Oxaliplatin (oxaliplatin)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Oxaliplatin is a platinum-containing antineoplastic agent.
Oxaliplatin is a platinum-containing antineoplastic agent. The drug is an organoplatinum complex, consisting of a platinum atom complexed with 1,2-diaminocyclohexane (DACH) and a labile oxalate ligand. Oxaliplatin must undergo nonenzymatic activation before antineoplastic activity occurs.
In physiologic solutions, the labile oxalate ligand of oxaliplatin presumably is displaced, forming several transient reactive complexes (e.g., monoaquo DACH platinum, diaquo DACH platinum) that covalently bind to specific DNA base sequences, producing intrastrand and interstrand DNA cross-links. Cross-links between specific DNA base sequences (i.e., adjacent guanine residues, adjacent adenine and guanine residues, guanine residues separated by an intervening nucleotide) produced by transient reactive intermediates of oxaliplatin are thought to inhibit DNA replication and transcription. Some evidence indicates that the presence of the bulky DACH carrier ligand of oxaliplatin may contribute to a greater degree of inhibition of DNA synthesis and cytotoxicity compared with that observed with cisplatin and may result in the lack of cross-resistance between oxaliplatin and cisplatin.
Oxaliplatin is cycle-phase nonspecific.
Oxaliplatin has been shown to exhibit antitumor activity against colon carcinoma in vivo. Synergistic antiproliferative activity of oxaliplatin and fluorouracil has been demonstrated in vitro and in vivo in several tumor models (i.e., HT29 (colon), GR (mammary), L1210 (leukemia)).
Because oxaliplatin undergoes rapid and extensive nonenzymatic biotransformation to numerous platinum-containing transient reactive intermediates, pharmacokinetic parameters of the drug generally are expressed in terms of platinum-containing complexes rather than the parent compound. Following a 2-hour IV infusion of oxaliplatin, approximately 15% of the administered platinum is present in the systemic circulation while the remaining 85% is rapidly distributed into tissues or eliminated in urine. A fraction of the platinum-containing complexes distributed into peripheral tissues is irreversibly bound to and accumulates (approximately twofold) in erythrocytes, where the complexes appear to have no relevant activity.
Approximately 90% of the platinum in the systemic circulation is irreversibly bound to plasma proteins, principally albumin and gamma globulins. It is thought that antineoplastic activity of oxaliplatin resides only in platinum-containing species present in the ultrafilterable plasma fraction (biotransformed, nonprotein-bound species); however, the pharmacodynamic relationship between platinum ultrafiltrate concentrations and safety or efficacy of oxaliplatin has not been established. There is no evidence that platinum accumulates in plasma following administration of 85 mg/m2 dosages of oxaliplatin once every 2 weeks; however, a progressive accumulation of platinum in erythrocytes has been reported.
Oxaliplatin undergoes rapid and extensive nonenzymatic biotransformation; there is no evidence of cytochrome P-450 (CYP)-mediated metabolism in vitro. As many as 17 platinum-containing derivatives, including several cytotoxic species (e.g., monochloro DACH platinum, dichloro DACH platinum, monoaquo DACH platinum, diaquo DACH platinum) and various noncytotoxic species, have been isolated from plasma ultrafiltrate samples from patients receiving oxaliplatin. Distribution of platinum-containing derivatives appears to be triphasic, with the half-lives of the first, second, and third phases averaging approximately 0.43, 16.8, and 391 hours, respectively.
Platinum-containing derivatives are eliminated principally by renal excretion; renal clearance of ultrafilterable platinum appears to be directly proportional to glomerular filtration rate (GFR). Following administration of a single 2-hour IV infusion of oxaliplatin, approximately 54 or 2% of platinum-containing derivatives is excreted in urine and feces, respectively, within 5 days.
USES: This medication is used to treat advanced cancer of the colon and rectum. Oxaliplatin is a chemotherapy drug that contains platinum. It is used to slow or stop cancer cell growth.
Generic name: oxaliplatin
Pronunciation: (ox-AL-ih-plah-tin)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Oxaliplatin
Indications
The following indications are listed for Oxaliplatin:
- Lymph Node Positive Colorectal Carcinoma
- Metastatic Colorectal Cancer
Also known as: Stage Iii Colon Cancer.
Dosing
No dosing information is available for this tab.
No dosing information is available for this tab.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
History of hypersensitivity reactions to oxaliplatin, any ingredient in the formulation, or other platinum-containing compounds.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in 20% or more of patients receiving the oxaliplatin/fluorouracil/leucovorin regimen as adjuvant therapy for colon cancer and at an incidence that is at least 5% higher than that reported with fluorouracil/leucovorin alone include peripheral sensory neuropathy, nausea, vomiting, diarrhea, fatigue, anorexia, and pyrexia. Laboratory abnormalities reported in 20% or more of patients receiving the oxaliplatin/fluorouracil/leucovorin regimen and at an incidence that is at least 5% higher than that reported with fluorouracil/leucovorin alone include neutropenia, thrombocytopenia, anemia, elevated aminotransferase concentrations, and elevated alkaline phosphatase concentrations.
Adverse effects reported in 20% or more of patients receiving the oxaliplatin/fluorouracil/leucovorin regimen for previously untreated advanced colorectal cancer include adverse neurologic effects (i.e., neuropathy, including paresthesia, pharyngo-laryngeal dysesthesias), adverse GI effects (i.e., nausea, diarrhea, vomiting, stomatitis, anorexia, constipation, abdominal pain), fatigue, cough, and alopecia. Laboratory abnormalities reported in 20% or more of patients receiving the oxaliplatin/fluorouracil/leucovorin regimen include leukopenia, neutropenia, thrombocytopenia, and anemia.
Adverse effects reported in 20% or more of patients receiving the oxaliplatin/fluorouracil/leucovorin regimen for previously treated advanced colorectal cancer include adverse neurologic effects (i.e., neuropathy, including acute or persistent neuropathy), adverse GI effects (nausea, vomiting, diarrhea, stomatitis, abdominal pain, anorexia), fatigue, pyrexia, dyspnea, and constipation. Laboratory abnormalities reported in 20% or more of patients receiving the oxaliplatin/fluorouracil/leucovorin regimen include anemia, leukopenia, neutropenia, thrombocytopenia, and elevated aminotransferase concentrations.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy of oxaliplatin have not been established in pediatric patients. No substantial antitumor activity has been reported in clinical trials in 69 pediatric patients with solid tumors.
Oxaliplatin may cause fetal harm if administered to pregnant women based on its mechanism of action and animal findings. (See Fetal/Neonatal Morbidity and Mortality under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)
It is not known whether oxaliplatin or its metabolites are distributed into milk. Because of the potential for serious adverse reactions to oxaliplatin in nursing infants, women should be advised to discontinue nursing during therapy and for 3 months after the last dose of the drug. The effects of oxaliplatin on nursing infants or on milk production are unknown.
Clearance of ultrafilterable platinum does not appear to be affected substantially by age; however, the incidence of certain adverse effects (i.e., granulocytopenia, leukopenia, grade 3 or 4 neutropenia, diarrhea, dehydration, hypokalemia, fatigue, syncope) was higher in geriatric patients than in younger adults. In the study of adjuvant therapy for colon cancer, the effect on disease-free survival of the oxaliplatin/fluorouracil/leucovorin regimen compared with that of fluorouracil/leucovorin in patients 65 years of age or older was inconclusive. In patients receiving the oxaliplatin/fluorouracil/leucovorin regimen as first-line therapy for advanced colorectal cancer, no differences in efficacy were observed in patients 65 years of age or older compared with the overall study population. In patients receiving the oxaliplatin/fluorouracil/leucovorin regimen for previously treated advanced colorectal cancer, no differences in efficacy were observed in patients 65 years of age or older compared with younger adults.
ICD codes
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Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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