Oxaliplatin
From Wikipedia, the free encyclopedia
 |
|
 |
|
|
Oxaliplatin
|
|
| Systematic (IUPAC) name | |
| ethanedioate;platinum(+4)cation; (2-azanidylcyclohexyl)azanide | |
| Identifiers | |
| CAS number | |
| ATC code | L01 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C8H14N2O4Pt |
| Mol. mass | 395.27 g/mol |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | ? |
| Half life | ? |
| Excretion | Renal |
| Therapeutic considerations | |
| Pregnancy cat. |
? |
| Legal status | |
| Routes | Intravenous |
Oxaliplatin is a platinum-based chemotherapy drug in the same family as cisplatin and carboplatin. It is typically administered in combination with fluorouracil and leucovorin in a combination known as FOLFOX for the treatment of colorectal cancer. Compared to cisplatin the two amine groups are replaced by cyclohexyldiamine for improved antitumour activity. The chlorine ligands are replaced by the oxalato bidentate derived from oxalic acid in order to improve water solubility.
Oxaliplatin is marketed by Sanofi-Aventis under the trademark Eloxatin®.
Contents |
[edit] Mechanism of action and efficacy
The exact mechanism of action of oxaliplatin is not known. In vivo studies showed oxaliplatin has anti-tumor activity against colon carcinoma through its (non-targeted) cytotoxic effects. Median patient survival is approximately 5 months greater compared to the previous standard treatment.
[edit] Precautions
When receiving the drug oxaliplatin it is important to avoid cold food and drinks.
Blood counts will be monitored regularly while on oxaliplatin therapy. During a certain time period after receiving oxaliplatin there is an increased risk of getting infections. Caution should be taken to avoid unnecessary exposure to germs.
Patients with a known previous allergic reaction to chemotherapy drugs should tell their doctors.
Patients who may be pregnant or trying to become pregnant should tell their doctors before receiving oxaliplatin.
Chemotherapy can cause men and women to be sterile or not able to have children.
Patients with existing or previous tingling or numbness in their hands and feet should tell their doctor before receiving oxaliplatin.
Patients should check with their doctors before receiving live virus vaccines while on chemotherapy.
[edit] Side-effects
One of the most common side effects from receiving oxaliplatin is Nausea, vomiting, and/or diarrhea. Patients should be given medicines known as antiemetics before receiving oxaliplatin to help prevent, or decrease this side effect. Diarrhea and mouth sores have also been known to occur. The chance of these increase if the oxaliplatin is given along with the chemotherapy drug fluorouracil.
Oxaliplatin can commonly cause damage to nerves and nervous system tissues. Patients may feel tingling, numbness, and sometimes burning of the fingers and toes. This side effect is common, can be severe, and gets worse in the cold. Neuropathy, (both an acute, reversible sensitivity to cold and numbness in the hands and feet and a chronic, possibly irreversible foot/leg, hand/arm numbness, often with deficits in proprioception) The patient must inform the doctor if any of these symptoms are present. In addition, the patient may experience a tightness or spasm in their throat. The chance that this will happen increases if the patient is exposed to cold food or drinks while receiving oxaliplatin.
Low blood counts, referred to as myelosuppression, are expected due to oxaliplatin. The extent to which the blood counts fall due to oxaliplatin has been minimal. When the white blood cell count is low, this is called neutropenia and patients are at an increased risk of developing a fever and infections. There is a drug called Neupogen (filgrastim) that can be used to increase the white blood cell count.
Platelets are blood cells in the body that allow for the formation of clots. When the platelet count is low, patients are at an increased risk for bruising and bleeding. If the platelet count remains too low a platelet blood transfusion is an option. Low red blood cell counts, referred to as anemia, may also occur due to cisplatin administration. Low red counts make people feel tired and lacking energy. There is a drug called erythropoietin that can be used to increase the red blood cell count.
Oxaliplatin has caused severe allergic reactions known as anaphylaxis. The symptoms include difficulty breathing, drop in blood pressure, sweating, redness of the face, dizziness, headache, and a fast heart beat. This appears to be more common after several treatments with the drug oxaliplatin.
Less common side effects include hair loss (alopecia), fever, rash on hands and feet when given with fluorouracil, and Fatigue. Oxaliplatin rarely causes kidney damage or hearing damage, unlike cisplatin chemotherapy.
In addition, some patients may experience an allergic reaction to platinum-containing drugs.
All side effects a patient experiences should be reported to his or her doctor.
[edit] Recommended Dosages
An oxaliplatin dose can be determined using a mathematical calculation that measures a person's body surface area (BSA). This number is dependent upon a patient's height and weight. The larger the person the greater the body surface area. Body surface area is measured in the units known as square meter (m2). The body surface area is calculated and then multiplied by the drug dosage in milligrams per square meter (mg/m2). This calculates the actual dose a patient is to receive.
Oxaliplatin is a clear colorless solution administered by an infusion into a vein. The infusion time period can vary. It can be given as a one-time dose every three weeks infused over 20 minutes up to six hours. There are multiple doses of oxaliplatin used in clinical trials dependent upon the type of cancer being treated. The doses have ranged from 20 mg per square meter daily for several days to 130 mg per square meter for one day every three weeks. Listed below are example dose recommendations for colorectal cancer and ovarian cancer.
To Treat Metastatic Colorectal Cancer
Oxaliplatin alone has been given at 130 mg per square meter administered into a vein for one day every three weeks. This did not have very good response rates.
Oxaliplatin is also given at a dose of 130 mg per square meter administered into a vein as a two- to six-hour infusion for one day every three weeks in combination with the chemotherapy drug fluorouracil.
To Treat Advanced Ovarian Cancer
Oxaliplatin alone has been given at 59 mg to 130 mg per square meter administered into a vein for one day as a 20-minute or two-hour infusion every three weeks.
Combination treatment of oxaliplatin at a dose of 130mg per square meter administered into a vein as a two-hour infusion every three weeks. The oxaliplatin must immediately follow a two hour-infusion of the chemotherapy drug cisplatin at a dose of 100 mg square meter every three weeks.
[edit] History
Oxaliplatin was discovered in 1976 at Nagoya University in Japan by Professor Yoshinori Kidani, who was granted U.S. Patent 4,169,846 over the drug in 1979. Oxaliplatin was subsequently in-licensed by Debiopharm, a Swiss drug company headquartered in Lausanne and developed as an advanced colorectal cancer treatment. Debio licensed the drug to Sanofi-Aventis in 1994. Eloxatin gained European approval in 1999 and FDA approval in 2004.
[edit] Patent information
Eloxatin is covered by patent numbers 5338874 (Expiry Apr 07,2013), 5420319 (Expiry Aug 08,2016), 5716988 (Expiry Aug 07,2015) and 5290961 (Expiry Jan 12, 2013) (see Electronic Orange Book patent info for Eloxatin).[1] Exclusivity code I-441, which expires on Nov 04, 2007, is for use combination with infusional 5-FU/LV for adjuvant treatment stage III colon cancer patients who have undergone complete resection primary tumor-based on improvement in disease free survival with no demonstrated benefit overall survival after 4 years. Exclusivity code NCE, New Chemical Entity, expires on Aug 09, 2007. [2]
[edit] References
- Graham J, Mushin M, Kirkpatrick P (2004). "Oxaliplatin." (PDF). Nat Rev Drug Discov 3 (1): 11-2. PMID 14756144.
- Eloxatin web site
