Gemcitabine

Gemcitabine is an antimetabolite and has antitumor activity.

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Indications Gemcitabine

It is used in the treatment of the following diseases:

• cancer affecting the pancreas;
• carcinoma in the bladder, prostate or kidney area;
• breast or ovarian cancer;
• pulmonary carcinoma.

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Release form

The drug is released in the form of a lyophilisate, in vials with a capacity of 0.2 or 1 g.

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Pharmacodynamics

Gemcitabine has an inhibitory effect on DNA binding. The drug affects cells in the S and G1/S stages. The substance is metabolized to form 2-phosphate and 3-phosphate nucleosides. The former slow down RNA activity, while the latter are incorporated into RNA and DNA chains. As a result, DNA binding is blocked and pathogenic cells die.

The medicinal effectiveness of the drug in pancreatic carcinoma is noted. With monotherapy, 25-40% of patients show clinical improvement. The combination of the drug with cisplatin increases the therapeutic effect. At the same time, at lower concentrations, the drug has radiosensitizing properties.

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Pharmacokinetics

When infusing a dose of 1 g/m2 ^, plasma Cmax values are observed after 3-15 minutes; the medicinal properties of the drug are maintained for another 90 minutes.

The drug has a weak synthesis with protein. Metabolic processes occur inside the kidneys and liver, as a result of which the active element of the drug is converted into an inactive metabolic product.

Excretion occurs through the kidneys (89%), and when their function is weakened, the inactive decay product begins to accumulate.

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Dosing and administration

The medicine is administered intravenously, through a drip. Only 0.9% NaCl solution can be used as a solvent. First, 25 ml of solvent is poured into a container with 1 g of medicine, then shaken and diluted with the required amount of solution. The resulting mixture should not contain undissolved particles. It can be stored at room temperature for 24 hours.

Gemcitabine chemotherapy is administered as a monotherapy or in combination with platinum drugs (including oxaliplatin and cisplatin with carboplatin). Below are sample treatment regimens.

For carcinoma in the area of the bladder, 1.25 g/m2 of the substance is used ^on the 1st, 8th and 15th days of the cycle, with intervals of 28 days.

For pulmonary carcinoma, 1 g/m2 of the drug is administered ^once a week for 3 weeks in a row. Then you need to take a break of 7 days and repeat the above cycle.

During carcinoma in the pancreas area, 1 g/m2 of the drug is administered once a week ^for 7 consecutive weeks. Then, take a break for 7 days and continue therapy at the above dosage, with a single administration per week, for 21 consecutive days. With an increase in the frequency of injections, the toxic properties of the drug are potentiated.

During the treatment cycle, it is necessary to monitor the leukocyte and platelet counts. If the patient develops hematotoxicity, the dose is reduced or the injection is postponed. In addition, it is necessary to constantly monitor the functioning of the kidneys and liver.

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Use Gemcitabine during pregnancy

Prescribing Gemcitabine to pregnant women is prohibited.

Contraindications

The main contraindications are the patient’s intolerance to the drug, as well as the period of breastfeeding.

Caution is required when used in people with kidney or liver failure, suppressed bone marrow function, and diseases of bacterial or viral etiology.

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Side effects Gemcitabine

The use of the medication may lead to the appearance of some side effects:

• insomnia and headaches;
• bronchospasms, dyspnea, pulmonary edema and cough;
• arrhythmia and decreased blood pressure;
• anemia, leuko- or thrombocytopenia;
• stomatitis, diarrhea, nausea, and increased liver transaminase levels;
• hematuria or proteinuria;
• hair loss or rashes;
• pain in the back;
• facial swelling;
• myalgia.

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Overdose

Intoxication causes myelosuppression, chills, fatigue and cough. In addition, bleeding, pain in the lumbar region, paresthesia, blood in the urine and feces, and rashes on the epidermis appear.

Gemcitabine has no antidote. The patient should be under medical supervision; in addition, symptomatic procedures are performed and blood counts are monitored dynamically.

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Interactions with other drugs

Combination with immunosuppressants (including mercaptopurine, cyclophosphamide, chlorambucil, as well as cyclosporine and azathioprine with GCS) increases the likelihood of developing infections.

When radiation therapy is administered simultaneously with Gemcitabine, bone marrow suppression is enhanced. In pulmonary carcinoma, radiation therapy has resulted in toxic reactions (pneumonia and esophagitis) that are life-threatening.

Combination with viral vaccines resulted in the drug weakening the processes of antibody production.

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Storage conditions

Gemcitabine must be kept at a temperature not exceeding 25°C.

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Shelf life

Gemcitabine is allowed to be used within 36 months from the date of manufacture of the therapeutic agent.

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Application for children

Gemcitabine has been studied in limited Phase 1 and 2 clinical trials in children as a treatment for various types of neoplasms. The data from these trials do not allow us to determine the safety and therapeutic efficacy of the drug in children, which is why it is not used in pediatrics.

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Analogues

Analogues of the drug are the medications Gemcitera, Tolgecit, Hematix with Gemtaz, and in addition Cytogem, Dercin, Gemcibin with Oncogem, as well as Gemcitera and Strigem.

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Reviews

Gemcitabine demonstrates high efficiency in monotherapy during bladder cancer. However, in case of malignant neoplasms in other organs, the drug should be used in combination. During lung carcinoma, the substance is combined with cisplatin; with tarceva - in case of pancreatic carcinoma (locally advanced form). Such a scheme shows that with its use, patient survival increases.

Since the drug was usually used in combination with other drugs, it is quite difficult to assess its own therapeutic efficacy. One can rely solely on the data of randomized trials. Based on them, it can be concluded that no significant differences were found between the combinations of cisplatin with gemcitabine, as well as paclitaxel with carboplatin or cisplatin with paclitaxel.

Of the disadvantages, the most frequently mentioned in reviews are the negative effects caused by the drug.