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1

Outcome of anthracycline-related cardiomyopathy – experience of a cardiooncology clinic at a tertiary referral cancer centre

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Alahari Dhir A., Daddi A., Sawant S. P.

OncoReview

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2017

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vol. 7

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issue 4

155-161

EN

Introduction: The most common form of cardiotoxicity in cancer treatment is anthracycline-related cardiomyopathy. Objective: To study the factors affecting response to heart failure (HF) therapy in patients with anthracycline- related cardiomyopathy (ARC). Methods: Patients with ARC were included in the study. ARC was defined as left ventricular ejection fraction (LVEF) < 50% in patients who had received anthracycline based chemotherapy. 2Decho was done at baseline and every 3 months after starting anti-heart failure treatment. The primary endpoint of the study was response to anti-heart failure treatment. The patients were considered as responders when LVEF increased at least 10 absolute points. The secondary endpoint was overall survival. Results: 177 patients with ARC were included in the study. The median cumulative dose of doxorubicin was 275 mg/m2. Median clinical follow up duration was 19 months (range 3–73 months). 55% were responders. 25 cumulative doxorubicin dose of more than 200 mg/m2 increased the likelihood of non-response (p = 0.008), by a factor of 3.07 (95% CI: 1.34–7.05). 25 patients expired. There was a significant difference in overall survival among responders as compared to non-responders (p value: 0.002, log rank test). Conclusions: In patients with ARC cumulative doxorubicin dose of more than 200 mg/m2 increased the likelihood of non-response to anti-heart failure treatment. Responders have a better overall survival compared to non-responders in patients with ARC.

2

A simple model for predicting the free energy of binding between anthracycline antibiotics and DNA.

100%

Rudnicki W. R., Kurzepa M., Szczepanik T., Priebe W., Lesyng B.

Acta Biochimica Polonica

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2000

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vol. 47

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issue 1

1-9

EN

A theoretical model for predicting the free energy of binding between anthracycline antibiotics and DNA was developed using the electron density functional (DFT) and molecular mechanics (MM) methods. Partial DFT-ESP charges were used in calculating the MM binding energies for complexes formed between anthracycline antibiotics and oligodeoxynucleotides. These energies were then compared with experimental binding free energies. The good correlation between the experimental and theoretical energies allowed us to propose a model for predicting the binding free energy for derivatives of anthracycline antibiotics and for quickly screening new anthracycline derivatives.

3

Safety and efficacy of liposomal doxorubicin in a patient treated for metastatic breast cancer

100%

Borucka J.

OncoReview

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2015

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vol. 5

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issue 4

A151-154

EN

Breast cancer is the most common malignancy among women in Poland and all over the world. Despite the development of modern therapies, cytostatics still play one of the main roles in treatment of this disease. Classic anthracyclines, besides unquestionable efficacy in this disease, have a disadvantageous toxicity profile. Therefore, until now, there has been a limitation in using these drugs in patients with cardiological conditions and in patients who had previously taken anthracyclines. That was the cause for the development of a less toxic form of drug, which is liposomal doxorubicin – being as effective as classic anthracycline it has reduced cardiotoxicity. This article presents the case of a patient with metastatic breast cancer, in whom, after treatment with classic doxorubicin, liposomal form was administered which caused regression of liver metastases. Moreover, during treatment with liposomal doxorubicin, there has been no evidence of heart impairment.

4

Delayed anthracycline-induced cardiomyopathy – case report

100%

Wiater E., Charliński G., Magoń-Golińska M.

OncoReview

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2014

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vol. 4

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issue 4

A155-A159

EN

A 43-year-old man was admitted to the hematology department due to second recurrence of anaplastic lymphoma T-cell ALK+. Lymphoma was diagnosed 28 years earlier. The patient received COP regimen (17 cycles) and CHOP (5 cycles), radiotherapy and underwent splenectomy. He achieved complete remission at that time. Relapse of the disease was diagnosed 8 years later, which was treated with 6 cycles of chemotherapy (cytarabine, mitoxantrone, vepeside and glucocorticoids) and high-dose chemotherapy followed by hematopoietic stem cell transplantation. Second disease recurrence was found in 2013, it was anaplastic lymphoma T-cell ALK+ stage IIA by Ann Arbor. Echocardiography and myocardial perfusion scintigraphy revealed chronic heart failure NYHA class I. Angiotensin receptor antagonist (ramipril) and β-blocker (carvedilol) were recommended. The patient underwent 6 cycles of ESHAP, complete remission was reported after the second cycle. High-dose therapy with autologous stem cell rescue was considered at that time. However, having T-cell ALK+ lymphoma with a relatively good prognosis, previous prolonged complete remissions (respectively – 12 and 8 years), an insufficient yield from the harvest (3,33 × 106/kg CD34+ cells), heart failure and chronic active viral hepatitis B, the high risk intensive chemotherapy followed by hematopoietic stem cells transplantation was discontinued. The chemotherapy was complicated by brachial vein and superficial vein thrombosis of left upper limb and hypogammaglobulinemia. Follow-up echocardiography performed after completion of chemotherapy showed improvement in EF (64%).

5

The influence of intracellular idarubicin and daunorubicin levels on drug cytotoxicity in childhood acute leukemia.

88%

Styczyński J., Wysocki M., Dębski R., Kurylak A., Balwierz W., Rokicka-Milewska R., Matysiak M., Balcerska A., Kowalczyk J., Wachowiak J., Sońta-Jakimczyk D., Chybicka A.

Acta Biochimica Polonica

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2002

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vol. 49

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issue 1

99-107

EN

Uptake and efflux of two anthracyclines, idarubicin (IDA) and daunorubicin (DNR), was studied in childhood acute leukemia samples. A comparison of IDA and DNR transport phenomena in relation to drug cytotoxicity and expression of P-glycoprotein (PGP) was made. Intracellular content of IDA/DNR was determined by flow cytometry using the fluorescent properties of the drugs. In vitro drug cytotoxicity was measured by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. PGP expression was analysed by flow cytometry. The uptake and efflux rates were non-significantly higher for IDA than DNR. There were no differences between three types of leukemia with respect to drug content during accumulation and retention. After correction for the cell volume, intracellular concentration of both drugs in each moment of uptake and efflux was significantly lower in relapsed ALL and AML samples in comparison with initial ALL cells. Efflux, but not uptake, of both drugs was inversely correlated with PGP expression and IDA, but not DNR, cytotoxicity. The cytotoxicity was correlated with drug accumulation for both drugs and with drug retention for IDA. In conclusion, it seems that (1) intracellular content was related to the lipophilic properties of the drugs rather than to the type of leukemia, (2) decreased intracellular concentration of both drugs might have an impact on compromised therapy results in AML and relapsed ALL children, (3) IDA presents higher cytotoxicity, which possibly might be decreased by the presence of PGP. These results might have a practical impact on the rational design of new chemotherapy protocols.

6

Severe aortic stenosis in a patient with breast cancer

88%

Mańczak R., Wilk M., Walaszkowska-Czyż A., Florczyk M., Szmit S.

OncoReview

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2016

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vol. 6

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issue 2

A49-56

EN

We present a case of 68-year-old female with severe symptomatic aortic stenosis and locally advanced breast cancer disqualified from mastectomy due to heart failure and from aortic valve replacement due to malignant neoplasm. The patient received neoadjuvant chemotherapy without anthracyclines. The aortic valve replacement was performed and then mastectomy and lymphadenectomy were made without hemodynamic complications. Adjuvant hormonotherapy was started. During 42 months of follow-up the patient remained free of recurrent cancer disease as well as no progression of heart failure was observed.

Refine search results

Outcome of anthracycline-related cardiomyopathy – experience of a cardiooncology clinic at a tertiary referral cancer centre

A simple model for predicting the free energy of binding between anthracycline antibiotics and DNA.

Safety and efficacy of liposomal doxorubicin in a patient treated for metastatic breast cancer

Delayed anthracycline-induced cardiomyopathy – case report

The influence of intracellular idarubicin and daunorubicin levels on drug cytotoxicity in childhood acute leukemia.

Severe aortic stenosis in a patient with breast cancer