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Gemcitabine Mechanism

gemcitabine mechanism

Description

Gemcitabine is the first-line treatment for pancreatic adenocarcinoma, but is increasingly used to treat breast, bladder, and non-small cell lung cancers. Despite such broad use, intrinsic and acquired chemoresistance is common. In general, the underlying mechanisms of chemoresistance are poorly understood. Here, current knowledge of gemcitabine metabolism, mechanisms of action, sensitivity and chemoresistance reported over the past two decades are reviewed; and we also offer new perspectives to improve gemcitabine efficacy with particular reference to the treatment of pancreatic cancer.

Chemotherapy and HER2-Directed Therapy for Metastatic Breast Cancer

Gemcitabine (Gemzar, Eli Lilly, Indianapolis, IN) is a nucleoside analog that replaces cytidine during DNA replication. This process arrests tumor growth, because new nucleosides cannot be attached to the “faulty” nucleoside, resulting in apoptosis. Response rates to gemcitabine in the metastatic setting vary from 14% to 37% in chemotherapy-naive patients to 1% to 30% in patients who have previously received a taxane and/or an anthracycline.

Management of cardiac and pulmonary treatment–related side effects

Gemcitabine (Gemzar) is an antimetabolite that is effective as monotherapy or in combination with other drugs in a variety of solid tumors. Toxicity related to the cardiovascular system is rare. Preclinical and phase I data from 1997 described incidences of ventricular tachycardia in 1.4%, 0.7%, 0.2%, and 0%.160 Three case reports have described atrial fibrillation within 18 to 24 hours of gemcitabine infusion with recurrence following second and/or third subsequent infusions. One patient had paroxysmal atrial fibrillation before treatment, and two patients had advanced lung cancer.

Precautions:

Before starting Gemcitabine treatment, make sure you tell your doctor about any other medications you are taking (including prescription, over-the-counter, vitamins, herbal remedies, etc.).  Do not take aspirin or products containing aspirin unless your doctor specifically permits this. Do not receive any kind of vaccination without your doctor's approval while taking Gemcitabine.

Inform your health care professional if you are pregnant or may be pregnant prior to starting this treatment. Pregnancy category D (Gemcitabine may be hazardous to the fetus.  Women who are pregnant or become pregnant must be advised of the potential hazard to the fetus). For both men and women: Do not conceive a child (get pregnant) while taking Gemcitabine. Barrier methods of contraception, such as condoms, are recommended. Discuss with your doctor when you may safely become pregnant or conceive a child after therapy.

How Gemcitabine Works:

Cancerous tumors are characterized by cell division, which is no longer controlled as it is in normal tissue.   "Normal" cells stop dividing when they come into contact with like cells, a mechanism known as contact inhibition.  Cancerous cells lose this ability.  Cancer cells no longer have the normal checks and balances in place that control and limit cell division.  The process of cell division, whether normal or cancerous cells, is through the cell cycle.  The cell cycle goes from the resting phase, through active growing phases, and then to mitosis (division).

The ability of chemotherapy to kill cancer cells depends on its ability to halt cell division.  Usually, the drugs work by damaging the RNA or DNA that tells the cell how to copy itself in division.  If the cells are unable to divide, they die.  The faster the cells are dividing, the more likely it is that chemotherapy will kill the cells, causing the tumor to shrink.  They also induce cell suicide (self-death or apoptosis).

Chemotherapy drugs that affect cells only when they are dividing are called cell-cycle specific.  Chemotherapy drugs that affect cells when they are at rest are called cell-cycle non-specific.  The scheduling of chemotherapy is set based on the type of cells, rate at which they divide, and the time at which a given drug is likely to be effective.  This is why chemotherapy is typically given in cycles.

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