define equipoise

Oxaliplatin is an antineoplastic drug belonging to a new class of platinum derivatives in which the platinum atom is complexed with oxalate and 1,2-diaminocyclohexane. Oxaliplatin exhibits a wide spectrum of cytotoxic effects. It also exhibits activity in vitro and in vivo in different tumor models resistant to cisplatin. In combination with fluorouracil synergistic cytotoxic effects observed.
Studying the mechanism define equipoise of action of oxaliplatin supports the hypothesis that biotransformed, aqueous oxaliplatin derivatives interact with DNA through the formation of bridges between vnutrityazhevyh and inhibit DNA synthesis, which leads to cytotoxicity and antitumoral effect.
In vivo subject to significant metabolism and is not detected in the plasma ultrafiltrate to end 2 hours after administration at a dose of 130 mg / m ², while 15% of the injected substance in the blood, while the remaining 85% are rapidly distributed to the tissues or the kidneys. Excreted by the kidneys within 48 hours; Day 5 to about 54% of the dose is found in the urine and less than 3% – in the feces. A significant decrease in clearance from 17.55 to 9.95 l / h was observed in chronic renal failure, along with a decrease in distribution volume from 330 to 241 l.
When administered oxaliplatin every 2 weeks in a dose of 85 mg / m ² body surface or every three weeks at a dose of 130 mg / m surface accumulation of platinum in body ultrafiltrate of blood plasma is not observed, and an equilibrium state is reached after the first course of therapy.

Indications

• Adjuvant therapy for colorectal cancer III step (C at Duke) after radical resection of primary tumor in combination with fluorouracil / folinate calcium.
• Disseminated Colorectal cancer (as monotherapy or combination therapy in combination with fluoropyrimidines).
• Ovarian cancer (as therapy 2 th line).

Contraindications

– Hypersensitivity define equipoise to oxaliplatin or the other ingredients.
– Myelosuppression (neutrophil count <2000 / L and / or platelet count <100,000 / l) prior to the first course of treatment.
– Peripheral sensory neuropathy with functional impairment prior to first course of treatment.
– Severe violation renal function (creatinine clearance <30 ml / min)
– Pregnancy and lactation, children’s age.

Carefully

In allergic reactions to platinum compounds in the history of lactase deficiency, lactose intolerance, glkzhozo-galactose malabsorption.

Dosing and Administration

Oxaliplatin is used only in the adult. The drug is administered intravenously in a 2-6 hour infusion. Overhydration when using oxaliplatin is not required.
If oxaliplatin is used in combination with fluorouracil infusion of oxaliplatin should be preceded by the introduction of fluorouracil.
Adjuvant therapy for colorectal cancer – by 85 mg / m ² 1 every 2 weeks for 12 cycles (6 months).
Disseminated Colorectal Cancer : at 85 mg / m ² 1 every 2 weeks as monotherapy or in combination with fluorouracil.
ovarian Cancer: at 85 mg / m ² 1 every 2 weeks as monotherapy or in combination with other chemotherapeutic drugs.
Repeated administration of oxaliplatin produced only when the number of neutrophils> 1500 / l and platelets> 50,000 / microliter.

Recommendations for dose adjustment, and mode of administration of oxaliplatin.
In the case of hematological disorders (neutrophil count <1500 / L and / or platelet counts <50,000 / l) the appointment of the next course should be deferred until recovery laboratory parameters.
With the development of diarrhea grade 4 toxicity (WHO scale) Grade 3-4 neutropenia (neutrophil count <1000 / mm), grade 3-4 thrombocytopenia (platelet count <50,000 / ml) dose of oxaliplatin in subsequent administration should be reduced from 85 mg / m ² to 65 mg / m ², in addition to usual dose reduction fluorouracil in case of combination use.
Patients who during infusion or within a few hours after a 2-hour infusion developed acute laryngotracheal pharyngeal dysesthesia, following infusion of oxaliplatin should be performed within 6 hours.
Recommendations oxaliplatin dose adjustment the development of neurotoxicity:
– the symptoms of neurotoxicity, causing pain, lasting more than 7 days or if paresthesia without functional disorders, persisting until the next cycle, the subsequent dose define equipoise of oxaliplatin should be reduced by 25%.
– if paresthesia with functional impairment, persisting until the next cycle, oxaliplatin should be abolished;
– a decrease in the symptoms of neurotoxicity after the abolition of oxaliplatin can consider resuming treatment.
with the development of stomatitis and / or mucositis second and a degree of toxicity, oxaliplatin treatment should be suspended until their relief or reduction of the manifestations toxicity of 1 degree.

Patients with renal insufficiency . Data on the use of the drug in patients with severe renal impairment is not. Due to limited data on safety and tolerability in patients with moderate renal impairment, before use of oxaliplatin should be related to the risk and the benefit for the patient. Treatment in these patients may be initiated at the recommended dose under close monitoring of renal function. Mild renal dysfunction oxaliplatin dosage adjustment is required. Patients with impairment of liver function . Changing the dose in patients with slight or moderate form of liver disease is not required. Data on the use of oxaliplatin in patients with severe hepatic impairment is not. Elderly patients . The safety profile of oxaliplatin as a monotherapy or when combined with fluorouracil in patients over 65 years of age is similar to that observed in patients up to 65 years.

Instructions for the preparation of the drug solution

In the preparation and administration of oxaliplatin can not use the needle and other equipment containing aluminum. Do not dissolve and dilute 0.9% sodium chloride solution and do not mix with other salt (alkaline) solutions or solutions containing chlorides. Use water to dissolve the freeze-dried product define equipoise for injection or 5% dextrose solution. Thus in a bottle with 50 mg of oxaliplatin added to 10 ml of solvent and the vial with 100 mg -. 20 ml of a solvent to form a solution at a concentration of 5 mg / ml immediately after dissolving the lyophilizate should proceed to the preparation of a solution for infusion.Dissolved for preparation of infusion solution oxaliplatin was diluted in 250-500 ml 5% dextrose solution to obtain a concentration of at least 0.2 mg / ml. The solution for infusion is recommended to be used immediately after preparation. The infusion solution is stable for 24 hours at room temperature (not above 25 ° C). The solution to the sediment deposition signs must be destroyed. Use only clear solution.The solution of oxaliplatin should not be mixed in a single same infusion system with other drugs particularly with fluorouracil and calcium folinate. The drug should not be administered undiluted.

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