Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Lomustine”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 775 records · Page 43Linked to original sources
PubMed1981

Late results of multimodality therapy of high-grade supratentorial astrocytomas.

Fifty-one patients with histologically proved astrocytomas grades III and IV treated with postoperative irradiation and chemotherapy were evaluated with serial computerized tomographic (CT) scans and with special regard to their functional state 30 months after operation. Fourteen patients (27.4%) are still alive, but only 7 of them have a good performance status. The impaired functional state of 6 (11.7%) of the other 7 patients was caused by a secondary progressive dementia with radiological signs of diffuse cerebral atrophy and leukoencephalopathy, but no signs of recurrent tumors. The best explanation for this is a synergistic toxic action of whole brain irradiation and chemotherapy. Measuring survival time for evaluation of brain tumor therapy is of limited value without examination of the performance status and sequential CT scans.

Adult↗
PubMed1976

Nonhormonal chemotherapy for disseminated renal cell carcinoma.

Twenty-five patients with disseminated renal cell carcinoma have been followed for eleven months. These patients have been treated with CCNU, bleomycin, methotrexate, and platinum in various combinations. The results have been discussed in light of other studies using chemotherapeutic agents against this disease process.

Adenocarcinoma↗
PubMed1979

Effects of cancer chemotherapeutic agents on testicular DNA synthesis in the rat. Evaluation of a short-term test for studies of the genetic toxicity of chemicals and drugs in vivo.

Changes in the rate of testicular DNA synthesis in the rat were studied at various times after single doses of 12 cancer chemotherapeutic agents. The animals were given intravenous injections of [14C]thymidine and [3H]thymidine 24 and 3 h, resp., before they were killed. By combining measurements of the free serum radioactivity and the testicular incorporation of the differentially labelled precursor, different response patterns were obtained for agents with different modes of action. The DNA-damaging agents cyclophosphamide, chlorambucil, thio-TEPA, busulphan, CCNU and procarbacine, after some delay, caused a decrease of testicular thymidine incorporation and a corresponding increase of free serum radioactivity. The non-DNA-damaging agents 5-fluorouracil, methotrexate, hydroxyurea and cytosine arabinoside had a rapid effect on testicular thymidine incorporation and produced diverse response patterns different from that of the DNA-damaging agents. Actinomycin D and also vinblastine caused changes in testicular thymidine incorporation and showed response patterns different from those of the other agents. These results show that simple measurements of testicular DNA synthesis may provide useful information for the evaluation of genotoxic effects of chemical compounds and may help one to distinguish between DNA-damaging agents and metabolic inhibitors of DNA synthesis.

Animals↗
PubMed1988

Effects of CCNU therapy on human chromosomes.

Peripheral blood lymphocytes of 9 patients under CCNU therapy were examined for frequency of sister-chromatid exchanges (SCEs) and chromosomal aberrations (CAs). 7 out of 9 patients were treated with only CCNU, whereas the remaining 2 were treated with other chemotherapeutic agents in combination with CCNU. Compared to normal individuals, a significantly increased frequency of SCE was observed in the patients before starting anticancer therapy (P less than 0.001). Increased incidences of structural changes in chromosomes were observed in cells from all the treated patients. The most frequent aberrations were of chromatid type. After administration of a single dose of CCNU, an increase in SCE frequencies was observed which remained elevated even after 6 weeks. It was concluded that increases in SCEs and CAs in lymphocytes were caused by CCNU treatment. Further studies are needed to elucidate whether any CAs observed in the present study could participate in the induction of second neoplasm.

Aged↗
PubMed1991

Synergistic effect of CCNU and bleomycin on human lymphocytes exposed at late G1 and G2 states of the cell cycle.

The combined action of the antitumor antibiotic bleomycin and chloroethylnitrosourea (CCNU) was studied in human lymphocytes in vitro. All the experiments were carried out with 20 micrograms/ml bleomycin for a given treatment time. By adding 0.7 and 3.5 micrograms/ml CCNU at late G1-S phase we have demonstrated a considerable increase in both percent of aberrant cells and production of dicentrics and rings (5-fold, p less than 0.001). At late S-G2 the combined treatment led to a significant enhancement of breaks per cell (p less than 0.0001) and cells with more than 12 aberrations. A possible explanation could be the known repair-inhibitory potential of CCNU, but its pure clastogenic action still has to be considered. The results presented here point out the need for seeking chemotherapeutic regimens with reduced concentrations of the drugs in combination.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

Induction and reduction of sister chromatid exchange by CCNU in human lymphocytes in vitro.

Sister chromatid exchange (SCE) was studied in human lymphocytes treated with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in vitro. A dose-dependent increase of SCE was observed in cells exposed to 10(-5) - 10(-4) M CCNU. The maximal increase was 25-35 SCEs/cell over the control level, which is similar to the increase found in patients treated with CCNU in vivo. In the presence of rat liver microsomes (S-9 fraction) the frequency of CCNU-induced SCE was slightly higher than in parallel cultures without S-9, suggesting that microsomal metabolism may enhance the rate of decomposition of CCNU into reactive products. The CCNU-induced increase of SCE was greater in cells treated for longer time periods (up to 70 hr) than in cells subjected to a 1-hr treatment. This effect was most pronounced at higher concentrations of the drug (5 X 10(-5) M). The frequency of CCNU-induced SCE was also found to be dependent on the time of treatment in the cell cycle. A treatment for 1 hr during early G1-phase (about 20 hr before the first S-phase) gave rise to a higher increase of SCE than a 1 hr treatment immediately before or during the first or second S-phase. Thus, the CCNU-induced DNA damage leading to SCE seems to persist and may even increase during the prereplicative phase of the cell cycle. After replication in BrdUrd-free medium, the frequency of CCNU-induced SCEs decreased to the control level. The present results, taken together with other studies of strand break and cross-link formation by CCNU in mammalian cells in vitro, suggest that the major SCE-inducing damage by CCNU is DNA interstrand cross-links. These lesions then appear to be slowly removed, if at all, during the prereplicative phase of the cell cycle, and to disappear during or after replication in BrdUrd-free medium in vitro.

Biotransformation↗
PubMed1986

Sensitivity to DNA-damaging agents and mutation induction by UV light in UV-sensitive CHO cells.

Three UV-sensitive (UVs) mutants isolated from a CHO cell line were analyzed for survival after exposure to H2O2, EMS, MMC, CCNU, X-rays and for mutation induction after UV-irradiation. The UVs mutants showed normal sensitivities to EMS and H2O2, whereas they were hypersensitive to the bifunctional alkylating agents MMC and CCNU and to hypoxic X-irradiation. Compared to parental cells, one of the UV-sensitive clones showed approximately 3- and 7-fold enhancement in the mutagenic response per unit UV dose for 6-thioguanine and ouabain resistance, respectively.

Animals↗
PubMed1992

Potentiation of alkylating chemotherapy by dual function nitrofurans in multi-cell spheroids and solid tumors.

The cytotoxicity and chemosensitizing potential of four dual function nitrofurans was determined in human HT-29 multi-cell spheroids and rodent KHT sarcoma solid tumors. Spheroids were treated with a range of doses of the bioreductive drugs for a period of up to 48 h and the extent of cell kill was assessed at various times after treatment. Cytotoxicity was determined using a clonogenic cell-survival assay. The results demonstrated that two of the nitrofurans were even more toxic to spheroid cells than was the potent bioreductive nitroimidazole aziridine RSU 1069. The dose of the nitrofuran which, after a 24-h exposure, led to a survival value between 0.5 and 1.0, then was chosen for subsequent studies aimed at assessing the ability of these agents to potentiate the efficacy of the nitrosourea CCNU. Exposure to this chemotherapeutic agent was for a period of 1 h. The results indicated that all four dual function nitrofurans enhanced the cell killing of the conventional chemotherapeutic agent by factors ranging from 1.1 to 1.7. Subsequent studies evaluated the therapeutic benefit of combining these bioreductive agents and CCNU in KHT sarcoma-bearing C3H/HeJ mice. The nitrofurans were administered i.p. 0.5 h prior to the chemotherapy and tumor response was assessed by measuring the survival of clonogenic KHT cells 22-24 h after treatment. Normal tissue toxicity was determined using a bone marrow stem cell (CFU-GM) assay. Combining these bioreductive agents with CCNU increased the tumor cell kill by factors of 1.2 to 1.7.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Chemosensitization of CCNU in KHT murine tumor cells in vivo and in vitro by the agent RB 6145 and its isomer PD 144872.

The cytotoxicity and chemosensitizing potential of the nitrohetercyclic agent RB 6145 and its R enantiomer PD 144872 were determined in rodent tumor cells grown in tissue culture or as solid tumors. Using a clonogenic cell survival assay the degree of selective cytotoxicity of these bioreductive drugs was first determined in KHT/iv cells. Cells treated under hypoxic conditions were observed to be approximately 50-80-fold more susceptible to the action of RB 6145 or PD 144872 than were cells exposed under air. To assess the in vitro chemosensitizing potential of RB 6145 and PD 144872, doses of these agents which led to survival values between 0.5 and 1.0 under hypoxic conditions were administered, and were then combined concomitantly with variable doses of the nitrosourea CCNU. Exposure to the nitrosourea was for 1 h. The results showed that inclusion of either sensitizer enhanced the cell killing of the chemotherapeutic agent 2.4-2.6-fold. Subsequent experiments evaluated the therapeutic benefit of combining these bioreductive agents with CCNU in KHT sarcoma-bearing C3H/HeJ mice. When given at times ranging from 90 min before to 60 min after CCNU exposure, these bioreductive drugs increased the tumoricidal activity of the chemotherapeutic agent. Complete dose response curves combining RB 6145 and PD 144872 and a range of CCNU doses also were evaluated. The sensitizers (0.75 mmol/kg) were administered 30 min prior to the chemotherapeutic agent and survival of clonogenic tumor cells 22-24 h after treatment was used to assay tumor response.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Consolidative thoracic radiotherapy and prophylactic cranial irradiation in limited disease small cell lung cancer.

Between 1983 and 1990, 128 patients with limited disease small cell lung cancer (SCLC) received consolidative thoracic irradiation after reaching a complete (CR) or partial response (PR) to combination chemotherapy. Patients in CR (n = 85) received 35-36 Gy in 12-14 fractions and patients in PR (n = 43) 24-30 Gy in 3-6 fractions. Until 1989, prophylactic cranial irradiation (PCI) was given to patients in CR. There was no significant difference in survival between the CR and PR group. However, patients with residual tumor detected by radiology or bronchoscopy or cyto-/histology had significantly longer survival than those with residual tumor demonstrated by more than one of the above methods of investigation. Overall, local progression was observed in 22% and distant dissemination in 63% of patients. The rate of brain metastases was significantly lower in patients treated with methotrexate and nitrosurea containing schedules and PCI, compared to those who were treated with other schedules (irrespective of PCI).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Combined modality treatment of short duration in small cell lung cancer.

Fifty-seven patients with small cell lung cancer (SCLC) (limited disease = LD in 23, extensive disease = ED in 34) received the combination of CCNU, cyclophosphamide, vincristine and methotrexate (CCOM). A mean number of only 6 (range 1-17) courses of chemotherapy were given. All LD patients received consolidation locoregional radiation (30 Gy) after two courses of chemotherapy. A complete response (CR) was obtained in 61% of LD and 12% of ED patients, and a partial response in 22 and 35% respectively. Median survival was 54 and 34 weeks for LD and ED respectively. Five LD patients survived more than 2 yr, three of them remaining disease-free 4 yr after the cessation of treatment. A subset of 12 LD patients achieving a CR after two courses of chemotherapy was randomized to receive maintenance chemotherapy or observation only after the consolidation radiotherapy. In this small-sized randomized trial maintenance treatment showed a significant decrease of the patients' quality of survival compared to no maintenance treatment. We conclude that combined modality treatment of short duration proved effective in SCLC. Future randomized studies are necessary to show whether prolonged chemotherapy has a meaningful impact on survival, or otherwise the resulting morbidity will plead against it.

Adult↗
PubMed1984

Autologous bone marrow transplantation in the treatment of poor prognosis non-Hodgkin's lymphomas.

Twelve patients with non-Hodgkin's lymphomas of poor prognosis were treated by TACC high-dose chemotherapy (cyclophosphamide 45 mg/kg/day X 4, cytosine arabinoside 200 mg/m2 i.v. q 12 hr X 7,6-thioguanin 100 mg/m2 p.o. X 7 and CCNU 200 or 250 mg/m2 p.o., single dose) followed by autologous bone marrow transplantation (ABMI) (infused dose: 853-20,000 CFU-c/kg). Patients were divided into 2 groups: those in primary therapy with high tumor load (group 1; 3 initial diagnoses, 3 relapses) and those in consolidation therapy for a low tumor load (group 2; 5 complete and 1 partial remissions). Results show that: (1) the aplasia following autologous bone marrow transplantation was short. Leukocyte (greater than 10(9)/1) and platelet (greater than 50 X 10(9)/1) recoveries were observed on day 12 (range, 9-19) and day 14 (range, 8-27). (2) In group 1 there were 3 complete remissions (8,21, 45+ months) and 3 failures, including 1 death to toxicity of TACC. The 3 remissions occurred in patients in primary therapy and overall survival of these patients from the time of initial diagnosis was 48+, 48+ and 60+ months. In group 2 there were 5 persisting complete remissions (12+ to 40+ months) and 1 failure. Overall survival of these patients was 23+, 24+, 27+, 42+ and 70+ months. In both groups failures were associated with contamination of the frozen marrow by tumor. The toxicity of the association TACC + ABMT was acceptable and dominated by the risk of pericardial effusion and infection. The latter was absent in group 2 and occurred in 5/6 cases in group 1. These preliminary results indicate that autologous bone marrow transplantation has a possible role in the aggressive treatment of non-Hodgkin's lymphomas of high-grade malignancy and that its use should preferentially be in the consolidation mode.

Antineoplastic Combined Chemotherapy Protocols↗