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 1,135 records · Page 63Linked to original sources
PubMed1991

Alternating sequential intracarotid BCNU and cisplatin in recurrent malignant glioma.

The authors entered 43 patients with recurrent malignant glioma in a trial of alternating sequential intracarotid BCNU and cisplatin. Protocol design was alternating courses of BCNU (2 doses, 300 to 400 mg each) and cisplatin (2 doses, 150 to 200 mg each) each at 4-week to 6-week intervals. Eight of 40 patients (20%) evaluable after the first course of BCNU showed partial or minor response. Only 18 patients were evaluable after the first course of cisplatin, and 5 were evaluable after the second course of BCNU. Median survival was 9 months (range, 2 weeks to 6 years). Cerebral or ocular toxicity unique to this method of chemotherapy administration and failure to show clinical improvement were the most common reasons for removal from study. Because of the high attrition rate, the authors were unable to determine a meaningful response to alternating sequential BCNU and cisplatin or to test the clinical degree of cross-resistance to these agents in human malignant glioma.

Adult↗
PubMed1991

Second and third responses to the same induction regimen in relapsing patients with multiple myeloma.

From September 1975 to December 1986, 115 consecutive previously untreated patients with multiple myeloma (MM) were treated with combination chemotherapy consisting of BCNU, cyclophosphamide, melphalan, vincristine, and prednisone (M-2). No patients were excluded or lost during follow-up. Forty-three percent of the patients were Stage I plus II, and 57% were Stage III. Thirty-eight patients (33%) had blood urea nitrogen greater than or equal to 40 mg/dl (substage B). Reaching an objective response treatment was stopped, generally after 1 year, and restarted at relapse. After induction therapy, 94 patients (82%) responded and had a median duration of response (MDR) of 22 months. After first relapse, 26 of 38 patients (69%) responded again to the same regimen and had an MDR of 11 months. This response rate and MDR are significantly lower than the ones achieved in induction chemotherapy. After second relapse, 7 of 16 patients (44%) again responded with an MDR of 3.5 months. The median survival time (MST) was 50.5 months for all patients. The most relevant side effect was leukopenia. No case of secondary leukemia was noticed. The authors conclude that patients with MM can be treated safely without maintenance therapy after reaching remission because a high response rate can be obtained in first and even second relapse. The planned treatment pause at remission does not adversely affect the survival time. Secondary leukemia is infrequent after this policy. Quality of life improves during the treatment pause.

Adult↗
PubMed1992

A randomized trial of accelerated hyperfractionated radiation therapy and bis-chloroethyl nitrosourea for malignant glioma. A preliminary report of Radiation Therapy Oncology Group 83-02.

BACKGROUND: The third and final randomization of Radiation Therapy Oncology Group (RTOG) 83-02 was performed to identify the maximal tolerated dose and potential efficacy of accelerated hyperfractionated radiation therapy (AHRT) in 1.6 Gy twice-daily fractions for adult malignant glioma. METHODS: From December 1987 to July 1989, 304 patients with malignant glioma were stratified by age, performance status, and histologic findings and randomized to receive total AHRT doses of 48.0 or 54.4 Gy, with 80 mg/m2 of bis-chloroethyl nitrosourea (BCNU) for 3 days every 8 weeks. Distribution of other prognostic factors, including neurologic function, extent of surgery, tumor size, and sex, was comparable in each treatment arm. RESULTS: One Grade 5 radiation therapy (RT)-related toxic effect was reported (in the 54.4-Gy treatment arm), and the incidence of late Grade 3-5 RT-related toxic effects at 18 months was 1% at 48.0 Gy and 4% at 54.4 Gy. The median survival times (MST) for the 48.0 Gy and 54.4 Gy treatment arms were 11.7 and 10.8 months, respectively, comparable to the MST in prior RTOG trials with a similar proportion of patients with glioblastoma multiforme (79%). For the 123 patients who were 60 years of age or older, the MST for the 48.0 Gy and 54.4 Gy treatment arms were 8.9 and 10.4 months, respectively, and compare favorably with the MST of 6.0 months reported with standard RT and BCNU treatment used for 101 patients who were 60 years of age or older in two prior RTOG malignant glioma trials (74-01 and 79-18). Although these results differ significantly (P = 0.0015), this contrast is not significant when adjusted by performance status. CONCLUSIONS: The maximum tolerated dose of AHRT has yet to be identified, and pursuit of this information may most benefit patients with malignant glioma who are 60 years of age or older.

Carmustine↗
PubMed1994

Chemosensitivity testing of human malignant melanoma. A retrospective analysis of clinical response and in vitro drug sensitivity.

BACKGROUND: Clinical response rates in the treatment of patients with disseminated malignant melanoma are low and unpredictable. Several reports have documented that clonogenic assay systems for in vitro drug testing are capable of predicting resistance to therapy in vivo and might provide guidelines to improve clinical response rates. METHODS: Specimens from metastatic lesions of patients with malignant melanoma, predominantly from lymph nodes and skin, were disaggregated, exposed to a panel of 10 cytotoxic drugs for 1 hour, and subsequently cultured in agarose. Effects were calculated by the ability to form tumor colonies compared with an untreated control after 7-14 days. A retrospective comparison between the in vitro drug testing result and clinical response was possible in 19 cases. RESULTS: An average of 7.3 drugs per specimen were tested. A high degree of resistance was observed against all cytostatic agents studied independently of the tumor site. In 47 of 181 in vitro drug tests, tumor colony formation was reduced by 30-50%; in 17 of 181, the reduction was more than 50%. A retrospective analysis showed no clinical response in 11 cases and one mixed response in which patients received drugs that had been shown to be "resistant" in vitro. CONCLUSIONS: These results support the concept that in vitro drug testing promises to help avoid treatment with ineffective drugs and their associated toxic side effects. Furthermore, it may increase the likelihood of obtaining a clinical response in the treatment of disseminated malignant melanoma. The major limitation in the treatment of malignant melanoma is the lack of availability of effective agents for treatment.

Antineoplastic Agents↗
PubMed1994

Antiphospholipid syndrome associated with immunotherapy for patients with melanoma.

BACKGROUND: Immunotherapy for patients with cancer is associated with severe side effects, including the possible induction of autoantibodies. The latter was proven for antithyroid microsomal and antithyroglobulin antibodies. METHODS: This study was designed to evaluate antiphospholipid antibodies (APA) in 30 patients receiving three different forms of immunotherapy for disseminated melanoma using interleukin-2 (IL-2), alpha-interferon (alpha-interferon) or the combination of both. RESULTS: APA were detected in none of 18 patients treated with IL-2 alone, 2 of 4 (50%) treated with alpha-interferon alone, and 3 of 8 (37.5%) treated with the combination of both. In the last group, increased concentrations of APA were observed, while the patients were still receiving alpha-interferon alone. APA levels were not detected in any of 10 patients with melanoma who were not treated with alpha-interferon or IL-2. In patients with increased APA, five of five (100%) had a prolongation of the partial thromboplastin time and 4 or five (80%) had deep venous thrombosis, which in one patient was followed by pulmonary embolism. CONCLUSIONS: The high incidence of therapy-induced elevated APA concentrations suggests that these should be carefully monitored in all patients receiving immunotherapy with alpha-interferon.

Adult↗
PubMed1994

White matter changes are correlated significantly with radiation dose. Observations from a randomized dose-escalation trial for malignant glioma (Radiation Therapy Oncology Group 83-02).

BACKGROUND: A Phase I/II randomized dose-seeking trial was performed to document the severity, time course, and significance of white matter changes seen on serial imaging scans (magnetic resonance imaging, computed tomography) associated with bis-chlorethyl nitrosourea (BCNU) and hyperfractionated cranial irradiation. METHODS: Long term survivors (> or = 18 months) were identified from a prospective randomized dose-escalation Phase I/II trial designed to evaluate twice-daily radiotherapy for supratentorial high grade malignant gliomas. All scans were reviewed by a neuroradiologist who had no information about the prescribed dose and fractionation. In the trial, patients were assigned to receive 64.8 Gy, 72.0 Gy, 76.8 Gy, or 81.4 Gy (all fractionated as 1.2 Gy twice a day [bid]), or 48.0 Gy or 54.4 Gy (both in 1.6-Gy bid fractions). Bis-chlorethyl nitrosourea was administered every 8 weeks for 1 year. Of 747 randomized patients, 177 had analyzable scans. The scans reviewed were those acquired preoperatively, immediately postoperatively, 3, 6, 12, and 18 months after radiotherapy. Radiographic endpoints included no white matter change (Grade 0), minimal patchy white matter foci (Grade 1), start of confluence of white matter disease (Grade 2), large confluent areas (Grade 3), confluence with cortical/subcortical involvement (Grade 4), leukoencephalopathy (Grade 5), and possible necrosis (Grade 6) according to the classification of F. Fazekas et al. The effects were scored relative to the baseline preoperative scans. The dose pairs of 48 Gy and 54.4 Gy, 64.8 Gy and 72 Gy, and 76.8 Gy and 81.4 Gy were grouped together for analysis (low, intermediate, and high dose, respectively). Toxicity was analyzed in three ways: Grade 2 or worse, Grade 3 or worse, and Grade 6. RESULTS: Grade 2 or worse changes were observed in 26.6, 27.6, and 40.4% of patients in the low, intermediate, and high dose groups, respectively. Grade 3 or worse changes were observed in 8.3, 20.0, and 36.5% of patients in the low, intermediate, and high dose groups, respectively. Grade 6 changes were observed in 1.6, 4.6, and 19.2% of patients in the low, intermediate, and high dose groups, respectively. No statistically significant differences were observed among treatment groups when toxicity was evaluated as Grade 2 or worse. For toxicity of Grade 3 or worse, an chi-square test revealed P values of 0.04 (low vs. intermediate dose), 0.09 (intermediate vs. high dose), and 0.0005 (low vs. high dose). With the endpoint of possible necrosis (Grade 6), P values were 0.21 (low vs. intermediate dose), 0.05 (intermediate vs. high dose), and 0.003 (low vs. high dose). The median time to radiographic appearance of an effect (15 months) was not influenced by total dose or fraction size. CONCLUSIONS: A well described toxicity scale for white matter injury was applied successfully to patients with malignant glioma treated with definitive irradiation. Severe white matter changes continued to increase significantly as the total dose of hyperfractionated cranial irradiation was escalated. The time to onset of the white matter abnormalities appeared to be independent of dose. An ongoing Radiation Therapy Oncology Group study will allow correlation of white matter injury with prospective neuropsychometric testing.

Brain↗
PubMed2001

Detecting treatment-by-centre interaction in multi-centre clinical trials.

This paper considers several permutation tests for treatment-by-centre interaction in multi-centre clinical trials in which the endpoint is survival time subject to censoring. Some of the tests are based on existing tests and some are new. To evaluate and compare the tests with respect to power under different conditions, we generated survival times and censoring times through simulation. We used special methodology to handle the unusual problems that arise in power simulations when the tests under study are permutation tests. Different conditions yielded different interaction tests as the best performers. Although one test gave comparatively good power under almost all conditions, some of the other tests also appear to be useful. For the sample sizes and configurations in the simulations, power is generally low; thus it may not be possible to detect interaction reliably when it exists, a finding in agreement with the known low power for interaction tests in general.

Aged↗
PubMed2005

Mini-BEAM and autologous hematopoietic stem-cell transplant for treatment of post-transplant lymphoproliferative disorders.

Post-transplant lymphoproliferative disorder (PTLD) represents a spectrum of lymphoid proliferative diseases seen as result of immunosuppression in recipients of solid organ or hematopoietic stem-cell transplantation. Options of treatment include reduction or discontinuation of immunosuppressive agents, antiviral drugs, rituximab, chemotherapy, and radiation. We report two unique cases of PTLD (CNS and plasmacytoma-like) treated successfully with salvage chemotherapy, mini-BEAM chemotherapy, and autologous stem-cell transplant. In both cases, patients were also treated with sirolimus and prednisone as immunosuppression, and neither patient rejected their solid organ transplants. With over 30 months of follow-up, both patients remain in complete remission with excellent allograft function.

Adult↗
PubMed2006

Prophylaxis of central venous catheter-related thrombosis with minidose warfarin in patients treated with high-dose chemotherapy and peripheral-blood stem-cell transplantation: retrospective analysis of 228 cancer patients.

Patients with a central venous catheter (CVC) undergoing high-dose chemotherapy (HDC) followed by peripheral-blood stem-cell transplantation (PBSCT) for malignancies are at high risk of thrombosis, but the use of anti-coagulant prophylaxis remains debatable in this setting of patients. We analyzed the efficacy and the safety of minidose warfarin in 228 patients in whom CVCs had been placed and who had received 292 HDC courses of therapy. The catheters remained in place for a mean of 173 (range 40-298) days. All patients received prophylactic oral warfarin in the fixed dose of 1 mg/day starting on the day of CVC insertion. Prophylaxis was interrupted during aplasia when platelet counts fell below 50,000/dL. There were no toxic deaths related to the prophylaxis. Overall there were 4 thrombotic events. Three occurrences were directly related to the catheter, while the remaining event was a deep saphenous-vein thrombosis. A number of potential predictive factors were analyzed for their impact on thrombotic events without finding any significant correlation. Four episodes of bleeding occurred, with each of these individuals having a normal INR but a platelet count below 50,000/dL. Minidose warfarin is effective and safe to use for preventing thrombotic events in this setting of patients.

Administration, Oral↗
PubMed2007

Tandem high-dose chemotherapy and autologous stem cell transplantation in refractory/relapsed Hodgkin's lymphoma: a monocenter prospective study.

We designed a prospective study to evaluate the feasibility and efficacy of tandem high-dose chemotherapy (HDCT) in the treatment of refractory or relapsed Hodgkin's lymphoma (HL). Thirty-two patients were treated with salvage chemotherapy (IGEV, ifosfamide, gemcitabine, and vinorelbine) and chemo-sensitive patients received a first HDCT course with melphalan 200 mg/m(2) (MEL200) and a second BEAM course. The median time interval between the two HDCT courses was 66 days. The median number of reinfused CD34(+) cells was 4.7 x 10(6)/kg after MEL200 and 5.8 x 10(6)/kg after BEAM. The hematological reconstitution after both HDCT courses did not differ. No grade III or IV renal, hepatic, lung, cardiac, and neurological toxicity was observed. Severe (grade III and IV) oral mucositis was the most prominent complication affecting 60 and 50% of patients after MEL200 and BEAM, respectively. Fever of unknown origin occurred in 65 and 70% of patients after MEL200 and BEAM, respectively. One patient died from septic shock during the aplasia period following BEAM. In an intention-to-treat analysis, the overall response rate increased after each stage of protocol, ranging from 47% to 65% and 75% after IGEV, MEL200, and BEAM, respectively. Tandem HDCT is feasible and effective in patients with relapsed or refractory HL.

Adolescent↗
PubMed1979

The effect of BCNU and adriamycin on normal and G6PD deficient erythrocytes.

In cell free systems Adriamycin induces oxygen radicals. We have shown previously that Adriamycin generates peroxide in human erythrocytes. BCNU, by inhibiting glutathione reductase, interferes with the major erythrocyte pathway to degrade peroxide. In this investigation we looked at interactions of these drugs with normal and abnormal erythrocytes. In G6PD-deficient erythrocytes Adriamycin posed a significant oxidant stress as demonstrated by hexose monophosphate shunt (HMPS) activity, hydrogen peroxide (H2O2) production, and glutathione depletion. At similar molar concentrations Adriamycin was a stronger oxidant than acetylphenylhydrazine. BCNU=treated normal erythrocytes showed an enhanced susceptibility to oxidant stress as demonstrated by a lack of HMPS response to H2O2 and glutathione depletion during incubations with Adriamycin. The HMPS shunt of BCNU treated RBC was intact as shown by their nearly normal response to methylene blue stimulation. These BCNU studies also demonstrated the inability of H2O2 to react directly with NADPH. In conclusion Adriamycin poses a potent oxident stress to G6PD-deficient erythrocytes. BCNU promotes enhanced susceptibility of normal RBC to oxidant stress and BCNU can act as a probe to define drug interactions with the HMPS. These studies add to a growing body of evidence postulating the importance of oxygen radicals in the therapeutic and/or effects of Adriamycin.

Carmustine↗
PubMed1983

Serum-free light chain analysis by crossed immunoelectrophoresis: correlation with plasmapheresis in light chain disease nephropathy.

The technique of crossed immunoelectrophoresis (X-IEP) has been used to quantify free monoclonal light chains (LC) directly in the serum of patients with light chain disease, without preliminary gel or membrane filtration of serum to separate whole immunoglobulin. LC concentration is proportional to the area under an immunoprecipitin peak formed by LC in the patient's serum and an anti-LC antibody of appropriate specificity. Light chains of beta electrophoretic mobility can be processed in the standard X-IEP technique at pH 8.6. Light chains of gamma mobility must be processed in a modified technique using a pH of 5.0 and a carbamylated antiserum in the second dimension gel. Dose response curves obtained from the method in serial dilution experiments with sera from 18 patients gave correlation coefficients greater than or equal to 0.99. Replicate measurements of absolute LC concentration on the same specimens were within +/- 10%. The method can also detect polymerized light chains. Serum light chain levels were measured during the course of plasmapheresis therapy in three patients with light chain disease and renal failure. Light chain levels were shown to fall after plasmapheresis and to rise rather rapidly in the interval between treatments.

Acute Kidney Injury↗
PubMed1985

Treatment of the blastic transformation of chronic granulocytic leukemia using high dose BCNU chemotherapy and cryopreserved autologous peripheral blood stem cells.

Seven nonsplenectomized patients with blastic CGL have received high dose BCNU chemotherapy followed by cryopreserved peripheral blood stem cells (PBSC). The PBSC obtained at diagnosis were stored in the vapor phase of liquid nitrogen in 10% dimethyl sulfoxide for 11-46 months prior to use. Patients received 2.9 X 10(8) (1.9-7.8) thawed washed mononuclear cells/kg over 30 minutes with minimal morbidity. One patient was not rendered pancytopenic and died with blastic leukemia at 4 months. One patient, previously treated with daily busulfan, died of progressive hepatic failure 2 months after high dose BCNU. Restoration of the chronic phase of CGL was observed in the remaining five patients. Peripheral blood counts returned to normal ranges after a median of 19 days. Median survival for all patients is 11 months. Cytogenetic studies revealed elimination of acquired aneuploid cell lines in four of seven patients with persistence of Ph1. We conclude that: 1) frozen PBSC retain their viability for up to 4 years after cryopreservation and 2) the use of autologous PBSC following ablative chemotherapy may be associated with both symptomatic and karyotypic improvement in patients with blastic CGL.

Adolescent↗
PubMed1992

Allogeneic bone marrow transplantation for hematological malignancies following etoposide, cyclophosphamide, and fractionated total body irradiation.

Forty-three patients received etoposide, cyclophosphamide, and fractionated total body irradiation before allogeneic marrow transplantation. Fifteen patients had chronic myelogenous leukemia in chronic phase or acute leukemia in first remission (standard risk) and twenty-eight patients with more advanced disease (high risk). All patients received etoposide 1,500 mg/m2 intravenously on day -8, cyclophosphamide 60 mg/kg/day intravenously on days -7 and -6, and total body irradiation at 170 cGy twice a day on days -3, -2, and -1. During the first 100 days 12 high risk patients (43%) died from causes unrelated to relapse while none of the standard risk patients died. Renal and hepatic dysfunction were also significantly increased during the first 14 days in the high risk group. The addition of 1,500 mg/m2 of etoposide to the cyclophosphamide and total body irradiation was well tolerated for patients with standard risk. However, the regimen was poorly tolerated with high mortality in patients with more advanced disease.

Acute Disease↗
PubMed1998

Malignant glioma: who benefits from adjuvant chemotherapy?

We combined two randomized prospective Brain Tumor Study Group data sets to analyze the effects of prognostic factors on survival by treatment group. Adjuvant chemotherapy increased long-term survival regardless of prognostic factors. Pathological review revealed that oligo dendrogliomas were overrepresented among long-term survivors independent of therapy. Prognostic factors do not predict benefit from adjuvant nitrosourea in malignant gliomas, and long-term survival with chemotherapy is not explained by oligodendroglial tumors.

Adult↗
PubMed2006

Schisandrin B-induced increase in cellular glutathione level and protection against oxidant injury are mediated by the enhancement of glutathione synthesis and regeneration in AML12 and H9c2 cells.

To define the relative role of reduced glutathione (GSH) synthesis and regeneration in schisandrin B (Sch B)-induced increase in cellular GSH level and the associated cytoprotection against oxidative challenge, the effects of L-buthionine-[S,R]-sulfoximine (BSO, a specific inhibitor of gamma-glutamate cysteine ligase (GCL)) and 1,3-bis(2-chloroethyl)-1-nitrourea (BCNU, a specific inhibitor of glutathione reductase (GR)) treatments or their combined treatment were examined in control and Sch B-treated AML12 and H9c2 cells, without and/or with menadione intoxication. Both BSO and BCNU treatments reduced cellular GSH level in AML12 and H9c2 cells, with the effect of BSO being more prominent. The GSH-enhancing effect of Sch B was also suppressed by BSO and BCNU treatments, with the effect of the combined treatment with BSO and BCNU being semi-additive. While Sch B treatment increased the GR but not GCL activity in AML12 and H9c2 cells, it increased the cellular cysteine level. BSO treatment also suppressed the Sch B-induced increase in GR activity. BSO or BCNU treatment per se did not cause any detectable cytotoxic effect, as assessed by lactate dehydrogenase leakage, but the combined treatment with BSO and BCNU was cytotoxic, particularly in H9c2 cells. The cytotoxic effect of BSO and BCNU became more apparent following the menadione challenge. The cytoprotection afforded by Sch B pretreatment was partly suppressed by BSO or BCNU treatment, or completely abrogated by the combined treatment with BSO and BCNU. In conclusion, the results indicate that the cytoprotective action of Sch B is causally related to the increase in cellular GSH level, which is likely mediated by the enhancement of GSH synthesis and regeneration.

Animals↗
PubMed1981

Chemotherapy following palliative resection of gastric cancer.

Twenty-five patients with residual tumour after resection of a primary gastric cancer were randomized to receive either 5-Fluorouracil or BCNU postoperatively or kept under close observation. Some patients receiving chemotherapy may have benefited by a delay in progression of their disease but this was short lived and subsequently all but one patient has died within a 4-year period of follow-up. There does not seem to be any advantage in treating patients who have residual gastric cancer with 5-FU and BCNU therapy.

Aged↗