Henplatin

Oxaliplatin has a molecular formula of C₈H₁₄N₂O₄Pt.

Pharmacology: Oxaliplatin has toxicities commonly seen in platinum compounds and exhibits category-specific cardiac toxicity. No renal toxicity of cisplatin or bone marrow toxicity was observed. A relatively new platinum compound, it acts on DNA by producing alkylation conjugate and forms inter- and intrastrand Pt-DNA crosslinks, consequently, inhibits synthesis and replication of DNA. It rapidly combines with DNA, at most 15 min. Combination of cisplatin and DNA is divided into phases, which includes a delay phase after 48 hrs [In vivo, an hr after administration, determine presence of conjugate of adduct of leukocyte. DNA synthesis during replication, DNA separation after replication, synthesis of RNA and cell protein is inhibited]. It is effective for some cell lines resistant to cisplatin.
Pharmacokinetics: After 2 hrs of continuous infusion at a dose of 130 mg/m², the total plasma platinum reaches peak value of 5.1±0.8 mg/mL/hr, the stimulant AUC is 189±45 mg/mL/hr. After infusion, 50% of platinum combine with erythrocyte and the other 50% of platinum is present in plasma. 25% of plasma platinum is in free form; the other 75% plasma platinum combine with protein. Protein-combined platinum increases gradually and reaches stable level of 95%, 5 days after administration. The clearance is divided into 2 phases; the t_½ of clearance phase is about 40 hrs. Up to 50% of platinum is eliminated via urine within 48 hrs (55% of platinum is cleared in 6 days). Fecal excretion is limited (only 5% of platinum is eliminated through feces in 11 days). In patients with renal failure, only clearance of filterable platinum decreases and thus no dosage adjustment is necessary.
At 22nd day after administration, the level of erythrocyte-bonded platinum is 56% of plasma peak value, while at the same time, most plasma platinum have been eliminated. During latter administration periods, no significant increase in the levels of total plasma or plasma platinum was observed while erythrocyte-bonded platinum cumulative evidence.

Treatment of metastatic colorectal cancer in combination with fluorouracil and folinic acid. As adjuvant treatment of colon cancer after resection of the primary tumor.

In monotherapy or combination therapy, the suggested dosage is 130 mg/m² of body surface area, add into 250-500 mL 5% of glucose solution and infuse 2-6 hrs. If no major toxicity appears, repeat every 3 weeks. Adjust dosage according to safety, particularly safety of neurology.
Henplatin may be used singly or in combination with fluorouracil.

No antidote is available. When overdosage occurs, adverse reactions will aggravate, hematologic monitoring should be performed and take expectant treatment according to its toxicity.

Patients with a history of known allergy to platinum derivatives.
Use in pregnancy & lactation: Henplatin may cause harm and damage to the fetus and should not therefore be given to pregnant women. No study is performed about whether the product is excreted in human milk; Henplatin should not be administered during lactation.

Henplatin should be administered under the supervision of a qualified physician with experience in the use of cancer chemotherapeutic agents. Caution should be taken especially in combination therapy with potential neurotoxicity. CNS symptoms should be monitored strictly.
Henplatin is associated with digestive system toxicity, eg, nausea, vomiting, preventive and therapeutic antivomit medicine should be used.
When blood toxicity occurs (leukocyte <2000/mm³ or blood platelet <50,000/mm³), the next cycle should be delayed until recovery.
The blood amount and classification should be finished before each period of treatment and the neurologic symptoms should be checked before and after the treatment.

Henplatin may cause harm and damage to the fetus and should not therefore be given to pregnant women. No study is performed about whether the product is excreted in human milk; Henplatin should not be administered during lactation.

Hemopoietic System: It exhibits a certain extent of hematologic toxicity. Monotherapy may cause the following adverse reactions: Anemia, leukocytosis, granulocytopenia, thrombopenia, sometimes grade 3 and 4. In combination with 5-fluorouracil, the incidence of hematology toxicity events increases, including neutrophilic granulocytopenia and thrombocytopenia, etc.
Digestive System: Single administration of the agent may cause nausea, vomiting and diarrhea, which is sometimes very severe. When in combination with 5-fluorouracil, the adverse reactions increase significantly. Preventive or therapeutic antiemetic is recommended.
Nervous System: Peripheral and sensory neuropathy that is characterized by peripheral neuritis. These symptoms may be accompanied by convulsion and sensory disturbance around the mouth, at upper respiratory tract and upper digestive tract; even clinical conditions similar to laryngeal spasm, which may recover and without sequelae. These symptoms may often be severe. Abnormal sensation may relieve during resting period of treatment and when cumulative dose is over 800 mg/m² (6 cycles), permanent abnormal sensation or dysfunction may be caused. Several months after termination of treatment, neurotoxicity of over 3/4 patients is relieved and disappears. When reversible abnormal sensation occurs, it is not necessary to adjust the dosage of next administration. Dosage adjustment should be based on the duration and severity of observed neurotoxicity. If abnormal sensation occurs and continues during 2 periods of treatment and aching abnormal sensation and/or dysfunction begins to occur, the dose should be decreased by 25% (or 100 mg/m²). After symptoms partly or completely disappear, there is still possibility of administering the drug (full or decreased dose) depending on the physician's judgement.

Because of the incompatibility of oxaliplatin to sodium chloride and alkaline solution (eg, 5-fluorouracil), it should not be mixed with these agents or administered through same vein at the same time. In vitro study shows that no significant change occurs in protein-binding in the presence of erythromycin, salicylate, paclitaxel and sodium valproate. In vivo, animal and human study shows in combination with 5-fluorouracil, oxaliplatin exhibits synergic action.

Store at room temperatures not exceeding 25°C.

Cytotoxic Chemotherapy

L01XA03 - oxaliplatin ; Belongs to the class of platinum-containing antineoplastic agents. Used in the treatment of cancer.

Rx