Eortc Studies With Novel Nitrosoureas

Spreafico, F.; Filippeschi, Stefania; Falautano, P.; Eisenbrand, Gerhard; Fiebig, Heinz H.; Zeller, V.; Berger, Martin R.; Schmähl, D.; Putten, L.M. van; Smink, T.; Csányi, E.; Somfai-Relle, S.

doi:10.1016/b978-0-12-565060-1.50007-9

Cited by 6 publications

(12 citation statements)

References 5 publications

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“…Of the remaining two lipophilic N-nitroso derivatives, CNTMU exhibited the strongest carcinogenic effect with increased tumor risks in three tissues. CNTMU was, however, less toxic and less carcinogenic than its close analogue morpholino-CNU [19], which differs only by substitution of sulphur in the thiomorpholino ring by oxygen.…”

Section: Discussionmentioning

confidence: 99%

“…This derivative, one of the two hydrophilic compounds, turned out to be the second strongest carcinogen of the series tested. In comparison to the observed lower tumorgenic poten tial of HECNU, which was determined in a parallel study using the same animal strain [19] and which is in clinical use as well [7] the observed tumorigenicity of ACNU signifies a somewhat increased long-term toxi cologic risk in patients. The overall rate of malignan cies following 19 mg/m2 of ACNU was 2.2-fold higher than that following the same dose of its close analogue CNMPU.…”

Section: Discussionmentioning

confidence: 99%

“…2-Chloroethyl-N-nitrosoureas (CNUs) are among the most effective antineoplastic drugs in experimental systems [5,19]. This activity, however, was not ob served in most clinical studies [3,18].…”

Section: Introductionmentioning

confidence: 99%

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Carcinogenicity of 1-(4-Amino-2-Methylpyrimidine-5-yl)-Methyl-3-(2-Chloroethyl)-3-Nitrosoureahydrochloride and Three Related N-Nitroso Derivatives following Repeated Intravenous Administration to Male Wistar Rats

Berger

Petru

Schmähl³

1988

Oncology

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Long-term toxic evaluation of l-(4-amino-2-methylpyrimidine-5-yl)-methyl-3-(2-chloroethyl)-3-nitrosoureahydrochloride (ACNU), 1 -(2-chloroethyl)-1 -nitroso-3-(methylene-2-pyridylium)-urea-hydrochlo-ride (CNMPU), 1-(2-chloroethyl)-l-nitroso-3-(4-thiomorpholino)-urea (CNTMU) and 4-[N-(2-chloro-ethyl)-N-nitrosocarbamoyl]-morpholine (CNCM) which were administered each at five dosages, adapted to the clinical situation, revealed significantly increased tumor risks for the first three agents in the lung and the adrenal gland. Additionally, CNTMU and ACNU induced a significant rise in the tumor load of the neurogenic tissue; the latter compound, being in clinical use, was associated with a significantly increased number of mammary tumors as well. CNCM, however, did not exhibit significantly elevated carcinogenic activity, although the overall tumor load was up to 2.4-fold increased compared to controls. The results indicate no advantage of the newly developed ACNU with respect to its inherent carcinogenic risk as compared to clinically established 2-chloroethyl-N-nitroso derivatives.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Carcinogenicity of 1-(4-Amino-2-Methylpyrimidine-5-yl)-Methyl-3-(2-Chloroethyl)-3-Nitrosoureahydrochloride and Three Related N-Nitroso Derivatives following Repeated Intravenous Administration to Male Wistar Rats

Berger

Petru

Schmähl³

1988

Oncology

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“…In particular, the methanesulfonate analog HECNU-MS ( 333 ) possessed excellent antileukemic activity (Table ). HECNU-MS ( 333 ) was the weakest carcinogen of a series of open-chain compounds . Compounds 329 and 333 were characterized by a specific neoplastic effect on nervous tissue 296 and by a reduction of spontaneous tumors. , …”

Section: B Hydroxyalkyl Analogsmentioning

confidence: 99%

A Critical Appraisal of the Evolution ofN-Nitrosoureas as Anticancer Drugs

1997

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“…This compound, compared with other nitrosoureas, shows superior anticancer efficacy and less toxicity, especially after repeated applications [1,3]. HECNU was able to cure 100% of animals after intracerebral inoculation of L1210 and L5222 leukemias and was clearly superior to BCNU [4,5]. It was the aim of this study to investigate the ability of HECNU to penetrate the blood-brain barrier and to measure its concentration in the cerebrospinal fluid (CSF).…”

Section: Introductionmentioning

confidence: 99%

Brain uptake and CNS levels of 1-(2-chloroethyl)-1-nitroso-3-(2-hydroxyethyl)urea (HECNU)

Unger¹,

Eibl²,

Engel³

et al. 1987

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The uptake of 14C-labeled 1-(2-chloroethyl)-1-nitroso-3-(2-hydroxyethyl)urea (HECNU) into the brain was investigated in the rat after intracarotid injection according to the method of OLDENDORF, as well as in cisternal cerebrospinal fluid obtained by suboccipital puncture after i.v. injection of the drug. The brain uptake index was 31.9 +/- 2.9%. Cerebrospinal fluid/blood quotients after i.v. injection were 0.82 at 10 min and 1.10 at 60 min. The results of both methods clearly show that HECNU, in spite of its hydrophilic property, easily penetrates the blood-brain barrier.

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Eortc Studies With Novel Nitrosoureas

Cited by 6 publications

References 5 publications

Carcinogenicity of 1-(4-Amino-2-Methylpyrimidine-5-yl)-Methyl-3-(2-Chloroethyl)-3-Nitrosoureahydrochloride and Three Related N-Nitroso Derivatives following Repeated Intravenous Administration to Male Wistar Rats

Carcinogenicity of 1-(4-Amino-2-Methylpyrimidine-5-yl)-Methyl-3-(2-Chloroethyl)-3-Nitrosoureahydrochloride and Three Related N-Nitroso Derivatives following Repeated Intravenous Administration to Male Wistar Rats

A Critical Appraisal of the Evolution ofN-Nitrosoureas as Anticancer Drugs

Brain uptake and CNS levels of 1-(2-chloroethyl)-1-nitroso-3-(2-hydroxyethyl)urea (HECNU)

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