crizotinib

Crizotinib, also referred to as Xalkori, is a targeted cancer medication utilized in the treatment of advanced non-small cell lung cancer (NSCLC). This drug specifically targets NSCLC cases that exhibit alterations in either the anaplastic lymphoma kinase (ALK) gene or the ROS1 gene.

The survival probability at 4 years was 56.6% (95% CI, 48.3% to 64.1%) for patients treated with crizotinib and 49.1% (95% CI, 40.5% to 57.1%) for patients treated with chemotherapy. After adjusting for crossover, there was a significant improvement in overall survival favoring crizotinib (hazard ratio, 0.346; 95% bootstrap CI, 0.081 to 0.718).

The median progression-free survival (PFS) and overall survival (OS) after starting crizotinib treatment were 14.4 months (95% CI: 12.4-16.4) and 53.4 months (95% CI: 33.7-73.1), respectively.

The most frequently observed toxicities are visual, gastrointestinal, and constitutional disorders. These are followed by cardiovascular, respiratory, and minor neurologic dysfunctions. More worrisome occurrences include severe hepatotoxicity, interstitial lung disease/pneumonitis, bradycardia, and QT prolongation.

The results showed that crizotinib had a significantly longer progression-free survival compared to chemotherapy, with a median of 10.9 months for crizotinib and 7.0 months for chemotherapy. The hazard ratio for progression or death with crizotinib was 0.45, indicating a lower risk compared to chemotherapy. The 95% confidence interval ranged from 0.35 to 0.60, further supporting the superiority of crizotinib. Additionally, the objective response rates were 74% for crizotinib and 45% for chemotherapy, demonstrating a higher rate of response with crizotinib. These findings were statistically significant with a p-value of less than 0.001.

The trial end point values for crizotinib were not significantly different from the real-world evidence. Therefore, it can be concluded that crizotinib and entrectinib have similar effectiveness in treating ROS1-positive non-small-cell lung cancer.

The drug concentration of crizotinib in the plasma was found to be 237 ng/mL (0.53 ?¼mol/L), while in the CSF it was only 0.616 ng/mL (0.0014 ?¼mol/L), resulting in a CSF-to-plasma ratio of 0.0026. This indicates that the drug has limited ability to penetrate the blood-brain barrier.

Compared to standard second-line chemotherapy, crizotinib treatment demonstrated a notable increase in progression-free survival, response rates, symptom reduction, and overall improvement in global quality of life.

The median progression-free survival (PFS) and overall survival (OS) after starting crizotinib treatment were 14.4 months (95% CI: 12.4-16.4) and 53.4 months (95% CI: 33.7-73.1), respectively.

The study included 82 ALK-positive patients who received crizotinib. The median overall survival from the start of crizotinib treatment has not been determined, with a 95% confidence interval ranging from 17 months to not reached. The 1-year overall survival rate was 74%, with a 95% confidence interval of 63-82. The 2-year overall survival rate was 54%, with a 95% confidence interval of 40-66.

According to a report published in the Journal of Pharmacy and Pharmacology, doxorubicin is considered to be one of the most powerful chemotherapeutic drugs approved by the Food and Drug Administration. However, the article highlights that its major drawback is its harmful impact on healthy cells in the body.

Doxorubicin is widely regarded as one of the most potent chemotherapy drugs ever developed for breast cancer. Its effectiveness extends to all stages of the cancer cell’s life cycle, making it a valuable treatment option for various types of cancer, beyond just breast cancer.

Drug Class: Crizotinib, Opdivo (nivolumab), Retevmo (selpercatinib)
Reviews: 7 reviews for Crizotinib, 81 reviews for Opdivo (nivolumab), 4 reviews for Retevmo (selpercatinib)
Side Effects: Multikinase inhibitors, Anti-PD-1 and PD-L1 monoclonal antibodies (immune checkpoint inhibitors), Multikinase inhibitors

Immunotherapy side effects tend to decrease in severity after the initial treatment, while chemotherapy side effects typically dissipate once treatment is finished. A benefit of chemotherapy is that its side effects manifest at the start of treatment and largely disappear once treatment is discontinued.

Immunotherapy has demonstrated effectiveness in treating various types of cancers, such as lung cancer, head and neck cancer, bladder cancer, kidney cancer, and Hodgkin lymphoma, among others.

Crizotinib was found to effectively prevent disease relapse during treatment and improve event-free survival (EFS) and overall survival (OS) rates, comparable to previous chemotherapy regimens. However, there was an unexpected rise in the occurrence of thromboembolic events.

Immunotherapy offers the potential for long-term protection against cancer by harnessing the immune system’s ability to recognize and remember cancer cells, in contrast to the temporary effects of chemotherapy.

In a clinical trial involving 26 patients with ALK+ Anaplastic Large Cell Lymphoma (ALCL), Xalkori treatment resulted in a positive response in 88% of patients. Among the 23 patients who responded, 22% maintained their response for up to 12 months after beginning treatment.

Immunotherapy can enhance the effectiveness of other cancer treatments, such as chemotherapy, by minimizing side effects. Unlike other therapies that affect all cells in the body, immunotherapy specifically targets the immune system, resulting in fewer adverse reactions.

Crizotinib inhibits receptor tyrosine kinases such as ALK, Hepatocyte Growth Factor Receptor (HGFR, c-Met), and Recepteur d’Origine Nantais (RON). The ALK gene can be affected by translocations, leading to the production of oncogenic fusion proteins.

During clinical trials, it was found that visual disturbances, such as photopsia, blurred vision, and vitreous floaters, were the most common adverse events experienced by patients taking crizotinib. These effects were observed in approximately 40-60% of patients, with most occurrences happening within the first week of starting treatment with crizotinib.

The occurrence of alopecia due to crizotinib is 8%, with a range of 4.9% to 13.2%. There is limited data available on the rate of alopecia caused by other ALK inhibitors. However, there has been a reported case of diffuse alopecia in a patient who had previously received crizotinib but did not experience alopecia, after being treated with alectinib.

Crizotinib is priced at $130.00 per tablet. Pemetrexed is priced at $0.21 per mg according to the ODB Formulary. Docetaxel is priced at $0.27 per mg according to the CCO.

Crizotinib is a medication that inhibits tyrosine kinase receptors, specifically targeting anaplastic lymphoma kinase (ALK), hepatocyte growth factor receptor (HGFR, c-MET), ROS1 (c-ros), and Recepteur d’Origine Nantais (RON).

If you experience dizziness, tiredness, blurred vision, or any other vision problems such as flashes of lights, floaters, or sensitivity to light while taking this medicine, it is important to avoid driving or engaging in any activities that could be dangerous until you understand how this medicine affects you.

Crizotinib is prescribed for the treatment of inflammatory myofibroblastic tumors (IMTs), a specific type of cancer that affects mucosal tissues in the abdominal region. This medication is used when surgical intervention is not possible or when the tumor has not responded to previous treatment or has recurred. IMTs can occur in various organs such as the lungs, bladder, stomach, uterus, liver, or intestines.

Crizotinib, an ALK inhibitor, is being studied as a potential treatment for neuroblastoma patients with somatic activating mutations in the tyrosine kinase domain of the ALK gene. Overall, Crizotinib is well tolerated and only a small number of side effects have been observed in patients receiving this treatment.

Crizotinib is a small molecule TKI that can be taken orally and targets the ALK, c-MET, and ROS1. It works by competitively binding to the ATP-binding pocket of these kinases, inhibiting ALK phosphorylation and downstream signal transduction. This ultimately leads to G1/S phase cell cycle arrest and apoptosis.

Crizotinib inhibits the activation of the ALK enzyme by binding to its ATP binding site, preventing the binding of ATP and subsequent autophosphorylation.

Crizotinib is usually well tolerated, but common side effects include visual disturbances, gastrointestinal issues, and peripheral edema. It has also been observed to cause decreases in heart rate, with sinus bradycardia listed as a warning in the product information.

Xalkori oral treatment demonstrated efficacy in slowing or reducing the growth of lung cancer tumors for a duration of 10.9 months in ALK-positive (ALK+) non-small cell lung cancer (NSCLC) patients and 18.3 months in ROS1+ NSCLC patients.