克里唑蒂尼(Xalkori)

【Function and Indications】
Crizotinib (Xalkori) is the first new drug approved by the US FDA for the treatment of lung cancer in 6 years. It is used to treat locally advanced or metastatic non-small cell lung cancer (NSCLC) that is positive for anaplastic lymphoma kinase (ALK).

【Model and Specifications】
250 mg and 200 mg, 60 tablets.

【Usage and Dosage】
Take twice a day, 1 tablet each time, before or after meals.

Depending on individual safety and drug resistance, the dose may need to be reduced to once a day, 1 tablet each time.

【Clinical Research】
On August 26, 2011, the US Food and Drug Administration (FDA) approved crizotinib (Xalkori) for the treatment of advanced (locally advanced or metastatic) non-small cell lung cancer (NSCLC) with abnormal anaplastic lymphoma kinase (ALK) gene expression. The clinical treatment plan of Xalkori is a single drug. The dosage form of this product is pills, and patients take it twice a day.
Xalkori was approved in conjunction with its genetic test, the first genetic test called the Vysis ALK Break Apart FISH Probe Kit, which helps diagnose whether a patient has an ALK gene abnormality. Xalkori is the second targeted therapy approved by the FDA this year.
Two multicenter, single-arm trials involving 225 patients with advanced ALK-positive NSCLC demonstrated the safety and efficacy of Xalkori. Before patients were enrolled in the trials, lung tumor tissue samples were collected to detect whether the ALK gene was abnormal. The trials evaluated the objective response rate of treatment by the proportion of patients who experienced complete or partial shrinkage of their tumors. Most of the patients in the trials had previously received chemotherapy. The objective response rate in the first trial was 50%, with a median response time of 42 weeks; the objective response rate in the second trial was 61%, with a median response time of 48 weeks.
The most common side effects observed in the Xalkori treatment group included visual impairment, nausea, diarrhea, vomiting, swelling (edema), and constipation. Visual disturbances include visual impairment, astigmatism, blurred vision, floaters, diplopia, light sensitivity, and visual field loss. Life-threatening lung tissue inflammation (pneumonitis) has been associated with the use of XALKORI. Patients who have been treated for pneumonitis should not be treated with XALKORI. Pregnant women are contraindicated to use this drug.

[Precautions]
(1) Pneumonitis: Severe, including fatal, treatment-related pneumonitis has been observed. Monitor patients for pulmonary symptoms indicative of pneumonitis. Permanently discontinue in patients diagnosed with treatment-related pneumonitis.
(2) Liver laboratory abnormalities: Concurrent elevations of ALT and total bilirubin have occurred. Monitor monthly and more frequently as clinically indicated for patients with Grade 2-4 elevations. When indicated, temporarily withhold, reduce dose, or permanently discontinue XALKORI.
(3) QT interval prolongation: Patients with a history or predisposition to QTc prolongation, or taking medications known to prolong the QT interval, should consider monitoring ECGs and electrolytes regularly.
(4) ALK testing: Patients selected for treatment with ALKORI should be tested for ALK-positive NSCLC using an FDA-approved test that is indicated for this purpose.

(5) Pregnancy: XALKOR may cause fetal harm when administered to pregnant women.

[Adverse Reactions and Contraindications]
The most common adverse reactions (≥25%) are visual impairment, nausea, diarrhea, vomiting, edema, and constipation.

[Contraindications]
Crizotinib (Xalkori) is contraindicated in pregnant women.

[Use in Pregnant Women]
Crizotinib (Xalkori) is contraindicated in pregnant women.

[Drug Interactions]
(1) CYP3A Inhibitors: Avoid concomitant use of XALKORI with strong CYP3A inhibitors.

(2) CYP3A Inducers: Avoid concomitant use of XALKORI with strong CYP3A inducers.

(3) CYP3A Substrates: Dose reduction may be required for coadministered drugs that are primarily metabolized by CYP3A. Avoid concomitant use of XALKORI with CYP3A substrates with a narrow therapeutic index.

【Storage】
Store at room temperature away from light.

【Manufacturer】
Pfizer Pharmaceuticals, Inc.