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PubMed1986

[Antitumor effects of a podophyllotoxin derivative, VP 16-213].

Single and combination chemotherapies of VP 16-213, a new antitumor agent were evaluated for its antitumor effect against several murine tumors. Dose-dependent antitumor effects were observed when VP 16-213 was administered via any of the three routes, i.p., i.v. and orally, on days 1 and 5 after i.p. or s.c. inoculation of Ehrlich carcinoma and sarcoma 180. The drug also proved effective against i.v. inoculated EL-LP-12 (subline of Ehrlich carcinoma), i.p. or s.c. inoculated P388 and B16 melanoma, i.p. inoculated colon 26, and s.c. inoculated colon 38 and Lewis lung carcinoma. However, oral administration of the drug was not effective against B16 melanoma, colon 26 and Lewis lung carcinoma despite the fact that the doses employed for this route was higher than those employed for i.v. and i.p. routes. The optimum dosing schedule was also investigated with oral administration of the drug against s.c. inoculated Ehrlich carcinoma. A single dose (day 1) or two doses (days 1 and 5) were more effective than three doses (days 1, 3 and 5) or five consecutive daily doses. VP 16-213 showed additive and more than additive effects in combination with the antitumor agents, cyclophosphamide, BCNU, mitomycin C or cisplatin against s.c. inoculated Ehrlich carcinoma and i.v. inoculated EL-LP-12.

Administration, Oral↗
PubMed1985

Metabolic studies of a podophyllotoxin derivative (VP16) in the isolated perfused liver.

The metabolism of VP16 was studied in isolated perfused rat liver. The rate of elimination into the medium and excretion in bile were determined by h.p.l.c. with u.v. detection. With high VP16 concentrations (180 micrograms/ml medium), the elimination half-life of the compound was prolonged markedly (156 v. 45 min for lower doses), the percentage recovered in bile was more than halved and drug accumulation in the hepatic tissue was three times greater. These findings indicate saturation of metabolism and of biliary elimination during high-dose treatment. The presence of glucuronides in the bile of VP16 perfused livers indicates that VP16 undergoes conjugation with glucuronic acid. Formation of picro isomer of VP16 in the liver also occurs.

Animals↗
PubMedDate not supplied

Clinical study of the new podophyllotoxin derivative, 4'-demethylepipodophyllotoxin 9-(4,6-o-ethylidene- beta-D-glucopyranoside) (NSC-141540; VP-16-213), in solid tumors.

The new semisynthetic epipodophyllotoxin, 4'-demethylepipodophyllotoxin 9-(4,6-o-ethylidene- beta-D-glucopyranoside) (NSC-141540), was tested for antitumor activity against solid tumors and for clinical toxicity in 30 patients. The first two courses were given intravenously (60 mg/m2/day times 5, every 21 days), and subsequent courses were given orally (60-120 mg/m2/day times 5, every 21 days). The drug was subjectively well tolerated but induced considerable leukothrombocytopenia and alopecia. It demonstrated significant activity in oat cell carcinoma of the lung (eight responses out of 11 patients) and ovarian cancer (-our responses out of six patients). NSC-141540 has valuable cytostatic activity against these two tumors and warrants further clinical trials, especially in combination chemotherapy.

Administration, Oral↗