Disease relevance of lomustine

• Quality and duration of survival in glioblastoma multiforme. Combined surgical, radiation, and lomustine therapy [1].
• Chemotherapy for bronchogenic carcinoma. Methotrexate, doxorubicin, cyclophosphamide, and lomustine [2].
• Among the major subtypes of gliomas, oligodendrogliomas are distinguished by their remarkable sensitivity to chemotherapy, with approximately two thirds of anaplastic (malignant) oligodendrogliomas responding dramatically to combination treatment with procarbazine, lomustine, and vincristine (termed PCV) [3].
• Theophylline-induced lomustine toxicity [4].
• One hundred twenty-five assessable patients with advanced-stage Hodgkin's disease were randomized to receive mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or MOPP alternating with lomustine (CCNU), doxorubicin, bleomycin, and streptozocin (CABS) [5].

Psychiatry related information on lomustine

• These results indicate that in mice with a limited tumor burden, psychological stress favors the progression of TLX5 lymphoma, and reduces the effectiveness of the antitumor drug, CCNU [6].

High impact information on lomustine

• The radiation dose was 65 Gy in each group, and chemotherapy included vindesine, cyclophosphamide, cisplatin, and lomustine [7].
• Combined modality therapy was MACC which is intravenous methotrexate, intravenous doxorubicin, intravenous cyclophosphamide, and oral lomustine (CCNU), on day 1 and 28 [8].
• Treatment of one ET patient with CCNU (Lomustine) decreased the platelet count and, to a lesser extent, the white blood cell count [9].
• PURPOSE: Oligodendroglial tumors are chemotherapy-sensitive tumors, with two thirds of patients responding to combination chemotherapy with procarbazine, lomustine, and vincristine (PCV) [10].
• Phase II trial of procarbazine, lomustine, and vincristine as initial therapy for patients with low-grade oligodendroglioma or oligoastrocytoma: efficacy and associations with chromosomal abnormalities [11].

Chemical compound and disease context of lomustine

• Data for the activity of 1,3-bis(2-chloroethyl)-1-nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea, and 1-(2-chloroethyl)-3-(piperidine-3,6-dion-3-yl)-1-nitrosourea against 9L rat brain tumor cells are presented [12].
• PURPOSE: As reported earlier, a chemotherapy regimen that consisted of dacarbazine, vincristine, lomustine, and bleomycin (DOBC) combined with natural leukocyte interferon (IFN) has been administered with favorable results to patients with metastatic melanoma [13].
• Randomized phase III trial in childhood high-grade astrocytoma comparing vincristine, lomustine, and prednisone with the eight-drugs-in-1-day regimen. Childrens Cancer Group [14].
• This antiapoptotic activity is specific for death ligand/receptor-mediated apoptosis since APRIL does not protect glioma cells from the cytotoxicity of the drugs, teniposide, vincristine, lomustine or cisplatin [15].
• The effect of combining the radiosensitizer misonidazole (MISO) with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) prior to radiation on the response of various KHT sarcoma cell subpopulations was evaluated [16].

Biological context of lomustine

• The extent of DNA damage caused by 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea has been related to the same amount of damage resulting from exposure of cells to low doses of gamma-irradiation [17].
• A nonrandom, in vivo alkylation of chromatin DNA by equimolar concentrations of MNU and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) was revealed by digestion of nuclei from drug-treated cells with micrococcal nuclease and DNase I [18].
• PURPOSE: A recent report suggests that alterations of chromosome arms 1p and 19q are associated with chemotherapeutic response and overall survival in anaplastic oligodendroglioma patients treated with procarbazine, lomustine, and vincristine chemotherapy [19].
• The majority expressed O6-methylguanine-DNA-methyltransferase (MGMT; Mex+ phenotype) that confers resistance to CCNU independent of their MMR status [20].
• Liver microsomal hydroxylation of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea was shown to occur on the cyclohexyl ring at positions 3 and 4 [21].

Anatomical context of lomustine

• Autologous bone marrow grafts in dogs treated with lethal doses of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea [22].
• Two human colon carcinoma cell lines which differ greatly in their content of O6-alkylguanine-DNA alkyltransferase were analyzed for their response to 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and 2-chloroethyl(methylsulfonyl)methanesulfonate (ClEtSoSo) before and after treatment with O6-alkylguanines [23].
• The synergism achieved by the AmB-actinomycin combination was accompanied by an AmB-induced increase in uptake of actinomycin D by the HL-60 cells, whereas the synergism of the AmB-1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea combination could be linked to potentiation by 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea of AmB-induced oxidative injury [24].
• These studies provided evidence which establish NADPH-cytochrome P-450 reductase rather than PB cytochrome P-450 as the enzyme in the hepatic endoplasmic reticulum responsible for CCNU reductive metabolism [25].
• This regimen takes advantage of oral administration, the in vitro synergy of these drugs and their first-line efficacy in lymphoma, and the ability of lomustine and procarbazine to cross the blood-brain barrier [26].

Associations of lomustine with other chemical compounds

• The failure of alkylating agents, such as carmustine [1,3-bis(2-chloroethyl)-1-nitrosourea; BCNU], lomustine [1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea; CCNU], and streptozotocin, to yield consistent therapeutic results further suggests that one of these mechanisms may be the high expression of O6-methylguanine-DNA methyltransferase (MGMT) [27].
• Patients were randomized for preirradiation chemotherapy, consisting of two cycles of ifosfamide, etoposide, methotrexate, cisplatin, and cytarabine (n = 40), or chemotherapy after irradiation, consisting of eight cycles with cisplatin, vincristine, and lomustine (n = 23) [28].
• Chemotherapy consisted of vincristine during radiotherapy and eight 6-week cycles of vincristine, cis-platinum, and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) [29].
• CCNU sensitivity of the Mex+ cells was analyzed after treatment with the MGMT inhibitor O6-benzylguanine [20].
• Chemotherapy consisted of cyclophosphamide 500 mg/m2 intravenously (IV) day 1, epirubicin 50 mg/m2 IV day 1, and cisplatin 80 mg/m2 IV day 1 (CE'P regimen) alternating every 4 weeks with methotrexate 30 mg/m2 IV day 1, etoposide 200 mg/m2 IV day 1, and lomustine (CCNU) 70 mg/m2 orally day 1 (MEC' regimen) until progression [30].

Gene context of lomustine

• CCNU-dependent potentiation of TRAIL/Apo2L-induced apoptosis in human glioma cells is p53-independent but may involve enhanced cytochrome c release [31].
• Thus, defective MMR and p53 influence CCNU sensitivity in opposite directions [32].
• The hMLH1/p53 defective variants displayed a less prominent cell cycle arrest and reduced apoptosis after CCNU treatment [32].
• An increase in cell killing and in the frequency of micronuclei was observed after CCNU exposure in 2 hPMS2-defective clones (clones 6 and 7) compared with the parental HeLa cells [33].
• Hypersensitivity to CCNU was not seen in the MMR- cell lines DLD1, HEC1A, and HCT116, suggesting that other parameters, besides the MGMT and MMR defects, affect the cell's response to this drug [20].

Analytical, diagnostic and therapeutic context of lomustine

• A retrospective evaluation of the quality and length of survival of 74 patients nonrandomly receiving lomustine, 100 to 110 mg/sq m, following craniotomy and irradiation for glioblastoma multiforme was performed [1].
• Procarbazine, lomustine, and vincristine (PCV) chemotherapy for anaplastic astrocytoma: A retrospective review of radiation therapy oncology group protocols comparing survival with carmustine or PCV adjuvant chemotherapy [34].
• Nevertheless, in preliminary Phase I and II clinical trials, 2 patients who had been treated with multiple chemotherapies including alkylating agents [1-(2-chloroethyl)-3- cyclohexyl-1-nitrosourea, 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide, platinum derivatives], presented complete or partial remission after CMSOEN2 treatment [35].
• PATIENTS AND METHODS: Pulmonary function testing with measurement of lung volume, spirometry, and diffusion capacity was performed in 28 patients who had received CCNU and/or radiation therapy as treatment for a malignant brain tumor [36].
• Growth response of B16 melanoma to in vivo treatment with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) at the initial stage after tumor transplantation [37].

References