Carboplatin alkylating agent

Other subgroups of alkylating agents are the nitrosoureas (examples carmustine, BCNU lomustine, CCNXJ) and the triazenes (example dacarbazine, DTIC). Platinum derivatives (cisplatin, carboplatin, oxaliplatin) have an action that is analogous to that of alkylating agents (formation of crosslinks) and therefore are appended to this class, as well. 

Carboplatin -atypical alkylating agent leading to DNA strand breakage during replication -bone marrow suppression—particularly thrombocytopenia -nausea and vomiting -liver function test abnormalities -uncommon neurotoxicity, ototoxicity... 

Despite the fact that alkylating agents exhibit a common mechanism of action, their clinical use varies depending on differences in pharmacokinetics, metabolism, hpid solubility, ability to penetrate membranes, and toxicity. They can be classified as nitrogen-containing mustard derivatives (mechorethamine, chlorambucil, melfalan, cyclophosphamide, ifos-famide), derivatives of ethylenimine (thiotepa), nitrosoureas (carmustine, lomustine, strep-tozocin), alkylsulfonates (busulfan), and derivatives of platinum (cwplatin, carboplatin). 

Heavy metal compounds used to treat cancer include cisplatin, carboplatin, and oxaliplatin (see Table 36-6). These drugs, which contain platinum, are also known as platinum coordination complexes.10,27 Heavy metal drugs act like the alkylating agents that is, they form strong cross-links between and within DNA strands,... 

Combination chemotherapy is the standard approach to stage III and stage IV disease. Randomized clinical studies have shown that the combination of paclitaxel and cisplatin provides survival benefit compared with the previous standard combination of cisplatin plus cyclophosphamide. More recently, several studies have shown that carboplatin and paclitaxel yields clinical results similar to what is achieved with the cisplatin plus paclitaxel combination however, because of reduced toxicity and greater ease of administration, carboplatin plus paclitaxel has now become the treatment of choice. In patients who present with recurrent disease, the topoisomerase I inhibitor topotecan, the alkylating agent altretamine, and liposomal doxorubicin are used as single agent monotherapy. 

Compared to other solid tumors, ovarian cancer is relatively responsive to chemotherapy, but unlike testicular cancer, cure is not common for patients with advanced disease. Prior to the incorporation of cisplatin or carboplatin into treatment regimens, chemotherapy for advanced-stage ovarian cancer consisted of combinations of alkylating agents and doxorubicin. Response rates from such regimens were of the order of 33-65%, and fewer than 10% of patients survived 5 years [51]. 

Alkylating agents and related compounds act by forming covalent bonds with DNA. thus impeding DNA replication. They can be divided into five subgroups (i) nitrogen mustards (e.g. chlorambucil, cyclophosphamide, melphalan and mustine (ii) platinum drugs (coordination complexes of platinum) (e.g. cisplatin and carboplatin) ... 

Cisplatin (Fig. 21.7) behaves in a manner analogous to an alkylating agent in that it cross-links guanine nucleotides. The N7 positions of adjacent guanines on a single strand of DNA react with cisplatin. Cisplatin only has a short half-life in plasma since it is hydrolysed in water quite rapidly. Transplatin is less effective as a cytotoxic agent. In part this may be because it is less effectively taken up by cells but also it can only cross-link between two DNA strands which is less effective as a cytotoxic mechanism since the lesion is more readily repaired. Carboplatin is less reactive than cisplatin and has reduced renal toxicity in comparison with it, while... 

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