Crizotinib- This is a drug approved by the FDA in 2011 for treatment of lung cancer. Some studies have shown that administration of Crizotinib for treatment of lung cancer has caused kidney injury in individuals.1 In this article, we will discuss about how does this drug work, its potential side effects and how does it affect the kidneys resulting in kidney injury. In this article, we will also discuss a case study, which virtually proves Crizotinib as being responsible for acute kidney injury.
What Is Crizotinib and How Does It Work?
- Crizotinib is basically used for treatment of advanced stage non-small cell lung cancer, which have certain mutation in ALK gene.2
- It is also being researched for use in other forms of cancers as well.
- Crizotinib is also known as kinase inhibitor.
- Kinase is a type of protein near the surface of cells, which transmit signals to the control center of the cells located within cellular plasma.
- Mutation of the ALK gene results in creation of a kinase, which makes the cells grow and divide uncontrollably.
- Kinase is a protein molecule that lies near the surface of cell, which transmits signals to the control center of the cell.
- Control center is located within cellular plasma.
- Crizotinib blocks the mutated form of ALK kinase and prevents multiplication of cells and cancer growth.
- Studies show that only a very small part of non-small cell lung cancers have mutated ALK genes; therefore, before starting Crizotinib the physician will look into the cancer cells to look for the mutated ALK gene.
What Are The Side Effects Of Crizotinib or Kinase Inhibitor?
The Side Effect Profile of Crizotinib or Kinase Inhibitor Is Divided Into Three Categories as Follows-
- Less common
Common Side Effects of Crizotinib or Kinase Inhibitor
- Visual disturbance
- Swelling of the extremities as well as the facial areas
- Feeling fatigued
- Appetite loss
Less Common Side Effects of Crizotinib or Kinase Inhibitor
Rare Side Effects of Crizotinib or Kinase Inhibitor
- Changes in rhythm of the heart
- Swelling of lungs
- Renal cysts
- Depressed platelet counts
- Death as a result of severe liver damage or a clot in the lungs
How Does Crizotinib or Kinase Inhibitor Affect The Kidneys?
- Metabolism- Liver metabolizes Crizotinib or Kinase Inhibitor and the kidneys excrete some of the Crizotinib.
- Excretion- Crizotinib or Kinase Inhibitor causes direct effects on kidney tubules, but the microscopic effects is yet not studied or published.
- Kidney Malfunction- Kidney dysfunction causes less excretion of Crizotinib, which results in more quantity of the drug remaining in the body. Relatively larger quantity of active drug causes severe side effects in few patients.3
What Do The Studies Say About The Relation Of Crizotinib or Kinase Inhibitor with the Kidneys?
- Colorado Study- A study done at the University of Colorado Cancer Center shows that use of Crizotinib or Kinase Inhibitor for treatment of non-small cell lung cancer with mutated ALK gene reduces kidney function when it was assessed by the most common clinical methods. Whether this is a true reflection of the relationship between Crizotinib and the kidneys is still subject to ongoing research.
- Renal Function Test- It has also been shown that the kidney function normalized in almost every case after Crizotinib was stopped, but since patients may be on Crizotinib chronically for years researchers are of the belief that additional renal function tests need to be done to find out about the true relationship between Crizotinib and the renal function.
Kidney Toxicity: Crizotinib or Kinase Inhibitor Causing Kidney Injury
This is a case of an individual with advanced non-small-cell lung cancer who was treated with standard treatments of cisplatin, bevacizumab and chemotherapy, but the cancer was not able to be controlled.4 Upon evaluating the cancer cell ALK gene mutation was identified. Crizotinib was then started on this individual. When the treatment with Crizotinib started the renal function of the individual was normal but with the administration of Crizotinib there were two occasions where the serum creatinine level of the individual was found to rise significantly along with macroscopic hematuria. At that time, a renal biopsy was performed identifying acute tubular necrosis, which pointed to a recent renal insult or injury. These renal injuries were extremely closely related to the administration of Crizotinib, which potentially verifies the role of Crizotinib in Acute Kidney Injury.
1. Ceritinib in ALK-rearranged non-small-cell lung cancer.
Shaw AT1, Kim DW, Mehra R, Tan DS, Felip E, Chow LQ, Camidge DR, Vansteenkiste J, Sharma S, De Pas T, Riely GJ, Solomon BJ, Wolf J, Thomas M, Schuler M, Liu G, Santoro A, Lau YY,
Goldwasser M, Boral AL, Engelman JA.
N Engl J Med. 2014 Mar 27;370(13):1189-97.
2. Protein kinase inhibitors to treat non-small-cell lung cancer.
Minuti G1, D’Incecco A, Landi L, Cappuzzo F.
Expert Opin Pharmacother. 2014 Apr 19.
3. Crizotinib and renal insufficiency: A case report and review of the literature.
Martín Martorell P1, Huerta Alvaro M2, Solís Salguero MA3, Insa Molla A2.
Lung Cancer. 2014 Mar 12. pii: S0169-5002(14)00122-6.
4. Acute kidney injury following crizotinib administration for non-small-cell lung carcinoma.
Gastaud L1, Ambrosetti D, Otto J, Marquette CH, Coutts M, Hofman P, Esnault V, Favre G.
Lung Cancer. 2013 Nov;82(2):362-4.