Fluorouracil Methotrexate

Intrarenal delivery to tumors Doxorubicin, bleomycine, 5-fluorouracil, methotrexate... 

ADRIAMYCIN ETOPOSIDE TENIPOSIDE TOPOTECAN AMSACRINE 5-FLUOROURACIL METHOTREXATE HYDROXYUREA PALA... 

Sulfuric acid and potassium permanganate are used to dispose of doxorubicin or daunorubicin wastes. Doxorubicin shows mutagenicity only at high concentrations. Care must be exercised by wearing protective clothing when handling urine and feces after administration of doxorubicin, etoposides, fluorouracil, methotrexate, mitoxantrone, mustine, procarbazine, melphalan, mercaptopurine, vinblastine, vincristine, and hydroxyurea.217... 

One attraction of SHW is that it can be used for reversed-phase separations and is therefore readily applicable to a wide range of pharmaceutical compounds including barbiturates, sulfonamides, analgesics and steroids (Table 18-2), and anticancer drugs, including 5-fluorouracil, methotrexate, and... 

Endometrial Ewing s sarcomao" Gastric Head and neck,squamous cell Islet cell (pancreas) Kaposi s sarcoma Doxorubicin cisplatin + cyclophosphamide CAV Cyclophosphamide (or Ifosfamide) + doxorubicin (Adriamycin) + vincristine CF epirubidri + cisplatin 5-fluorouraci1 Cisplatin + S-fluorouracil Methotrexate Screptozotocin + S-fluorouracil Etoposide or interferon affa or vinblastine ABV doxorubicin (Adriamycin) + bteomycin + vincristine or vinblastine... 

Docetaxel and prednisone have recently been shown to improve survival in hormone-refractory metastatic prostate cancer and should be considered standard therapy. Single agents with modest activity in prostate cancer include cyclophosphamide, estramustine, 5-fluorouracil, methotrexate, dacarbazine, mitoxantrone, doxorubicin, pachtaxel, gemcitabine, vinorelbine, and cisplatin. If disease stabilization is included as a favorable response, response rates np to 46% have been reported. Several trials have evalnated the varions combination regimens containing the most active single agents. ... 

FLUOROURACIL METHOTREXATE i cytotoxic effect of methotrexate when fluorouracil is administered prior to methotrexate Fluorouracil prevents the conversion of 1 folates to dihydrofolate Always administer methotrexate prior to fluorouracil... 

Chemotherapeutic agents are grouped by cytotoxic mechanism. The alkylating agents, such as cyclophosphamide [50-18-0] and melphalan [148-82-3] interfere with normal cellular activity by alkylation deoxyribonucleic acid (DNA). Antimetabohtes, interfering with complex metaboHc pathways in the cell, include methotrexate [59-05-2] 5-fluorouracil [51-21-8] and cytosine arabinoside hydrochloride [69-74-9]. Antibiotics such as bleomycin [11056-06-7] and doxombicin [23214-92-8] h.a.ve been used, as have the plant alkaloids vincristine [57-22-7] and vinblastine [865-21-4]. 

The antimetabolites interfere with various metabolic functions of cells, thereby disrupting normal cell functions. They inactivate enzymes or alter the structure of DNA, changing the DNA s ability to replicate These drag are most effective in the treatment of rapidly dividing neoplastic cells. Examples of the antimetabolites include methotrexate and fluorouracil (Adrucil). 

Azathioprine, chloramphenicol, colchicine, cyclophosphamide, cytarabine, 5-fluorodeoxyuridine, 5-fluorouracil, hydroxyurea, mercaptopurine, metformin, methotrexate, phenobarbital, phenytoin, primidone, proton pump inhibitors, pyrimethamine, sulfasalazine, and vinblastine... 

Cytotoxic drugs that have been used alone and in combination as adjuvant therapy in breast cancer include doxorubicin, epirubicin, cyclophosphamide, methotrexate, fluorouracil,... 

Cyclophosphamide 600 mg/m2 IV, day 1 Methotrexate 40 mg/m2 IV, day 1 Fluorouracil 600 mg/m2 IV, days 1 and 8 Repeat cycles every 28 days for 6 cycles Dose-dense AC —> paclitaxel Doxorubicin 60 mg/m2 IV bolus, day 1 Cyclophosphamide 600 mg/m2 IV, day 1 Repeat cycles every 14 days for 4 cycles (must be given with growth factor support) Followed by ... 

Biodegradable poly(phosphoester-urethanes) containing bisglycophosphite as the chain extender were synthesized. Methylene bis-4-phenyl isocyanate (MDI) and toluene diisocyanate (TDI) were initially used as diisocyanates. Since there was a concern that the degradation products could be toxic, the ethyl 2,6-diisocyanatohexanoate (LDI) was synthesized and replaced the MDI (or TDI). The hydrolytic stability and solubility of these polymers were tested. Preliminary release studies of 5-fluorouracil from MDI based poly(phosphoester-urethane) and methotrexate from LDI based poly(phosphoester-urethane) are also reported. 

Chemical structure of monomers and intermediates was confirmed by FT-IR and FT-NMR. Molecular weight distribution of polymers was assessed by GPC and intrinsic viscosity. The thermal property was examined by differential scanning calorimetry. The hydrolytic stability of the polymers was studied under in vitro conditions. With controlled drug delivery as one of the biomedical applications in mind, release studies of 5-fluorouracil and methotrexate from two of these polymers were also conducted. 

Carnauba 30-800 Chemoembolism TDS for intra-arterial delivery of cytostatics 5-Fluorouracil, CCNU, methotrexate... 

AC, Adriamycin (doxorubicin), Cytoxan (cyclophosphamide) CAF, Cytoxan (cyclophosphamide), Adriamycin (doxorubicin), 5-fluorouracil CEF, cyclophosphamide, epirubicin, 5-fluorouracil CMF, cyclophosphamide, methotrexate, 5-flourouracil FAC, 5-fluorouracil, Adriamycin (doxorubicin), cyclophosphamide FEC, 5-fluorouracil, epirubicin, cyclophosphamide TAC, Taxol (paclitaxel), Adriamycin (doxorubicin), cyclophosphamide. 

On the other hand, several probe substrates of carrier-mediated transport systems in the small intestine have been reported to be not absorbed by carrier-mediated mechanism in the rat colon in situ. Those include L-carnitine [23], methotrexate [18], cephradine [18], and 5-fluorouracil [18], as substrates of the L-carnitine carrier, folate carrier, peptide carrier, and pyrimidine carrier, respectively (Table 3.3). It is based on the nonsaturable nature of their transport. Particularly, the apparent membrane permeabilities of L-carnitine and methotrexate are negligibly low, suggesting that these compounds are practically unabsorbable from the colon. In the case of 5-fluorouracil, Na+-independence of transport was observed in situ [18] and also in everted sacs in vitro in the colon [21], while its carrier in the small intestine is known to be Na+-dependent. Furthermore, for ascorbate and nicotinate, as described in everted sacs in vitro [21], and L-dopa, as described in situ [24], carrier-mediated transport cannot be observed in the rat colon. 

THC is effective in several chemotherapy regimens, including methotrexate and the doxorubicin/cyclophosphamide/fluorouracil combination. Cisplatin treatment, however, is more resistant. Side effects of THC are generally well tolerated, and use may be limited in the elderly or with higher doses. Nabilone is a synthetic cannabinoid that is more effective than prochlorperazine in chemotherapy-induced emesis, including cisplatin. Its side effects are similar to THC. Levonantradol is another synthetic cannabinoid with antiemetic effects, and may be administered orally or intramuscularly. The side effect of dysphoria may limit its use. 

Let s start with three examples of antitumor drugs that work by the inhibition of DNA synthesis methotrexate (MTX, Methopterin), 5-fluorouracil (Fluril), and 6-mercaptopurine (Purinethol). These are all old cancer drags, marketed under numerous trade names, including those indicated above. Although the mechanism of action of each one is different, at the end of the day they all inhibit DNA synthesis. 

Antimetabolites (inhibition of purine and pyrimidine nucleotide synthesis) Methotrexate Folic acid antagonist, inhibits tetrahydrofolate reductase and therefore dTMP synthesis 6-Mercaptopurine Interferes with purine synthesis 5-Fluorouracil Inhibits dTMP synthesis ... 

Ciclosporin, a calcineurin inhibitor, is a potent immunosuppressant useful in the prevention of rejection in organ transplants and grafting procedures. Ciclosporin is markedly nephrotoxic. Vincristine is a vinca alkaloid cytotoxic agent fluorouracil and methotrexate are both antimetabolite cytotoxic agents and bleomycin is a cytotoxic antibiotic. 

Dolnick BJ, Pink JJ. Effects of 5-fluorouracil in dihydrofolate reductase and dihydrofolate reductase mRNA from methotrexate-resistant KB cells. J Biol Chem 1985 260 3006-3014. 

In phase II studies with topotecan alone, there is cytotoxic activity in lung cancer with intermittent dose schedules (33), as well as in lung cancer patients with topoisomerase II refractory disease (34). In advanced head and neck cancer topotecan is well-tolerated and has single-agent activity similar to that of cisplatin, 5-fluorouracil, and methotrexate... 

B = bleomycin, C = chlorambucil, CT = chemotherapy, DFS = disease-free survival, Ep = epirubicin, F = fluorouracil, I = ifosfamide, M = mitomycin C, Mtx = methotrexate, O = vincristine, OS = overall survival, P = cisplatin, RT = radiation therapy, V = vinblastine. 

In Fig. 1 various targets of some important cytostatic agents are depicted. Their main mechanisms of action can be briefly summarized as follows. Pentostatin blocks purine nucleotides by inhibiting adenosine deaminase. 6-Mercaptopurine and 6-thioguanine inhibit purine ring biosynthesis and they inhibit nucleotide interconversions. Methotrexate by inhibiting dihydrofolate reduction blocks thymidine monophosphate and purine synthesis. 5-Fluorouracil also blocks thymidine monophosphate synthesis. Dactinomycin, daunorubicin, doxorubicin and mitoxantrone intercalate with DNA and inhibit RNA synthesis. L-asparaginase deaminates... 

Fig. 2. Target enzymes for methotrexate and 5FU. 5-FU = 5-Fluorouracil THF = tetrahydrofolic acid DHF = dihydrofolic acid dUMP = deoxyuridine-monophosphate dTMP = deoxythymidine-monophosphate.

Other routes of administration can be employed in certain situations. Methotrexate and cytarabine are given intrathecally or intraventricularly to prevent relapses in the meninges in acute lymphocytic leukemia and to treat carcinomatous meningitis. Thiotepa and bleomycin have been administered by intravesical instillation to treat early bladder cancers. Fluorouracil can be applied topically for certain skin cancers. 

Cyclophosphamide is a component of CMF (cyclophosphamide, methotrexate, 5-fluorouracil) and other drug combinations used in the treatment of breast cancer. Cyclophosphamide in combination may produce complete remissions in some patients with ovarian cancer and oat cell (small cell) lung cancer. Other tumors in which benehcial results have been reported include non-oat cell lung cancers, various sarcomas, neuroblastoma, and carcinomas of the testes, cervix, and bladder. Cyclophosphamide also can be employed as an alternative to azathioprine in suppressing immunological rejection of transplant organs. 

Salicylates, probenecid, and sulfonamides inhibit the renal tubular secretion of methotrexate and may displace it from plasma proteins. Asparaginase inhibits protein synthesis and may protect cells from methotrexate cytotoxicity by delaying progression from Gj-phase to S-phase. Methotrexate may either enhance or inhibit the action of fluorouracil, depending on its sequence of administration. 

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