cardiovascular-agents and Breast-Neoplasms

Natural products, whether pure compounds or standardized plant extracts, offer unlimited opportunities for other drug sources due to the unequaled availability of chemical diversity. Stinging Nettle (Urtica dioica) is a unique herbaceous perennial flowering plant with stinging hairs. The leaf extract of nettle was one of the herbal remedies which the experimental, clinical and trials have complemented each other. It is a very well-known plant with a wide historical background use of stems, leaves and roots. It has a long history of use as power sources such as soup or curry, and also used as fiber and a medicinal plant. Urtica dioica has traditionally been used in the control of cardiovascular disorders especially hypertension. The leaf extract of Urtica dioica has been reported to improve glucose homeostasis in vivo. Nettle root could prevent some of the effects of prostatic hyperplasia. Extracts of nettle leaf are used as anti-inflammatory remedies for rheumatoid arthritis. Urtica dioica extract significantly increased the sensitivity of breast cancer cells to paclitaxel. This article aims to review the very wide ranging of pharmacological effects of Urtica dioica extract.. Articles on PuBmed between 1980 and 2019.. Description and critical review of the pharmacological effects of Urtica dioica and other uses.. The nettle is actually a plant with many qualities and uses. The interest in it is deserved and it is given by other studies and investigations.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Arthritis, Rheumatoid; Biological Products; Breast Neoplasms; Cardiovascular Agents; Drug Evaluation, Preclinical; Female; Humans; Male; Plant Extracts; Plant Leaves; Plant Roots; Prostatic Hyperplasia; Urtica dioica

Breast cancer treatments have evolved over the past decades, although several widely used treatments have adverse cardiac effects. Radiotherapy generally improves the survival of women with breast cancer, although its deleterious cardiovascular effects pose competing risks of morbidity and/or mortality. In the past, radiation-associated cardiovascular disease was a phenomenon considered to take more than a decade to manifest, but newer research suggests that this latency is much shorter. Knowledge of coronary anatomy relative to the distribution of the delivered radiation dose has improved over time, and as a result, techniques have enabled this risk to be decreased. Studies continue to be performed to better understand, prevent and mitigate against radiation-associated cardiovascular disease. Treatments such as anthracyclines, which are a mainstay of chemotherapy for breast cancer, and newer targeted agents such as trastuzumab both have established risks of cardiotoxicity, which can limit their effectiveness and result in increased morbidity and/or mortality. Interest in whether β-blockers, statins and/or angiotensin-converting enzyme (ACE)-inhibitors might have therapeutic and/or preventative effects in these patients is currently increasing. This Review summarizes the incidence, risks and effects of treatment-induced cardiovascular disease in patients with breast cancer and describes strategies that might be used to minimize this risk.

Topics: Animals; Antineoplastic Agents; Breast Neoplasms; Cardiovascular Agents; Cardiovascular Diseases; Female; Humans; Incidence; Primary Prevention; Radiation Injuries; Radiotherapy; Risk Assessment; Risk Factors; Treatment Outcome

Although having high clinical efficacy in the treatment of human epidermal growth factor receptor-2 (HER2+) metastatic breast cancer, trastuzumab has been associated with cardiotoxicity, and the etiology and pathogenesis of this condition is currently under investigation.. This paper reviews the cardiotoxicity, associated with trastuzumab use and discusses the risk assessment and management of cardiac dysfunction.. The increased risk of cardiotoxicity is lower when trastuzumab is given as monotherapy (3%-7%) compared with anthracyclines + trastuzumab therapy (27%). Type II cardiac changes occur in trastuzumab-treated patients, which do not appear to be dose-related, are not associated with histological changes, and are generally reversible. Several risk factors for cardiac events have been identified and assessing levels of troponin I and N-terminal pro-brain B-type natriuretic peptide before and after treatment with trastuzumab may allow early detection of cardiotoxicity. A symptomatic and functional evaluation scheme for patients indicated for treatment with trastuzumab has also been proposed to work alongside therapeutic options for the treatment of heart failure.. The risk of cardiac dysfunction associated with trastuzumab can be justified given the increase in overall survival. This risk is lower when trastuzumab is given as monotherapy. The paradigm for cardiologists remains the same: treat the cancer effectively whilst preventing cardiotoxicity.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Breast Neoplasms; Cardiovascular Agents; Cardiovascular Diseases; Female; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Receptor, ErbB-2; Risk Factors; Stroke Volume; Trastuzumab; Troponin I

In women, breast cancer is the second most common form of cancer and the leading cause of death caused by malignancy. The anthracycline antibiotics are potent anti-tumor agents used in a wide spectrum of malignancies. They are part of the gold standard adjuvant therapy for breast cancer and in metastatic disease they provide significant increases in response rate, time to disease progression, and overall survival. The addition of trastuzumab augments the effects of anthracycline-based therapy in both the adjuvant and metastatic settings. The successful use of anthracyclines is, however, restricted by the risk of developing life-threatening congestive heart failure. This risk increases exponentially with cumulative dose, and is further augmented by the addition of trastuzumab. Studies have reported that 10% to 26% of patients administered cumulative anthracycline doses above those recommended (> or =500 mg/m2 for doxorubicin and 1,000 mg/m2 for epirubicin) develop congestive heart failure, and that more than 50% of patients administered these doses will experience measurable functional impairment months to years after the end of therapy. The susceptibility of patients to anthracycline-induced cardiotoxicity varies widely, with a dramatic increase with advancing age. The onset of clinical and subclinical cardiac damage is delayed and occurs more than 3 months after the cessation of treatment, indicating a crucial time for functional impairment to occur and highlighting the ineffectiveness of monitoring left ventricular ejection fraction as an endpoint during anthracycline therapy. Possible future treatment options for managing anthracycline-induced cardiotoxicity include agents such as dexrazoxane that prevent oxygen-free radical generation. Further investigation is required into the use of angiotensin-converting enzyme inhibitors to redress cardiac damage and new methods of identifying patients at high risk of congestive heart failure before cardiac damage has occurred.

Topics: Age Factors; Anthracyclines; Antineoplastic Agents; Breast Neoplasms; Cardiovascular Agents; Disease Susceptibility; Female; Free Radical Scavengers; Heart; Heart Diseases; Heart Failure; Humans; Remission Induction; Risk Factors; Survival Rate

The aim of this article is to review (based on the literature data) the mechanism of chemotherapy- and radiation-induced cardiac toxicity, diagnostic procedures and methods of reducing this toxicity. Cardiac toxicity associated with chemotherapy and radiotherapy may be life threatening, can limit the dose and duration of the treatment and certainly adversely affect short-term and long-term quality of life. A development of new strategies for reduction and prophylaxis of cardiac toxicity has great clinical impact. Chemotherapeutic agents may cause acute myocardial injury or chronic complications (e.g. congestive heart failure). Among cardiotoxic agents anthracyclines cause most serious cumulative, dose-limiting and dose-related cardiomyopathy. Most of them are subclinical changes, however studies demonstrate that symptomatic congestive heart failure in 6-10% of adults who received a cumulative, bolus doses of 550 mg/m2. The frequency of cardiomyopathy may be reduced by modifying the schedule of administration, patients selection considering risk factors, careful cardiac monitoring during chemotherapy, using less toxic doxorubicin analogues and liposomal formulation. The use of pharmacological protection with dexrazoxane remains controversial. A substantial risk of cardiotoxicity may be associated with radiotherapy of the chest and mediastinum. Moreover, radiotherapy may have an additive affect to chemotherapy-induced toxicity. However, with the use of modern treatment techniques radiation cardiomyopathy is uncommon. A group of patients at risk of cardiac complication are patients with breast cancer, Hodgkin's and non-Hodgkin's lymphomas and soft tissue sarcomas.

Topics: Antibiotics, Antineoplastic; Breast Neoplasms; Cardiomyopathy, Dilated; Cardiovascular Agents; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Female; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Neoplasms; Radiotherapy, Adjuvant; Razoxane; Risk Factors; Sarcoma

Women frequently chose alternatives to hormone replacement therapy (HRT) for treatment of menopause even though medical indications for estrogens may be present. Prior breast cancer or fear of breast cancer is a major consideration. This review of alternatives to estrogen discusses the evidence linking breast cancer to HRTs and compares potential risks and benefits of HRT to nonHRT alternatives for relief of vasomotor symptoms, vaginal atrophy, neurocognitive changes and prevention of heart disease and osteoporosis. Practical guidelines are suggested for use of alternatives for each problem.

Topics: Aged; Antidepressive Agents; Atrophy; Bone Density; Bone Resorption; Breast Neoplasms; Calcitonin; Calcium; Cardiovascular Agents; Cardiovascular Diseases; Clinical Trials as Topic; Contraindications; Diphosphonates; Double-Blind Method; Estrogen Replacement Therapy; Estrogens; Estrogens, Non-Steroidal; Female; Fractures, Bone; Hot Flashes; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Isoflavones; Life Style; Menopause; Mental Disorders; Meta-Analysis as Topic; Middle Aged; Multicenter Studies as Topic; Osteoporosis, Postmenopausal; Phytoestrogens; Phytotherapy; Plant Preparations; Randomized Controlled Trials as Topic; Risk; Safety; Selective Estrogen Receptor Modulators; Urothelium; Vagina

Approximately 25,000 patients have been treated to date with the humanized anti-HER2 monoclonal antibody, Herceptin. This therapy has proved effective and well tolerated in patients with HER2-positive metastatic breast cancer; adverse events were generally infusion-related fever and chills of mild-to-moderate severity. Cardiotoxicity and infusion-related reactions emerged as the two main safety concerns with the use of Herceptin. Retrospective analysis revealed a higher incidence of heart failure when Herceptin was combined with anthracyclines than that expected with anthracyclines alone. Age, anthracycline exposure and cardiac risk factors were found to be predictors of cardiac adverse events. Patients experiencing cardiac dysfunction responded well to standard cardiac medication and the majority improved. Cardiac function should be monitored regularly and Herceptin should be discontinued if significant heart failure develops unless the benefits for an individual patient outweigh the risks. Of 25,000 patients, 74 (0.3%) were reported to have experienced a serious infusion-related reaction. The majority occurred during or shortly after the first infusion and were characterized by respiratory symptoms. Most patients were successfully treated; a total of 33 patients continued Herceptin therapy with no recurrence of infusion reactions. Although the benefit to risk ratio of Herceptin remains favorable, physicians must be vigilant and aggressive in managing cardiotoxicity and infusion-related reactions.

Topics: Animals; Antibiotics, Antineoplastic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cardiovascular Agents; Chills; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Drug Interactions; Female; Fever; Heart Diseases; Heart Failure; Humans; Immunotherapy; Infusions, Intravenous; Neoplasm Metastasis; Pain; Palliative Care; Respiratory Insufficiency; Retrospective Studies; Risk Factors; Safety; Salvage Therapy; Trastuzumab; Treatment Outcome

Dexrazoxane prevents the dose-limiting cardiotoxicity of the anthracyclines without reducing their antitumor efficacy and without new adverse side effects. Dexrazoxane reduces the severity of gastrointestinal symptoms of the anthracycline containing combination doxorubicin, 5-fluorouracil, cyclophosphamide and most surprisingly and importantly, dexrazoxane increases the median survival time of advanced breast cancer responders to the doxorubicin, 5-fluorouracil, cyclophosphamide regimen. The median survival time is doubled as compared to controls to nearly 3 years.

Topics: Adult; Anthracyclines; Antineoplastic Agents; Breast Neoplasms; Cardiovascular Agents; Child; Clinical Trials as Topic; Heart Diseases; Humans; Razoxane

Two large multicenter placebo controlled trials (088001 and 088006) in metastatic breast cancer found a significant cardioprotective effect of dexrazoxane when administered with doxorubicin. A delayed dose analysis found a protective effect even after a cumulative dose of doxorubicin of 300 mg/m2. Exploratory analysis combing the arms on the two studies found a cardioprotective effect of dexrazoxane either initially or after 300 mg/m2 when administered in patients older than 65 years, compared to patients receiving only placebo. Also, patients with an ejection fraction within 10% above the lower limit of normal were protected with dexrazoxane. Objective response rates were borderline significantly lower for patients receiving dexrazoxane. Recommendations are to administer dexrazoxane after 300 mg/m2.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cardiovascular Agents; Dose-Response Relationship, Drug; Doxorubicin; Female; Heart Diseases; Humans; Multicenter Studies as Topic; Neoplasm Metastasis; Randomized Controlled Trials as Topic; Razoxane

Topics: Antibiotics, Antineoplastic; Breast Neoplasms; Cardiovascular Agents; Clinical Trials as Topic; Combined Modality Therapy; Dose-Response Relationship, Drug; Doxorubicin; Female; Heart; Heart Diseases; Humans; Iron; Myocardium; Razoxane; Safety; Treatment Outcome

Current medical practice recommends the use of alternatives to estrogen-replacement therapy for the treatment of menopausal sequelae in younger women with breast cancer, although this clinical recommendation is undergoing reappraisal. Until prospective randomized studies addressing hormone use in this population are available, estrogen use in breast cancer patients will remain controversial. Because estrogen-replacement therapy is not the standard of practice and there is limited information available on nonestrogen therapies, women with breast cancer who are menopausal may not be prescribed or counseled about nonestrogen options. The efficacy, safety, and extent of use of most nonestrogen treatment modalities (other hormonal preparations, nonhormonal drugs, homeopathic preparations, and non-drug treatments) are not well documented and, unlike estrogen, many are selective in their benefit and do not share estrogen's universal impact. The use of several nonestrogen approaches for the prevention and treatment of osteoporosis has been promising. Traditional recommendations to maintain skeletal integrity, such as weight-bearing exercise; a diet rich in calcium and limited in caffeine, alcohol, and protein; avoidance of smoking; and measures to minimize trauma have been expanded to include the use or investigation of drugs (either alone or in combination). These drugs include progestins, vitamin D metabolites, injectable and intranasal synthetic salmon calcitonin, bisphosphonates, sodium fluoride, parathyroid hormone, growth factors, tamoxifen, etc. Strict control of the known risk factors, such as smoking, dyslipidemia, and hypertension as well as exercise, weight control, and the use of tamoxifen, are employed for the prevention and treatment of cardiovascular complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Age Factors; Antineoplastic Agents; Atrophy; Biological Factors; Breast Neoplasms; Calcitonin; Cardiovascular Agents; Cardiovascular Diseases; Complementary Therapies; Female; Flushing; Humans; Life Style; Menopause, Premature; Mental Disorders; Middle Aged; Osteoporosis, Postmenopausal; Ovariectomy; Plant Extracts; Primary Ovarian Insufficiency; Progestins; Risk Factors; Survivors; Tamoxifen; Vagina

Anthracyclines (ANTs) are a class of active antineoplastic agents with topoisomerase-interacting activity that are considered the most active agents for the treatment of breast cancer. We investigated the efficacy of carvedilol in the inhibition of ANT-induced cardiotoxicity.. In this randomized, single-blind, placebo-controlled study, 91 women with recently diagnosed breast cancer undergoing ANT therapy were randomly assigned to groups treated with either carvedilol (n = 46) or placebo (n = 45). Echocardiography was performed before and at 6 months after randomization, and absolute changes in the mean left ventricular ejection fraction, left ventricular end diastolic volume, and left ventricular end systolic volume were determined. Furthermore, the percentage change in the left atrial (LA) diameter and other variables of left ventricular (LV) diastolic function, such as transmitral Doppler parameters, including early (E wave) and late (A wave) diastolic velocities, E/A ratio and E wave deceleration time, pulmonary venous Doppler signals, including forward systolic (S wave) and diastolic (D wave) velocities into LA, late diastolic atrial reversal velocity, and early diastolic tissue Doppler mitral annular velocity (e') were measured. In addition, tissue Doppler mitral annular systolic (s') velocity, as a marker of early stage of LV systolic dysfunction, E/e' ratio, as a determinant of LV filling pressure, and troponin I level, as a marker of myocardial necrosis were measured.. At the end of follow-up period, left ventricular ejection fraction did not change in the carvedilol group. However, this parameter was significantly reduced in the control group (P < 0.001). Echocardiography showed that both left ventricular end systolic volume and LA diameter were significantly increased compared with the baseline measures in the control group. In pulse Doppler studies, pulmonary venous peak atrial reversal flow velocity was significantly increased in the control group. Moreover, a significant decrease in the mitral annuli early diastolic (e') and peak systolic (s') velocities and a significant increase in the E (the peak early diastolic velocity)/e' ratio in the control group were also observed. However, none of these variables were adversely changed at the end of follow-up in the carvedilol group. Furthermore, the TnI level was significantly higher in the control group than in the carvedilol group (P = 0.036) at 30 days after the initiation of chemotherapy.. Prophylactic use of carvedilol may inhibit the development of anthracycline-induced cardiotoxicity, even at low doses.

Topics: Adult; Aged; Anthracyclines; Antibiotics, Antineoplastic; Atrial Function, Left; Biomarkers; Breast Neoplasms; Carbazoles; Cardiotoxicity; Cardiovascular Agents; Carvedilol; Echocardiography, Doppler, Pulsed; Female; Heart Diseases; Humans; Iran; Middle Aged; Propanolamines; Risk Assessment; Risk Factors; Single-Blind Method; Stroke Volume; Time Factors; Treatment Outcome; Troponin I; Ventricular Function, Left; Young Adult

To evaluate the cardioprotective effects of dexrazoxane (DEX) on breast cancer patients who received anthracycline-containing chemotherapy.. A total of 122 breast cancer patients after operation were randomly divided into two groups: The experimental group of 61 cases treated with EPI plus DEX (DEX:EPI = 10:1) as adjuvant chemotherapy regimen, and the control group of 61 cases treated with EPI but without DEX. All patients received four cycles of adjuvant chemotherapy and their changes of specific cardiac functional status and hematology status before and after chemotherapy, as well as non-cardiac toxicity were observed and analyzed.. Brain natriuretic peptide (BNP) before chemotherapy and after four cycles of chemotherapy in the control group was (106.78 ± 4.52)×10(-6) µg/ml and (187.19 ± 8.71)×10(-6) µg/ml, respectively, with a significant difference between them (P < 0.05). It in the experimental group was (102.34 ± 8.76)×10(-6) µg/ml and (105.29 ± 7.21)×10(-6) µg/ml, respectively, without a significant difference (P > 0.05). Cardiac troponin T (cTnT) before chemotherapy and after four cycles of chemotherapy in the control group was (12.55 ± 2.73)×10(-3) µg/ml and ( 31.05 ± 7.10 )×10(-3) µg/ml, respectively, with a significant difference between them (P < 0.05). It in the experimental group was (12.70 ± 2.15)×10(-3) µg/ml and (13.65 ± 7.82)×10(-3) µg/ml, respectively, without a significant difference (P > 0.05). The hart rate (HR) before chemotherapy and after four cycles of chemotherapy in the control group, was 75.32 ± 7.14 bpm and 89.60 ± 9.21 bpm, respectively, with a significant difference (P < 0.05). It in the experimental group was 78.60 ± 6.29 bpm and 83.10 ± 7.56 bpm, respectively, without a significant difference (P > 0.05). The left ventricular ejection fraction (LVEF) before chemotherapy and after four cycles of chemotherapy in the control group was (65.23 ± 7.82)% and (55.21 ± 7.23)%, respectively, with a significant difference between them (P < 0.05). It in the experimental group was (64.12 ± 6.25)% and (59.6 ± 4.72)%, respectively, without a significant difference (P > 0.05). The absolute neutrophil count before chemotherapy and after four cycles of chemotherapy in the control group was (3.95 ± 1.36)×10(9)/L and (3.50 ± 1.52)×10(9)/L, respectively, without a significant difference (P > 0.05). It in the experimental group, was (4.96 ± 1.41)×10(9)/L and (3.10 ± 1.26)×10(9)/L, respectively, with a significant difference (P < 0.05). The incidence of grade I-IV bone marrow suppression in the experimental group was 21.3%, 16.4%, 24.6%, and 4.9%, respectively. It in the control group was 16.4%, 11.5%, 9.8%, and 5.5%, respectively, with a significant difference (P < 0.05).. Cardiac toxicity after anthracycline treatment in breast cancer patients may be significantly reduced by DEX, without increase of non-cardiac and and non-hematologic toxicity. DEX combined with anthracycline increases the risk of bone marrow suppression, therefore, peripheral blood picture should be monitored or routine bone marrow support may be needed.

Topics: Adolescent; Adult; Aged; Antibiotics, Antineoplastic; Bone Marrow; Breast Neoplasms; Cardiovascular Agents; Chemotherapy, Adjuvant; Epirubicin; Female; Follow-Up Studies; Heart Rate; Humans; Leukocyte Count; Middle Aged; Natriuretic Peptide, Brain; Neutrophils; Razoxane; Stroke Volume; Young Adult

In order to better explore the toxicity and the activity of high dose epirubicin (120 mg/m2, 3 weeks) we analyzed a population of 127 metastatic breast cancer patients, treated in a randomized clinical trial conducted to evaluate the cardioprotective effect of dexrazoxane against epirubicin induced cardiotoxicity. All the patients had a diagnosis of metastatic breast cancer, an ECOG performance status < or = 2 and normal hematologic, renal, hepatic and cardiac function. No prior adjuvant chemotherapy including anthracycline was allowed. Epirubicin was given at the dose of 120 mg/m2 i.v. bolus every 3 weeks. One hundred twenty five patients were evaluable for toxicity and response. Seventeen patients (11%) had a complete response and 47 patients (37%) a partial response, for an overall response rate of 48%. The median progression free and overall survivals were 8.3 months and 18.3 months, respectively. Grade 3 and 4 leukopenia were observed in 8% and 7% of the patients, respectively. The most frequent nonhematological grade 3 toxicities were alopecia (87%), nausea and vomiting (16%), and mucositis (8%). Cardiotoxicity, defined as occurrence of congestive heart failure, decrease in resting left ventricular ejection fraction (L-VEF) to < or = 45%, or 20 EF units decrease from baseline L-VEF, was observed in 19% of the patients, after a median cumulative dose of epirubicin of 720 mg/m2 (range 120-1440). This study confirms in a large series of patients the activity of high dose epirubicin; however, the high incidence of cardiotoxicity requires a careful evaluation of cardiac risk factors before treatment.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Breast Neoplasms; Cardiovascular Agents; Epirubicin; Female; Heart Failure; Humans; Injections, Intravenous; Middle Aged; Razoxane; Treatment Outcome; Ventricular Dysfunction, Left

We conducted a randomized trial to evaluate primarily the cardioprotective effect of dexrazoxane (DEX) in patients with advanced breast cancer and soft tissue sarcomas (STS) treated with high-dose epirubicin (EPI). We wished also to determine the value of radioimmunoscintigraphy (RIS) in the assessment of anthracycline cardiotoxicity.. Patients with breast cancer (n = 95) or STS (n = 34) received EPI 160 mg/m2 by intravenous (I.V.) bolus every 3 weeks with or without DEX 1,000 mg/m2 I.V. Cardiac monitoring included multigated radionuclide (MUGA) scans with determination of resting left ventricular ejection fraction (LVEF), and RIS with indium 111 antimyosin monoclonal antibodies.. In either disease, antitumor response rates, time to progression, and survival did not significantly differ between the two arms. There was little difference in noncardiac toxicity for the two treatment groups. All methods of cardiac evaluation clearly documented the cardioprotective effect of DEX. Four patients developed congestive heart failure (CHF), all in the EPI arm. The decrease in LVEF from baseline was significantly greater in the control group. An abnormal antimyosin uptake was observed early in both arms and progressively increased during treatment. However, this increase was significantly higher in the EPI group (P = .004).. DEX significantly protects against the development of cardiotoxicity when high single doses of EPI are used. Apparently, there was no evidence of an adverse impact of DEX on antitumor activity. Although RIS is a sensitive technique in detecting anthracycline cardiac damage, its specificity is low and it cannot be considered a primary test for guiding anthracycline treatment.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Breast Neoplasms; Cardiovascular Agents; Drug Monitoring; Epirubicin; Female; Heart; Heart Rate; Humans; Male; Middle Aged; Neoplasm Staging; Prospective Studies; Radionuclide Imaging; Razoxane; Sarcoma; Ventricular Function, Left

To determine the cardioprotective effect of dexrazoxane (DZR) used in a doxorubicin-based combination therapy in advanced breast cancer.. Between November 1988 and January 1991, 534 patients with advanced breast cancer were randomized to two multicenter, double-blind studies (088001 and 088006). Patients received fluorouracil, doxorubicin, and cyclophosphamide (FAC) with either DZR (DZR-to-doxorubicin ratio, 10:1) or placebo (PLA) every 3 weeks and were monitored with serial multiplegated acquisition (MUGA) scans.. The hazards ratio (HR) of PLA to DZR for a cardiac event, which was predefined ejection fraction changes or congestive heart failure (CHF), was 2.63 (95% confidence interval [CI], 1.61 to 4.27; P < .001) for 088001 and 2.00 (95% CI, 1.01 to 3.96; P = .038) for 088006. The objective response rates for 088001 were 46.8% for DZR and 60.5% for PLA, a difference of 14% (95% CI, -25% to -2%; P = .019), and for 088006 were 53.7% for DZR and 49.3% for PLA, a difference of 4% (95% CI, -13% to 22%; P = .63). Time to progression and survival were not significantly different between treatment arms in either study. Toxicities on the DZR arms included lower granulocyte and platelet counts at nadir (P = .009 and P = .004, respectively) and more pain on injection (P = .001), with no difference in the rates of fever, infection, or hemorrhage.. DZR had a significant cardioprotective effect as measured by noninvasive testing and clinical CHF. One of the two studies (088001) showed a lower response rate with DZR, but time to progression and survival were not significantly different. DZR is the first agent shown to reduce cardiotoxicity from doxorubicin.

Topics: Aged; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cardiovascular Agents; Cyclophosphamide; Disease-Free Survival; Double-Blind Method; Doxorubicin; Female; Fluorouracil; Heart Failure; Humans; Prospective Studies; Razoxane; Risk Factors; Survival Analysis; Treatment Outcome

To assess whether dexrazoxane (DZR) given after a cumulative doxorubicin dose of 300 mg/m2 confers cardioprotection in patients with advanced breast cancer treated with fluorouracil, doxorubicin, and cyclophosphamide (FAC).. In two multicenter studies (088001 and 088006), patients were randomized to receive FAC and placebo (PLA) versus FAC and DZR. After a protocol amendment, all patients received open-label DZR after they had reached a cumulative doxorubicin dose of 300 mg/m2. Two groups were compared: 99 patients randomized to the PLA arms before the amendment who received FAC and PLA for at least seven courses (PLA group), and 102 patients randomized to the PLA arms after the amendment who received FAC and PLA for six courses followed by open-label DZR (PLA/DZR group).. The hazards ratio of PLA to PLA/DZR was 3.5 (95% confidence interval [CI], 2.2 to 5.7; P < .001, logrank and generalized Wilcoxon tests) for the doxorubicin dose at any cardiac event, ejection fraction changes, or congestive heart failure (CHF). The hazards ratio of PLA to PLA/DZR was 13.1 (95% CI, 3.7 to 46.0; P < .001, logrank and generalized Wilcoxon tests) for the doxorubicin dose at the development of CHF. The overall incidence of CHF in the PLA/DZR group was 3%, compared with 22% in the PLA group (P < .001, Fisher's exact test). Twenty-six percent of PLA/DZR patients received at least 15 courses of therapy, compared with 5% of patients in the PLA group. These results do not appear to be attributable to a time trend.. DZR is a highly effective cardioprotective agent when used in patients with advanced breast cancer who continue to receive doxorubicin-based chemotherapy after a cumulative doxorubicin dose of 300 mg/m2 has been reached.

Topics: Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cardiovascular Agents; Cyclophosphamide; Disease-Free Survival; Double-Blind Method; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Heart Failure; Humans; Middle Aged; Prospective Studies; Razoxane; Treatment Outcome

Dexrazoxane was found effective in reducing doxorubicin cardiotoxicity when given at a dose ratio (dexrazoxane: doxorubicin) of 20:1. Preclinical studies indicated that dexrazoxane at a dose ratio of 10 to 15:1 also protected against epirubicin-induced cardiotoxicity. The main objective of this study was to investigate the efficacy of dexrazoxane, given at a dose ratio of 10:1 against epirubicin cardiotoxicity.. One hundred sixty-two advanced breast cancer patients were randomized to receive epirubicin-based chemotherapy with or without dexrazoxane. Patients who had previously received adjuvant chemotherapy that contained anthracyclines were treated with cyclophosphamide 600 mg/m2 intravenously (IV), epirubicin 60 mg/m2 IV, and fluorouracil 600 mg/m2 IV, on day 1 every 3 weeks. The other patients were treated with epirubicin 120 mg/m2 IV on day 1 every 3 weeks. Cardiac toxicity was defined as clinical signs of congestive heart failure, a decrease in resting left ventricular ejection fraction (LVEF) to < or = 45%, or a decrease from baseline resting LVEF of > or = 20 EF units.. One hundred sixty patients were evaluated. Cardiotoxicity was recorded in 18 of 78 patients (23.1%) in the control arm and in six of 82 (7.3%) in the dexrazoxone arm. The cumulative probability of developing cardiotoxicity was significantly lower in dexrazoxane-treated patients than in control patients (P = .006; odds ratio, 0.29; 95% confidence limit [CL], 0.09 to 0.78). Noncardiac toxicity, objective response, progression-free survival, and overall survival were similar in both arms.. Dexrazoxane given at a dexrazoxane:epirubicin dose ratio of 10:1 protects against epirubicin-induced cardiotoxicity and does not affect the clinical activity and the noncardiac toxicity of epirubicin. The clinical use of dexrazoxane should be recommended in patients whose risk of developing cardiotoxicity could hamper the eventual use and possible benefit of epirubicin.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cardiovascular Agents; Epirubicin; Female; Heart Diseases; Humans; Middle Aged; Razoxane

Anthracyclines are among the most effective and commonly-prescribed antitumor agents but have dose-limiting cumulative cardiotoxicity. We performed a pharmacoeconomic evaluation of the ability of dexrazoxane to prevent cardiac-related adverse events in patients with Stage IIIB or IV metastatic breast cancer who were treated with a median of 10 cycles of intravenous FAC (5-fluorouracil, doxorubicin and cyclophosphamide) at doses of 500/50/500 mg/m2 respectively. Dexrazoxane was given at 500 mg/m2 commencing at the seventh cycle of treatment. We determined the cost of each cardiac event prevented and the cost of each additional life-year saved by dexrazoxane use. The cost per cardiac event prevented was CDN $5745 and the cost per additional life-year saved was CDN $2856. With the increasing use of anthracyclines in Stages I and II breast cancer, these favorable clinical and economic results may broaden the range of therapeutic possibilities for anthracyclines in adjuvant and metastatic therapy of breast cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cardiovascular Agents; Cost-Benefit Analysis; Cyclophosphamide; Decision Support Techniques; Doxorubicin; Economics, Pharmaceutical; Female; Fluorouracil; Health Care Costs; Heart; Heart Diseases; Humans; Markov Chains; Middle Aged; Models, Economic; Neoplasm Staging; Razoxane; Sensitivity and Specificity

Twenty females with disseminated breast cancer received courses of polychemotherapy with 21-day intervals. The regimen comprised adriamycin (ADM), cyclophosphamide and 5-fluorouracil in the dose 50, 500 mg/m2, respectively. 30 minutes prior to the treatment the patients were given the cardioprotector cardioxan (1000 mg/m2). Cardiological control (ECG, EF according to echo-CG and radionuclide ventriculography, PP/EP M1/M2, T1/T2 according to echo-polycardiography and Doppler cardiography) was performed before the treatment and at ADM total dose 200-300 mg/m2 followed by measurements at each dose increase by 100 mg/m2. The findings showed no evidence of ADM-related cardiac damage up to ADM dose 900-1000 mg/m2 in the case of cardioxan protection, though there was a tendency to M1/M2 increase which needs further studies as it suggests worsening of left ventricular diastolic contractility.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cardiomyopathies; Cardiovascular Agents; Cyclophosphamide; Doxorubicin; Female; Fluorouracil; Heart; Humans; Middle Aged; Myocardial Contraction; Razoxane; Time Factors

High rates of discontinuation undermine the effectiveness of adjuvant endocrine therapy (AET) among hormone-receptive breast cancer patients. Patient prognosis also relies on the successful management of cardiovascular risk, which affects a high proportion of postmenopausal women. As with AET, adherence with cardiovascular drugs is suboptimal. We examined whether patient adherence with cardiovascular drugs was associated with the rate of AET discontinuation in a French nationwide claims database linked with hospitalisation data.. We identified postmenopausal women starting AET between 01/01/2016 and 31/12/2020 and taking at least two drugs for the primary prevention of cardiovascular disease (antihypertensive drugs, lipid-lowering drugs and platelet aggregation inhibitors) before AET initiation. Adherence was assessed for each drug class by computing the proportion of days covered. Women were categorised as fully adherent, partially adherent or fully non-adherent with their cardiovascular drug regimen based on whether they adhered with all, part or none of their drugs. AET discontinuation was defined as a 90-day gap in AET availability. Time to AET discontinuation according to levels of cardiovascular drug adherence was estimated using cumulative incidence curves, accounting for the competing risks of death and cancer recurrence. Multivariate cause-specific Cox regressions and Fine-and-Gray regressions were used to assess the relative hazards of AET discontinuation.. In total, 32,075 women fit the inclusion criteria. Women who were fully adherent with their cardiovascular drugs had the lowest cumulative incidence of AET discontinuation at any point over the 5-year follow-up period. At 5 years, 40.2% of fully non-adherent women had discontinued AET compared with 33.5% of partially adherent women and 28.8% of fully adherent women. Both partial adherence and full non-adherence with cardiovascular drugs were predictors of AET discontinuation in the two models (cause-specific hazard ratios 1.16 [95% CI 1.10-1.22] and 1.49 [95% CI 1.39-1.58]; subdistribution hazard ratios 1.15 [95% CI 1.10-1.21] and 1.47 [95% CI 1.38-1.57]).. Clinicians should be aware that patients who do not adhere with their entire cardiovascular drug regimen are also more likely to discontinue AET. This stresses the importance of integrated care, as suboptimal adherence with both treatment components poses a threat to achieving ideal patient outcomes.

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Cardiovascular Agents; Chemotherapy, Adjuvant; Female; Humans; Medication Adherence; Neoplasm Recurrence, Local; Postmenopause; Retrospective Studies; Survival Analysis

The aim of this study was to evaluate the influence of an approaching cancer death on end-of-life aspirin use, a frequently prescribed medication for cardiovascular disease prevention.. This study was conducted using linked cancer registry and prescribing data. Breast (n=1151) and colorectal (n=1859) cancer decedents were matched to cancer survivors and the probability of either initiating aspirin, or continuing established aspirin use, was estimated in consecutive periods over the 5 years approaching a cancer-specific death (decedents) or matched index date (survivors).. Using the linked data sets, we identified patients who died of their cancer (decedents) between 1 January 2001 and 31 December 2009. In the 5 years prior to death, we compared (1) the probability of initiating aspirin use for the first time, and (2) the probability of continuing aspirin use. In comparison to matched cancer survivors, an approaching cancer death was not associated with a reduction in aspirin initiation by breast or colorectal cancer decedents. However, the probability of continuing established aspirin use declined considerably in the 24 months approaching death and at the time of a death was significantly lower for breast (risk difference (RD) -0.26, 95% CI -0.33 to -0.20) and colorectal (RD -0.38, 95% CI -0.46 to -0.30) cancer decedents versus matched survivors.. A significant proportion of patients discontinue their aspirin in the time approaching a breast or colorectal cancer-specific death. The safety and benefits of this are unclear and empirical data are needed to guide decisions about aspirin use in the end of life.

Topics: Aged; Aged, 80 and over; Aspirin; Breast Neoplasms; Cancer Survivors; Cardiovascular Agents; Cardiovascular Diseases; Colorectal Neoplasms; Female; Humans; Male; Prospective Studies; Terminal Care

Oncologic inpatients often require multiple drug therapy. They may be at higher risk of experiencing prescribing errors, which pharmacist interventions may help to avoid. This study aimed to evaluate the types of prescribing errors, pharmaceutical interventions and differences in clinical significance, in prescriptions for hospitalised patients with breast and gynaecological cancer. A cross-sectional, prospective study was conducted at the oncology ward of a clinic specialised in breast and gynaecology cancer. A clinical pharmacist analysed prescriptions, identified errors, performed interventions and classified clinical significance. A total of 1,874 prescriptions of 248 patients were evaluated; 11.5% prescriptions were involved at least in one prescribing error, totalising 283 errors. The most common error was unsafe medication due to drug interaction (89[31.4%]). Drugs for the alimentary tract and metabolism, and nervous system were the most involved in errors with statistical association (p = .0246 and p = .0002 respectively). Of the 294 interventions, 73.5% were accepted. The clinical significance of prescribing errors and interventions were classified as significant and very significant respectively. The pharmacist interventions obtained a good acceptance rate and impact significantly, avoiding prescribing errors classified as significant.

Topics: Anti-Infective Agents; Brazil; Breast Neoplasms; Cardiovascular Agents; Central Nervous System Agents; Cross-Sectional Studies; Drug Interactions; Female; Gastrointestinal Agents; Genital Neoplasms, Female; Hematinics; Hospitalization; Hospitals, Teaching; Humans; Medical Staff, Hospital; Medication Errors; Pharmacists; Professional Role; Prospective Studies

Anticancer drug treatment, particularly with anthracyclines, is frequently associated with cardiotoxicity, an effect exacerbated by trastuzumab. Several compounds are in use clinically to attenuate the cardiac-damaging effects of chemotherapy drugs, including angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, the anti-diabetic drug metformin, and dexrazoxane. However, there is concern that the cardiac-preserving mechanisms of these drugs may also limit the anticancer efficacy of the chemotherapeutic agents.. Herein two breast cancer cell lines, SKBr3 and BT474, overexpressing human epithelial receptor 2 (HER2), the target of the humanised antibody trastuzumab, were treated with a range of concentrations (20-2000 nM) of doxorubicin with and without trastuzumab in the presence of clinically relevant doses of the ACE inhibitor enalapril, the beta-blocker carvedilol, metformin or dexrazoxane, and cell survival determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.. None of the drugs reduced the anticancer effect of doxorubicin or trastuzumab (nor of the two drugs combined). Using Chou and Talalay's combination index, dexrazoxane and doxorubicin were found to act synergistically on the SKBr3 cells. (18)F-Fluoro-2-deoxy-D-glucose ((18)F-FDG) incorporation was reduced by treatment of SKBr3 cells with doxorubicin and this was shown to be due to reduced phosphorylation of (18)F-FDG in doxorubicin-treated cells. Treatment of SKBr3 cells with doxorubicin and dexrazoxane further reduced (18)F-FDG incorporation, indicating that the synergy in the cytotoxicity of these two drugs was reflected in their combined effect on (18)F-FDG incorporation.. Commonly administered cardioprotective drugs do not interfere with anticancer activity of doxorubicin or tratsuzumab. Further studies to establish the effect of cardioprotective drugs on anticancer drug efficacy would be beneficial.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carbazoles; Cardiomyopathies; Cardiotonic Agents; Cardiovascular Agents; Carvedilol; Cell Line, Tumor; Cell Survival; Dexrazoxane; Dose-Response Relationship, Drug; Doxorubicin; Drug Interactions; Enalapril; Female; Fluorodeoxyglucose F18; Humans; Metformin; Propanolamines; Radionuclide Imaging; Radiopharmaceuticals; Receptor, ErbB-2; Trastuzumab

Breast cancer tends to occur in an older age group of women also burdened with comorbidities such as cardiovascular disease (CVD). Numerous medications used to manage CVD (e.g., statins and antihypertensives) are hypothesized to alter breast cancer risk, but there are few studies on breast cancer outcomes. The COmmonly used Medications and Breast Cancer Outcomes (COMBO) cohort was developed to study how medications and co-morbidities influence breast cancer prognosis. Cohort study among adult women, diagnosed with incident early stage breast cancer, and enrolled in an integrated health plan. Data sources included health plan administrative databases, Surveillance, Epidemiology, and End Results tumor registry, and medical records. Statins, angiotensin-converting enzyme inhibitors (ACEI), beta blockers (BB), calcium blockers, and diuretics were the exposures of interest. The outcome was second breast cancer events (SBCE) defined as recurrence or second primary breast cancer. We used multivariable Cox proportional hazards models to estimate hazard ratios (HR) and 95 % confidence intervals (CI) for SBCE, and components of SBCE. 4,216 women were followed for a median of 6.3 years, and 13.2 % experienced a SBCE (first of: n = 415 recurrences and n = 143 s primary breast cancers). Compared to non-users, we observed an increased risk of second primary breast cancer with ACEI use (HR = 1.66; 95 % CI, 1.06-2.58) and an increased risk of recurrence with BB use (HR = 1.29; 95 % CI, 1.01-1.64). There was suggestion of a reduced risk of SBCE with statin use (HR = 0.82; 95 % CI, 0.62-1.08) and second primary breast cancer with BB use (HR = 0.77; 95 % CI, 0.50-1.19). No differences in outcomes were observed by duration of medication use. A majority of CVD medications evaluated in this study appear safe with respect to SBCE, but ACEI and BB use warrant further evaluation. The study presented is one example of the questions that can be addressed using the COMBO cohort.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Breast Neoplasms; Cardiovascular Agents; Cardiovascular Diseases; Comorbidity; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasms, Second Primary; Prognosis; Retrospective Studies; Washington; Young Adult

Doxorubicin, an anthracycline antibiotic commonly used as a chemotherapeutic agent for breast cancer, is well known to cause cardiotoxicity. We report the case of an active, otherwise healthy 57-year-old breast cancer survivor who, 17 years after chemotherapy, presented with symptoms of overt heart failure. She had no cardiac risk factors, and neither laboratory nor imaging findings suggested myocarditis or dilated cardiomyopathy. Echocardiographic findings and differential diagnosis led us to attribute her condition to late doxorubicin-induced cardiomyopathy. By virtue of tapered medical therapy, her left ventricular ejection fraction improved from 0.20 to 0.55 in 8 months, and she was asymptomatic after 1 year. The reversibility of left ventricular dysfunction in our patient and the very late appearance of cardiotoxicity secondary to doxorubicin therapy raise questions about the pathogenesis and prevalence of late doxorubicin-induced cardiomyopathy and how to improve outcomes in patients who present with related symptoms of heart failure.

Topics: Antibiotics, Antineoplastic; Breast Neoplasms; Cardiomyopathies; Cardiovascular Agents; Chemotherapy, Adjuvant; Doxorubicin; Electrocardiography; Female; Heart Failure; Humans; Magnetic Resonance Imaging; Mastectomy, Segmental; Middle Aged; Recovery of Function; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

We report a case of capecitabine-induced cardiotoxicity (effort angina) in a woman with metastatic breast carcinoma. Due to cancer progression, rechallenge of therapy with capecitabine was attempted, using several strategies in order to prevent cardiotoxicity. The most (even if not fully) effective strategy was reducing capecitabine dosage together with nitrates, calcium-channel blockers and trimetazidine therapy.

Topics: Angina Pectoris; Antimetabolites, Antineoplastic; Breast Neoplasms; Capecitabine; Cardiovascular Agents; Coronary Vasospasm; Deoxycytidine; Echocardiography, Doppler, Color; Echocardiography, Doppler, Pulsed; Electrocardiography; Female; Fluorouracil; Humans; Middle Aged

Anthracyclines are highly effective and widely used cytotoxic agents, but their application is often limited by cumulative dose-dependent cardiotoxicity. Dexrazoxane has been shown in several clinical trials to prevent the development of this serious toxicity. The aim of our study was to analyze the incidence of cardiac dysfunction over a 10-year period in patients with breast cancer who were treated with anthracycline-based regimens with addition of dexrazoxane, mainly in an adjuvant setting.. We conducted a retrospective analysis on a population of women with breast cancer treated at our institution between January 1993 and October 2003. We reviewed patients' medical records and data on patient characteristics, treatment history, and adverse events that were collected, starting from the time of first visit before starting therapy, with the use of software created and designed for clinical records management in our institution (1999 OK-DH). Patients underwent an ECG assessment prior to starting chemotherapy, and were clinically monitored for cardiac failure. Those who developed signs and symptoms suggestive of cardiac dysfunction underwent further ECG. If clinical findings indicated, echocardiography and further cardiologic investigations were performed. The main outcome measure was the development of signs and symptoms indicative of congestive heart failure (CHF).. A total of 318 female patients were treated with an anthracycline (doxorubicin or epirubicin)-based combination chemotherapy regimen during this time, in most cases in the adjuvant setting (n = 285). Most patients (n = 302) had early-stage disease and only 16 women presented with metastatic disease with good life expectancy (at least 1 year). All patients received dexrazoxane 1000 mg/m(2) intravenously prior to anthracycline administration during each chemotherapy cycle. The median follow-up duration was 35 months. During this time, five patients (1.57%) developed signs and symptoms of CHF. No patient at our institution died of heart failure during the period analyzed. Dexrazoxane was well tolerated, with no reports of adverse events associated with this drug.. The reported incidence of cardiotoxicity in this study represents a marked reduction compared with historical data for patients receiving anthracycline-based chemotherapy without dexrazoxane. Dexrazoxane appears to have a cardioprotective effect in women with early-stage or advanced breast cancer treated with anthracycline-based combination chemotherapy, mainly as an adjuvant treatment. Prospective, randomized, controlled clinical trials in adjuvant setting should be performed to confirm these results.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cardiovascular Agents; Dose-Response Relationship, Drug; Doxorubicin; Electrocardiography; Epirubicin; Female; Follow-Up Studies; Heart Failure; Humans; Incidence; Life Expectancy; Middle Aged; Neoplasm Metastasis; Razoxane; Retrospective Studies

The development of an autoantibody to human Factor VIII is rare and presents many problems for diagnosis and treatment. We have seen several cases at our institution recently with widely heterogenous clinical and laboratory presentations. A wide range of treatment modalities were used in these cases with no gold standard of treatment or widely accepted guidelines existing. This has prompted us to examine all cases of this condition presenting at Fremantle Hospital over the last decade. We describe four cases which demonstrate the heterogeneity of this condition and its treatment and review the recent literature on the subject.

Topics: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Autoantibodies; Autoimmune Diseases; Azathioprine; Breast Neoplasms; Cardiovascular Agents; Cardiovascular Diseases; Chlorambucil; Cyclophosphamide; Factor VIII; Female; Hematoma; Hemophilia A; Humans; Immunoglobulin G; Immunosuppressive Agents; Infections; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Neoplasms, Multiple Primary; Partial Thromboplastin Time; Prednisolone; Retrospective Studies

Topics: Antibiotics, Antineoplastic; Breast Neoplasms; Cardiovascular Agents; Doxorubicin; Heart Failure; Humans; Razoxane

1) Should dexrazoxane be used routinely in patients with advanced or metastatic cancer who are at risk of developing cardio toxicity when receiving chemotherapy containing doxorubicin or epirubicin? 2) Do the available data support the use of dexrazoxane when anthracyclines are being used in the adjuvant setting for patients at risk of developing cardiotoxicity?. To make recommendations regarding the use of dexrazoxane to prevent cardiotoxicity in patients with nonhematological malignancies who are receiving anthracycline- containing chemotherapy.. Clinical and subclinical cardiotoxicity, noncardiac toxicity and impact on efficacy outcomes such as response and overall survival are considered.. Evidence was selected, reviewed and synthesized by 2 members of Cancer Care Ontario's Systemic Treatment Disease Site Group (STDSG), formerly the Systemic Treatment Program Committee. Drafts of this document have been circulated and reviewed by members of the STDSG. The STDSG comprises medical oncologists, pharmacists, supportive care personnel and administrators. Community representatives did not participate in the development of this guideline, but they will be included in future guidelines.. Seven randomized controlled trials (RCTs), 2 with placebo control, were available for analysis.. Data for clinical cardiotoxicity from 6 trials were pooled (n = 1070). The meta-analysis indicated that the risk of experiencing clinical cardiotoxicity was significantly reduced by dexrazoxane (risk ratio 0.24; 95% confidence interval [CI] 0.11 to 0.52; p = 0.00031). There was no significant benefit shown in individual trials for objective response or survival.. One of the RCTs revealed a significantly lower objective response rate in the dexrazoxane arm. However, a meta-analysis of objective response across 5 trials of breast cancer patients (n = 818) did not confirm this effect (odds ratio 0.85; 95% CI 0.61 to 1.18; p = 0.33). The use of dexrazoxane increased the incidence of myelosuppression and other noncardiac toxicities, but these were generally mild.. The evidence supports the use of dexrazoxane to provide protection against the cardiotoxicity associated with conventional-dose doxorubicin in patients with advanced but anthracycline-sensitive cancer, in whom the continued use of anthracycline-containing chemotherapy is indicated in the opinion of the treating physician and who have received 300 mg/m2 or more of doxorubicin. The evidence supports the use dexrazoxane to provide protection against the cardiotoxicity associated with conventional-dose epirubicin in patients with advanced but anthracycline-sensitive cancer, in whom the continued use of anthracycline-containing chemotherapy is indicated in the opinion of the treating physicians. There are no data indicating the optimal cumulative dose of epirubicin at which dexrazoxane should be instituted. For doxorubicin, use of dexrazoxane is recommended after the cumulative dose reaches 300 mg/m2 (i.e., 55% of the recommended maximum). A similar formula could be used for epirubicin, that is, institution of dexrazoxane when the cumulative dose of epirubicin reaches 550 mg/m2, as the recommended maximum cumulative dose in Canada is 1000 mg/m2. Preclinical studies did not show any cardioprotectant effect for dexrazoxane when used with mitoxantrone, and no clinical studies have been done. Therefore, dexrazoxane is not recommended for use with mitoxantrone. There is no evidence for or against the use of dexrazoxane in the adjuvant setting for any tumour type. Because of concerns that dexrazoxane may reduce the efficacy of anthracyclines, and because data are not yet available on long-term toxicities, further studies should be performed before the drug is used in this setting.

Topics: Aged; Antibiotics, Antineoplastic; Antineoplastic Agents; Breast Neoplasms; Cardiovascular Agents; Clinical Trials as Topic; Doxorubicin; Drug Administration Schedule; Epirubicin; Evidence-Based Medicine; Female; Heart; Heart Failure; Humans; Neoplasms; Odds Ratio; Randomized Controlled Trials as Topic; Razoxane; Time Factors; Treatment Outcome

The recognition of the activity of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in metastatic breast cancer led to attempts to combine this drug with other active agents. Two agents that have received particular attention are doxorubicin and cisplatin. Initial pilot and phase I trials by the Eastern Cooperative Oncology Group (ECOG) led to the development of a three-arm, prospective randomized trial comparing single-agent doxorubicin, single-agent paclitaxel, and the combination of doxorubicin and paclitaxel (E 1193). This trial is currently closed to accrual and the initial results are being analyzed. Based on data from Gianni et al (J Clin Oncol 13:2688-2699, 1995), the ECOG is currently involved in two trials attempting both to confirm the superior activity of the regimen used by Gianni et al and, in a phase I/II trial, to ameliorate its cardiac toxicity through the addition of dexrazoxane. Similarly, both the ECOG and the Hoosier Oncology Group were unable to confirm the strikingly positive results obtained by the Vancouver group when cisplatin was combined with paclitaxel (Semin Oncol 22:108-111, 1995 [suppl 6]: Proc Am Soc Clin Oncol 13:71, 1994 [abstr 88]). Indiana University investigators are currently involved in a phase I trial attempting to combine carboplatin and paclitaxel in a biweekly schedule.

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cardiovascular Agents; Cisplatin; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Doxorubicin; Female; Heart; Humans; Multicenter Studies as Topic; Neoplasm Metastasis; Paclitaxel; Pilot Projects; Prospective Studies; Randomized Controlled Trials as Topic; Razoxane

Topics: Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cardiovascular Agents; Cyclophosphamide; Doxorubicin; Female; Fluorouracil; Heart; Heart Failure; Humans; Radionuclide Ventriculography; Razoxane; Treatment Outcome

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cardiovascular Agents; Clinical Trials as Topic; Cyclophosphamide; Doxorubicin; Female; Fluorouracil; Heart; Heart Failure; Humans; Razoxane

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cardiomyopathies; Cardiovascular Agents; Cyclophosphamide; Doxorubicin; Drug Evaluation; Drug Interactions; Female; Fluorouracil; Heart; Humans; Middle Aged; Razoxane; Remission Induction