Cisplatin with vindesine

Roth JA, Pass HI, Flanagan MM, Graeber GM, Rosenberg JC, Steinberg S. Randomized clinical trial of preoperative and postoperative adjuvant chemotherapy with cisplatin, vindesine, and bleomycin for carcinoma of the esophagus. J Thorac Cardiovasc Surg 1988 96(2) 242-248. 

The Phase I studies of vindesine determined the maximum tolerated dose of the compound to be 3-4 mg/m (body surface area) when given once weekly (i.v.) 78). Mild leukopenia ensues, reaching a nadir after about 4 days, and is accompanied by neurotoxicity. Several patients responded to drug treatment during this initial trial, including several complete responders with acute leukemias and partial responders with malignant melanoma and non-Hodgkin s lymphoma. Subsequent studies indicated that vindesine was active in vincristine-resistant childhood lymphocytic leukemia and, when combined with cisplatin, was effective in... 

The RT consisted of 45 Gy in 3 wk using 1.5 Gy bid concurrent with either cisplatin/etoposide or carboplatin/vindesine after the same drugs had been given alone at higher dosage. Acute toxicity was acceptable and treatment-related deaths were 9% or... 

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. 

Morinaga (6) observed that the stilbene derivative (Z)-l-(3-(2-amino-3-hydroxypropamidc)-4-mcthoxyphcnyl)-2-(3,4,5-trimethoxyphenyl)cthanc, (VI), in conjunction with the neoplasm inhibitor Cisplatin , (NH3)2Cl2Pt(II), strongly inhibited mitosis without patient weight loss associated with other antitumor agents such as Vindesine . 

Five patients developed ischemic stroke within 2-5 days of finishing a 4-day course of fluorouracil plus low-dose cispla-tin by continuous infusion (57). Whilst cisplatin has been implicated as having produced central ischemic events, most commonly in combination with vindesine and bleomycin, there has only been one other report involving fluorouracil. Although the causal link was not conclusive, the circumstantial evidence was strong. 

Vinorelbine is a semisynthetic vinca alkaloid. Single-agent activity has been demonstrated in advanced NSCLC, with response rates of up to 33%, median survivals of 40 weeks, and 1-year survival rates of 24% to 30%. The combination of vinorelbine plus cisplatin has demonstrated superior efficacy to either agent alone, and to vindesine plus cisplatin in randomized phase in trials. ... 

A study in 9 patients with a variety of malignant diseases found that treatment with antineoplastics reduced the absorption of a single 160-mg oral dose of verapamil. The verapamil AUC in 8 patients was reduced by 40% (range 7 to 58%), and one patient conversely had a 26% increase. Five patients reeeived a modified COPP regimen (cyclophosphamide, vincristine, procarbazine, prednisone) and four received VAC (vindesine, doxornbicin, cisplatin). It is believed that these antineoplastics damage the lining of the upper part of the small intestine, which impairs the absorption of verapamil. The clinical relevance of this reduction does not appear to have been studied. Note that verapamil may affect levels of anthracyclines , (p.611), etoposide , (p.631), and possibly docetaxel , (p.662). In addition, nifedipine may affect the levels of vincristine , (p.671). 

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