incident diseases during 14 years of follow-up, with about the same incidence as women without breast cancer. Mortality associated with any incident disease was similar among breast cancer survivors (MRR = 7.1, 95% confidence interval (CI): 6.7, 7.4) and comparison women (MRR = 7.5, 95% CI: 7.3, 7.7). Among breast cancer patients, relative mortality associated with incident diseases was higher among patients treated with chemotherapy (MRR = 10, 95% CI: 8.7, 12) and radiotherapy (MRR = 9.8, 95% CI: 8.8, 11) than among patients who received surgery (MRR = 7.0, 95% CI: 6.7, 7.4) or hormonal therapy (MRR = 6.3, 95% CI: 5.8, 6.9).ConclusionThere were no marked differences in mortality of diseases among breast cancer survivors and women from the general population. Among breast cancer patients, new diseases were more often fatal in patients treated with chemotherapy and radiotherapy. Five-year breast cancer survivors have similar risk of dying from new chronic medical conditions as women from the general population without breast cancer.     

Vitamin C and survival among women with breast cancer: A Meta-analysis

BackgroundThe association between dietary vitamin C intake and breast cancer survival is inconsistent and few studies have specifically examined vitamin C supplement use among women with breast cancer. The purpose of this study was to summarise results from prospective studies on the association between vitamin C supplement use and dietary vitamin C intake and breast cancer-specific mortality and total mortality.MethodsStudies were identified using the PubMed database through February 6, 2014 and by examining the references of retrieved articles. Prospective studies were included if they reported relative risks (RR) with 95% confidence intervals (95% CIs) for at least two categories or as a continuous exposure. Random-effects models were used to combine study-specific results.ResultsThe ten identified studies examined vitamin C supplement use (n = 6) and dietary vitamin C intake (n = 7) and included 17,696 breast cancer cases, 2791 total deaths, and 1558 breast cancer-specific deaths. The summary RR (95% CI) for post-diagnosis vitamin C supplement use was 0.81 (95% CI 0.72–0.91) for total mortality and 0.85 (95% CI 0.74–0.99) for breast cancer-specific mortality. The summary RR for a 100 mg per day increase in dietary vitamin C intake was 0.73 (95% CI 0.59–0.89) for total mortality and 0.78 (95% CI 0.64–0.94) for breast cancer-specific mortality.ConclusionResults from this meta-analysis suggest that post-diagnosis vitamin C supplement use may be associated with a reduced risk of mortality. Dietary vitamin C intake was also statistically significantly associated with a reduced risk of total mortality and breast cancer-specific mortality.     

Unrelieved symptoms of female cancer patients during their last months of life and long-term psychological morbidity in their widowers: A nationwide population-based study

AimTo investigate if a cancer patient’s unrelieved symptoms during the last 3 months of life increase the risk of long-term psychological morbidity in the surviving widower.MethodsMen (n = 907) younger than 80 years and living in Sweden, who had lost their wives due to cancer, were asked 4–5 years after their loss to answer an anonymous postal questionnaire that included questions about their current psychological morbidity and their wives’ unrelieved symptoms during the last 3 months of life.ResultsIf the wife suffered unrelieved anxiety or pain during the last 3 months of her life, then the widowers had a higher risk of sleep-related problems 4–5 years after the loss. When the wife had suffered from anxiety, the relative risks (RR) for the widowers’ sleep-related problems were: difficulty falling asleep (RR 1.7, 95% CI 1.0–3.0) and waking up at night with anxiety (RR 4.9, 95% CI 1.5–15.7). When the wife had unrelieved pain, the widowers years later had an increased risk of difficulty falling asleep at night (RR 1.8, 95% CI 1.0–3.3).ConclusionsThe unrelieved patients’ end-of-life problems increase the risk of widowers’ long-term mental suffering. Efficient and effective diagnoses and treatment of pain and anxiety in terminally ill cancer patients are critical for both patients and their surviving widowers.     

Ca/Mg infusions for the prevention of oxaliplatin-related neurotoxicity in patients with colorectal cancer: a meta-analysis

BackgroundOxaliplatin-related neurotoxicity is the main limitation for its continuation in adjuvant and palliative chemotherapy for patients with colorectal cancer. The purpose of this meta-analysis was to determine the efficacy of calcium and magnesium (Ca/Mg) infusions in oxaliplatin-induced neurotoxicity.MethodsTwo independent authors conducted database searches of the literature to find clinical-controlled trials analyzing Ca/Mg infusions in oxaliplatin-induced neurotoxicity. The keywords used to search were oxaliplatin, neurotoxicity, calcium, magnesium, neuropathy, and peripheral. Clinical studies that included at least one primary or secondary event were eligible for the analysis, where primary events were incidences of acute and cumulative neurotoxicity, and secondary events were the total doses and cycles of oxaliplatin, response rate (RR), overall survival (OS), and progression-free survival (PFS). Odds ratios (ORs) and weighted mean differences (MD) were analyzed using models of fixed and random effects.ResultsThis meta-analysis comprised four prospective randomized clinical trials and three retrospective clinical trials involving 1170 colorectal cancer patients, of which 802 received Ca/Mg infusions (Ca/Mg group) and 368 did not (control group). According to the National Cancer Institute-Common Terminology Criteria for Adverse Events, the incidence of grade 3 acute neurotoxicity in those who received Ca/Mg was significantly lower than that of the control group (OR = 0.26; 95% confidence interval (CI), 0.11 to 0.62; P = 0.0002). The total rate of cumulative neurotoxicity, and that of grade 3 in particular, was significantly lower in the Ca/Mg group than in the control group (OR = 0.42; 95% CI 0.26–0.65; P = 0.0001; OR = 0.60; 95% CI 0.39–0.92; P = 0.02, respectively). The differences in total doses and cycles of oxaliplatin were also significant between the Ca/Mg and control group (MD = 246.73 mg/m²; 95% CI 3.01–490.45; P = 0.05; MD = 1.55; 95% CI 0.46–2.63; P = 0.005, respectively). No significant differences were found in median PFS (MD = 0.71 month; 95% CI -0.59–2.01; P = 0.29), median OS (MD = 0.10 month; 95% CI -0.41–0.61; P = 0.70) or RRs (OR = 0.82; 95% CI 0.61–1.10; P = 0.18).ConclusionCa/Mg infusions tend to decrease the incidence of oxaliplatin-induced acute and cumulative neurotoxicity and thus enhance patients' tolerance to oxaliplatin, without significantly altering the efficacy of chemotherapy.     

Gemcitabine versus gemcitabine plus dalteparin thromboprophylaxis in pancreatic cancer

BackgroundAnnualised figures show an up to 7-fold higher incidence of vascular thromboembolism (VTE) in patients with advanced pancreatic cancer (APC) compared to other common malignancies. Concurrent VTE has been shown to confer a worse overall prognosis in APC.MethodsOne hundred and twenty three APC patients were randomised to receive either gemcitabine 1000 mg/m² or the same with weight-adjusted dalteparin (WAD) for 12 weeks. Primary end-point was the reduction of all-type VTE during the study period. NCT00462852, ISRCTN: 76464767.FindingsThe incidence of all-type VTE during the WAD treatment period (<100 days from randomisation) was reduced from 23% to 3.4% (p = 0.002), with a risk ratio (RR)of 0.145, 95% confidence interval (CI) (0.035–0.612) and an 85% risk reduction. All-type VTE throughout the whole follow-up period was reduced from 28% to 12% (p = 0.039), RR = 0.419, 95% CI (0.187–0.935) and a 58% risk reduction. Lethal VTE <100 days was seen only in the control arm, 8.3% compared to 0% (p = 0.057), RR = 0.092, 95% CI (0.005–1.635).InterpretationWeight adjusted dalteparin used as primary prophylaxis for 12 weeks is safe and produces a highly significant reduction of all-type VTE during the prophylaxis period. The benefit is maintained after dalteparin withdrawal although decreases with time.     

Site-specific cancer risk in the Baltic cohort of Chernobyl cleanup workers, 1986–2007

ObjectiveTo assess site-specific cancer risk in the Baltic cohort of Chernobyl cleanup workers, 1986–2007.MethodsThe Baltic cohort includes 17,040 men from Estonia, Latvia and Lithuania who participated in the environmental cleanup after the accident at the Chernobyl Nuclear Power Station in 1986–1991 and who were followed up for cancer incidence until the end of 2007. Cancer cases diagnosed in the cohort and in the male population of each country were identified from the respective national cancer registers. The proportional incidence ratio (PIR) with 95% confidence interval (CI) was used to estimate the site-specific cancer risk in the cohort. For comparison and as it was possible, the site-specific standardised incidence ratio (SIR) was calculated for the Estonian sub-cohort, which was not feasible for the other countries.ResultsOverall, 756 cancer cases were reported during 1986–2007. A higher proportion of thyroid cancers in relation to the male population was found (PIR = 2.76; 95% CI 1.63–4.36), especially among those who started their mission shortly after the accident, in April–May 1986 (PIR = 6.38; 95% CI 2.34–13.89). Also, an excess of oesophageal cancers was noted (PIR = 1.52; 95% CI 1.06–2.11). No increased PIRs for leukaemia or radiation-related cancer sites combined were observed. PIRs and SIRs for the Estonian sub-cohort demonstrated the same site-specific cancer risk pattern.ConclusionConsistent evidence of an increase in radiation-related cancers in the Baltic cohort was not observed with the possible exception of thyroid cancer, where conclusions are hampered by known medical examination including thyroid screening among cleanup workers.     

Cardiorespiratory fitness,lifestyle factors and cancer risk and mortality in Finnish men

BackgroundPhysical fitness along with lifestyle factors may have important roles in the prevention of cancer. We examined the relationship between common lifestyle factors such as energy expenditure, physical activity and maximal oxygen uptake (VO_2max), nutrition and smoking habits and the risk of cancer.MethodsA population-based cohort study was carried out in 2268 men from Eastern Finland with no history of cancer. They were followed up for an average of 16.7 years. The outcome measures were cancer incidence (n = 387) and cancer mortality (n = 159).ResultsMen with VO_2max of more than 33.2 mL/kg/min (highest tertile) had 27% (95% confidence interval (CI) 0.56–0.97) decreased cancer incidence and 37% (95% CI 0.40–0.97) reduced cancer mortality than men with VO_2max of less than 26.9 mL/kg/min (lowest tertile) after adjustment for age, examination year, alcohol, smoking, socioeconomic status, waist-to-hip ratio and energy, fibre and fat intake. The risk reduction was mainly due to decreased risk of lung cancer in fit men. The adjusted risk of cancer was 0.73 (95% CI 0.55–0.98) among fit (VO_2max ? 26.9 mL/kg/min) men with the total energy expenditure of physical activity over 2500 kcal/week. A total of 290 active (energy expenditure >2500 kcal and at least 2 h of physical activity per week) men with a favourable lifestyle (good fitness, balanced diet and non-smoking) had an adjusted relative risk of 0.63 (95% CI 0.46–0.87) for cancer.ConclusionFavourable lifestyle including good cardiorespiratory fitness and healthy dietary habits with active and non-smoking lifestyle considerably reduces the risk of cancer.