<prompt> In treatment of osteosarcoma, all of the following are used EXCEPT:High dose methotrexateCyclophosphamideVincristineDoxorubicin  <response>: Methotrexate Mtx: It is one of the oldest and highly efficacious antineoplastic drugs; inhibits dihydrofolate reductase DHFRase-blocking the conversion of dihydrofolic acid DHFA to tetrahydrofolic acid THFA which is an essential coenzyme required for one carbon transfer reactions in de novo purine synthesis and amino acid interconversions. The inhibition is pseudoirreversible because Mtx has 50,000 times higher affinity for the enzyme than the normal substrate. Methotrexate is apparently curative in choriocarcinoma: 15-30 mg day for 5 days orally or 2G-40 mgm2 BSA i.m. or i.v. twice weekly. It is highly effective in maintaining remission in children with acute leukaemias, but not good for inducing remission: 2.5-15 mgday. It is also useful in other malignancies, rheumatoid ahritis, psoriasis and as immunosuppressant.The use of folinic acid rescue has permitted much higher doses of Mtx and has enlarged its scope to many difficult-to-treat neoplasms. USES: 1NEOPLASMS 2MENINGEAL LEUKEMIA 3OSTEOSARCOMA 4RHEUMATOID AHRITIS 5PSORIASIS 6BREAST CANCER 7HEAD AND NECK CANCER 8MYCOSIS FUNGOIDES Cyclophosphamide: It is inactive as such: produces few acute effects and is not locally damaging. Transformation into active metabolites aldophosphamide, phosphoramidemustard occurs in the liver, and a wide range of anti tumour actions is exeed. It has prominent immunosuppressant propey. Thus, it is one of the most popular anticancer drugs. It is less damaging to platelets, but alopecia and cystitis due to another metabolite acrolein are prominent. Chloramphenicol retards the metabolism of cyclophosphamide. USES: 1MALIGNANT DISEASES 2NEPHROTIC SYNDROME 3JUVENILE IDIOPATHIC AHRITIS 4LUPUS NEPHRITIS 5BREAST CANCER 6NON HODGKIN LYMPHOMA 7SYSTEMIC SCLEROSIS Vincristine oncovin :It is a rapidly acting drug, very useful for inducing remission in childhood acute leukaemia, but is not good for maintenance therapy. Other indications are lymphosarcoma, Hodgkin;s disease, Wilms; tumour, Ewing;s sarcoma and carcinoma lung. Prominent adverse effects are peripheral neuropathy and alopecia. Bone marrow depression is minimal. USES: Acute Leukemia 1.4 mgm2 IV qWeek Combination Therapy Cancers Hodgkin;s Disease, Non Hodgkin;s Malignant Lymphomas, Rhabdomyosarcoma, Neuroblastoma, and Wilm;s Tumor Consult dose modifications in multi-drug regimens Uveal Melanoma Orphan Indicated for metastatic uveal melanoma Orphan indication sponsor Hana Biosciences, Inc; 7000 Shoreline Cou; Suite 370; South San Francisco, CA 94080 Renal Impairment Dose adjustment not necessary Hepatic Impairment Decrease dose 50 if direct bilirubin 3 mgdL Monitor: CBC Other Indications Uses ALL, AML, CML, Hodgkin;s disease, NHL, neuroblastoma, sarcomas, small cell lung cancer, Wilms; tumor, brain tumors Off-label: breast cancer, idiopathic thrombocytopenic purpura, Kaposi;s sarcoma, bladder cancer Daunorubicin Rubidomycin, Doxorubicin These are antitumour antibiotics with quite similar chemical structures. However, utility of daunorubicin is limited to acute leukaemia in which it is highly active while doxorubicin, in addition, is effective in many solid tumours. Effective in Cancers such as: Cancer of breast, ovary, prostate, stomach, thyroid; small cell cancer of lung, liver; squamous cell cancer of head and neck; multiple myeloma, Hodgkin;s disease, lymphomas, ALL, AML 60-75 mgm2 IV q21Days 60 mgm2 IV q14Days O 40-60 mgm2 IV q21-28Days OR 20 mgm2dose qweek Hepatocellular Carcinoma Orphan Orphan indication sponsor Delcath Systems, Inc; Rockefeller Center, 23rd Floor; New York, NY 10020 Renal Impairment Dose adjustment not necessary Hepatic Impairment Serum bilirubin 1.2 mgdL: Dose adjustment not necessary Serum bilirubin 1.2-3 mgdL : Give 50 dose Serum bilirubin: 3.1-5 mgdL : Give 25 dose Severe hepatic impairment: Contraindicated Administration Limit lifetime cumulative dose to 550 mgm2 to reduce risk of cardiotox Monitor: CBC, cardiac function, LFTs REFERENCE:ESSENTIALS OF MEDICAL PHARMACOLOGYK.D.TRIPATHI,SIXTH EDITION, PAGE NO:822,823,825.826 reference.medscape.com 