Phase I trial of taxol given as a 3-hour infusion every 21 days

299 and tobacco-specific N-nitrosamines (TSNA), benzo(a)pyrene (GAS: 50-32-8), and polonium210. The carcinogenic TSNA in the five snuff brands ranged from 9600 to 289,000 ppb. These concentrations exceeded the nitrosamine concentrations of other consumer products by at least 2 orders of magnitude. Polonium amounted to 0.16-1.22 pCi/g dry snuff. Trace amounts of benzo(a)pyrene (0.1-63 ppb) were indicative of contamination of the tobacco with thermal degradation products, probably due to fire curing or flue curing. The findings from this study, the biologic activity of snuff in animal models, and the epidemiologic studies on snuff use and oral cancer strongly suggest the need for reduction of carcinogens and especially of nitrosamines and polonium-210 in snuff.

Phase I trial of tax01 given as a %-hour infusion every 21 days Kris MG; O’Connell JP; Gralla W; et al CANCER TREAT. REP.; 70/5 (605~07)/1986~ Taxol is a unique plant product that promotes in vitro assembly of microtubules. In a phase I trial, adults with advanced solid tumors were given tax01 (formulated with cremophor EL and dehydrated alcohot) as a 3-hour iv infusion every 21 days. The total dose administered ranged from 15 to 230 mg/m” in nine escalation steps. Leukopenia, thrombocytopenia, nausea and vomiting, alopecia, stomatitis, transient rashes, increases in serum triglyceride levels, and hypersensitivity reactions were observed. Hypersensitivity reactions characterized by acute dyspnea, generalized erythema, and hypotension immediately following the initiation of the tax01 infusion occurred in three of five patients receiving b or = 190 mg/m” (18% of patients overall). No antitumor activity was observed. Hypersensitivity reactions constituted a treatment-limiting toxicity for this preparation of tax01 given on this schedule over the dosage range examined. With the severity and unpredictability of the hypersensitivity reactions, further usage of tax01 is not indicated with this drug formulation on this administration schedule. Further studies are warranted to uncover ways to permit the safe administration of taxol.

Neurotoxicity and efficacy of combined vinea alkaloids in breast cancer Stewart DJ; Maroun JA; Lefebvre B; Heringer R CANCER TREAT. REP.; 70/5 (571~573)/1986/ We treated 17 patients with metastatic breast cancer with the four-drug combination of vincristine (0.5-1.0 mg), vinblastine (4 mglma), doxorubicin (40 mg/m2f, and cyclophosphamide (400 mg/m2). The two vinca alkaloids appeared to be synergistic in causing acute, reversible neurotoxicity, manifested primarily as diffuse pains involving one or more of jaws, limbs (particularly joints), chest, and abdomen. The response rate of 70% was no higher than that noted previously with a regimen identical to this one except for the exclusion of vincristine. Further studies of combined vinca alkaloids are not recommended in the treatment of breast cancer

Inhibition of 3-methyicholanthrene-induced skin tumorigenicity in BALBlc chronic oral feeding of trace amounta of eltagit acid in drinking water Mukhtar H; Das M; Bickers DR CANCER RES. ; 46/5 (2262-2265)/1986/

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Chronic p.o. feeding of small amounts of ellagic acid, a naturally occurring dietary plant phenol, to BALB/c mice in drinking water afforded significant protection against skin tumorigenesis induced by 3-methylcholanthrene, a polycyclic aromatic hydrocarbon carcinogen. A significant increase in the latent period for the development of skin tumors

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