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At least 19 recordsLinked to original sources
PubMed1975

Treatment of mycosis fungoides with topical nitrosourea compounds: Further studies.

Twenty-six patients with mycosis fungoides were treated topically with three nitrosourea compounds: carmustine (BCNU), lomustine (CCNU), and 1-methyl-1-nitrosourea. A high percentage experienced good to excellent results. Remissions following treatment of individual lesions varied from one month to at least three years. Remissions following total body surface treatment varied from two weeks to at least four months. Two of 13 patients treated over the entire body suffered temporary bone marrow depression, indluding one with severe pancytopenia. This toxic effect was attributed to lomustine and was not seen in patients treated with carmustine alone. Thirteen patients highly allergic to mechlorethamine hydrochloride showed no cross-sensitivity to nitrosourea compounds. A primary irritant dermatitis occurred in about one half of the patients and telangiectasia in two. Two patients developed hypersensitivity to nitrosourea compounds. Carmustine is the preferred nitrosourea compound for topical therapy of mycosis fungoides.

Administration, Topical↗
PubMed1976

Mutagenicity of streptozotocin and several other nitrosourea compounds in Salmonella typhimurium.

The following nitrosourea compounds were compared for their ability to induce mutation (to histidine independence) in the histidine-requiring auxotroph Salmonella typhimurium his G46: MNU, streptozotocin (SZ, streptozocin) and its analogs SZA1 and SZA2, and the antitumor drugs BCNU, CCNU and DCNU. At equitoxic doses SZ, SZA1, SZA2 and MNU were almost equally mutagenic causing 150, 42, 140 and 170 mutants/106 survivors at 20% lethal dose (ID20) ALTHOUGH, ON A WIEGHT BASIS, SZ was the most mutagenic of all the compounds tested. At ID20 BCNU, CCNU and DCNU gave about 0.5 mutants/106 survivors. Our results show that these nitrosoureas, in common with many other drugs (such as cyclophosphamide, daunomycin, etc.) used in cancer chemotherapy, are highly mutagenic. The implication of our results in the screening of drugs for their mutagenicity to man is discussed.

Histidine↗
PubMed1978

Mutagenicity of nitrosourea compounds for Salmonella typhimurium.

The nitrosourea derivatives 1,3-bis(2-chloroethyl)-1-nitrosourea (NSC-409962), 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU; NSC-79037), 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (Me-CCNU; NSC-95441), and 1-methyl-1-nitrosourea (MNU; NSC-23909) were screened for mutagenic potential with Salmonella typhimurium strains G46 and TA1530 in vitro and in vivo. Alu were also mutagenic in the host-mediated assay. Four additional chemotherapeutic nitrosoureas were tested in vitro, three of which were mutagenic. The lack of activity of the fourth agent was probably a reflection of its stability in solution rather than a true indication of mutagenic potential. All eight agents were tested in a repair test with S. typhimurium strains TA1978 and TA1538. Results of this test were negative, reflecting the insensitivity of these strains to ethylating and methylating agents. The insensitivity of the host-mediated assay is also discussed.

Carmustine↗
PubMed1980

An analysis of the interaction between two nitrosourea compounds and X-radiation in rat brain tumour cells.

Experimental measurements have shown that both BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea] and CCNU [1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea] are toxic in rat 9L brain tumour cells and also sensitize these cells to the action of ionizing radiation. The interaction of BCNU and CCNU with radiation has been interpreted using a recently developed extension of the molecular theory of cell survival. The experimental results are shown to be compatible with the mathematical equations predicted by the model and the analysis indicates that the sensitizing effect is caused by a synergistic interaction between sublethal damage caused by the nitrosourea compound and the radiation at the molecular level. The analysis of the dependence of the interaction on the time between nitrosourea treatment and radiation indicates that the optimal interaction occurs with a 5 hour interval.

Animals↗
PubMed1995

Determination of nitrosourea compounds in brain tissue by gas chromatography and electron capture detection.

A relatively simple, high-sensitivity gas chromatographic assay is described for nitrosourea compounds, such as BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea] and MeCCNU [1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea], in small biopsy samples of brain and other tissues. After extraction with ethyl acetate, secondary amines in BCNU and MeCCNU are derivatized with trifluoroacetic anhydride. Compounds are separated and quantitated by gas chromatography using a capillary column with temperature programming and an electron capture detector. Standard curves of BCNU indicate a coefficient of variance of 0.066 +/- 0.018, a correlation coefficient of 0.929, and an extraction efficiency from whole brain of 68% with a minimum detectable amount of 20 ng in 5-10 mg samples. The assay has been facile and sensitive in over 1000 brain biopsy specimens after intravenous and intraarterial infusions of BCNU.

Animals↗
PubMed1992

[Contribution of a new nitrosourea compound: fotemustine].

Fotemustine is a new nitrosourea which is active against disseminated malignant melanoma. A global response rate (RR) of 24.2% was obtained in a multicenter trial including 153 patients. The RR was 25% on cerebral metastases. A multivariate analysis of the long term survival considering the main prognostic factors, has been achieved. It confirms the efficacy of fotemustine. As a matter of fact, the best survival of good responders compared to non responders is not correlated to the metastatic site. The combination of fotemustine and dacarbazine led to a global RR of 27.2%, up to 40% in non visceral metastases. As an other way of research the administration of fotemustine by the intraarterial hepatic route in the treatment of hepatic metastases of malignant ocular melanoma seems to give higher response rates than those obtained with chemotherapies administered by intravenous route (near 40% of response rate). Fotemustind alone or associated with cisplatinum allowed also interesting results in the treatment of metastatic non small cell lung cancer (NSCLS).

Antineoplastic Agents↗
PubMed1988

[Chemotherapeutic characterization of new nitrosourea compounds].

The development of new nitrosoureas is described using selected examples. Results obtained with water-soluble analogs and with compounds linked to biomolecules as for instance amino acids, oligopeptides and steroids, are presented. The pronounced antineoplastic effect of some water-soluble analogs is paralleled by an increased rate of DNA-interstrand cross-links and by an increased suppression of hematopoietic stem cells. The suppression of bone marrow stem cells is followed by their rapid regeneration. Water-soluble nitrosoureas induce significant less inhibition of glutathione reductase as compared with established compounds. With regard to long-term toxicity and carcinogenicity water-soluble are superior to established compounds as for instance BCNU. Linking of the nitrosourea moiety to amino acids and oligopeptides led to some analogs with outstanding therapeutic ratio. Out of a group of steroid-linked nitrosoureas, CNC-L-alanine-estradiol-17-ester (CNC-ala-17-E2) is chosen to demonstrate the possibility of reducing bone marrow toxicity despite unchanged or increased therapeutic activity by attachment of the nitrosourea moiety to a steroid. Results of a comparative interspecies in vitro evaluation of CNC-ala-17-E2 in transplanted MXT mammary carcinoma of the mouse, MNU-induced autochthonous rat mammary carcinoma and primary human mammary carcinomas are presented and the question is discussed to what extent in vitro activity of such receptor agents using the tumor stem cell assay reflects their in vivo activity.

Animals↗
PubMed1989

Effects of tauromustine, a water-soluble nitrosourea compound on NMU-1 murine lung tumor.

This study assessed the antitumor activity of 1-(2-chloroethyl)-3-/2-(dimethylaminosulfonyl)ethyl-1-nitrosourea (TCNU), a newly soluble nitrosourea, on NMU-1 lung tumor, a transplantable murine model poorly sensitive to BCNU. TCNU delivered orally was more effective after weekly than after biweekly treatments. When TCNU was given weekly intravenously, its therapeutic index was higher than after oral treatment. Compared with BCNU, TCNU showed superior antitumor effects on NMU-1 murine lung tumor. In this experimental model, TCNU activity was comparable to that of drugs active on human lung cancer.

Animals↗
PubMed1984

[Phase II study of the water-soluble nitrosourea compound ACNU in advanced colorectal carcinomas].

In a phase-II study 46 patients with advanced colorectal cancer were treated with the new nitrosourea ACNU [1-(2-chloroethyl)-1-nitroso-3 (4-amino-2-methyl-5-pyrimidinyl)methyl-3-nitrosourea]. From 43 evaluable patients, 86% presented distant metastases and 14% an unresectable primary tumour or a recurrent tumour. 24 patients presented a colon and 19 a rectal cancer. Prior anticancer drug treatment was given to 34 patients (79%), 11 (26%) were pretreated with a nitrosourea. ACNU was administered every 4-6 weeks as a single intravenous push injection of 100 mg/m2. Most patients received 2-3 courses. From 43 evaluable patients, one patient achieved a complete and 3 a partial remission (CR + PR 9%). 5 patients reached a minimal regression (tumour regression of less than 50%) and 5 a no change for at least 2 months. The median duration (time from beginning of ACNU therapy until tumour progression) of the 14 responders was 132 days. The median survival time was significantly longer for responders in comparison to patients with progressive disease (9.8 versus 4.1 months). The dose limiting toxicity was delayed bone marrow suppression predominantly in the form of thrombocytopenia. 22/42 patients (52%) presented a thrombocytopenia of under 50.000/mm3 with a nadir after 27 days. Leucocytopenia under 2.000/mm3 were observed in 22/40 patients (30%). A fall of haemoglobin of more than 2 g/dl was seen in 71%. Nausea or vomiting over 1-2 days were found in 59% of the treatment courses. Other drug related side effects were not encountered. ACNU has a similar activity in colorectal cancer as BCNU and CCNU.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1976

Type-C RNA viruses and leukemogenesis: relation of type-C virus infectivity and leukemogenesis induced by nitrosourea compounds in mice.

Correlation between infectivity of type-C RNA virus) murine leukemia virus, MLV) and development of leukemia was tested in female ICR/JCL mice treated with either 1-ethyl-1-nitrosourea (ENU) or 1-butyl-1-nitrosourea (BNU). Continuous administration of either chemicals resulted in the occurrence of thymic lymphoma in every mouse with a short latent period. The time of appearance and distribution pattern of MLV infectivity in various tissues were examined by the XC plaque assay technique at fixed intervals during the leukemogenic treatment. In ENU- or BNU-treated mice, only a few samples of the thymus showed MLV infectivity with rather low titers during incubation period and the presence of MLV was not consistent even in leukemic cases though the thymus was almost invariably the target of leukemogenesis. On the other hand, many samples of the uterus, spleen, and mesenteric node from non-leukemic and leukemic mice harbored a good quantity of MLV. In tissues such as the liver, kidney, bone marrow, and muscle, positive cases occurred only sporadically. Observations on the MLV infectivity in untreated controls were almost comparable with those in leukemogen-treated mice. These results indicate that the infectivity of MLV, detected by the XC plaque assay technique, is not necessarily related to the induction of leukemia in mice by exogenous agents.

Animals↗
PubMed1978

Multidisciplinary treatment for central nervous system tumours with nitrosourea compounds.

The authors report the results of a controlled clinical trial in patients with primitive and metastatic CNS tumours treated with combined therapy: surgery, radiotherapy, and chemotherapy (BCNU or CCNU). A total of 102 patients were treated, 50 with BCNU, and 52 with CCNU. The overall response (R. + P.R.) was 68% for the BCNU group, and 65% for the CCNU group. No significant differences were found between the two types of treatment, either in terms of response or in terms of quality and length of survival.

Adolescent↗
PubMed1979

Tumors of the rat kidney induced by nitrosourea compounds.

Apart from other lesions, 51 renal neoplasms were induced in rats by administration of methylethy-, dimethyl- and phenylmethylnitrosourea. 3 tumors originated from the renal pelvis and were classified as transitional cell papilloma (1) or transitional cell carcinoma (2). 48 neoplasms were considered as "mesenchymal tumors". These growths were regarded as rat kidney specific tumors. They display a wide spectrum of histological structures: spindle cells which are capable to differentiate into smooth muscle cells, fibroblasts, angioblasts, fat cells, and even into cartilage thus forming the typical microscopical features which are completed by the tendency of mesenchymal cells to swirl around preexisting renal tubules in several closely investing layers. As the cell of origin is not yet established the term "mesenchymal tumor" seems to be the most suitable one. There is no basis for classifying these tumor as nephroblastomas and the two entities should be strictly separated.

Animals↗