Efficacy of 5′-nor-anhydrovinblastine (vinorelbine), against freshly explanted clonogenic human tumor cells in vitro
- 27 Downloads
- 1 Citations
Summary
Vinorelbine (5′-nor-anhydrovinblastine) is a semisynthetic vinca alkaloid currently undergoing extensive clinical evaluation. We have studied the antitumor effect of vinorelbine (final concentrations: 8.4–1000.0 ng/ml) against freshly explanted clonogenic cells from 102 human tumors using a capillary soft agar cloning system and have compared the compound's activity with vinblastine, vincristine, vindesine, paclitaxel, docetaxel, and other clinically used anticancer agents. Four specimens were excluded from further analyses (3 bacterial or fungal contamination, 1 benign histology). Fifty-one of the remaining 98 (52%) specimens had adequate colony formation in control capillaries. Vinorelbine showed concentration-dependent antitumor activity against a variety of solid rumors. At clinically relevant concentrations (0.1 × peak plasma concentrations in humans) vinorelbine inhibited 21 of 49 specimens (43%) and was as active as vinblastine, vincristine, vindesine, bleomycin, doxorubicin, 5-fluorouracil, mitomycin-C, cisplatin, methotrexate, and etoposide. However, paclitaxel (71% inhibition, p = 0.006) and docetaxel (78% inhibition, p = 0.002) were significantly more active than vinorelbine. Moreover, vinorelbine showed antitumor activity against several tumor types and in particular against breast cancer but also in non-small cell lung cancer. We conclude that vinorelbine has a wide spectrum of in vitro activity against freshly explanted human tumors and that the clinical activity of this compound against breast cancer and non-small cell lung cancer is reflected in vitro.
Key words
vinorelbine clonogenic growth human tumorsPreview
Unable to display preview. Download preview PDF.
References
- 1.Potier P: The synthesis of Navelbine prototype of a new series of vinblastine derivatives. Semin Oncol 16(Suppl 14):2–4, 1989Google Scholar
- 2.Krikorian A, Breillout F: Vinorelbine (Navelbine). A new semisynthetic vinca alkaloid. Onkologie 14:7–12, 1991Google Scholar
- 3.Cros S, Wright M, Morimoto M, Lataste H, Couzinier JP, Krikorian A: Experimental antitumor activity of Navelbine. Semin Oncol 16(Suppl 14):15–20, 1989Google Scholar
- 4.Cros S, François G, Guillon R: Experimental antitumoral activity of Navelbine. In: Fabre P (ed) Navelbine (Vinorelbine) Update and New Trends. John Libbey Eurotext Ltd., Montrouge, France, 1991, pp 35–42Google Scholar
- 5.Marty M, Extra JM, Espie M, Leandri S, Besenval M, Krikorian A: Advances in vinca-alkaloids: Navelbine. Nouvelle Revue Française d'Hématologie 31:77–84, 1989Google Scholar
- 6.Jehl F, Quoix E, Leveque D, Pauli G, Breillout F, Krikorian A, Monteil H: Pharmacokinetic and preliminary metabolic fate of navelbine in humans as determined by high performance liquid chromatography. Cancer Res 51:2073–2076, 1991Google Scholar
- 7.Boré P, Rahmani R, van Cantfort J, Focan C, Cano JP: Pharmacokinetics of a new anticancer drug, navelbine, in patients. Cancer Chemother Pharmacol 23:247–251, 1989Google Scholar
- 8.Alberts DS, Chen HSG: Tabular summary of pharmacokinetic parameters relevant to in vitro drug assay. In: Salmon S (ed) Cloning of Human Tumor Stem Cells. Alan R. Liss, New York, 1980, pp 351–359Google Scholar
- 9.Wiernik PH, Schwartz EL, Strauman JJ, Dutcher JP, Lipton RB, Paietta E: Phase I clinical and pharmakinetic study of taxol. Cancer Res 47:2846–2493, 1987Google Scholar
- 10.Extra JM, Rousseau F, Bruno R, Clavel M, Le Bail N, Marty M: Phase I and pharmacokinetic study of Taxotere (RP 56976; NSC 628503) given as a short intravenous infusion. Cancer Res 53:1037–1042, 1993Google Scholar
- 11.Hanauske A-R, Hanauske U, Von Hoff DD: The human tumor cloning assay in cancer research and therapy. Curr Probl Cancer 9:1–50, 1985Google Scholar
- 12.Maurer HR, Ali-Osman F: Tumor stem cell cloning in agar-containing capillaries. Narurwiss 68:381–383, 1981Google Scholar
- 13.Von Hoff DD, Forseth BJ, Huong M, Buchok JB, Lathan B: Improved plating efficiencies for human tumors cloned in capillary tubes versus petri dishes. Cancer Res 46:4012–4017, 1986Google Scholar
- 14.Hanauske U, Hanauske A-R, Marshall MH, Muggia VA, Von Hoff DD: Biphasic effects of vanadium salts on in vitro tumor colony growth. Int J Cell Cloning 5:170–178, 1987Google Scholar
- 15.Maral R, Bourut C, Chenu E, Mathé G: Experimental antitumor activity of 5′-nor-anhydrovinblastine navelbine. Cancer Lett 22:49–54, 1984Google Scholar
- 16.Ashizawa T, Miyoshi K, Asada M, Kobayashi E, Okabe M, Morimoto M, Gomi K, Hirata T: Antitumor activity of navelbine (vinorelbine ditartrate), a new vinca alkaloid analog. Gan-To-Kagaku-Ryoho 20(1):59–66, 1993Google Scholar
- 17.Canobbio L, Boccardo F, Pastorino G, Brema F, Martini C, Resasco M, Santi L: Phase II study of navelbine in advanced breast cancer. Semin Oncol 16(Suppl 14):33–36, 1989Google Scholar
- 18.Toussaint C, Spielmann JIM, Merle S, May-Levin F, Armand JP, Lacombe D, Tursz T, Sunderland M, Chabot GG, Cvitkovic E: Phase I/II trial of continuous infusion vinorelbine for advanced breast cancer. J Clin Oncol 12:2102–2112, 1994Google Scholar
- 19.Garcia-Conde J, Lluch A, Martin M, Casado A, Gervasio H, De Oliveira C, De Pablo JL, Gorostiaga J, Gilrón GC, Cervantes A, Marinez A, Oezous N, Delgado FM, Diáz Rubio E: Phase II trial of weekly IV vinorelbine in first-line advanced breast cancer chemotherapy. Ann Oncol 5:854–857, 1994Google Scholar
- 20.Fumoleau P, Delgado FM, Delozier T, Monnier A, Gil Delgado MA, Kerbrat P, Garcia-Giralt E, Keiling R, Namer M, Closon MT, Goudier MJ, Chollet P, Lecourt L, Montcuquet P: Phase II trial of weekly intravenous vinorelbine in first-line advanced breast cancer chemotherapy. J Clin Oncol 11:1245–1252, 1993Google Scholar
- 21.Degardin M, Bonneterre J, Hecquet B, Pion J-M, Adenis A, Horner D, Demaille A: Vinorelbine (Navelbine) as a salvage treatment for advanced breast cancer. Ann Oncol 5:423–426, 1994Google Scholar
- 22.Romero A, Rabinovich MG, Vallejo CT, Perez JE, Rodiriguez R, Cuevas MA, Machiavelli M, Lacava JA, Langhi M, Romero Acuna L, Amato S, Barbieri R, Sabatini C, Leone BA: Vinorelbine as first-line chemotherapy for metastatic breast carcinoma. J Clin Oncol 12:336–341, 1994Google Scholar
- 23.Depierre A, Lemarie E, Dabouis G, Gamier G, Jacoulet P, Dalphin JC: Efficacy of Navelbine (NVB) in non-small cell lung cancer (NSCLC). Semin Oncol 16(Suppl 14):26–29, 1989Google Scholar
- 24.Gasparini G, Caffo O, Barni S, Frontini S, Testolin A, Guglielmi RB, Ambrosini G: Vinorelbine is an active antiproliferative agent in pretreated advanced breast cancer patients: a phase II study. J Clin Oncol 12:2094–2101, 1994Google Scholar
- 25.Le Chevalier T, Brisgand D, Douillard JY, Pujol JI, Alberola V, Monnier A, Riviere A, Lianes P, Chomy P, Cigolari S, Gottfried M, Ruffle P, Panizo A, Gaspard MH, Ravaioli A, Besenval M, Besson F, Martinez A, Berthaud P, Tursz T: Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non-small cell lung cancer: result of a European multicenter trial including 612 patients. J Clin Oncol 12:360–367, 1994Google Scholar
- 26.O'Rourke M, Crawford J, Schiller J, Laufman L, Yanovich S, Ozer H, Langleben A, Barlogie B, Koletsky A, Clamon G, Purvis J, Tuttle R, Hohneker J: Survival advantage for patients with stage IV NSCLC treated with single agent navelbine in a randomized controlled trial (Abstract). Proc Am Soc Clin Oncol 12:343, 1993Google Scholar