Crizotinib: Transforming the Treatment Landscape for ALK-Positive Lung Cancer

The field of oncology has witnessed a revolution in recent years, thanks to the advent of targeted therapies that hone in on specific genetic mutations driving tumour growth. One of the earliest and most impactful of these therapies is Crizotinib, a first-in-class ALK inhibitor used to treat non-small cell lung cancer (NSCLC). For patients with ALK-positive mutations, Crizotinib has become a cornerstone in treatment protocols, offering significant survival benefits and improved quality of life.

As lung cancer remains the leading cause of cancer-related death globally, identifying effective treatments is crucial. Crizotinib has emerged as a game-changer, especially for patients who previously had few treatment options. Its use has extended beyond lung cancer into other ALK or ROS1-positive malignancies, opening new avenues for personalised therapy.

In this article, we delve into how Crizotinib works, its role in cancer treatment, its clinical success, and the availability of formulations such as Crizalk 250 MG Tab for patients seeking accessible, high-quality care.

What Is Crizotinib?

Crizotinib is an oral small-molecule tyrosine kinase inhibitor (TKI) that targets three key proteins involved in cancer development:

• ALK (anaplastic lymphoma kinase)

• ROS1 (c-ros oncogene 1)

• MET (hepatocyte growth factor receptor)

Abnormal activity of these genes—due to mutations, rearrangements, or overexpression—leads to uncontrolled cell growth and cancer proliferation. Crizotinib inhibits their activity, effectively blocking the growth signals and halting tumour development.

The drug is FDA-approved and globally recognised for the treatment of ALK-positive metastatic NSCLC and ROS1-positive metastatic NSCLC. By offering a more focused attack on cancer cells than traditional chemotherapy, Crizotinib has redefined the standard of care for certain subtypes of lung cancer.

The Science Behind Crizotinib

ALK and ROS1 are genes that produce proteins involved in cell growth and division. In certain cancers, especially non-small cell lung cancer, these genes can undergo rearrangements—fusing with other genes to create hybrid, cancer-promoting proteins. These fusion proteins act like a stuck accelerator, continuously signalling the cells to divide and multiply.

Crizotinib works by binding to these fusion proteins and blocking their kinase activity, thereby interrupting the cancer-promoting signals. This leads to a reduction in tumour size, slowed disease progression, and, in many cases, a prolonged life expectancy for patients.

What sets Crizotinib apart is its ability to target multiple oncogenic drivers at once, especially ALK and ROS1. Its oral formulation also makes it a convenient option for patients, allowing outpatient treatment without the need for hospital-based infusions.

Who Is Crizotinib For?

Crizotinib is prescribed for adults with:

• ALK-positive metastatic NSCLC

• ROS1-positive metastatic NSCLC

• Certain rare cancers that exhibit ALK or ROS1 gene rearrangements

These mutations are more commonly found in:

• Younger non-smokers or light smokers

• Patients with adenocarcinoma subtype of NSCLC

• Individuals who have never been treated with chemotherapy

Before initiating therapy, oncologists confirm ALK or ROS1 positivity through molecular diagnostic testing, typically via tissue biopsy or liquid biopsy. Identifying these gene rearrangements is crucial to determining a patient’s eligibility for Crizotinib therapy.

Crizotinib in Clinical Trials: A Proven Performer

The approval of Crizotinib was based on impressive clinical data from trials such as PROFILE 1001, PROFILE 1005, and PROFILE 1014. These studies demonstrated significant benefits for patients with ALK-positive NSCLC.

Key Outcomes:

• Overall Response Rate (ORR): Up to 74% in ALK-positive patients

• Progression-Free Survival (PFS): Median of 10.9 months, compared to 7 months with chemotherapy

• Improved Quality of Life: Faster symptom relief, better physical functioning, and emotional well-being

• High Response in ROS1-positive NSCLC: With ORR over 70% in some studies

These findings confirmed that Crizotinib is not only effective but also tolerable, even in patients who had previously received chemotherapy. Its early use in treatment protocols is now standard in guidelines worldwide.

Crizalk 250 MG Tab: Trusted Indian Brand of Crizotinib

One of the most recognised formulations of Crizotinib available in India is Crizalk 250 MG Tab. Manufactured to international standards, Crizalk delivers high-quality, reliable Crizotinib in a convenient once-daily oral tablet.

Each tablet contains 250 mg of Crizotinib and is taken either as monotherapy or in combination with supportive medications. It’s typically prescribed twice a day (total daily dose of 500 mg), with or without food.

Crizalk offers:

• Global trust as one of the earliest branded versions

• Consistent bioavailability and absorption

• Wider availability in Indian cancer centres and pharmacies

• Cost-effective access for patients who may not afford imported alternatives

For many patients in India, Crizalk has become a lifeline, offering the benefits of cutting-edge therapy at a significantly reduced cost compared to its international counterparts.

Side Effects and Management

Crizotinib, like all medications, may cause side effects. However, most patients tolerate it well with proper monitoring and early intervention.

Common side effects include:

• Nausea and vomiting

• Visual disturbances (e.g., light flashes, blurred vision)

• Diarrhoea or constipation

• Edema (swelling of hands or feet)

• Elevated liver enzymes

• Fatigue

• Bradycardia (slow heart rate) in rare cases

Management tips:

• Use antiemetics for nausea

• Adjust diet to manage gastrointestinal symptoms

• Regular liver function tests

• Eye check-ups if visual symptoms persist

• Cardiological evaluation in patients with pre-existing heart disease

Most side effects subside with dose adjustments or temporary treatment interruption. In rare cases of severe toxicity, Crizotinib may be discontinued or replaced with second-generation ALK inhibitors.

Monitoring and Follow-Up

Patients on Crizotinib should undergo regular follow-ups, including:

• CT scans to monitor tumour response

• Liver function tests (LFTs)

• Complete blood counts (CBCs)

• ECG if cardiac symptoms arise

• Eye evaluations in cases of visual disturbances

Early detection of adverse effects can significantly reduce complications and improve treatment outcomes.

Resistance to Crizotinib and Next Steps

While Crizotinib is effective, some patients eventually develop resistance to the drug. This can happen through:

• Additional mutations in the ALK gene

• Activation of alternative signalling pathways

• Inadequate penetration into the central nervous system (brain)

For these patients, second- and third-generation ALK inhibitors such as Alectinib, Brigatinib, or Lorlatinib may be used. These therapies are designed to overcome resistance and offer better brain penetration.

Nonetheless, Crizotinib remains a valuable first-line treatment, especially in regions where advanced drugs are not easily available or affordable.

Importance of Genetic Testing in NSCLC

The key to successfully using Crizotinib lies in accurate and timely genomic profiling. Identifying ALK or ROS1 rearrangements allows oncologists to personalise therapy and avoid the trial-and-error approach of traditional treatment.

Patients newly diagnosed with NSCLC, especially those who are young, non-smokers, or have adenocarcinoma, should undergo testing for:

• ALK rearrangement

• ROS1 rearrangement

• EGFR mutation

• KRAS and BRAF mutations

• PD-L1 expression (for immunotherapy eligibility)

Comprehensive profiling ensures that the right therapy is chosen from the outset, increasing the chances of long-term remission.

Global and Indian Perspective

Crizotinib has become a global standard of care in the treatment of ALK-positive lung cancer. In India, its availability in the form of brands like Crizalk has expanded access to precision medicine.

Government initiatives, insurance coverage, and NGOs are increasingly supporting the inclusion of molecular testing and targeted therapy in standard cancer care protocols.

Patients now have a realistic path toward recovery, even with metastatic lung cancer—once considered a terminal diagnosis.

Final Thoughts

Crizotinib is a landmark therapy in the era of personalised medicine. Its effectiveness in targeting ALK and ROS1 gene rearrangements has transformed the prognosis for many lung cancer patients worldwide.

Formulations like Crizalk 250 MG Tab ensure that patients in India have access to this powerful therapy at an affordable price without compromising on quality.

If you or a loved one has been diagnosed with advanced NSCLC, speak to your oncologist about molecular testing. Finding out whether your tumour has an ALK or ROS1 fusion could be the key to accessing life-changing treatments like Crizotinib—and living a longer, healthier life.