Alkylating cytostatics

Alkylating cytostatics

Alkylating agents generate reactive covalent bonds between their alkyl-groups and nucleic acids of DNA. These agents are actively taken up by cells. Alkylating cytostatics act by alkylation with nucleophilic substitution of DNA. Thereby the interstrand cross-links are formed, which are toxic to the cell. Moreover, the interstrand cross-links inhibit DNA replication. The helicases, which unwind the DNA under normal conditions, are not able to break the cross-links. The same is true in case of RNA transcription. Alkylating cytotoxic drugs cause severe myelosuppression. Cisplatin and its analogue carboplatin are nonclassic alkylating agents. Like the other alkylating agents they bind to DNA to form interstrand cross-links with platinum. Oxaliplatin is another

platinum-containing cytostatic drug, which interacts with DNA and thereby disturbing the synthesis.

Cisplatin is often used in combination therapy to treat metastised and widespread tumors of testis, bladder, ovary, cervix and lung. Also many carcinomas can be treated with cisplatin. Carboplatin is indicated for treatment of ovary carcinomas. Oxaliplatin is used in combination with 5-FU in the treatment of colorectal cancers.

In general, cisplatin, oxaliplatin and carboplatin have much larger toxicity than other oncolytics. Vomiting, nausea and myelosuppression appear in more than 30% of the patients after a single dose. Hyperhydration can reduce the incidence of acute nephrotoxicity when administering cisplatin. In addition, carboplatin develops less nephrotoxicity and less vomiting.

Cyclophosphamide and iphosphamide also belong to the group of alkylating cytostatics. The use of alkylating agents is widespread because they are highly lipophilic and have low bone marrow toxicity. The main indications are different leukemias, prostate cancer and breast cancer. The main adverse effects are vomiting, nausea, myelosuppression, cystitis and damage of mucous membranes.

1

Which of the following are alkylating agents?

2

Which of the following statements is NOT true?