Use Of Anthracyclines Research Articles

Anthracycline-Related Cardiotoxicity in Patients with Acute Myeloid Leukemia and Down Syndrome: A Literature Review.

Pediatric patients with Down syndrome (DS) are at an increased risk of developing certain cancers. Specifically, patients with DS have a reported 10-20-fold increased risk of developing acute myeloid leukemia (AML). Anthracycline-based treatment regimens achieve good results in patients with DS and AML. It has been proposed that DS status constitutes a risk factor for the cardiotoxicity associated with the use of anthracyclines in the pediatric setting. However, published evidence pointing toward an increased risk of cardiotoxicity in patients with DS is relatively scarce and conflictive. This concise review compiles literature relating to the incidence of anthracycline-related cardiotoxicity in pediatric patients with DS. In general, reports from trials using anthracyclines at the maximum recommended dose showed increases in the incidence of anthracycline-related cardiotoxicity in patients with DS in comparison with trials that used anthracyclines at reduced doses. Evidence from the literature suggests that patients with DS can achieve favorable therapeutic outcomes after receiving treatment with reduced doses of anthracyclines to minimize the potential for cardiotoxicity. Further prospective trials, along with the available evidence, would assist the design of treatment protocols for patients with pediatric leukemias and DS.

A case of chemotherapy-induced congestive heart failure successfully treated with Chinese herbal medicine

A case is presented to illustrate a potential effect of Chinese herbal medicine (CHM) formulas in treating chemotherapy-induced cardiotoxicity. An 18-year-old adolescent male with refractory acute lymphoblastic leukemia (ALL) had experienced anthracycline-induced congestive heart failure (CHF) for 3 weeks. Under intensive care with conventional therapy, the patient still had exercise intolerance and depended on supplemental oxygen all day. Therefore, he consented to treatment with traditional Chinese medicine (TCM) for alternative therapy. This patient was treated with modified Zhi Gan Cao Tang (ZGCT), three times a day for 2 months. After 6 days of CHM treatment, the patient could tolerate daily activity without supplemental oxygen. After 2 months of CHM treatment, the follow-up chest X-ray showed great improvements in pulmonary edema and cardiomegaly. In this case, anthracycline-induced cardiotoxicity resolved slowly following the administration of modified ZGCT. It is suggested that the CHM formula has a protective effect on the progression of CHF secondary to the use of anthracyclines in pediatric cancer. Further studies to determine the mechanism and clinical trials are warranted.

Subclinical Ventricular Dysfunction Detected by Speckle-Tracking Two Years after Use of Anthracycline

Dear Editor We would like to congratulate the authors for the publication of their article Subclinical Ventricular Dysfunction Detected by Speckle-Tracking Two Years after Use of Anthracycline, considering the great practical applicability of the theme. Cardiotoxicity secondary to chemotherapy drugs is a reality that imposes, on cardiologists and oncologists, the challenge of prevention and/or early detection of this complication, which has high morbidity and mortality1. In this regard, we read with interest the abovementioned article, which highlights the usefulness of speckle-tracking to attain an early diagnosis of subclinical ventricular dysfunction, although this finding does not directly imply in implementing treatment due to the lack of current scientific evidence, which makes studies in this area even more important. However, we would like to point out some aspects to add to the scientific information brought on by this article. In the Results section, the authors demonstrate that almost 80% of patients had also received cyclophosphamide as a chemotherapy drug, an alkylating agent that may be associated with ventricular dysfunction rates of up to 25% of the cases2,3, which cannot be minimized in the Discussion and Conclusion sections of this study. This same rationale can be applied to the more than 50% of patients receiving radiotherapy in the mediastinal region, regardless of the treated hemithorax, since the incidence of coronary heart disease in these patients is a side effect of significant incidence4. We also observed a high rate of hypertension in both groups of patients and controls and that the systolic and diastolic BP levels were higher in the latter than in the first group. We would like to know if there was any difference between the groups regarding the class of antihypertensive drug used, as data in the literature suggest some protective effect of ACE inhibitors and beta-blockers on the incidence of ventricular dysfunction and major clinical outcomes5.

Disease Characteristics, Patterns of Care, and Survival in Very Elderly Patients with Diffuse Large B-Cell Lymphoma

Context: Despite having the highest incidence of diffuse large B-cell lymphoma (DLBCL), individuals older than 80 years are rarely included in DLBCL clinical trials or epidemiological studies. We sought to better characterize DLBCL presentation, treatment, and survival patterns for this age group.Objective: We investigated demographic and clinical characteristics at diagnosis, treatment selection factors, and the impact of treatment regimen on overall survival (OS) and lymphoma-related survival (LRS) for DLBCL patients >80 years. We hypothesized that patients >80 years were more likely to undergo observation and less likely to receive standard-of-care rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). We also hypothesized that patients >80 years who received R-CHOP would have superior OS and LRS, even after controlling for demographic and clinical factors.Methods: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to examine DLBCL patients diagnosed from 1999-2009 and followed through 2010. Our population-based cohort contained 5,924 DLBCL patients aged ≥66 years; 1,422 were >80 years. Only patients treated within 6 months of diagnosis with R-CHOP; cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP); cyclophosphamide, vincristine, and prednisone (CVP); rituximab plus CVP (R-CVP); or patients undergoing observation were included in order to examine factors associated with the use of anthracyclines. Chi-squared tests compared characteristics and initial treatments of DLBCL patients >80 years and 66-80 years. Multivariable logistic regression models examined treatment selection factors in patients >80 years. Standard and propensity score-adjusted multivariable Cox proportional hazards models adjusted for patient demographics, clinical characteristics, comorbidities, performance status, and year of diagnosis examined relationships between treatment regimen, treatment duration, and survival.Results: Among patients >80 years, 58% were female, 91% were Caucasian, 36% had stage III/IV disease, 39% had extranodal involvement, 7% had B-symptoms, 28% had poor performance status, and 14% had ≥2 comorbidities. Patients >80 years were less likely to receive R-CHOP (43% vs. 61%) and more likely to be observed (30% vs. 15%) or receive R-CVP (12% vs. 4%); all p<0.0001.Sex, marital status, area-level poverty, year of diagnosis, performance status, and disease site were associated with R-CHOP treatment in patients >80 years. The initial receipt of R-CHOP was more commonly associated with female sex (odds ratio (OR) 1.31, 95% confidence interval 1.01-1.71), being married (OR 1.69, 1.07-2.66) and a diagnosis after 2001 (OR for 2002 11.71, 6.32-21.70; persistently increased ORs thereafter). The initial receipt of R-CHOP was less commonly associated with extranodal disease (OR 0.71, 0.55-0.91), poor performance status (OR 0.57, 0.44-0.75), and residence in a census tract with >12% of residents living in poverty (OR 0.69, 0.50-0.96). Initial observation was more commonly associated with the same factors that were less commonly associated with R-CHOP use and was less commonly associated with stage III/IV disease (OR 0.66, 0.50-0.87).Kaplan-Meier survival curves revealed that in patients >80 years, R-CHOP was associated with the best OS and LRS. Multivariable Cox proportional hazards models revealed that R-CHOP for >4 cycles was associated with the best OS in patients >80 years of all stages (hazard ratio (HR) 0.48, 0.37-0.62). Among stage III/IV patients, R-CHOP for >4 cycles (HR 0.48, 0.31-0.72) and R-CVP for >4 cycles (HR 0.40, 0.21-0.76) demonstrated significantly longer OS.Conclusions:Although DLBCL patients >80 years were less likely to receive R-CHOP, this regimen conferred the best survival. The failure of very elderly DLBCL patients to receive R-CHOP may occur due to clinical factors such as poor performance status, but commonly varies across demographic factors such as area-level poverty, which may reflect bias in the under-utilization of R-CHOP in very elderly patients that is not based on clinical parameters. Further studies are needed to characterize the impact of DLBCL treatment on quality of life in very elderly patients, and algorithms should be developed to help guide therapy in this population. DisclosuresNo relevant conflicts of interest to declare.

Steroid-Induced Hypertension during Induction Chemotherapy for Acute Lymphoblastic Leukemia in US Children’s Hospitals

Background: Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. The induction phase of chemotherapy, including high-dose corticosteroids, is critical and effective as 98% of patients achieve remission after induction. It is generally understood that most non-life threatening side effects of chemotherapy during induction should be tolerated and treated with additional medication (if necessary) rather than reducing or discontinuing chemotherapeutic medication. Although hypertension (HTN) is a known possible complication of high-dose corticosteroids, the actual incidence and risk factors for this adverse event are poorly understood. Our objective was to utilize a national administrative data source to begin to answer these uncertainties.Methods: The Pediatric Health Information System (PHIS) database consists of inpatient information from 43 US free-standing pediatric hospitals representing 25% of US pediatric centers and the majority of tertiary care pediatric hospitals. The PHIS database includes de-identified demographic data, discharge diagnoses, and medications prescribed among other data. Our study examined all new cases of ALL from age 0 to 28 years from Jan 1, 2009 to Dec 31, 2013. We defined our population of ALL patients receiving induction chemotherapy as those who: 1) had a non-relapse ALL ICD-9 code (204.0, 204.00, 204.01) and 2) received induction chemotherapy medications within the first 14 days of admission. Patients receiving antihypertensive medication before or on the date of chemotherapy initiation were excluded from our population. Due to the unknown sensitivity and specificity of ICD-9 codes for hypertension in this patient population, we elected to define hypertension based on recorded use of anti-hypertensive medications rather than diagnostic codes.Results: We identified 4,917 unique patients who received induction chemotherapy for ALL. Of these patients, 13.0% received anti-hypertensive drugs during their admission. Adjusted logistic regression demonstrated increased odds of developing steroid-induced hypertension in obese patients [2.3; 95% CI: (1.42-3.71)] and those receiving anthracycline drugs [1.3; 95% CI: (1.004-1.67)]. Decreased odds of developing steroid-induced hypertension were independently associated with the 5 to 9 year age group [0.61; 95% CI: (0.49-0.76)] as compared to the 0 to 4 year age group.To assess the reliability of using ICD-9 codes to identify patients with hypertension, sensitivity and specificity were calculated. Using receipt of anti-hypertensive drugs as the gold standard, the sensitivity of ICD-9 codes to detect hypertension was 0.60 [95% CI: (0.56-0.64)] and specificity was 0.96 [95% CI: (0.96-0.97)].Conclusion: To our knowledge, this was the first study of steroid-induced HTN in pediatric ALL patients using a national data source. We found that HTN is a common complication of induction ALL therapy. Increased risk for HTN was independently associated with obesity and anthracycline use. Although ICD-9 codes are very useful in ruling out hypertension, they are significantly less accurate in detecting those patients with hypertension. The lack of sensitivity of the HTN ICD-9 codes was notable and suggests underreporting of HTN by physicians. This study is limited as patient information is from a single inpatient admission. As cure rates of pediatric ALL approach 85%, the long-term effects of steroid-induced HTN deserves further study. DisclosuresNo relevant conflicts of interest to declare.

Is it safe to give anthracyclines concurrently with trastuzumab in neo-adjuvant or metastatic settings for HER2-positive breast cancer? A meta-analysis of randomized controlled trials.

Concurrent use of anthracyclines and trastuzumab used to be avoided in the treatment of HER2-positive breast cancer due to the high risk of cardiac toxicity. However, several newly published studies challenged this view and demonstrated that concomitant use of the two agents significantly improved the clinical outcome without causing additional cardiac toxicity. This meta-analysis summarized available data to investigate the safety and efficacy of concurrent use of anthracyclines and trastuzumab. Eligible studies were identified through several search strategies and assessed for quality. Data were extracted from studies in terms of baseline characteristics and key statistics, which were utilized to calculate pooled effect size. Eight studies were included in the meta-analysis to evaluate the cardiac safety of concurrent use of anthracyclines and trastuzumab. It is demonstrated that concomitant administration was moderately associated with increased risk of cardiac-related adverse events (RR = 1.97, 95% CI 1.49-2.60, P < 0.001) by fixed effect model. In addition, subgroup analysis showed combined use of anthracyclines and trastuzumab significantly increased the likelihood of cardiac toxicity in neo-adjuvant setting (RR = 1.51, 95% CI 1.10-2.07, P = 0.01) as well as in palliative setting (RR = 3.92, 95% CI 2.11-7.27, P < 0.001). Also, we found concurrent treatment as in neo-adjuvant treatment setting slightly increased pCR rate by randomized effect model with the pooled RR being 1.52 (95% CI 1.05-2.20, P = 0.03). Concurrent use of anthracyclines and trastuzumab increased the risk of cardiac toxicity in both neo-adjuvant and metastatic settings, although moderately increased pCR rate as neo-adjuvant treatment.

The use of anthracycline at first-line compared to alkylating agents or nucleoside analogs improves the outcome of salvage treatments after relapse in follicular lymphoma The REFOLL study by the Fondazione Italiana Linfomi.

Follicular lymphoma (FL) patients experience multiple remissions and relapses and commonly receive multiple treatment lines. A crucial question is whether anthracyclines should be used at first-line or whether they would be better "reserved" for relapse and whether FL outcome can be optimized by definite sequences of treatments. Randomized trials can be hardly designed to address this question. In this retrospective multi-institutional study, time-to-next-treatment after first relapse was analyzed in 510 patients who had received either alkylating agents- or anthracycline- or nucleoside analogs-based chemotherapy with/without rituximab at first-line and different second-line therapies. After a median of 42 months, median time-to-next-treatment after relapse was 41 months (CI95%:34-47 months). After adjustment for covariates, first-line anthracycline-based chemotherapy with/without rituximab was associated with better time-to-next-treatment after any salvage than alkylating agents-based chemotherapy with/without rituximab or nucleoside analogs-based chemotherapy with/without rituximab (HR:0.74, P = 0.027). The addition of rituximab to first-line chemotherapy had no significant impact (HR:1.22, P = 0.140). Autologs stem cell transplantation performed better than any other salvage treatment (HR:0.53, P < 0.001). First-line anthracycline-based chemotherapy significantly improved time-to-next-treatment even in patients receiving salvage autologs stem cell transplantation (P = 0.041). This study supports the concept that in FL previous treatments significantly impact on the outcome of subsequent therapies. The outcome of second-line treatments, either with salvage chemoimmunotherapy or with autologs stem cell transplantation, was better when an anthracycline-containing regimen was used at first-line.

Congestive heart failure during induction with anthracycline-based therapy in patients with acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is a highly curable malignancy. However, 30% of patients die during therapy induction from bleeding, differentiation syndrome (DS), and/or infection. Recommendations suggest that congestive heart failure (CHF) is a presenting feature of DS. To assess the incidence of CHF during induction in patients with APL. A retrospective chart review was performed of patients diagnosed with APL from December 2004 to July 2013 and managed at Georgia Regents University Cancer Center. Baseline and follow-up ejection fractions (EF) were recorded and patients with a drop in EF during the induction period were evaluated. Of the 40 evaluable patients, 37 received idarubicin-based chemotherapy. 16 of the 37 patients had a repeat ECHO for suspected cardiomyopathy, and 6 of the 16 patients (37.5%) demonstrated a decrease in EF (absolute drop, 10%-35%). The cardiac function recovered completely in 4 patients and partially in 1 patient. Gender, history of hypertension, and body mass index did not seem to correlate with incidence of CHF. The patient population is very small given the rarity of the disease. Present practice patterns do not routinely address CHF in the differential diagnosis. Patients with APL are at risk for cardiac toxicity for a number of reasons, including cytokine storm and inflammatory state, use of anthracyclines, and DS. The clinical presentation of DS most commonly involves dyspnea and fluid retention, which are also symptoms of heart failure. Prompt cardiac evaluation should be undertaken to rule out CHF in APL patients who are going to receive an anthracycline-based therapy, because early intervention may result in an improved outcome.

Eribulin treatment patterns in patients with and without prior anthracycline use.

292 Background: Eribulin mesylate is indicated for patients with metastatic breast cancer after treatment with ≥2 prior chemotherapeutic regimens for metastatic disease. Prior therapy should have included an anthracycline and a taxane. Evidence examining the effects of prior exposure to anthracyclines on eribulin therapy is limited. The purpose of this study was to compare demographic characteristics and treatment patterns for anthracycline-experienced patients vs. anthracycline-naïve patients treated with eribulin. Methods: A retrospective analysis using electronic medical record (EMR) data from 1/1/08 to 3/1/14 was conducted. Chemotherapy drugs were identified by the treatment name field in the EMR. Index date was defined as the first eribulin treatment. Patients with ≥2 eribulin administrations, continuous eligibility including a 6 month pre-period prior to the index date, and no treatment gaps more than 6 months were included. Patients were stratified into an anthracycline experienced cohort (treated prior to eribulin therapy) or without anthracycline cohort (never treated with this drug class prior to eribulin therapy). Demographics (gender, age, receptor status) and treatment characteristics (number and days of eribulin therapy) were compared between the cohorts. Results: 190 patients received eribulin; 46 (24%) with prior anthracycline use, 144 (76%) without. The majority of patients were female (87% for prior anthracycline, 97% without), and the average age of both groups was 59 yrs. Most patients were HR+/HER2- (56% overall; 70% for prior anthracycline, 51% for without), followed by TNBC (29% overall; 24% prior anthracycline, 31% without). Some patients had been treated previously with trastuzumab (15% overall; 7% for prior anthracycline, 17% for without). The number of eribulin administrations did not differ significantly between cohorts (8.2 administrations for anthracycline vs. 9.6 without, p=0.268). Likewise the number of days of therapy did not differ significantly (88.1 days for prior anthracycline vs. 104 without, p=0.369). Conclusions: There was no significant difference detected for prior anthracycline use impacting the number of eribulin administrations or days of therapy.

Clinical effects of prior anthracycline or taxane use on eribulin as first-line treatment for HER+/- locally recurrent or metastatic breast cancer (BC): Results from 2 phase 2, multicenter, single-arm studies.

140 Background: Eribulin mesylate, a nontaxane microtubule dynamics inhibitor, has demonstrated an overall survival benefit relative to other commonly used agents in patients (pts) with at least 2 prior MBC cytotoxic therapies. Primary data presented from 2 phase 2 trials, Study 206 (eribulin in HER2- BC pts) and Study 208 (combination eribulin + trastuzumab [TRAS] in HER2+ BC pts), showed clinical activity and acceptable tolerability profiles as first-line cytotoxic therapy (tx). Here we present prespecified efficacy data for both trials based on prior anthracycline (A) and taxane (T) use. Methods: In both studies, pts received eribulin mesylate 1.4 mg/m2 IV on days 1 and 8 of each 21-day cycle. Pts in Study 208 (HER2+) also received initial TRAS (8 mg/kg IV/Day 1), followed by 6 mg/kg/day 1 of each subsequent cycle. Objective response rate (ORR), progression-free survival (PFS), and tolerability were assessed. Results: In Study 206 (N=56), 48% and 46% received prior A and T, and in Study 208 (N=52), 21% and 44% received prior A and T, respectively. ORR, the primary endpoint, was similar in pts, regardless of prior A or T, except in pts w/o prior T in Study 208 whose ORR trended higher (table). Clinical benefit rate (CBR), PFS, and duration of response (DOR) were either similar or trended higher in pts w/o prior A or T. PFS was higher in HER2+ BC patients receiving eribulin + TRAS who had not received prior A or T compared with those who had. Grade (G) 3-5 adverse event rates were similar or lower in pts who had not received prior A or T. Conclusions: As first-line therapy, eribulin in HER2- BC pts and eribulin + TRAS in HER2+ BC pts were effective and well tolerated, regardless of prior A or T tx. However, in HER2+ BC pts receiving eribulin + TRAS, the lack of prior A or T tx may be a lead to longer median PFS. Clinical trial information: NCT01268150/NCT01269346. [Table: see text]

Treatment including anthracyclines versus treatment not including anthracyclines for childhood cancer.

One of the most important adverse effects of anthracyclines is cardiotoxicity. A well-informed decision on the use of anthracyclines in the treatment of childhood cancers should be based on evidence regarding both antitumour efficacy and cardiotoxicity. This review is the second update of a previously published Cochrane review. To compare antitumour efficacy (survival and tumour response) and cardiotoxicity of treatment including or not including anthracyclines in children with childhood cancer. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 6), MEDLINE (1966 to July 2013) and EMBASE (1980 to July 2013). In addition, we searched reference lists of relevant articles and conference proceedings, the International Society for Paediatric Oncology (SIOP) (from 2002 to 2012) and American Society of Clinical Oncology (ASCO) (from 2002 to 2013). We have searched for ongoing trials in the ISRCTN register and the National Institute of Health register (both screened August 2013) (http://www.controlled-trials.com). Randomised controlled trials (RCTs) comparing treatment of any type of childhood cancer with and without anthracyclines and reporting outcomes concerning antitumour efficacy or cardiotoxicity. Two review authors independently performed the study selection, risk of bias assessment and data extraction. Analyses were performed according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. We identified RCTs for seven types of tumour, acute lymphoblastic leukaemia (ALL) (three trials; 912 children), Wilms' tumour (one trial; 316 children), rhabdomyosarcoma and undifferentiated sarcoma (one trial; 413 children), Ewing's sarcoma (one trial; 94 children), non-Hodgkin lymphoma (one trial; 284 children), hepatoblastoma (one trial; 255 children) and acute myeloid leukaemia (AML) (one trial; 394 children). All studies had methodological limitations. For ALL no evidence of a significant difference in antitumour efficacy was identified in the meta-analyses, but in most individual studies there was a suggestion of better antitumour efficacy in patients treated with anthracyclines. For both Wilms' tumour and Ewing's sarcoma a significant difference in event-free and overall survival in favour of treatment with anthracyclines was identified, although for Wilms' tumour the significant difference in overall survival disappeared with long-term follow-up. For rhabdomyosarcoma and undifferentiated sarcoma, non-Hodgkin lymphoma and hepatoblastoma no difference in antitumour efficacy between the treatment groups was identified. The same was true for AML, with the exception of overall survival in a post hoc analysis in a subgroup of patients with relapsed core binding factor (CBF)-AML in which patients treated with anthracyclines did better. Clinical cardiotoxicity was evaluated in four RCTs; no significant difference between the treatment groups was identified, but in all individual studies there was a suggestion of a lower rate of clinical cardiotoxicity in patients who did not receive anthracyclines. None of the studies evaluated asymptomatic cardiac dysfunction. No RCTs were identified for other childhood cancers. At the moment no evidence from RCTs is available which underscores the use of anthracyclines in ALL. However, 'no evidence of effect', as identified in this review, is not the same as 'evidence of no effect'. For Wilms' tumour, rhabdomyosarcoma and undifferentiated sarcoma, Ewing's sarcoma, non-Hodgkin lymphoma, hepatoblastoma and AML only one RCT was available for each type and, therefore, no definitive conclusions can be made about the antitumour efficacy of treatment with or without anthracyclines in these tumours. For other childhood cancers no RCTs were identified and therefore no conclusions can be made about the antitumour efficacy of treatment with or without anthracyclines in these tumours.

Comparative Study of Utilization Pattern of Chemotherapeutic Agents Among Self Funded and Government Funded Patients of Breast Cancer in a Developing Country

ABSTRACT Aim: This study was conducted to assess and compare utilization pattern and appropriateness of anti-cancer drugs among self funded (SF) and government funded (GF) patients of breast cancer. Methods: In a prospective study medication orders of patients on chemotherapy for breast cancer were reviewed and patients were interviewed to assess treatment pattern and its appropriateness in a specialty oncology hospital having dedicated GF wards. Clinical stage of the disease, tumor characteristics, drug selection, dose, administration technique and anti-emetics used were reviewed for patients in general wards and GF wards of the study hospital, with respect to standard international recommendations to evaluate the appropriateness of the chemotherapy. Results: A total of 126 patients (SF patients (n = 68), GF patients (n = 58)) were followed over six months. A use of anthracycline based regimen was higher compared to cyclophosphamide, methotrexate and 5-fluorouracil regimen in both, SF & GF patients. Targeted therapy was prescribed to only 33% of HER2 positive SF patients and no targeted therapy was prescribed for HER2 positive GF patients (n = 7).Endocrine therapy, as either anti-estrogens or aromatase inhibitor was prescribed for 100% of SF and GF patients. Selection of chemotherapy regimen was appropriate in 94% of SF patients and 96% of GF patients. Doses of anti-cancer drugs were not calculated as per latest body surface area during subsequent cycle for 22% of SF patients and 38% of GF patients. Inappropriate administration of drugs was found due to excess dilution of drugs (In SF patients: 25%, In GF patients: 40%) and improper infusion time (In SF patients (29%), In GF patients (41%)). Choice of anti-emetics was inappropriate in 38% of SF cases and 56% of GF cases. Dose and frequency of anti-emetics were inappropriate in 28% of SF patients and 42% of GF patients. Conclusions: Selection of anti-cancer agents was observed to be well compliant with standard recommendations in both, SF and GF settings. However, lack of adherence to the prescribed chemotherapy was found higher due to inappropriate administration in both settings. Use of targeted therapy was limited due to economic considerations. Inappropriate use of anti-emetics was found more in GF patients due to limited budget. Appropriate nursing education and training can improve the delivery of chemotherapy. Disclosure: All authors have declared no conflicts of interest.

Ventricular arterial coupling in early breast cancer patients following treatment with anthracycline-containing adjuvant chemotherapy.

9591 Background: Use of anthracyclines is limited by dose-dependent cardiotoxicity. Research has focused on cardiac specific damage, although injury may extend beyond the heart to the vascular netw...

Trends in the use of adjuvant anthracycline- and taxane-based chemotherapy regimens in early-stage breast cancer, by surgery type.

e12017 Background: Anthracyclines (A) and taxanes (T) are widely used in adjuvant chemotherapy (chemo) treatment for early-stage breast cancer (BC). Recent changes in chemo regimen choice have been...

Clinical effects of prior anthracycline or taxane use on eribulin as first-line treatment for HER+/- locally recurrent or metastatic breast cancer (BC): Results from two phase II, multicenter, single-arm studies.

Clinical effects of prior anthracycline or taxane use on eribulin as first-line treatment for HER+/- locally recurrent or metastatic breast cancer (BC): Results from two phase II, multicenter, single-arm studies.

The role of front-line anthracycline-containing chemotherapy regimens in peripheral T-cell lymphomas

Peripheral T-cell lymphomas (PTCLs) are a heterogenous group of aggressive non-Hodgkin's lymphomas that are incurable in the majority of patients with current therapies. Outcomes associated with anthracycline-based therapies are suboptimal, but remain the standard of care for most patients, even though the benefits of this approach remain uncertain. This study retrospectively examined outcomes in a cohort of North American PTCL patients treated with both anthracycline- and nonanthracycline-containing regimens. The incorporation of anthracycline-containing regimens was associated with improved progression-free survival (PFS) and overall survival (OS). Patients treated with nonanthracycline-containing regimens were more likely to have high-risk features and were less likely to undergo high-dose therapy and stem cell transplantation. However, anthracycline use remained an independent predictor of improved PFS and OS when adjusting for these confounding variables. Anthracycline-based regimens and consolidation with high-dose therapy and autologous stem cell transplantation in appropriately selected patients remains a viable option for patients unable to participate in a clinical trial. Long-term disease-free survival is not optimal, highlighting the need for an improved understanding of disease pathogenesis, and the development of novel therapeutic strategies.

The role of anthracyclines in the treatment of early breast cancer.

We review the use of anthracyclines, their associated cardiotoxicity, and the role of taxanes in the treatment of early breast cancer. The efficacy of anthracyclines has been proven in multiple large cohort trials and meta-analyses. The addition of a taxane to an anthracycline-based regimen in the adjuvant setting has improved the disease-free survival and overall survival in patients with early breast cancer. The use of the monoclonal antibody trastuzumab combined with an anthracycline and taxane regimen has had significant benefit both in disease-free survival and overall survival in patients with human epidermal growth factor receptor 2(HER2)-positive disease. However, the development of significant cardiotoxicity related to anthracyclines and the emergence of newer agents that appear to limit the cardiotoxicity but with similar anticancer efficacy have called the role of anthracyclines into doubt. Taxane/trastuzumab-based chemotherapy without anthracyclines is now a widely accepted adjuvant regimen in patients with HER2-positive early breast cancer. Indeed, the use of taxanes in early breast cancer has overtaken the use of anthracyclines, particularly in women with HER2-positive breast cancer. Concerns regarding anthracycline cardiotoxicity and positive data from taxane-based regimens likely have contributed to this change in practice. Ongoing trials will determine whether taxane-based chemotherapy has equivalent efficacy to anthracycline-based regimens in adjuvant therapy of HER2-negative early breast cancer. Moving forward, the use of anthracyclines as initial chemotherapy in early breast cancer may continue to be replaced by taxane-based and novel regimens in the future.

What is the Standard Regimen for Patients with Acute Promyelocytic Leukemia?

Modern guidelines based on a large international consensus indicate that treatment of newly diagnosed acute promyelocytic leukemia (APL) requires distinguishing at presentation low-intermediate (<10 × 10(9)/L WBC) from high-risk (>10 × 10(9)/L WBC) disease. The concomitant use of all-trans retinoic acid (ATRA) and anthracycline based chemotherapy, with inclusion of AraC in consolidation for hyperleucocytic patients, has remained the standard of care for the past two decades. The advent of arsenic trioxide (ATO) and results from a large randomized trial, have recently challenged the standard ATRA-chemotherapy approach suggesting that at least patients in the low-intermediate category may be cured without chemotherapy using the ATRA-ATO combination.

Cardiac dosimetry for adjuvant left‐sided breast radiotherapy: Patterns with 2D‐ versus 3D‐era planning and correlates of coronary dose with maximum depth of myocardial exposure

The purpose of this study was to evaluate the cardiac dosimetry delivered before and after routine 3D CT whole-breast radiotherapy planning, including cardiac contouring and the relevance of a 15-mm maximum myocardial depth (MMD) planning tolerance threshold. The PULp FICTion study permitted cardiac dosimetry comparisons for 140 patients (70 in the 'before-contouring era' (BC) and 70 in the 'post-contouring era' (PC) ). Comparisons were made of MMD and dosimetry for whole heart, anterior myocardium and left anterior descending (LAD)/coronary artery (overall, superior and inferior) by contouring era. The MMD mean was 15.6 mm (range 1-40). If the internal mammary chain (IMC) was treated, the MMD increased from 15 to 27.7 mm (P < 0.0001). Excluding IMC patients revealed no difference in MMD between conservation and mastectomy (14.9 vs 17.4, P = 0.3), boost and no boost (14.5 vs 15.5, P = 0.41) or BC and PC (15.7 vs 14.5. P = 0.33) and no differences related to treating clinician, anthracycline use or age. Only in potentially low-risk patients defined as not requiring IMC or boost treatment was there a difference in MMD by era, with 17.7 mm (1-40) in the BC era and 13.9 mm (1-31) mm in the PC era (P = 0.013). Inferior LAD mean doses increased from 49% to 84% of the prescribed breast dose when MMD was >15 mm, and the proportion of patients with a mean dose <40% of the prescribed breast dose fell from 48% to 8%. Changes in cardiac dosimetry associated with routine cardiac contouring have initially been minor and restricted to low-risk patients. A 15-mm MMD reasonably represents a transition from low mean distal LAD doses to substantial doses.

Effects of ramipril and darbepoetin on electromechanical activity of the heart in doxorubicin-induced cardiotoxicity

Cardiac toxicity is a deadly condition caused by impaired cardiac activity similar to congestive heart failure (CHF). Doxorubicin (DOX) is a potent anticancer drug having a potential of myocardial damage [ [1] Minotti G. Menna P. Salvatorelli E. Cairo G. Gianni L. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev. 2004; 56: 185-229 Crossref PubMed Scopus (2860) Google Scholar ]. Doxorubicin induced experimental toxicity has been characterized by heart failure and anaemia [ [2] Noiri E. Nagano N. Negishi K. et al. Efficacy of darbepoetin in doxorubicin-induced cardiorenal injury in rats. Nephron Exp Nephrol. 2006; 104: e6-e14 Crossref PubMed Scopus (20) Google Scholar ]. In human patients, risks for the use of anthracyclines have been reported associated with cardiac death which is the most prevalent of QT prolongation that triggered Torsades de Pointes [ [3] Arbel Y. Swartzon M. Justo D. QT prolongation and Torsades de Pointes in patients previously treated with anthracyclines. Anticancer Drugs. 2007; 18: 493-498 Crossref PubMed Scopus (31) Google Scholar ]. The anaemia of CHF patient is evidently due to the excessive cytokine production [ [4] Silverberg D. Wexler D. Blum M. Wollman Y. Iaina A. The cardio-renal anaemia syndrome: does it exist?. Nephrol Dial Transplant. 2003; 18: viii7-12 PubMed Google Scholar ]. Pre-treatment with erythropoietin hormone alone protected the myocardium against DOX induced impaired cardiac function and cardiomyocyte apoptosis [ [5] Kim K.H. Oudit G.Y. Backx P.H. Erythropoietin protects against doxorubicin-induced cardiomyopathy via a phosphatidylinositol 3-kinase-dependent pathway. J Pharmacol Exp Ther. 2008; 324: 160-169 Crossref PubMed Scopus (93) Google Scholar ]. Therefore, the present study was designed to investigate the effects of ramipril and darbepoetin alfa, used either alone or together, on electromechanic activity of heart in an experimental toxicity model.