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PubMed1994

Chemohormone therapy of metastatic melanoma with megestrol acetate plus dacarbazine, carmustine, and cisplatin.

BACKGROUND: Chemotherapy with dacarbazine, carmustine, and cisplatin produces a modest objective response rate in melanoma. Megestrol acetate may ameliorate cachexia, abrogate drug resistance, and increase survival time in melanoma. METHODS: Nineteen patients with metastatic melanoma (16 evaluable) treated with dacarbazine (220 mg/m2/day for 3 days, intravenously [IV]), cisplatin (25 mg/m2/day for 3 days IV) every 3 weeks, and carmustine (150 mg/m2 IV single dose every 6 weeks) together with megestrol acetate (160 mg/day by mouth continuously) starting 2 days before chemotherapy. RESULTS: This regimen was well tolerated and resulted in a mean net weight gain of 1.45 kg. A 47% objective response rate was observed in all patients, including visceral sites of response, with a 39+ week median duration of response and median survival time of 16.7+ months in all evaluable patients. CONCLUSIONS: In this small Phase II study, the authors showed that megestrol acetate may contribute to a high objective response rate and prolonged median survival when used with a chemotherapy regimen of dacarbazine, carmustine, and cisplatin.

Adult↗
PubMed1994

Acute effect of carmustine on glucose metabolism in brain and glioblastoma.

BACKGROUND: Adjuvant chemotherapy benefits a minority of patients with recurrent glioblastoma; a critical question therefore is how to select such responders. Metabolic reaction of the tumor, studied by positron emission tomography (PET) with [18F]-fluoro-2-deoxy-D-glucose (FDG), may be a suitable test of tumor responsiveness. In an effort to evaluate their prognostic value, the early effects of carmustine on brain and recurrent glioblastoma glucose metabolism were studied. METHODS: Positron emission tomography with [18F]fluoro-2-deoxy-D-glucose was used to study 10 patients with recurrent glioblastoma before and 24 hours after a first dose of carmustine (120 mg/m2). Absolute quantification of glucose metabolism was obtained, and metabolic changes were analyzed and confronted with survival duration. RESULTS: The mean ratios of pre- to postchemotherapy values were 0.98 +/- 0.06 (range, 0.90-1.06) for the cortex and 0.97 +/- 0.06 (range, 0.89-1.09) for the white matter. There was no statistical difference between pre- and post-chemotherapy metabolism. In the glioblastoma, individual ratios of pre- to postchemotherapy values were considerably more scattered than in the nonneoplastic tissues, ranging from 0.76 to 1.51. A significant positive correlation (P < 0.002) was found between post- to pre-chemotherapy ratios of glucose metabolism and survival length. CONCLUSIONS: In patients with recurrent glioblastoma, the first administration of carmustine produces no acute change of glucose metabolism in the noninvolved cerebral tissues. Acute changes of glucose metabolism in tumor tissue in response to this treatment varied, and a hypermetabolic reaction possibly predicts longer survival.

Adult↗
PubMed2007

Does high-dose carmustine increase overall survival in supratentorial high-grade malignant glioma? An EBMT retrospective study.

Radiotherapy plus concomitant and adjuvant temozolomide have demonstrated improved survival for glioblastoma. However, prognosis remains poor. High-doses chemotherapy with carmustine is another way to improve response and survival by increasing the dose delivered. Myelotoxicity imposes autologous stem cell rescue. European Group for Blood and Marrow Transplantation experience of this treatment in patients with high-grade glioma was reported here. A retrospective analysis of 217 patients from European Group for Blood and Marrow Transplantation database was realized. Ninety-six patients underwent complete surgical resection while the 121 others had partial resection or only biopsy and were evaluable for an antitumor effect. Patients received 800 mg/m2 of carmustine intravenously at least 1 month after neurosurgery. Forty-eight to 72 hr after chemotherapy, 108 patients received autologous hematopoietic stem cells from bone marrow harvest and 109 patients autologous hematopoietic stem cells from peripheral blood. Radiotherapy was started approximately 40 days after transplantation. Ten deaths were related to the treatment. Of the 121 patients evaluable for tumor response, 64 (53%) presented an objective response. This protocol appear feasible, but with toxicity-related mortality of 4.5%. Median overall survival was 20 months and median time to treatment failure was 7 months. Overall survival and time to treatment were correlated with age, quality of resection and histological subtypes. In glioblastoma multiforme, age and surgery quality appeared to be prognostic factors. Compared with Stupp et al.'s recent study, this study did not favor high-dose carmustine for patients with glioblastoma multiforme with complete surgical resection.

Adolescent↗
PubMed1977

Degradation of carmustine in aqueous media.

The degradation rate of carmustine was investigated in buffered aqueous media at several pH values. The buffering agents studied were those with potential use in parenteral formulations of this drug: acetate, citrate, and phosphate. The apparent first-order degradation rate constants were calculated using a linear regression procedure. A pH range over which minimum degradation occurred was ascertained. General acid and specific base catalysis was demonstrated for the degradation of carmustine. From the data at 5, 22, and 37 degrees, the apparent activation energies for carmustine degradation in buffered aqueous media were computed and were strongly pH dependent.

Buffers↗
PubMed1979

Pulmonary toxicity from carmustine (BCNU): a case report.

A patient who had a pneumonectomy for lung carcinoma was treated with carmustine when brain metastases developed. His pulmonary function was mildly compromised prior to the pneumonectomy by many years of smoking. After six months of carmustine therapy [total dose: 2,250 mg (1,200 mg/m2)] he developed interstitial pulmonary fibrosis with histologic changes consistent with drug toxicity. With seven previously reported cases of this drug-effect and the addition of our case, carmustine must be added to the list of cancer chemotherapeutic agents that can cause pulmonary toxicity.

Autopsy↗
PubMed2002

Successful therapy with high-dose steroids and cyclosporine for the treatment of carmustine-mediated lung injury.

The treatment of the pulmonary toxicity induced by carmustine is nowadays based on the use of corticosteroids that generally lead to a rapid resolution of pneumonitis. On the contrary, no therapeutic alternatives are reported for those patients who do not respond to steroids. We describe a case of non-Hodgkin's lymphoma in a patient who developed a severe interstitial pneumonitis after an autologous transplantation including carmustine in the conditioning regimen. He was successfully treated with an association of steroids and cyclosporine A with a rapid improvement of symptoms and a complete resolution of pneumonitis. This is, to our knowledge, the first case of carmustine-induced pneumonitis, resistant to steroids alone, successfully treated with cyclosporine A. This suggests an immunoallergic mechanism in the pathogenesis of the damage, which can be reversed with prompt therapy.

Adult↗
PubMed2002

Antiproliferative effect of thalidomide alone and combined with carmustine against C6 rat glioma.

Thalidomide could have therapeutic applications in neoplasms and in other diseases, particularly those of autoimmune origin. The objective of this study was to investigate the effect of various doses of thalidomide on the growth of C6 glioma in rats, and to determine its effects on parameters of cell proliferation and angiogenesis. Additionally, we investigated a potential enhancement of the antitumoral action of thalidomide when combined with a low dose of the antineoplastic carmustine. C6 glioma cells were implanted subcutaneously in Wistar rats. A highly malignant glioma developed in 80% of animals. When the tumour reached 2.0 cm diameter thalidomide was administered at doses of 100, 200 or 400 mg/kg/day. When given at a dose of 400 mg/kg/day thalidomide significantly reduced the tumour volume, the mitotic index and cell proliferation but not the vascular density. The combination of thalidomide plus carmustine increased the inhibitory effect on tumoral growth. Our results indicate that thalidomide is effective against malignant glioma; apparently by an antiproliferative effect, rather than by inhibition of angiogenesis; when combined with carmustine it could increase the response of glioma to antineoplastic treatment.

Angiogenesis Inhibitors↗
PubMed1990

Active lung fibrosis up to 17 years after chemotherapy with carmustine (BCNU) in childhood.

BACKGROUND: Carmustine (BCNU) is an anticancer drug known to produce pulmonary fibrosis as a side effect within three years of treatment. It is not known whether pulmonary fibrosis can appear later. METHODS: To investigate the clinical range of this side effect, we studied the survivors among 31 children treated with carmustine for brain tumors between 1972 and 1976. Fourteen had died of their tumor; of the remaining 17, 6 had died of lung fibrosis--2 within 3 years of treatment and 4 from 8 to 13 years after treatment. This report focuses primarily on the 11 survivors, 8 of whom were available for detailed study 13 to 17 years (mean, 14) after treatment. RESULTS: Of the eight survivors studied, six had abnormal chest radiographs showing predominantly upper-zone fibrotic changes. These patients also had abnormal CT scans, showing a previously undescribed pattern of upper-zone fibrosis. All the survivors studied had restrictive spirometric defects (mean [+/- SD] vital capacity, 54 +/- 19 percent of the predicted value). Bronchoalveolar-lavage fluid contained abnormal proportions of specific macrophage subgroups. Light and electron microscopy in six patients revealed interstitial fibrosis and elastosis with damage to epithelial and endothelial cells. Four patients had symptoms (shortness of breath, cough, or both). CONCLUSIONS: Carmustine chemotherapy in childhood causes lung fibrosis that may remain asymptomatic for many years or become symptomatic at any time.

Acute Disease↗
PubMed1983

Sustained release of carmustine (BCNU) for treatment of experimental intraocular malignancy.

Sustained release of carmustine (1,3-bis[2-chloroethyl]-1-nitrosourea, or BCNU) via an episcleral implanted silicone device was used to treat Greene hamster melanoma implanted in the anterior chamber of rabbit eyes. Group 1 animals received carmustine intravenously; group 2 received the drug by local sustained release via an episcleral implanted silicone device; group 3 received the drug by both local sustained release and intravenous injection (a total dosage more than twice that in group 1); and group 4 was not treated. The effectiveness of the various administration routes was compared by clinical observation of tumour size and systemic and local toxic reactions, and by histopathological examination. Carmustine delayed the growth of Greene melanoma in all 3 treated groups, but was most effective when a lower dose of the drug administered intravenously was combined with an additional higher dose administered by local sustained release. Local side effects included corneal clouding and conjunctival oedema and congestion at the early stage of local drug delivery via the episcleral implanted device.

Animals↗
PubMed1989

Permeability of two nitrosoureas, carmustine and fotemustine in rat cortex.

Carmustine and fotemustine were perfused using a bolus retrograde infusion into the right external carotid artery of rats. The right jugular vein gave blood samples. Using a previously described method, nitrosoureas were continuously measured in rat brain by voltammetry and in blood samples by high-performance liquid chromatography for 15 min. Cerebrovascular permeability coefficients calculated in the first 2 min were 0.9.10(-4) cm.s-1 for carmustine and 0.5.10(-4) cm.s-1 for fotemustine. These high brain permeability coefficients were compared to literature values for carmustine and other nitrosoureas determined with a radioactive procedure.

Animals↗
PubMed1995

High-dose cyclophosphamide, carmustine, and etoposide followed by allogeneic bone marrow transplantation in patients with lymphoid malignancies who had received prior dose-limiting radiation therapy.

PURPOSE: To evaluate a high-dose chemotherapy regimen without total-body irradiation (TBI) followed by allogeneic (allo) bone marrow transplantation (BMT) in patients with lymphoid malignancies who had received prior dose-limiting radiotherapy. PATIENTS AND METHODS: Fifty-six patients with non-Hodgkin's lymphoma (NHL, n = 26), Hodgkin's disease (HD, n = 17), or acute lymphoblastic leukemia (ALL, n = 13) with a history of previous radiation therapy were treated with cyclophosphamide (7.2 g/m2), carmustine (300 mg/m2 or 600 mg/m2), and etoposide (2,400 mg/m2; CBV) followed by allo BMT. RESULTS: Nine of 56 patients are alive and disease-free a median of 1,091 (range, 512 to 1,784) days post-transplant. The probabilities of transplant-related mortality, relapse, and event-free survival at 2 years for the entire group of 56 patients were .62, .59, and .17, respectively. Patients who received 600 mg/m2 of carmustine had a higher incidence of grade 3 or 4 regimen-related toxicities (RRTs) (14 of 22) than did patients who received 300 mg/m2 (12 of 33; P < .04), whereas there was no difference in relapse (.34 and .53, respectively, P = .73). Fourteen of 16 patients who received allo BMT for advanced disease (n = 12) or less-advanced disease (n = 4) but who were also eligible for auto BMT relapsed (n = 4) or died of transplant-related complications (n = 10). CONCLUSIONS: Allo BMT following a high-dose CBV regimen resulted in long-term disease-free survival in 17% of patients with lymphoid malignancies who had received prior dose-limiting radiotherapy. A high incidence of transplant-related complications, especially fatal idiopathic pneumonia syndrome (IPS) and a high relapse rate limited success. Morbidity and mortality associated with carmustine 600 mg/m2 were high and were not associated with a decrease in relapse. The number of patients in this study eligible for either allo or auto BMT was limited and precluded meaningful analysis of relative effectiveness.

Adolescent↗
PubMedDate not supplied

Carmustine, vincristine, and prednisone in the treatment of canine lymphosarcoma.

A chemotherapeutic protocol using carmustine in combination with vincristine and prednisone was tested in dogs with multicentric malignant lymphosarcoma. Of seven dogs treated, six (85.7%) achieved complete remission. A partial response occurred in one dog. Median survival time was 224 days (mean 386 days), and median duration of remission was 183 days (mean 323 days). Marked neutropenia was observed following carmustine administration. There were no significant alterations in platelets and red blood cell counts during treatment, and no abnormalities attributable to the chemotherapy were found in serum biochemical profiles. Results of this study showed that carmustine is an effective alternative option in the treatment of canine lymphosarcoma.

Animals↗
PubMed2002

Association of high-dose cyclophosphamide, cisplatin, and carmustine pharmacokinetics with survival, toxicity, and dosing weight in patients with primary breast cancer.

This report investigates relationships between the pharmacokinetics and pharmacodynamics of high-dose alkylators used for the treatment of primary breast cancer. Eighty-five women with primary breast cancer involving >or=10 lymph nodes received four cycles of standard-dose chemotherapy followed by a high-dose regimen consisting of: cyclophosphamide (1875 mg/m(2) once daily x 3), cisplatin (165 mg/m(2) given over 72 h), carmustine (600 mg/m(2)), and stem cell transplantation. Dosages were attenuated in patients whose body weight exceeded their calculated ideal weight by >20%. Pharmacokinetics of the high-dose chemotherapeutic agents were evaluated in each patient by collection and analysis of serial blood samples. Area under the concentration time curve (AUC) for cyclophosphamide and carmustine was highly variable (>10-fold inter-patient range) with coefficients of variation > 50%, in contrast to cisplatin exposures (2-fold range; coefficient of variation 12%). The dosing method for overweight patients resulted in significantly lower systemic exposure to cisplatin (P = 0.035). The parent cyclophosphamide clearance on the 1st day of administration was significantly higher in patients who experienced acute cardiac toxicity (n = 5; P = 0.011), whereas carmustine disposition was not found to be different in those developing pulmonary toxicity (n = 25; P = 0.96). Kaplan-Meier analysis (median follow-up of 5.9 years) demonstrated that patients with lower cyclophosphamide AUC (faster parent drug clearance to potentially cytotoxic compounds) survived longer (P = 0.031). Inter-individual differences in the pharmacokinetic disposition of high-dose chemotherapy may explain variability in both response and toxicity. Prospective strategies, which attempt to individualize AUC, should be evaluated in this setting.

Adult↗
PubMedDate not supplied

Effects of temperature, solution composition, and type of container on the stability and absorption of carmustine.

The stability and absorption of carmustine were studied comparatively in glass flasks and Stedim 6 bags. Stedim 6 is a new, multilayer, polyethylene-lined film. When stored at room temperature (22 degrees C +/- 2 degrees C) in the dark, carmustine decomposed in 5% dextrose solution and more so in 0.9% sodium chloride solution. When stored at 4 degrees C +/- 0.5 degrees C, the losses were identical in the glass flasks and Stedim 6 bags (about 11% after 72 hours). As long as they are kept in the dark at 4 degrees C, carmustine admixtures can be prepared up to 48 hours before administration, in either dextrose or sodium chloride isotonic solutions, and stored in either glass flasks or Stedim 6 bags.

Absorption↗
PubMed1987

Effect of inhibition of glutathione reductase by carmustine on central nervous system oxygen toxicity.

Exposure of animals to O2 at increased partial pressures above 2.5 atmospheres absolute results in seizures. The endogenous intracellular antioxidant defense mechanisms are thought to play a protective role in mitigating such seizures. Investigations were carried out to determine if inhibiting brain glutathione reductase with carmustine would result in an alteration in time to seizures of rats exposed to high pressure O2. Treatment of air-breathing rats with carmustine (12.5, 25 and 50 mg/kg i.v.) resulted in a dose-dependent decrease (P less than .001) in whole-brain glutathione reductase activity without affecting the activities of the other components of the antioxidant defense mechanisms determined. This treatment also resulted in a dose-dependent decrease (P less than .001) in time to seizure of rats exposed to four atmospheres absolute O2. Conversely, treatment of rats with lomustine (30 mg/kg i.v.), a nitrosourea compound related to carmustine, failed to affect the activity of brain glutathione reductase or any other component of the antioxidant defense mechanism determined, or did it influence the seizure time of rats exposed to four atmospheres absolute O2. These results suggest that glutathione reductase is an integral component of the antioxidant defense mechanisms. Inhibition of this enzyme results in an alteration in sensitivity of the organism to the toxic effects of O2.

Animals↗
PubMed1985

Topical carmustine therapy for lymphomatoid papulosis.

Seven patients with lymphomatoid papulosis were treated with solutions of topical carmustine, a nitrosourea compound. Recently used schedules have employed 10 mg of carmustine in dilute alcohol applied to the total skin surface daily for four to 17 weeks (total dosage, 280 to 1,180 mg). All patients experienced a rapid reduction in the number and size of lesions. Maintenance therapy consisted of local applications of carmustine (2 to 4 mg/mL of 95% ethanol) to individual new papules. This method was effective in suppressing disease activity and reduced by half the average life cycle of individual lesions. However, long-term lesion-free remissions were not seen. Bone marrow depression did not occur.

Administration, Topical↗
PubMed1982

[Alternative treatment with carmustine, vindesine and tamoxifen in previously cytostaticly (VAC, FMC) treated patients with metastatic breast cancer].

Looking for an alternative treatment for patients with advanced breast carcinoma resistant to the common treatment regimens, vindesine, carmustine (BCNU) and tamoxifen were used for further treatment. 27 patients were admitted to a two-step-treatment-schedule including a step I with tamoxifen alone and a step II with vindesine, carmustine and tamoxifen. Within the step I with tamoxifen 7 of 14 patients (50%) and within the consecutive step II with vindesine, carmustine and tamoxifen 4 of 20 patients (20%) responded to this regimen. The mean duration of the response was + 7.4 and + 9.0 months, respectively. The results suggest that effective palliation is still possible in some patients suffering from progressive disease after therapy with vincristine + adriamycin + cyclophosphamide and 5-fluorouracil + methotrexate + cyclophosphamide.

Adult↗
PubMed1995

Chronic relapsing polyradiculoneuropathy in IgG lambda monoclonal gammopathy of undetermined significance (MGUS)--complete remission following carmustine treatment.

A previously healthy 43 year-old female developed IgG lambda monoclonal gammopathy of undetermined significance (MGUS) and ascending sensorimotor polyradiculoneuropathy which relapsed 11 times within 2 years. Marked improvement was noted repeatedly after plasmapheresis. However, on each occasion symptoms and signs of polyradiculoneuropathy recurred almost exactly 3 weeks after plasma-pheresis. Following 6 weeks of treatment with carmustine (70 mg/week), nearly complete recovery was established, which has persisted up to now (82 months after the end of therapy). The close temporal correlation between clinical relapse and recurrence of the IgG paraprotein and its permanent absence in stable clinical remission after carmustine treatment suggest a causal relationship between the paraprotein and the polyradiculoneuropathy. However, further studies are required to confirm this observation, as well as the efficacy of carmustine therapy.

Adult↗