Vindesine lung cancer

VP Vinblastine/vindesine, cisplatinum Non-small cell lung cancer... 

Furuse K, Fukuoka M, Kawahara M, et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III nonsmall cell lung cancer. J Clin Oncol 1999 17 2692-2699. 

Focan, C., Doalto, L., Mazy, V., et al. [48-hour continuous infusion of vindesine (followed by cisplatin) in advanced lung cancer Chronopharmacokinetic data and clinical efficacy.] Bull. Cancer 76 909-912, 1989. 

Sorensen JB, Hansen HH. Is there a role for vindesine in the treatment of non-small cell lung cancer Invest. New Drugs 1993 11 103-133. 

LeChevalier T, Brisgand D, Douillard J, et al. Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non-small-cell lung cancer Results of a European multicenter trial including 612 patients. J Clin Oncol 1994 12 360-367. 

Masuda N, Fukoka M, Negro S, et al. Randomized trial comparing cisplatin (CDDP) and irinotecan (CPT-11) versus CDDP and vindesine (VDS) versus CPT-11 alone in advanced nonsmall cell lung cancer (NSCLC), a multicenter phase III study. Proc Am Soc Clin Oncol 1999 18 1774 (Abstract). 

VINDESINE is given i.v. in a dose of 3 mg/ m once weekly in the treatment of lung cancer (not the type with small cells), malignant melanoma and acute lymphatic leukaemia in children. 

The Eli Lilly company developed several series of derivatives with modifications in the vindoline part of the dimeric structure, culminating with the approval of vindesine, Fig. (1), for clinical treatments. Vindesine, with the commercial name Eldisine and Enisone , has a vincristine-like spectrum of activity, and is used mainly in the treatment of melanoma, acute lymphoblastic leukaemia and advanced non-small cell lung cancer [13, 14, 16]. Vindesine is approved in Europe and other areas but, in the United States, vindesine is approved only for investigational use [15]. 

The vinca alkaloids, vincristine and vinblastine, inhibit tumor growth by destroying microtubules which are essential for cell structure and mitosis. They differ in that vinblastine "blasts" bone marrow while vincristine spares marrow. Vincristine however, causes peripheral neuropathy which is manifested by decreased reflexes, foot drop, weak fingers and decreased autonomic function. Another vinca alkaloid, vindesine is being investigated for the treatment of nonsmaU cell lung cancers. Vindesine causes both marrow suppression and neurotoxicity. 

Pharmacology V., together with vincristine and the semisynthetic vindesine (deacetyl-V.-23-amide), is now established in modem cytostatic therapy (i.v.). It acts in the same was as colchicine (see phenethyltetra-hydroisoquinoline alkaloids) as an inhibitor of mitosis and arrests the metaphase by binding to microtubular proteins. In addition, V. inhibits DNA polymerase and thus also DNA biosynthesis. In combination with other cytostatic agents it is used in therapy for (non)-Hodgkin s lymphomas, testicular, breast, and lung cancer. ... 

Soon after clinical impact of these phytochemicals in curative and palliative cancer chemotherapies, a number of studies focused on design of their semisynthetic derivatives were developed. These efforts led to important anticancer agents, including vindesine (21), vinorelbine (22), and vinilunine (23). Vinorelbine has been administered for treating non-smaU ceU lung cancer (NSCLC), metastatic breast cancer, and rhabdomyosarcoma [98], Vindesine is usually used to treat leukemia, lymphoma, melanoma, and breast and lung cancers. Vinflunine is a fluoiinated vinblastine derivative and has been submitted to phase III clinical studies in patients with NSCLC and bladder cancer [99]. 

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