To evaluate the incidence of chemotherapy-induced amenorrhea (CIA) and its therapeutic impact in premenopausal breast cancer patients. A systematic search was performed to identify clinical studies that compared the incidence of CIA with different chemotherapy regimens and oncological outcomes with and without CIA. The fixed-effects and random-effects models were used to assess the pooled estimates. Heterogeneity and sensitivity analyses were performed to explore heterogeneity among studies and to assess the effects of study quality. A total of 15,916 premenopausal breast cancer patients from 46 studies were included. The cyclophosphamide-based regimens, taxane-based regimens, and anthracycline/epirubicin-based regimens all increased the incidence of CIA with pooled odds ratios of 2.25 (95 % CI 1.26-4.03, P = 0.006), 1.26 (95 % CI 1.11-1.43, P = 0.0003) and 1.39 (95 % CI 1.15-1.70, P = 0.0008), respectively. The three-drug combination regimens of cyclophosphamide,anthracycline/epirubicin, and taxanes (CAT/CET) caused the highest rate of CIA compared with the other three drug combinations (OR 1.41, 95 % CI 1.16-1.73, P = 0.0008). Tamoxifen therapy was also correlated with a higher incidence of CIA, with an OR of 1.48. Patients with CIA were found to exhibit better disease-free survival (DFS) and overall survival (OS) compared with patients without CIA. With respect to molecular subtype, this DFS advantage remained significant in hormone-sensitive patients (HR 0.61, 95 % CI 0.52-0.72, P < 0.00001). The current meta-analysis has demonstrated that anthracycline/epirubicin, taxanes, cyclophosphamide, and tamoxifen all contributed to elevated rates of CIA, and CIA was not merely a side effect of chemotherapy but was a better prognostic marker, particularly for ER-positive premenopausal early-stage breast cancer patients. However, this topic merits further randomized control studies to detect the associations between CIA and patient prognosis after adjusting for age, ER status, and other influential factors.

To evaluate systemic safety of ranibizumab for diabetic macular edema.

Cardiotoxic and other side effects limit the usefulness of treatments for cancer.

We performed a systematic review and meta-analysis of mucocutaneous toxicities associated with sorafenib, an oral multi tyrosine kinase inhibitor. Eligible studies included randomized Phase II and III trials of patients with solid tumors on sorafenib daily describing events of hand foot skin reaction, skin rash, alopecia, stomatitis or pruritis. Patients treated with sorafenib had a significantly increased risk of all-grade mucocutaneous toxicities. The RR of all-grade hand foot skin reaction, skin rash, alopecia, stomatitis and pruritis were 4.33 (95% CI: 3.06-6.14), 2.67 (95% CI: 1.86-3.83), 3.93 (95% CI: 2.07-7.45), 2.9 (95% CI: 2.26-3.73), 2.29 (95% CI: 1.87-3.03); respectively. Exploratory subgroup analysis showed no effect of tumor types or treatment regimen (monotherapy versus combination) on the RR of mucocutaneous toxicities. Our meta-analysis has demonstrated that sorafenib is associated with a higher risk of developing all grade mucocutaneous toxicities compared with control.

Large interests have been focused on the role of drug-eluting stents in the setting of ST-segment elevation myocardial infarction (STEMI) and concerns have emerged regarding an higher risk of stent thrombosis. Aim of the current study was to perform a meta-analysis using individual patient data to evaluate the long-term safety and effectiveness of sirolimus-eluting stent (SES) as compared to paclitaxel-eluting stent (PES) in patients undergoing primary percutaneous coronary intervention (PCI) for STEMI. The literature was scanned by formal searches of electronic databases (MEDLINE and CENTRAL). We examined all completed randomized trials of SES versus PES for STEMI. No language restriction was applied. Primary study endpoint was the occurrence of major adverse cardiac events (MACE). Secondary endpoints were the occurrence of death, reinfarction, stent thrombosis, target-vessel revascularization (TVR). Individual patient data were obtained from 4 out of 5 trials identified, including a total of 1,000 patients, 504 (50.4 %) randomized to SES and 496 (49.6 %) randomized to PES. At long-term follow-up (1,021 [372–1,351] days), no difference was observed between SES and PES in terms of TVR (10 vs 11.6 %, HR [95 % CI 0.73 [0.45–1.16], p = 0.18, p het = 0.92]) (primary endpoint) or death (9.4 vs 10.4 %, HR [95 % CI 0.95 [0.58–1.54], p = 0.82, p het = 0.89]), reinfarction (8.2 vs 10.4 %, HR [95 % CI 0.91 [0.53–1.57], p = 0.73, p het = 0.83]), stent thrombosis (7.4 vs 4.6 %, HR [95 % CI 1.04 [0.55–2.05], p = 0.92, p het = 0.65]), and MACE (10 vs 13.6 %, HR[95 % CI 0.86 [0.63–1.18], p = 0.36, p het = 0.84]) (secondary endpoints). The present pooled patient-level meta-analysis demonstrates that, among STEMI patients undergoing primary PCI, SES and PES are associated with a similar outcome at long-term follow-up, in terms of death, reinfarction, stent thrombosis, TVR and MACE.

Ovarian cancer is the leading cause of death among gynecological tumors. Carboplatin/paclitaxel represents the cornerstone of front-line treatment. Instead, there is no consensus for management of recurrent/progressive disease, in which pegylated liposomal doxorubicin (PLD) ± carboplatin is widely used. We performed a systematic review and metaanalysis to evaluate impact of PLD-based compared with no-PLD-based regimens in the ovarian cancer treatment. Data were extracted from randomized trials comparing PLD-based treatment to any other regimens in the January 2000-January 2013 time-frame. Study end-points were overall survival (OS), progression free survival (PFS), response rate (RR), CA125 response, and toxicity. Hazard ratios (HRs) of OS and PFS, with 95% CI, odds ratios (ORs) of RR and risk ratios of CA125 response and grade 3-4 toxicity, were extracted. Data were pooled using fixed and random effect models for selected endpoints. Fourteen randomized trials for a total of 5760 patients were selected and included for the final analysis, which showed no OS differences for PLD-based compared with other regimens (pooled HR: 0.94; 95% CI: 0.88-1.02; P = 0.132) and a significant PFS benefit of PLD-based schedule (HR: 0.91; 95% CI: 0.86-0.96; P = 0.001), particularly in second-line (HR: 0.85; 95% CI: 0.75-0.91) and in platinum-sensitive (HR: 0.83; 95% CI: 0.74-0.94) subgroups. This work confirmed the peculiar tolerability profile of this drug, moreover no difference was observed for common hematological toxicities and for RR, CA125 response. PLD-containing regimens do not improve OS when compared with any other schedule in all phases of disease. A marginal PFS advantage is observed only in platinum-sensitive setting and second-line treatment.

A large number of studies have tried to combine sorafenib with TACE for patients with unresectable hepatocellular carcinoma (HCC) and the results were controversial. We conducted this systematic review and meta-analysis to evaluate the safety and efficacy of combination therapy of sorafenib and TACE in the management of unresectable HCC.

Chemotherapy is essential for long-term survival of osteosarcoma patients. However, the impact of dosage and dosage intensity (DI) of chemotherapeutic agents on patients with high-grade osteosarcoma is largely unknown.

Chemotherapy-induced cognitive impairments are reported by many cancer survivors. Research to date has not provided a clear description of their nature, extent, mechanisms, and duration. To investigate the impairments and factors that could influence their identification and severity, the present meta-analysis brings together research on this topic in adult cancer patients.

To investigate the rate of endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents, the spectrum of causative organisms, and associated visual acuity outcomes.

Mechanistic and epidemiologic studies provide considerable evidence for a protective association between calcium intake and incident colorectal cancer (CRC). While the relationship has not been substantiated by short-duration randomized controlled trials (RCTs) of CRC, trials do show a benefit on adenomas, a precursor to CRC. To address some of this inconsistency, we conducted dose-response meta-analyses by sources of calcium intake, based on prospective observational studies published up to December 2013 identified from PubMed, Embase, and BIOSIS. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. For total calcium intake, each 300 mg/day increase was associated with an approximately 8% reduced risk of CRC (summary RR = 0.92, 95% CI = 0.89-0.95, I(2)  = 47%, 15 studies with 12,305 cases, intake = 250-1,900 mg/day, follow-up = 3.3-16 years). While the risk decreased less steeply in higher range of total calcium intake (P(non-linearity)  = 0.04), the degree of curvature was mild and statistical significance of non-linearity was sensitive to one study. For supplementary calcium, each 300 mg/day increase was associated with an approximately 9% reduced risk of CRC (summary RR = 0.91, 95% CI = 0.86-0.98, I(2)  = 67%, six studies with 8,839 cases, intake = 0-1,150 mg/day, follow-up = 5-10 years). The test for non-linearity was not statistically significant (P(non-linearity)  = 0.11). In conclusion, both dietary and supplementary calcium intake may continue to decrease CRC risk beyond 1,000 mg/day. Calcium supplements and non-dairy products fortified with calcium may serve as additional targets in the prevention of CRC. RCTs of calcium supplements with at least 10 years of follow-up are warranted to confirm a benefit of calcium supplements on CRC risk.

Hypertension is one of the major side effects of sorafenib, and reported incidences vary substantially among clinical trials. A systematic review was conducted using Medline, PubMed, Embase, and the Cochrane Library for all longitudinal studies to investigate the incidence and risk of hypertension events in cancer patients treated with sorafenib. A total of 14 randomized controlled trials and 39 prospective single-arm trials involving 13,555 patients were selected for the meta-analysis. The relative risk of all-grade and high-grade hypertension associated with sorafenib were 3.07 (95% confidence interval [CI], 2.05–4.60; P<.01) and 3.31 (95% CI, 2.21–4.95; P<.01), respectively. The overall incidence of sorafenib-induced all-grade and high-grade hypertension were 19.1% (95% CI, 15.8%–22.4%) and 4.3% (95% CI, 3.0%–5.5%), respectively. A significantly higher incidence of hypertension was noted in patients with renal cell carcinoma (RCC) compared with those with non-RCC malignancies (all-grade: 24.9% [95% CI, 19.7%–30.1%] vs 15.7%[95% CI, 12.1%–19.3%]; P<.05; high-grade:8.6% [95% CI, 6.0%–11.2%] vs 1.8% [95% CI, 0.9%–2.6%]; P<.05). The trials with median progression-free survival (PFS) longer than 5.3 months (mean PFS) demonstrated a significantly higher incidence of high-grade hypertension than trials with shorter PFS (6.3% [95% CI, 4.1%–8.5%] vs 2.6% [95% CI, 1.4%– 3.8%]; P<.05). Findings of the meta-analysis indicated a significantly high risk of sorafenib-induced hypertension. Patients with RCC have a significantly higher incidence of hypertension and the occurrence of hypertension may be associated with improved prognosis.

This meta-analysis aims to evaluate the effects of common polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene on the toxicity and clinical responses of irinotecan-based chemotherapy in patients with colorectal cancer (CRC).

Although most prostate cancers initially respond to castration with luteinizing hormone- releasing analogues or bilateral orchiectomy, progression eventually occurs. Based on the exciting results of several randomized controlled trials (RCTs), it seems that patients with metastatic castration-resistant prostate cancer (mCRPC) might benefit more from treatment withabiraterone. Therefore we conducted a systematic review to evaluate the efficacy and toxicity of abiraterone in the treatment of mCRPC.

We performed a systematic review and meta-analysis to assess the efficacy and tolerability of degarelix for lower urinary tract symptom relief, prostate volume reduction and quality of life improvement in men with prostate cancer (PCa).

The risk of fatal adverse events (FAEs) due to bevacizumab-based chemotherapy has not been well described; we carried out an updated meta-analysis regarding this issue.

Abstract Methotrexate (MTX) is a key component of chemotherapeutic regimens for childhood acute lymphoblastic leukemia (ALL), and enters the cell via active transport mediated by the reduced folate carrier (RFC1). A major single-nucleotide polymorphism of the RFC1 gene, G80A, which affects the activity of RFC1, may influence MTX toxicity in pediatric ALL. We collected all studies that investigated the association of RFC1 G80A polymorphism and MTX toxicity in pediatric ALL, and found inconsistency among their results. The aim of this meta-analysis was to summarize all of these studies in order to clarify the correlation between the RFC1 G80A polymorphism and MTX toxicity in pediatric ALL. A recessive model demonstrated no influence of the RFC1 G80A genotype on MTX toxicity. In conclusion, the RFC1 G80A polymorphism does not seem to be a good marker of MTX-related toxicity in pediatric ALL.

Palonosetron, a 5-hydroxytryptamine 3 receptor antagonist (5-HT(3)RA) with a strong binding affinity and long half-life, has been used in numerous trials for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV). We systematically reviewed the efficacy and safety of palonosetron compared to other 5-HT(3)RAs in CINV prophylaxis.

To evaluate the safety and efficacy of Endostar combined with chemotherapy in the treatment of end-stage colorectal cancer.