Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Carmustine”

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 1,009 records · Page 56Linked to original sources
PubMed1997

Results of high-dose therapy and autologous bone marrow/stem cell transplantation during remission in poor-risk intermediate- and high-grade lymphoma: international index high and high-intermediate risk group.

We have conducted a pilot study to investigate the role of high-dose therapy and autologous bone marrow/stem cell transplantation (ASCT) during first complete or partial remission in 52 patients with poor-risk aggressive lymphoma. There were 42 patients with intermediate-grade or immunoblastic lymphoma who were considered to be high (60%) and high-intermediate risk (40%) groups at diagnosis based on the age-adjusted International Prognostic Index (IPI) and 10 patients with high-grade, SNCCL (small non-cleaved cell, Burkitt's, and non-Burkitt's), who at presentation had poor-risk features defined as elevated serum lactate dehydrogenase level, stage IV, and bulky mass >/=10 cm. The median age was 34 years (range, 16 to 56 years). Thirty-nine were transplanted in first complete remission and 13 in first partial remission after conventional therapy. Conditioning regimens consisted of total body irradiation (TBI) administered as a single fraction 750 cGy in 3 patients and in fractionated doses for a total of 1,200 cGy in 44 patients, in combination with 60 mg/kg etoposide and 100 mg/kg cyclophosphamide. Five patients with prior radiotherapy received 450 mg/m2 carmustine instead of TBI. Stem cell sources were either bone marrow and/or peripheral blood. No in vitro purging was used. All patients engrafted. Two SNCCL patients died of venoocclusive disease at 25 days and acute leukemia at 27 months posttransplantation. There were six relapses at 1.5 to 12.8 months posttransplantation. At a median follow-up of 44 months (range, 1 to 113 months), the estimated 3-year overall survival (OS) and disease-free survival (DFS) for all patients was 84% (95% confidence interval [CI], 70% to 92%) and 82% (95% CI, 68% to 91%), respectively. In the subset of patients with intermediate-grade and immunoblastic lymphoma, the 3-year DFS was 89% (95% CI, 74% to 96%) for all patients, 87% (95% CI, 67% to 96%) for high-risk patients, and 92% (95 CI, 61% to 99%) for high-intermediate risk patients. The 3-year OS and DFS for SNCCL patients were identical at 60% (95% CI, 30% to 84%). These results suggest that high-dose therapy and ASCT during first remission may improve the survival and prognosis of patients with poor-risk intermediate- and high-grade lymphoma. A prospective randomized study comparing high-dose therapy and ASCT with conventional chemotherapy in IPI high-risk patients with aggressive non-Hodgkin's lymphoma should be undertaken.

Adolescent↗
PubMed1998

Primary diffuse large B-cell lymphoma of the mediastinum: outcome following high-dose chemotherapy and autologous hematopoietic cell transplantation.

We performed a retrospective analysis of 35 patients with primary diffuse large B-cell lymphoma of the mediastinum treated with high-dose cyclophosphamide, carmustine, and etoposide (CBV) plus autologous hematopoietic cell transplantation to determine outcome and prognostic features for progression-free survival (PFS). Thirty-five patients with primary diffuse large B-cell lymphoma of the mediastinum in first response (complete remission [CR] or partial remission [PR]) with poor prognostic features, with primarily refractory disease, or with relapsed disease following conventional chemotherapy, were treated with CBV and autologous hematopoietic cell transplantation. PFS and overall survival were assessed by the Kaplan-Meier method. Patient characteristics before transplantation were examined by univariate analysis using the log-rank test and by Cox's proportional hazards regression analysis to determine predictors of PFS. Estimated 5-year PFS varied significantly with patient disease status at transplantation. Patients transplanted in first response had an estimated 5-year PFS rate of 83%, compared with 58% and 27% for primarily refractory and relapsed patients, respectively (P = .02). The strongest predictor of PFS was chemotherapy responsiveness immediately before transplantation. Patients with chemotherapy-responsive disease had a significantly greater PFS rate than patients with chemotherapy-nonresponsive disease (risk ratio, 3.60; 95% confidence interval [CI], 1.14 to 11.4). No other factors were found to be significant on univariate or multivariate analysis. Patients with primary diffuse large B-cell lymphoma of the mediastinum can achieve prolonged PFS following high-dose chemotherapy and autologous hematopoietic cell transplantation. Outcomes are strongly correlated with disease status (first response v refractory v relapsed) at transplantation and chemotherapy responsiveness immediately before transplantation.

Adolescent↗
PubMed1998

Practical guidelines for the treatment of malignant gliomas.

The treatment of patients with malignant gliomas is palliative and encompasses surgery, radiotherapy, and chemotherapy. Outcome measures have demonstrated improvement in both survival and neurologic performance in patients undergoing complete or near-complete tumor resection. After surgery, involved-field radiotherapy (radiotherapy administered to the tumor and to the tissue in a 3-cm radius surrounding the tumor) has been shown to further improve survival rates when given in a total dose of 6000-6500 cGy. Survival is further improved by the coadministration of the chemoradiopotentiator hydroxycarbamide (hydroxyurea). The role of adjuvant or boost stereotactic radiotherapy is unclear, despite its frequent use. In addition, adjuvant chemotherapy has been shown to improve survival rates in approximately one-quarter of patients with glioblastoma multiforme and in the majority of patients with anaplastic astrocytoma. No a priori method exists, however, to predict which patient will benefit from adjuvant chemotherapy. As a consequence, all physiological young patients with good performance status or limited neurologic disability are treated with chemotherapy. The best results of adjuvant chemotherapy are achieved with a nitrosourea chemotherapy, either carmustine (BCNU) or a combination of procarbazine and lomustine (CCNU) and vincristine, known as PCV-3 therapy. Salvage chemotherapy is reserved for patients with tumor progression, some of whom benefit from a re-operation. Occasional patients with recurrent gliomas may be palliated by stereotactic radiotherapy.

Algorithms↗
PubMed1998

Randomized study of filgrastim versus molgramostim after peripheral stem cell transplant in breast cancer.

BACKGROUND AND OBJECTIVE: The aim of this study was to compare the efficacy and toxicity of Filgrastrim (granulocyte colony-stimulating factor-G-CSF) versus molgramostim (granulomonocyte colony-stimulating factor-GM-CSF) after autologous peripheral blood stem cell transplant (PBSCT) in patients with breast cancer. To the best of our knowledge no randomized studies comparing filgrastrim and molgramostim have been published. DESIGN AND METHODS: Forty-two patients with breast cancer were randomized to receive filgrastrim versus molgramostim subcutaneous at a dose of 5 mcgr/kg starting on day 6 after PBSCT. PBSC were collected in all patients after stimulation with filgrastrim and infused following conditioning with cyclophosphamide, cisplatin and carmustine (n = 25) or cyclophosphamide, carboplatin and thiotepa (n = 17). RESULTS: The median days to reach > 0.5 x 10(9)/L granulocytes was similar for patients receiving filgrastrim (10.5 +/- 0.8 days) and molgramostim (10.2 +/- 0.9 days). No significant differences were observed in time taken to reach 20 x 10(9)/L platelets 10.8 +/- 2.2 vs 12 +/- 2.9 for filgrastrim and molgramostim, respectively, but in time to reach 50 x 10(9)/L was slightly lower in the filgrastrim arm (15.1 +/- 2.9 vs 18.9 +/- 8.4, p = 0.03). Nevertheless there were no differences in the number of platelets transfused. Time of discharge was two days earlier in the filgrastrim arm (15 +/- 4.2 vs 17.4 +/- 4.7, p = 0.04). Finally, the incidence of adverse side effects attributable to the cytokines (filgrastrim or molgramostim) was equivalent and only present in 19% of the patients. INTERPRETATION AND CONCLUSIONS: This randomized study shows that filgrastrim and molgramostim yield quite similar toxicity and efficacy for early hematopoietic reconstitution after PBSCT in breast cancer patients.

Administration, Cutaneous↗
PubMed1998

Cellular resistance against the novel hybrid anthracycline N-(2-chloroethyl)-N-nitrosoureidodaunorubicin (AD 312) is mediated by combined altered topoisomerase II and O6-methylguanine-DNA methyltransferase activities.

N-(2-Chloroethyl)-N-nitrosoureidodaunorubicin (AD 312), a novel semisynthetic compound with combined anthracycline and nitrosourea alkylating functionalities, circumvents resistance conferred by either reduced DNA topoisomerase II (topo II) or increased P-glycoprotein expression with less myelosuppression and cardiotoxicity than adriamycin (doxorubicin; ADR). Cellular resistance to AD 312 could arise from a novel mechanism that confers resistance to both functions simultaneously, or one or more mechanisms common to anthracyclines and/or alkylating agents. The mechanism contributing to AD 312 resistance was investigated following selection of AD 312-resistant murine J774.2 macrophage-like cells and human NCI-H460 non-small-cell lung carcinoma cells. Murine J/312-400 (> 4.7-fold) and human H/312-40 cells (6.3-fold) were cross-resistant to topo II inhibitors (ADR, teniposide, etoposide) and nitrosoureas (carmustine, lomustine) but remained sensitive to vinblastine, colchicine, and camptothecin. There was approximately a twofold decrease in topo II decatenation activity and protein. Decreased net intracellular drug accumulation was not observed. There were no increases in glutathione content or glutathione-S-transferase activity. Increased O6-methylguanine-DNA methyltransferase (MGMT) activity (2.3-fold) was detected in J/312-400, and AD 312 resistance was partially reversed by O6-benzylguanine, a potent inhibitor of MGMT activity. The results suggest that AD 312 resistance arose through selective pressure by both cytotoxic functions in a serial manner.

Animals↗
PubMed1997

Activity of temozolomide against human tumor colony-forming units.

8-Carbamoyl-3-methylimidazo(5,1-d)-1,2,3,5-tetrazin-4(3H)-one (temozolomide) is a new imidazole tetrazinone compound with promising preclinical and clinical activity in nitrosourea-sensitive and -resistant models and manageable toxicity in Phase I and II clinical trials. In this study, we investigated the antiproliferative activity of temozolomide against a large variety of human tumors taken directly from patients in an in vitro soft agar tumor cloning system. Temozolomide was studied using a continuous exposure at final concentrations from 0.1 to 10.0 microM against a total of 222 tumor specimens, of which 101 (45%) were evaluable. A decrease in tumor colony formation was considered significant if survival of colonies treated with temozolomide was </=50% of that in controls. In vitro responses were seen in 9 of 101 [9%; 95% confidence interval (CI), 3-14], 16 of 100 (16%; 95% CI, 8. 5-23), and 35 of 101 (35%; 95% CI, 26-45) tumor specimens at concentrations of 0.1, 1.0, and 10.0 microM, respectively (P < 0. 001). The level of O6-guanine-alkyl-transferase was evaluable in 19 specimens before treatment but did not correlate with a response to temozolomide. At a concentration of 10 microM, a good cytotoxic activity was seen in breast (42%; 95% CI, 15-72), ovarian (36%; 95% CI, 11-69), and non-small cell lung cancers (27%; 95% CI, 6-61). Interestingly, activity was also seen in renal cell carcinomas (50%; 95% CI, 19-81), colon cancers (42%; 95% CI, 15-72), melanomas (33%; 95% CI, 13-59), and some other tumors, including sarcomas and both prostatic and pancreatic carcinomas that are usually considered very resistant to several conventional chemotherapy agents. Moreover, we observed that a subset of tumors that were not sensitive to dacarbazine, carmustine, cisplatin, doxorubicin, 5-fluorouracil, etoposide, and vinblastine were sensitive to temozolomide. These data indicate both that temozolomide is an active drug in vitro against a large variety of human tumors, including some tumors usually resistant to conventional chemotherapy, and that further clinical evaluation is warranted.

Adrenal Gland Neoplasms↗
PubMed1998

DNA topoisomerases as repair enzymes: mechanism(s) of action and regulation by p53.

DNA topoisomerases regulate the organization of DNA and are important targets for many clinically used antineoplastic agents. In addition, DNA topoisomerases modulate the cellular sensitivity toward a number of DNA damaging agents. Increased topoisomerase II activities were shown to contribute to the resistance of both nitrogen mustard- and cisplatin-resistant cells. Similarly, cells with decreased topoisomerase II levels show increased sensitivity to cisplatin, carmustine, mitomycin C and nitrogen mustard. Recent studies propose that topoisomerases may be involved in damage recognition and DNA repair at several different levels including: 1) the initial recognition of DNA lesions; 2) DNA recombination; and 3) regulation of DNA structure. The stress-activated oncogene suppressor protein p53 can modulate the activity of at least three different human topoisomerases, either directly by molecular associations or by transcriptional regulation. Since DNA topoisomerases have considerable recombinase activities, inappropriately activated topoisomerases in tumor cells lacking functional p53 may contribute to the genetic instability of these cells.

Animals↗
PubMed1998

Pharmacokinetics of O6-benzylguanine and its active metabolite 8-oxo-O6-benzylguanine in plasma and cerebrospinal fluid after intrathecal administration of O6-benzylguanine in the nonhuman primate.

O6-Benzylguanine (O6BG) irreversibly inactivates the single-turnover DNA repair protein alkylguanine-alkyltransferase. Thus, O6BG increases tumor-cell sensitivity to alkylating agents such as carmustine, lomustine, procarbazine, and temozolomide. We investigated the pharmacokinetic behavior of O6BG and O6-benzyl-8-oxoguanine (8-oxo-O6BG) in cerebrospinal fluid (CSF) and plasma after intraventricular administration of O6BG in a nonhuman primate model. In our study, three animals received a single 1-mg dose of O6BG into the lateral ventricle. CSF from the 4th ventricle and plasma samples were collected after administration, and O6BG and 8-oxo-O6BG concentrations were measured by high-performance liquid chromatography. Four additional animals received 1 mg of O6BG via the intralumbar route weekly for 6 weeks to assess the feasibility and toxicity of this route of administration. The peak O6BG CSF concentration was 412+/-86 microM, the t1/2 was 0.52+/-0.02 h, the clearance was 0.22+/-0.01 ml/min, and the area under the concentration-time curve was 319+/-15 microM x h in 4th ventricular CSF. The peak CSF concentration of 8-oxo-O6BG in CSF was 1.9+/-0.4 microM, the t1/2 was 0.76+/-0.03 h, and the area under the concentration-time curve was 5.0+/-1.1 microM x h. Both O6BG and 8-oxo-O6BG were detected in the plasma 0.5-3 h after intraventricular O6BG administration. The plasma peak concentration of O6BG was 0.4 microM at 30 min, and the concentration was <0.1 microM by 3 h. The plasma concentration of 8-oxo-O6BG was 0.2 microM at 30 min and 0.6 microM at 3 h. The animals tolerated the single intraventricular dose and 6 weekly intralumbar doses of O6BG without toxicity. We concluded that intrathecal administration of O6BG is well tolerated in the nonhuman primate and seems to have a substantial pharmacokinetic advantage over systemic administration for meningeal tumors.

Animals↗
PubMedDate not supplied

[Comparison of 2 regimens of polychemotherapy in refractory acute leukemia or in relapse].

OBJECTIVE: To compare the effectiveness of two chemotherapy regimens for the treatment of relapsed and refractory acute leukemias. METHODS: We randomly assigned 24 patients in two groups: the LARR1 group received induction with 4 days of etoposide and 4 days of high-dose ara-C; the LARR2 group received induction therapy with 4 days of etoposide plus 3 days of mitoxantrone. Consolidation was given using the same drugs at the same dosage. Maintenance therapy was the same for both groups alternating methotrexate, vincristine, L-asparaginase, carmustine, cyclophosphamide and Ara-C. Every 15 weeks both groups repeated consolidation according to their group. Granulocyte-colony stimulating factor was used in both groups. RESULTS: Median survival for both groups was 5 months (range 1-17). Ten months after starting therapy three patients were disease free in the LARR1 group and two in the LARR2 group. There were no statistically significant differences in complete remission rate (p = 0.62), refractoriness (p = 0.58), deaths in induction (0.14) and other parameters. CONCLUSIONS: Our results were comparable with those of others. The only advantage we found was the possibility of using the LARR1 treatment in patients who have reached or are about to reach cardiotoxic-anthracycline doses.

Acute Disease↗
PubMed1982

Clinical correlations with drug sensitivities in the clonogenic assay: a retrospective study.

We tested the ability of the in vitro clonogenic assay (CLAS) to predict clinical response for patients with solid tumors. Patients had objectively measurable disease and received at least one course of chemotherapy. The correlation between clinical responses and in vitro sensitivity was evaluated retrospectively. Tumor types included melanoma (19), sarcoma (five), hepatoma (one), and carcinoma of the stomach (two), colon (three), lung (one), and breast (one). Five patients received two separate courses of chemotherapy with different drugs or drug regimens. In nine of 11 (82%) instances, tumors were sensitive to a particular drug, and the patient had at least 50% regression of tumor following treatment with the tested drug. Two patients whose tumors were sensitive in vitro had no evidence of clinical response. In 25 of 26 assays, the CLAS accurately predicted tumor resistance, and only one patient had evidence of clinical response (96%). Associations of in vitro results with clinical responses were highly significant. The CLAS can accurately predict the chemosensitivity of a variety of solid tumors.

Antineoplastic Agents↗