Gemcitabine is a nucleoside analog or look alike, also called an antimetabolite, used as a chemotherapeutic drug. It is produced by Eli Lily and Company and marketed under the name Gemzar. Nucleosides are molecules in the body that are the building blocks for the bases that make up DNA and RNA. These are bases that are linked to sugar molecules that can have a phosphate group added by enzymes called kinases in a cell.
Chemically, gemcitabine is very similar to deoxycytidine, where the hydrogen at the 2′ carbon position in deoxycytidine is replaced with fluorines to make gemcitabine. Gemcitabine is a pyridimine type of nucleoside that replaces deoxycytidine, the normal building block of cytidine. These imitation cytidine molecules containing gemcitabine are used as the “C” bases during DNA replication to make new DNA. Once these “look alike” bases are inserted, the growing tumor cells arrest their growth since new nucleosides cannot be attached to this “look alike”. Cells that succumb to this trick enter into what is called programmed cell death or apoptosis, the way that cells in the body are killed when there is something wrong with them. This way cancer cells die rapidly rather than growing rapidly. Unfortunately, this does not target only cancer cells, and therefore kills all cells in the body undergoing DNA replication.
Gemcitabine is used in the treatment of mesothelioma, non-small cell lung cancer, pancreatic cancer, bladder cancer, esophageal cancer and breast cancer. Along with cisplatin, gemcitabine is used as a first-line treatment for metastatic or locally advanced non-small cell lung cancer that cannot be removed by surgery. For pancreatic cancer, it is used alone as a first-line treatment if the cancer is metastatic or locally advanced and cannot be surgically removed or for pancreatic adenocarcinomas. Gemcitabine along with another chemotherapy drug called paclitaxel is an FDA approved treatment for metastatic breast cancer after the patient has received another drug called anthracycline or was unable to receive anthracycline for medical reasons. Gemcitabine is used along with the chemotherapeutic agent carboplatin to treat women whose ovarian cancer returned six months after treatment with a platinum-based chemotherapy.
It has also been used successfully in the treatment of advanced pancreatic cancer, rather than just with earlier stages of pancreatic cancer and for these patients it was found in clinical studies to be less harsh than other types of chemotherapeutic agents used for advanced pancreatic cancer. In combination with cisplatin, gemcitabine has been shown to be a more effective chemotherapy drug that has lower toxicity in the treatment of bladder cancer with stage four metastases when compared to the chemotherapy agent previously used for this type of cancer.
Gemcitabine treatment is given in a doctor’s office, clinic or hospital depending on the patient’s condition and what is most suitable. It is administered as an IV drip or infusion of the drug dissolved in liquid to give a clear fluid. It is given through a fine tube that is carefully inserted into a larger vein for short term therapy. For longer term therapy a central line or port, also called a PICC line, is usually inserted under the skin into a vein near the collarbone, or a peripherally inserted central catheter is put into a vein in the crook of the patient’s arm. These ports once kept clean and infection-free, are an easier way to administer gemcitabine without the patient requiring needle sticks each time. Administering the drug through IV usually takes about half an hour, but it can take longer if additional drugs or fluids are administered along with gemcitabine.
As is always the case with every medication, each person’s reaction to any chemotherapy regimen is different. While some people may have very few side effects, others may experience more than normal. The side effects observed with gemcitabine administration vary from patient to patient and also change depending on whether the patient is on more than one chemotherapy drug.
The most common side effects include a lowered resistance to infection due to a reduced production of white blood cells by the bone marrow; a reduced production of platelets leading to an ease in bruising and bleeding; anemia; nausea and vomiting; a loss of appetite; reduced liver and kidney function; itchy and scratchy skin; a flu-like illness; tiredness and drowsiness; and fluid retention. Less common side effects are mouth sores and ulcers; hair thinning or hair loss; breathlessness; taste changes; and diarrhea.
Gemcitabine can also affect fertility, lessening the ability of the patient to become pregnant or father a child. The infertility is actually a good effect since it is not unadvisable to become pregnant or father a child while taking gemcitabine, as the developing fetus may be harmed.
As with many chemotherapy drugs, there is financial assistance available for patients that should receive gemcitabine therapy for their mesothelioma but cannot afford it or are uninsured or underinsured.
