Gemcitabin & 5-fu

Gemcitabin & 5-fuNahid AarabiFellow of pediatric hematology& oncologyMofid Hospital1391/8/27

ReferencesPrinciple &practice of pediatric Oncology; P.Pizzo, sixth editionThe Complete Drug Reference; Martindale,35th edition Cure4kids.orgDrug Interactions in the therapy of malignant tumors(BAXTER Pub.)Drugs.com

Gemcitabin Hydrochloride(Gemzar )

Gemcitabin is an analogue of cytarabine , which inhibit DNA synthesis & induce apoptosisIt is primarily active against cells in S- phase

Is given for solid tumors including: bladder, breast, lung, pancreas. Also being tried in cancers of cervix & ovaryPharmacokineticsAfter IV doses, is rapidly cleared from blood & metabolised by cytidine de-aminase in liver, kidney, blood & other tissue.

Clearance is 25%, lower in women than in menAlmost all of doses is excreted in urine, only 1% in faecesIntracellular metabolism produces mono-, di-, and tri-phosphate metabolites , the latter two active

Half-life 42 94 minutes, depending on age & genderIn children: - volume distribution is greater with longer infusion 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.

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Uses and AdministrationIn adults: - Ovarian Cancer - Breast Cancer -Non-Small Cell Lung Cancer -Pancreatic Cancer

In children: as a single agent not have a clearly defined role in treatment of childhood solid tumors

In combination with vinorelbin there is substantial antitumor activity in recurrent Hodgkin lymphomaIn combination with docetaxel, there is modest antitumor activity in refractory sarcomas of bone

In children is not active in recurrent or refractory leukemias Dose : most commonly used dose of Gemcitabine is 1000 mg/ m2 at a 30-minute infusion weekly * 3 weeks every 28 days.

Is given by infusion over 30 to 60 minutes

Dose are adjusted according to response and toxicityConcentration of infusion solution should not exceed equivalent gemcitabine 40 mg/ mlAdverse EffectsMyelosuppression, nausea, vomiting, flu-like syndrome, swelling, dyspnea, alopecia, fatigue, increased serum transaminases, fever, diarrhea, mucositis, rash Rarely : hypotension, severe pulmonary toxicity, somnolence, thrombocytopenic purpura, Haemolytic uremic syndromePatients should not drive or operate machinary

Gemcitabine should be stopped at the first signs of microangiopathic hemolytic anemia

Life threatening esophagitis and pneumonitis has been seen in patients given radical radiotherapy to thoraxDosage Forms :

Gemcitabine for Injection is a white to off-white lyophilized powder available in sterile single-use vials containing 200 mg or 1 g Gemcitabine.

preparationRecommended diluent for reconstitution of Gemcitabine is 0.9% Sodium Chloride Injection without preservatives, upon reconstitution is 40 mg/mL Reconstitution at concentrations greater than 40 mg/mL may result in incomplete dissolution, and should be avoided.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

Prolongation of the infusion time beyond 60 minutes and more frequent than weekly dosing have been shown to increase toxicity If particulate matter or discoloration is found, do not administerGemcitabine solutions are stable for 24 hours at controlled room temperature 20 to 25C (68 to 77F) . Discard unused portion . Solutions of reconstituted Gemcitabine should not be refrigerated, as crystallization may occurDose modificationDosage Reduction GuidelinesAbsolute granulocyte count ( *1,000,000/L) Platelet count( *1,000,000/L )% of full dose> 1000And>100,000100500 - 999or50,000 99,99975