Clinical Pharmacodynamics of Anticancer Drugs
Hartmut Derendorf, Günther Hochhaus in Handbook of Pharmacokinetic/Pharmacodynamic Correlation, 2019
Pharmacokinetic studies of epirubicin and glucuronidated metabolite were evaluated in 48 patients with a variety of solid tumors receiving epirubicin 25 to 100 mg/m2.28 Plasma drug concentrations were obtained for 4 to 48 h after the bolus injection. AUC0-4 hours was estimated for epirubicin and its glucuronides. Percentage of change in WBC was determined as the (pretreatment count − day 14 count/pretreatment count) × 100. The ratio of glucuronide metabolite to parent compound was used to define distinct patient populations. Twenty-four patients had metabolic ratios <0.9 and >0.9, respectively. The change in leukocyte and granulocyte count was greater in those patients with a metabolic ratio >0.9 (56 and 67%, respectively) compared with the <0.9 group (30 and 30%, respectively). In addition, patients with a high ratio had a poorer response rate (30 vs. 65%). Although tumor heterogeneity within the two groups may confound the response findings in this study, studies of the epirubicin glucuronide:epirubicin ratio in patients with similar systemic exposure of epirubicin are required to determine the contribution of this metabolite to epirubicin’s toxicity and therapeutic effects.
Cancer
Vincenzo Berghella in Maternal-Fetal Evidence Based Guidelines, 2022
Radiation therapy is usually postponed until postpartum. As the pregnancy advances, the fetus has increased proximity to the breast and radiation field increasing exposure risk. Neoadjuvant chemotherapy with large tumors at presentation allows pathologic evidence of response to therapy which can be prognostic. The regimen used should adhere to the standard recommended chemotherapy regimens in the non-pregnant population [30]. The majority of pregnant women reported in the literature are treated with cyclophosphamide (C), doxorubicin (A) or epirubicin (E), with or without 5-fluouracil (5FU). AC or EC alone are preferable as recent evidence reveals no survival benefit of 5FU in breast cancer patients. A single study reported dose dense AC (every 2 weeks) but majority of case reports and small series administer AC every 3 weeks [44]. Currently doxorubicin is the preferred anthracycline to use during pregnancy and is commonly included in the regimens to treat various types of cancer during pregnancy. Data regarding the use of epirubicin in pregnancy is accumulating in Europe as it has lower myelotoxic and cardiotoxic properties and is better tolerated in non-pregnant patients. Transient neonatal cardiomyopathy has been reported after idarubicin exposure and the use of this anthracycline is not recommended during pregnancy [5, 6].
Soft Tissue Sarcomas
Pat Price, Karol Sikora in Treatment of Cancer, 2020
Doxorubicin and ifosfamide have been demonstrated to be the most active chemotherapy agents in widely disseminated STS. For doxorubicin, objective response rates between 20% and 40% for the single agent have been reported; few are CRs and response duration averages 8 months. A steep dose–response curve for objective responses has been described. Epirubicin has similar structure and clinical features. There is also a dose–response for ifosfamide. Dacarbazine (DTIC) by itself has a modest response rate of approximately 16%. The related compound, temozolomide, has similar activity. Cyclophosphamide appears less active in adults than in children and less active than the related compound ifosfamide. Gemcitabine with or without a taxane is active in a subset of patients with sarcomas. Angiosarcoma of the scalp and face may respond to paclitaxel. A pegylated liposomal formulation of doxorubicin has activity against sarcomas. Gemcitabine has been shown to have modest single-agent activity in previously treated patients, as does vinorelbine. Studies have shown a 24% 6-month disease progression control rate using trabectidin, ecteinascidin-743, in patients with advanced pre-treated sarcoma. Other less active agents include methotrexate, topotecan, carboplatin, bendamustine, and cisplatin. Pazopanib and sunitinib are expensive and have only modest activity, but are oral agents with usually mild toxicity. Bevacizumab and sorafenib46 are under study as are many targeted agents including mammalian target of rapamycin (MTOR) inhibitors, anti-insulin-like growth factor 1 receptor (IGF-1R) antibody, and newer agents such as brostacillin and eribulin.
Regulation of Fas in response to bortezomib and epirubicin in colorectal cancer cells
Published in Journal of Chemotherapy, 2020
Ercan Cacan, Zeliha C. Ozmen
Epirubicin is known as an anthracycline agent which can be used with other chemotherapeutic drugs in the treatment of several cancer types including post-surgical breast cancer, ovarian cancer and lung cancer. Epirubicin functions as an intercalating agent results in complex formation which interferes with DNA and RNA synthesis.22,23 It can also affect the regulation of gene expression by inhibiting polymerase activity.24 Epirubicin may have an anti-tumor effect against broad-spectrum tumor cells. However, it is a non-specific chemotherapeutic agent that can cause high toxicity if not used in appropriate doses. It has been observed that epirubicin triggers the release of calreticulin, an immunogenic marker in tumor cells and increases the antitumor effect in breast cancer when used with other chemotherapeutic agents.25,26 Therefore, we think that the use of epirubicin with another immunogenic agent would induce tumor immunogenicity and increase the immunogenic cell death.
Enhanced antitumor efficacy using epirubicin and schisandrin B co-delivery liposomes modified with PFV via inhibiting tumor metastasis
Published in Drug Development and Industrial Pharmacy, 2020
Ming Jing, Xiao-Jie Bi, Xue-Min Yao, Fuyi Cai, Jing-Jing Liu, Min Fu, Liang Kong, Xin-Ze Liu, Lu Zhang, Si-Yu He, Lian-Qun Jia, Xue-Tao Li
Epirubicin is a broad-spectrum and highly effective antineoplastic drug. As an isomer of adriamycin, it is widely used in many malignant tumors, including breast cancer. Epirubicin can directly intercalate between DNA nucleotide pairs, interfere with the transcription process and block the formation of mRNA, thus inhibiting the synthesis of DNA and RNA [20]. However, there are serious side effects such as cardiotoxicity, liver and kidney function damage, allergic reaction, and so on [21]. Schisandrin B is one of biphenylcyclooctene lignan. It is one of the most important active substances purified from the Schisandra chinensis. Studies have shown that it can reduce cell invasion and migration, destroy the VM channel and restrain the formation of angiogenesis [22,23]. As far as we know, there are no reports to evaluate the inhibitory effect about the combination of epirubicin and schisandrin B on tumor metastasis of breast cancer.
Enhanced antitumour efficiency of R8GD-modified epirubicin plus tetrandrine liposomes in treatment of gastric cancer via inhibiting tumour metastasis
Published in Journal of Liposome Research, 2021
Xue-Tao Li, Ming Jing, Fu-Yi Cai, Xue-Min Yao, Liang Kong, Xiao-Bo Wang
As an anthracycline drug, epirubicin possesses an antitumor effect against a wide spectrum of tumours. It is used alone or in combination with other drugs in patients with early gastric cancer and metastatic cancer. The antitumour effect of epirubicin is achieved by interaction with DNA in a variety of different ways, DNA strand breakage and inhibition with the enzyme topoisomerase II (Gomhor et al.2018, Bahreyni et al.2019, Schneeweiss et al.2019). For the poor targeting effect during treatment, the main adverse effects of epirubicin are myelosuppression and cardiotoxicity. Tetrandrine is a bibenzyl isoquinoline alkaloid with analgesic, anti-inflammatory and hypotensive effects. It has been used clinically to treat cardiovascular diseases such as hypertension and arrhythmia. In recent years, it is reported that tetrandrine has a certain antitumour effect via inhibiting tumour metastasis and reversing multidrug resistance. It can cut off the energy supply and inhibit the invasion of tumour cells to reduce the incidence of tumour metastasis (Xiao et al.2015, Li et al.2016, Chen et al.2017).
Related Knowledge Centers
- Anthracycline
- DNA
- Doxorubicin
- Breast Cancer
- Chemotherapy
- Cyclophosphamide
- Methotrexate
- Medication
- Radical
- Chemotherapy Regimen