Different anthracycline derivates for reducing cardiotoxicity in cancer patients
ABSTRACT The use of anthracyclines is limited by the occurrence of cardiotoxicity. In an effort to prevent this cardiotoxicity, different anthracycline derivates have been studied.
To determine the occurrence of cardiotoxicity with the use of different anthracycline derivates in cancer patients.
We searched The Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library, Issue 2, 2009), MEDLINE (1966 to 29 May 2009) and EMBASE (1980 to 2 June 2009). In addition, we searched reference lists of relevant articles, conference proceedings and ongoing-trials-databases.
Randomised controlled trials (RCTs) in which different anthracycline derivates were compared in cancer patients (children and adults).
Two authors independently performed study selection, assessment of risk of bias and data-extraction including adverse effects.
We identified five RCTs of varying quality addressing epirubicin versus doxorubicin (1036 patients) with the same dose. The meta-analysis showed no evidence for a significant difference in the occurrence of clinical heart failure between the treatment groups (RR = 0.36, 95% CI 0.12 to 1.11). However, there is some suggestion of a lower rate of clinical heart failure in patients treated with epirubicin.We identified two RCTs with varying quality addressing liposomal-encapsulated doxorubicin versus conventional doxorubicin (521 patients). The meta-analysis showed a significantly lower rate of both clinical heart failure and clinical and subclinical heart failure combined in patients treated with liposomal-encapsulated doxorubicin (RR = 0.20, 95% CI 0.05 to 0.75 and RR = 0.38, 95% CI 0.24 to 0.59 respectively). It should be noted that in one of the studies patients in the liposomal-encapsulated doxorubicin group received a higher cumulative anthracycline dose than patients in the doxorubicin group.For the other possible combinations of different anthracycline derivates only one RCT (epirubicin versus liposomal-encapsulated doxorubicin) or no RCT was identified.
We are not able to favour either epirubicin or doxorubicin when given with the same dose. Based on the currently available evidence on heart failure, we conclude that in adults with a solid tumour liposomal-encapsulated doxorubicin should be favoured over doxorubicin. For both epirubicin versus doxorubicin and liposomal-encapsulated doxorubicin versus conventional doxorubicin no conclusions can be made about the effects of treatment in children treated with anthracyclines and also not in patients diagnosed with leukaemia. More research is needed. For other combinations of anthracycline derivates not enough evidence was available to make definitive conclusions about the occurrence of cardiotoxicity in patients treated with anthracyclines.
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ABSTRACT: As the function of transient receptor potential melastatin member 8 (TRPM8) in osteosarcoma is still unknown, we aim to investigate the possible effects and potential mechanisms of TRPM8 on cell proliferation, metastasis and chemosensitivity in osteosarcoma cells. We find that TRPM8 is aberrantly over-expressed in human osteosarcoma tissues and cell lines. Knockdown of TRPM8 by siRNA in osteosarcoma cells leads to the impaired regulation of intracellular Ca(2+) concentration and then the Akt-GSK-3β pathway and the phosphorylation of p44/p42 and FAK are suppressed. Knockdown of TRPM8 not only negatively influences the cell proliferation and metastasis but also enhances epirubicin-induced cell apoptosis. Such results reveal that TRPM8 is worthy further investigation for its potential as a clinical biomarker and therapeutic target in osteosarcoma.International journal of biological sciences 01/2013; 10(1):90-102. DOI:10.7150/ijbs.7738 · 4.37 Impact Factor
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ABSTRACT: Cardiotoxic and other side effects limit the usefulness of treatments for cancer. This article is based on pertinent articles that were retrieved by a selective search in PubMed and other databases, and on the guidelines of the European Society of Cardiology, the Association of Scientific Medical Societies in Germany, and the European Society of Medical Oncology. Prospective studies have shown that some treatments for cancer are cardiotoxic. The heart damage that they cause can manifest itself as arrhythmia, arterial hypertension, thromboembolism, angina pectoris, myocardial infarction, or heart failure. It has been observed that potentially lethal complications can arise as late as 40 years after treatment of the original cancer. The anthracycline drug doxorubicin, given in a dose of 500 mg/m2 of body surface area, has been found to cause cardiac complications in 4-36% of the patients treated with it. Trastuzumab and epirubicin cause dose-limiting cardiac events in 1.7-5% of patients, depending on the dosage. Paclitaxel causes bradycardia, intracardiac conduction block, or arrhythmia in 0.5% of patients. 18% of patients treated with sunitimib or sorafenib have clinical manifestations relating to the heart (angina pectoris, dyspnea). 5-fluorouracil can cause angina pectoris at the beginning of treatment and rarely causes myocardial infarction. Cardiac radiation therapy, a form of treatment practiced in earlier decades, can cause cardiac complications 20 years after the event. The opportunity to prevent cardiac complications of anthracycline drugs with dexrazoxane is decidedly limited, but initial studies have shown that treatment with beta-blockers and ACE inhibitors lessens the likelihood of cardiotoxic side effects. When cardiac complications arise, the generally applicable rules for the treatment of each type of cardiac problem should be followed. The oncological treatment protocol should be adjusted or switched to one that is less damaging to the heart. Treating physicians need to be thoroughly acquainted with the cardiotoxic effects of anti-cancer drugs so that they can diagnose them early on and avoid jeopardizing the overall success of treatment.Deutsches Ärzteblatt International 03/2014; 111(10):161-8. DOI:10.3238/arztebl.2014.0161 · 3.61 Impact Factor
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ABSTRACT: Purpose: Chemotherapy regimens containing anthracyclines and taxanes represent the landmark of neoadjuvant systemic therapy of breast cancer. In advanced breast cancer patients liposomal anthracyclines (LA) have shown similar efficacy and less cardiac toxicity when compared to conventional anthracyclines. We performed this retrospective analysis in order to evaluate the efficacy and tolerability of neoadjuvant regimens including LA outside of clinical trials in routine clinical practice. Methods: Fifty operable or locally advanced, HER2 negative, breast cancer patients were retrospectively identified in 5 Italian cancer centres. Nineteen patients had received 4 cycles of non-pegylated liposomal doxorubicin (NPLD) and cyclophosphamide, followed by 4 cycles of docetaxel, every 3 weeks. In 25 patients the reverse sequence was employed, and a third subgroup of 6 patients received 4 cycles of NPLD/cyclophosphamide every 3 weeks followed by 4 cycles of weekly carboplatin and paclitaxel. Results: We observed 10 pathological complete responses (pCR) (20.0%, 95%CI, 9% to 31%), and 35 (70%, 95%CI, 57.3% to 82.7%) partial responses (pPR), whereas no patients progressed onto therapy. In the small subset of triple negative tumors the pCR rate was 37.5%, and in tumors expressing ER and/or PgR it was 16.7%. A pCR rate of 26.5% was observed in tumors with high Ki-67, whereas in tumors with low Ki-67 only one (6.2%) pCR was observed (p=0.14). Treatments were well tolerated. The most common toxicities were myelosuppression and palmar-plantar erytrodysesthesia; 4 asymptomatic and transient LVEF decrease have been recorded, without any case of clinical cardiotoxicity. Conclusions: NPLD-cyclophosphamide and taxanes sequential regimens were proven effective and well tolerated in breast cancer patients with contra-indication to conventional anthracyclines undergoing neoadjuvant chemotherapy, even outside of clinical trials in everyday clinical practice.04/2014; 5(6):398-405. DOI:10.7150/jca.9132This article is viewable in ResearchGate's enriched formatRG Format enables you to read in context with side-by-side figures, citations, and feedback from experts in your field.