Anthracycline based chemotherapy

Contemporary Phase I-Ii Trials of Primary Anthracycline-Based Chemotherapy, Followed by Surgery and Radiation... 

Mrs CR first presented 18 months previously with grade 3 invasive breast cancer which was oestrogen receptor negative. She was initially treated with surgery (wide local excision and axillary clearance), adjuvant anthracycline-based chemotherapy and radiotherapy. Mrs CR has no other significant past medical history. 

This guidance is relevant to Mrs CR as she has HER-2,3+ disease, she has not had any previous treatment for metastatic breast cancer (she has only received adjuvant treatment for early stage breast cancer) and she is not suitable for anthracycline-based chemotherapy as she has already received this in the adjuvant setting less than 2 years ago. 

Circulating cardiac troponin (cTn) is the most widely used biomarker for detection of myocardial injury (Newby et al. 2011). With regard to its employment in the context of drug-induced cardiotoxicity, most data to date have examined anthracycline-based chemotherapy, and so the broader applicability of these data is currently nncertain (Christenson et al. 2015). However, a notable 2004 publication from the Expert Working Gronp on Biomarkers of Drug-induced Cardiac Toxicity (Wallace et al. 2004) reported that troponin I (cTnl) and troponin T (cTnT) are sensitive, specific, and robust biomarkers of drug-induced cardiotoxicity. 

Erhola M, Kellokumpu-Lehtinen P, Metsa-Ketela T, Alanko K, Nieminen MM (1996) Effects of anthracyclin-based chemotherapy on total plasma antioxidant capacity in small cell lung cancer patients. Free Radic Biol Med 21 383-390... 

Chan A, Chen C, Chiang J, Tan SH, Ng R. Incidence of febrile neutropenia among early-stage breast cancer patients receiving anthracycline-based chemotherapy. Supportive Care Cancer 2012 20(7) 1525-32. 

Campone M, Cortes-Funes H, Vorobiof D, et al, Vinflunine A new active drug for second-line treatment of advanced breast cancer. Results of a phase II and pharmacokinetic study in patients progressing after first-line anthracycline/taxane-based chemotherapy, Br J Cancer 95 1161-1166, 2006. 

Doxorubicin is an antineoplastic/anthracycline antibiotic. It binds DNA and inhibits nucleic acid synthesis. Cell structure studies have demonstrated rapid cell penetration and perinuclear chromatin binding, rapid inhibition of mitotic activity and nucleic acid synthesis, and induction of mutagenesis and chromosomal aberrations. It is indicated in treatment of ovarian cancer in patients whose disease has progressed or recurred after platinum-based chemotherapy and in treatment of AIDS-related Kaposi s sarcoma in patients whose disease has progressed on prior combination chemotherapy or who are intolerant to such therapy. 

Screening of microbial products has led to the discovery of a number of growth-inhibiting compounds that have proved to be clinically useful in cancer chemotherapy. Many of these antibiotics bind to DNA through intercalation between specific bases and block the synthesis of RNA, DNA, or both cause DNA strand scission and interfere with cell replication. All of the anticancer antibiotics now being used in clinical practice are products of various strains of the soil microbe Streptomyces. These include the anthracyclines, bleomycin, and mitomycin. 

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