Summary
To determine whether there is any difference between the two epipodophyllotoxin derivatives etoposide and teniposide in their therapeutic effect in small cell carcinoma of the lung (SCCL), they were compared against five human SCCL cell lines in vitro. When the two were compared at equimolar concentrations teniposide was found to be 8–10 times more potent than etoposide, both with 1-h incubation and with continuous incubation in a clonogenic assay and in inducing cell cycle perturbations monitored by flow cytometry. Published pharmacokinetic data suggest that this potency difference is not accompanied by an equivalent increase in toxicity.
The concentrations used for the 1-h incubation were about 100-fold the concentrations used in the experiments with continuous incubation to obtain the same degree of cell kill for both drugs. This suggests that they should be given according to a continuous rather than an intermittent schedule.
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References
Allen LM, Creaven PJ (1975) Comparison of the human pharmacokinetics of VM-26 and VP-16, two antineoplastic epipodophyllotoxin glucopyranoside derivatives. Eur J Cancer 11:697–707
Allen LM (1978) Comparison of uptake and binding of two epipodophyllotoxin glucopyranosides, 4′-demethyl epipodophyllotoxin thenylidene-β-D-glucoside ind 4′-demethyl epipodophyllotoxin ethylidene-β-D-glucoside in the L1210 leukemia cell. Cancer Res 38:2549–2554
Bork E, Hansen M, Dombernowsky P, Hansen SW, Pedersen AG, Hansen HH, (1986) Teniposide (VM-26), an overlooked highly active agent in small cell lung cancer. Results of a phase II trial. J Clin Oncol 4:524–527
Christensen I, Hartmann NR, Keiding N, Larsen JK, Noer H, Vindeløv L (1978) Statistical analysis of DNA distributions from cell populations with partial synchrony. In: Lutz D (ed) Pulsecytophotometry, part 3. European Press Medicon, Ghent, pp 71–78
Creaven PJ (1982) The clinical pharmacology of VM-26 and VP-16-213, a brief overview. Cancer Chemother Pharmacol 7: 133–140
Creaven PJ, Newman SJ, Selawry OS, Cohen MH, Primack A (1974) Phase I clinical trial of weekly administration of 4′-demethylepipodophyllotoxin 9-(4, 6-O-ethylidene-β-D-glucopyranoside) (NSC-141540; VP-16-213). Cancer Chemother Rep 58:901–907
Dow LW, Sinkule JA, Look AT, Horvath A, Evans WE (1983) Comparative cytotoxic and cytokinetic effects of the epipodophyllotoxins 4′-demethylepipodophyllotoxin-9(4, 6-o-2-ethylidene-β-D-glucopyranoside) and 4′-demethylepipodophylllotoxin-9-(4,6-0-2-thenylidene-β-D-glucopyranoside) and their metabolites on human leukemie lymphoblasts. Cancer Res 43:5699–5706
Gupta RS (1983) Podophyllotoxin-resistant mutants of Chinese hamster ovary cells: Cross-resistance studies with various microtubule inhibitors and podophyllotoxin analogues. Cancer Res 43:505–512
Hill BT, Bellamy AS (1984) Establishment of an etoposide-resistant human epithelial tumour cell line in vitro: characterization of patterns of crossresistance and drug sensitivities. Int J Cancer 33:599–608
Hill BT, Price LA (1982) An experimental biological basis for increasing the therapeutic index of clinical cancer therapy. Ann NY Acad Sci 397:72–87
Jiang TL, Liu RH, Salmon SE (1983) Antitumor activity of didemnin B in the human tumor stem cell assay. Cancer Chemother pharmacol 11:1–4
Muggia FM, Selawry OS, Hansen HH (1971) Clinical studies with a new podophyllotoxin derivative, Epipodophyllotoxin, 4′-demethyl-9-(4,6-0-2-thenylidene-β-D-glucopyranoside) (NSC-122819). Cancer Chemother Rep 55:575–581
O'Dwyer PJ, Alonso MT, Leyland-Jones B, Marsoni S (1984) Teniposide: A review of 12 years of experience. Cancer Treat Rep 68:1455–1466
Pedersen AG, Hansen HH (1983) Etoposide (VP-16) in the treatment of lung cancer. Cancer Treat Rev 10:245–264
Pedersen AG, Bork E, Østerlind K, Dombernowsky P, Hansen HH (1984) Phase II study of teniposide in small cell carcinoma of the lung. Cancer Treat Rep 68:1289–1291
Roed H, Christensen IJ, Vindeløv LL, Spang-thomsen M, Hansen HH (1986) Inter-experiment variation and dependence on culture conditions in assaying chemosensitivity of human small cell lung cancer cell lines. Eur J Cancer (in press)
Rozencweig M, Von Hoff DD, Henney JE, Muggia FM (1977) VM-26 and VP-16-213: A comparative analysis. Cancer 40:334–342
Selby P, Buick RN, Tannock I (1983) A critical appraisal of the “human tumor stem-cell assay”. N Engl J Med 308: 129–134
Stähelin H (1973) Activity of a new glycosidic lignan derivative (VP-16-213) related to podophyllotoxin in experimental tumors. Eur J Cancer 9:215–221
Van Putten LM (1974) Are cell kinetic data relevant for the design of tumour chemotherapy schedules? Cell Tissue Kinet 7:493–504
Vindelov LL, Christensen IJ, Keiding N, Spang-Thomsen M, Nissen NI (1983a) Long-term storage of samples for flowcytometric DNA analysis. Cytometry 3:317–322
Vindelov LL, Christensen IJ, Nissen NI (1983b) A detergenttrypsin method for the preparation of nuclei for flow cytometric DNA analysis. Cytometry 3:323–327
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This work was supported by grants from the Lundbeck Foundation
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Roed, H., Vindelov, L.L., Christensen, I.J. et al. The effect of the two epipodophyllotoxin derivatives etoposide (VP-16) and teniposide (VM-26) on cell lines established from patients with small cell carcinoma of the lung. Cancer Chemother. Pharmacol. 19, 16–20 (1987). https://doi.org/10.1007/BF00296248
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DOI: https://doi.org/10.1007/BF00296248