Cyclohexane-1,2-diamine; 1,3-dioxa-2$l^{2}-platinacyclopentane-4,5-dione

DescriptionOxaliplatin is a second generation platinum drug prepared in three steps from either k2tCl4 or K2Ptl4. It has an antitumor spectrum similar to cisplatin, however, it is more effective against L1210 leukemia and cisplatin resistant L1210. It is also effective against B16 melanoma but has a dose limiting toxicity of peripheral sensory neuropathy that is reversible upon cessation of the drug. The (R,R)- enantiomer has greater activity than the (S,S)-isomer but this is tumor line dependent, e.g., there was no difference found for P-388 or Sarcoma 180. Clinical drug administration based on circadium timing showed it was better tolerated when given 16 h after the onset of light. Oxaliplatin binds to guanineN7 and can lead to bidentate chelation that results in the bending of DNA. This feature is recognized by high mobility group proteins (HMG) which impedes repair reactions and stops replication and transcription.

UsesThird generation platinum complex. An antitumor agent with activity against colorectal cancer. Cytotoxicity follows the formation of adducts with DNA. Antineoplastic.

UsesA potent anti-neoplastic agent that binds to DNA and shows efficacy in Cisplatin resistant cell lines

UsesOxaliplatin is a platinum-based antineoplastic agent that functions by forming DNA adducts specifically in cancer cells, preventing DNA replication and transcription which leads to cell death. Oxaliplatin has cytotoxic effects in a broad range of cell lines, including colon, ovarian, and lung cancer, with IC50 values ranging from 0.5-240, 0.12-19.8, and 2.6-6.1 μM, respectively. Through its general cytotoxic effects, oxaliplatin has anti-tumor activity against advanced colorectal cancer and is typically administered with fluorouracil and leucovorin in a combination known as FOLFOX.

General DescriptionOxaliplatin is available in 50- and 100-mg vials for IV administrationin the treatment of ovarian cancer, metastaticcolorectal cancer, and early stage colon cancer in combinationwith 5-fluorouracil/leucovorin. The activation of theagent occurs in low-chloride environments to give theaquated species, which subsequently reacts with DNA in amanner similar to cisplatin. The mechanisms of resistance aresimilar for the two agents; however, oxaliplatin is not recognizedby MMR enzymes and does not show cross-resistancewith cisplatin. The agent is widely distributed, highly proteinbound (85%–88%), and irreversibly binds to erythrocytes.Numerous metabolites have been identified many of whichare produced as a result of nonenzymatic processes and includechloro-, dichloro-, monoaquo-, and diaquo-species.The parent and metabolites are eliminated primarily in theurine with a long terminal elimination half-life of 240 hours.Neurotoxicity is dose limiting and normally presents as peripheralneuropathy, which may be exacerbated by exposureto low temperatures. The neurotoxicity is normally reversiblein contrast to that seen with cisplatin, which may be irreversible.Other adverse effects include nausea, vomiting, diarrhea,myelosuppression, and hypersensitivity reactions.Ototoxicity and renal toxicity occur only rarely in contrast tocisplatin.