In treatment of osteosarcoma, all of the following are used EXCEPT:
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 mg/m2 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 mg/day. 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: 1)NEOPLASMS 2)MENINGEAL LEUKEMIA 3)OSTEOSARCOMA 4)RHEUMATOID AHRITIS 5)PSORIASIS 6)BREAST CANCER 7)HEAD AND NECK CANCER 8)MYCOSIS 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: 1)MALIGNANT DISEASES 2)NEPHROTIC SYNDROME 3)JUVENILE IDIOPATHIC AHRITIS 4)LUPUS NEPHRITIS 5)BREAST CANCER 6)NON HODGKIN LYMPHOMA 7)SYSTEMIC 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 mg/m2 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 mg/dL 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 mg/m2 IV q21Days 60 mg/m2 IV q14Days O 40-60 mg/m2 IV q21-28Days OR 20 mg/m2/dose 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 mg/dL: Dose adjustment not necessary Serum bilirubin 1.2-3 mg/dL : Give 50% dose Serum bilirubin: 3.1-5 mg/dL : Give 25% dose Severe hepatic impairment: Contraindicated Administration Limit lifetime cumulative dose to <550 mg/m2 to reduce risk of cardiotox Monitor: CBC, cardiac function, LFTs REFERENCE:ESSENTIALS OF MEDICAL PHARMACOLOGY(K.D.TRIPATHI,SIXTH EDITION, PAGE NO:822,823,825.826) reference.medscape.com
High dose methotrexate
Cyclophosphamide
Vincristine
Doxorubicin
Chemotherapy