This drug, also called vinorelbine tartrate, belongs to the drug class called vinca alkaloids. There are four drugs within this classification approved for clinical use in the United States: vinblastine, vincristine, vindesine and vinorelbine. All of these drugs are produced using compounds found in the pink periwinkle plant or Vinca rosea as it is known in Latin. Vinorelbine is a semi-synthetic derivative of vinblastine.
Vinorelbine is composed of two structurally similar subunits, a vindoline ring and catharanthine ring, which are joined together by chemical bonds. Vinorelbine differs from the other drugs in its class because it is modified at the catharanthine ring instead of the vindoline. The 9-membered ring of catharanthine, which contains a hydroxyl, a compound containing an oxygen atom that shares a pair of electrons with a hydrogen atom, is replaced with an 8-membered ring. It is believed that this modification is the reason for vinorelbine’s lower toxicity level than the other drugs in its class. The lower toxicity makes it a good choice for treatment of elderly patients and others who may not have the physical strength to withstand treatment with more toxic drugs.
It also differs from the other drugs in its class in that it can be administered either intravenously or orally. Taking the drug orally reduces some of the side effects and does not, for the most part, affect the efficacy of the drug. However, this may not always be the case.
The ELVIS Trial
In a study titled The ELVIS Trial: A Phase III Study of Single-Agent Vinorelbine as First-Line Treatment in Elderly Patients with Advanced Non-Small Cell Lung Cancer, published in the February 2001 edition of The Oncologist, study participants were given intravenous vinorelbine. The researchers found that among the 71 patients evaluated, a complete response was seen in one case and partial responses in 14. Thirty percent of patients had stable disease and the disease progressed in 42 percent. However, in a study titled Oral vinorelbine given as monotherapy to advanced, elderly NSCLC patients: a multicentre phase II trial, published online August 28, 2004 in the European Journal of Cancer; researchers found that among the 32 patients evaluated, there were six partial responses and 25 stable disease responses. But the researchers did add that, “Oral vinorelbine appears to be a reasonable alternative to i.v. vinorelbine, both in terms of activity and tolerability, in advanced, elderly NSCLC (non-small cell lung cancer) patients.”.
Vinorelbine doesn’t work by altering DNA structure like other treatments for mesothelioma. Instead, it interferes with cell division.
During the cell division process known as mitosis, the cell’s DNA is copied so that there are two exact sets of chromosomes that will be used to make two new cells. This separation of the two sets of chromosomes involves spindle fibers, which are constructed with microtubules. It is the job of the microtubules to attach themselves to the chromosomes and pull one copy to one side of the dividing cell, and one copy to the other side. The microtubules are formed by long chains of a certain type of proteins called tubulins. Vinorelbine binds itself to these tubulins, which stops the microtubules from being made. Without functional microtubules, the cell cannot divide and will eventually die.
While it may be lower in toxicity, vinorelbine does have side effects. These include a reduction in the number of platelets and red blood cells, resulting in anemia. It can also cause granulocytopenia, a severe decrease in the number of white blood cells that fight infection. It is recommended that granulocyte (white blood cell) counts should be at least 1,000 cells/mm3 (per cubic millimeter) before vinorelbine is administered. The dosage will be adjusted when necessary depending on the blood counts taken on each treatment day. In addition, patients experience shortness of breath, constipation or diarrhea, hair loss and numbness in the hands or feet. Pregnant women should not take the drug because it has been known to cause birth defects.
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