Anthracyclines alkylating agents

Each category of chemotherapy drugs has similar side effects. Anthracyclines cause cardiac toxicity, which is related to the cumulative dose. Tubulin interactive agents are associated with neuropathy and ileus. Alkylating agents are associated with secondary malignancies. 

Alkylating agents are compounds capable of reacting covalently with DNA bases. If a compound of this type contains two reactive groups, intramolecular or intermolecular crosslinking of the DNA double helix and bending of the double strand occurs. Examples of this type shown here are cyclophosphamide and the inorganic complex cisplatin. Anthracyclines such as doxorubicin (adriamy-cin) insert themselves non-covalently between the bases and thus lead to local alterations in the DNA structure (see p. 254 B). 

Two patients with acute promyelocytic leukemia developed therapy-related myelodysplasia 2.0-2.5 years after complete remission and then acute myeloid leukemia both had received anthracyclines (39). In both cases the cytogenetic changes that usually occur after the use of alkylating agents were observed. There has only been one previous similar report after successful therapy with anthracyclines, but these observations suggest that anthracyclines can cause acute myeloid leukemia similar to that caused by alkylating agents. 

Cytotoxic antibiotics produce their effect mainly by direct action on DNA. Anthracyclines include the important drugs doxorubicin, aclarubicin and idarubicin. Related compounds are mitozantrone and epirubicin. Some others are the Streptomyces antibiotic dactinomycin. and the metalchelating glycopeptides especially bleomycins. Mitomycin effectively is a prodrug that is converted in the body to an alkylating agent. 

Category Alkylating agent Antibiotic, anthracycline Half-life 23-78 minutes... 

Chemotherapy was first used for the treatment of advanced lymphomas in the 1940s [1], Since then several classes of chemotherapeutic compounds such as alkylating agents, antimetabolites, anthracyclines, plant alkaloids, and later topoisomerase inhibitors and taxanes have been identified or synthesized to treat various forms of cancer [2, 3], Although numerous in vitro and animal studies have demonstrated their effectiveness in inducing cancer cell death (cytotoxic) or cell growth arrest (cytostatic), these promising anticancer activities seen in the controlled environment of the laboratory frequently do not translate well into the expected clinical outcomes [4-8]. 

Increased activity of repair enzymes Alkylating agents, platinum compounds, etoposide, anthracyclines Chabner et al. (1996) Zeller (1995)... 

Docetaxel is indicated, in combination with doxorubicin and cyclophosphamide, for adjuvant treatment of node-positive breast cancer and, in combination with doxorubicin, for treating locally advanced or metastatic breast cancer. It is also indicated as monotherapy or in combination with capecitabine for the treatment of locally advanced or metastatic breast cancer in patients who have relapsed or progressed after previous anthracycline or alkylating agents. It can be administered concurrently with trastuzumab, with which it is synergistic in vitro [1091], unlike paclitaxel, which appears to have simply an additive effect with trastuzumab [110 ]. 

Nitrogen mustard, aziridines, nitrosoureas, alkyl alkane sulfonates, nonclassic alkylating agents, anthracyclins, actinomycins, anthracenedions... 

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