VP-16 etoposide

Two compounds, VP-16 (etoposide) and a related drug, VM-26 (teniposide), are semisynthetic derivatives of podophyllotoxin, which is extracted from the mayapple root (Podophyllum peltatum). Both an intravenous and an oral formulation of etoposide are approved for clinical use in the USA. 

Fig. 3 Venn-diagram for selected compounds interacting with the key MDR-related ABC transporters. MDR-substrate anticancer agents. Abbreviations VCR vincristine, VP-16 etoposide, STER steroids, TAM tamoxiphen, TKI-INHIB tyrosin kinase inhibitors e.g. STI-571, DOX doxorubicine or adriamycin, DNR daunorubicin, EPIR epirubicin, MX mitoxantrone, TOPOT topotecan, iridotecan, BISANT bisanthrone, COLCH colchicin, ACT-D actinomycin D, MYTOM mytomycin, TX methotrexate, CPHAM cyclophosphamide, CHLB chlorambucil, CARM carmustine, LCV leucovorin, HUR hydroxy urea, CISPL cisplatin, TAXOL paclitaxel. (Reproduced from [4])...

Voltarol Optha diclofenac, vorozole [ban, inn, usan] (R 76713) is a non-steroid, with aromatase inhibitor (oestrogen synthetase inhibitor) activity. It is under investigation for some ANTICANCER applications. VP 16 etoposide. 

Podophyllotoxin 3 is a naturally occurring antitumor antibiotic . Attempts to reduce the toxicity have resulted in the synthesis of glucosidic phenolic derivatives, VP-16 (etoposide, a semisynthetic analog) 4a and VM-26 (teniposide) 4b. Their mode of action is thought to be associated with DNA breakage . Haim et al. proposed a mechanistic pathway entailing oxidation with subsequent 0-demethylation to form the o-quinone metabolite 5a (Equation 2). In vivo conversion of methoxyl to hydroxyl has been previously observed . Electrochemical oxidation of VP-16 and other methoxyphenols also leads to quinone products. 

T. W. Doyle, in Etoposide (VP-16) Current Status and New Developments, Academic Press, New York, 1984. 

Lorico A, Rappa G, Finch RA, Yang D, Flavell RA, Sartorelli AC. Disruption of the murine MRP (multidrug resistance protein) gene leads to increased sensitivity to etoposide (VP-16) and increased levels of glutathione. Cancer Res 1997 57(23) 5238-5242. 

Dexa-BEAM dexamethasone/ carmustine (BCNU)/ etoposide (VP-16)/ cytarabine (Ara-C)/ melphalan Dexamethasone 8 mg PO Q8H days 1 -10 BCNU 60 mg/M2 IV day 2 VP-16 75 mg/M2 IV days 4-7 Ara-C 100 mg/M2 IVQ12H days 4-7 Melphalan 20 mg/M2 IV day 3 REF Pfreundschuh etal. J Clin Oncol 1994 12 580-586 PREMEDICATIONS 1. Kytril 1 mg PO/IV 30 minutes before and 12 hours after chemotherapy on days 2 and 3 2. Compazine 10 mg PO/IV 30 minutes before chemotherapy on days 4-7 OTHER MEDICATIONS 1. Give non-cisplatin delayed emesis prophylaxis Repeat every 28 days Carmustine—maximum total dose is 1440 mg/M2 causes delayed myelosuppression... 

Lung Cancer Etoposide (VP-16) -plant alkaloid, topoisomerase II inhibitor -bone marrow suppression -nausea and vomiting -mucocutaneous effects (mucositis, stomatitis)—increased at higher doses -chemical phlebitis common -hypotension with rapid administration -hypersensitivity reactions -secondary leukemia... 

The major class of topoisomerase I inhibitors comprise of the camptothecins, while topoisomerase II inhibitors fall into several classes - anthracyclines (e.g. doxorubicin), anthracenediones (mitoxantrone), anthrapyrazoles (bianthrazole), actinomycins (actinomycin D), acridines (m-AMSA), ellipticines (9-hydroxy-ellipticine) and epidophyllotoxins (Etoposide (VP-16) and VM-26). The chemical... 

The vinca alkaloids vinblastine and vincristine are capable of producing the MDR phenotype in a wide variety of cell types. Furthermore, cells that are made resistant to antitumor drugs such as doxorubicin, actinomy-cin D, or the epipodophyllotoxins etoposide (VP-16) and teniposide (VM-26) are often resistant to the effects of the bisindole alkaloids. The structural and mechanistic diversity of these compounds is even more striking against the backdrop of collateral resistance. 

CAV = cyclophosphamide/doxorubicin/vincristine CEV = cyclophosphamide/epirubicin/vincristine CCM = cyclophosphamide/lomustine/methotrexate EA = etoposide/doxorubicin VMV/VAC = vincristine, methotrexate, VP-16/vincristine, doxorubicin, cyclophosphamide VAP = vincristine/doxorubicin/ procarbazine PE = cisplatin/etoposide. 

Since 1961, nine plant-derived compounds have been approved for use as anticancer drugs in the U.S. vinblastine (Velban), vincristine (Oncovin), etoposide (VP-16,1), teniposide... 

Etoposide [VP-16] (VePesid, Toposar) Vinblastine (Velban, Velbe)... 

Etoposide (VP-16) 50-100 mg/m2 daily for 5 days Nausea, vomiting, hypotension Alopecia, bone marrow depression... 

Rappa G, Shyam K, Lorico A et al (2000) Structure-activity studies of novobiocin analogs as modulators of the cytotoxicity of etoposide (VP-16). Oncol Res 12 113-119... 

Long BH. Mechanisms of action of teniposide (VM-26) and comparison with etoposide (VP-16). Semin Oncol 1992 19(2 Suppl 6) 3-19. 

Matsui H, litsuka Y, Seki K, Sekiya S. Pregnancy outcome after treatment with etoposide (VP-16) for low-risk gestational trophoblastic tumor. Int J Gynecol Cancer 1999 9(2) 166-169. 

Etoposide (VP-16 VePesid-Bristol-Myers Squibb Oncology, and others)... 

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