Gemcitabin & 5-fu. Nahid Aarabi Fellow of pediatric hematology& oncology Mofid Hospital 1391/8/27. References. Principle &practice of pediatric Oncology; P.Pizzo , sixth edition The Complete Drug Reference; Martindale,35 th edition Cure4kids.org
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Fellow of pediatric hematology& oncology
P.Pizzo, sixth edition
Gemcitabin is an analogue of cytarabine , which inhibit DNA synthesis & induce apoptosis
After IV doses, is rapidly cleared from blood & metabolised by cytidine de-aminase in liver, kidney, blood & other tissue.
Intracellular metabolism produces mono-, di-, and tri-phosphate metabolites , the latter two active
- volume distribution isgreaterwith longerinfusion duration
- in children receiving a 30- minute infusion, half- life is 14 minutes. In children receiving a 6- hour infusion, half-life is 62 minutes.
- Breast Cancer
-Non-Small Cell Lung Cancer
as asingle agentnothave a clearly defined role in treatment of childhood solid tumors
In combination with docetaxel, there is modest antitumor activity in refractorysarcomas of bone
Dose : most commonly used dose of Gemcitabine is 1000 mg/ m2 at a 30-minute infusion weekly* 3 weeks every 28 days.
Concentration of infusion solution should notexceed equivalent gemcitabine40 mg/ ml
Myelosuppression, nausea, vomiting, flu-like syndrome,swelling, dyspnea, alopecia, fatigue, increased serum transaminases, fever, diarrhea, mucositis, rash
Rarely : hypotension, severe pulmonary toxicity, somnolence, thrombocytopenicpurpura, Haemolytic – uremic syndrome
Gemcitabine for Injection is a white to off-white lyophilized powder available in sterile single-use vials containing 200 mg or 1 gGemcitabine.
Recommended diluent for reconstitution of Gemcitabine is 0.9% Sodium Chloride Injection without preservatives, upon reconstitution is 40 mg/mL
Prior to administration the appropriate amount of drug must be diluted with 0.9% Sodium Chloride Injection. Final concentrations may be as low as 1 mg/mL
Gemcitabine solutions are stable for 24 hours at controlled room temperature 20° to 25°C (68° to 77°F) . Discard unused portion . Solutions of reconstituted Gemcitabine should not be refrigerated, as crystallization may occur
Radiation Therapy: Data suggest that Gemcitabine can be started after the acute effects of radiation have resolved or at least one week after radiation.
Patients receiving Gemcitabine should be monitored prior to each dose with a complete blood count (CBC), including differential and platelet count.
Gemcitabine should be used with caution in patients with preexisting renal impairment or hepatic insufficiency as there is insufficient information from clinical studies to allow clear dose recommendation for these patient populations.
Administration of Gemcitabine in patients with concurrentliver metastases or a preexisting medical history of hepatitis, alcoholism, or liver cirrhosis may lead to exacerbation of the underlying hepatic insufficiency
( 5- Fu)
Analogue of pyrimidineuracil, acts as an antimetabolitis. The metabolism of fluorouracil in the anabolic pathway blocks the methylationreaction of deoxyuridylic acid to thymidylic acid. In this manner, fluorouracil interferes with the synthesis of DNA and, to a lesser extent, inhibits the formation of RNA.
Bioavailable fluorouracil prodrugs , such as eniluracil &tegafur-uracilhave been developed for oral administration that are converted to 5-FU after absorption& provide more prolonged drug exposure, similar to a prolonged intravenous infusion
After IV injection, is cleared rapidly from plasma, with a mean half-life about 16minutes ( 6-20 minutes), is distributed throughout body tissues & fluids , crossing the blood-brain barrier & appear in CSF & disappears from plasma within 3 hours
During continuous IV infusion , plasma 5-fu concentrations were highest in late morning & lowest shortly before midnight ( related to activity of catabolic enzyme , DPD, in peripheral mononuclear cells ).
Carac : Cream 0.5%
Efudex : Cream 5%
Fluorouracil : - Injection, solution 50 mg/mL- Cream 5%
- Solution 2%
- Solution 5%
Fluoroplex: Cream 1%
Parenteral: Palliative management of colon, rectum, breast, gastric, and pancreatic carcinoma.
TopicalCarac , Efudex , Fluoroplex: Multiple actinic or solar keratoses. Carac is only indicated for the face and anterior scalp areas.
Unlabeled Uses: Condylomataacuminata (topical).
parentral : Germ cell tumors
- bolus injection: 500 mg/m2/ day for 5 days
- continuous infusion over 24 hours: 800 – 1200 mg/m2
Myelosuppression, stomatitis, diarrhea, palmar-plantar dysesthesia(hand-foot syndrome),
reversible neurologic toxicity: somnolence, cerebellar ataxia, headache, ocular toxicity consisting of conjunctivitis & ectropion
May increase serum concentrations of fluorouracil and potentially increase toxicity.
Hydantoin plasma levels may be elevated, increasing the risk of toxicity.
Leucovorin may enhance GI toxicity of fluorouracil. Fatalities have occurred because of severe toxic enterocolitis.
Fluorouracil-inducedleukopeniamay be prolonged.
Anticoagulanteffect of warfarin may be increased.
Depressed bone marrow function; poor nutritional status; potentially serious infections.
Pregnancy; dihydropyrimidinedehydrogenase enzyme deficiency (except for 1% cream).
by IV infusion: usual doses (15 mg/kg daily to maximum of 1 gr daily) being infused in 500 ml of sodium chloride 0.9% or glucose 5% over 4 hours