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PubMed1986

Prevention of ocular toxicity of carmustine (BCNU) with supraophthalmic intracarotid infusion.

Intracarotid administration of carmustine (BCNU) is an increasingly accepted therapeutic modality for primary brain tumors. Its beneficial effect on prolonging survival, however, is countered by its frequent delayed complication of retinal toxicity and severe visual loss, which reportedly occurs in approximately 70% of the patients. Since this complication probably results from increased flow of the drug into the ophthalmic artery, the authors have attempted to infuse BCNU via a small intracarotid catheter advanced beyond the origin of the ophthalmic artery. In a series of nine patients (average follow-ups, 10.7 months), the authors were successful in treating six patients with exclusively supraophthalmic infusions. None of these patients developed any ocular toxicity. From the remaining three patients, two patients received one infraophthalmic infusion with no retinal toxicity. The third patient, however, who received three infraophthalmic infusions, developed ipsilateral retinopathy. These results suggest that retinopathic complications of intracarotid BCNU can be avoided if the infusion catheter is advanced beyond the origin of the ophthalmic artery.

Adolescent↗
PubMed1983

Topical carmustine (BCNU) for mycosis fungoides and related disorders: a 10-year experience.

A 10-year experience in eighty-six patients confirms the effectiveness of topical carmustine (BCNU) in mycosis fungoides (MF). Complete remission (CR) was achieved in 84% of those with less than 10% involvement (stage IA), median CR, 12 months, and in 52% with greater than 10% involvement (stage IB), median CR, 23 months. The probability of freedom from relapse for 1 year was 72% in stage IA and 37% in stage IB. No deaths in stages IA or IB were attributable to MF. Including all causes of death, the probability of 5-year survival for stage IA was 93% and for stage IB, 48%. Good results were obtained with only local BCNU in fourteen patients with mostly less than 5% involvement. Five of seven with poikilodermatous MF, two with parapsoriasis en plaques (PEP), and three with lymphomatoid papulosis did well. Persistent local therapy cleared deeply infiltrated lesions in some patients. With present schedules, the hazard of bone marrow depression is slight. Erythematous reactions and telangiectasia are troublesome but have not been accompanied by premalignant changes.

Administration, Topical↗
PubMed1999

Cytoprotective effects of trimetazidine in carmustine cholestasis.

Carmustine [1 ,3-bis(2-chloroethyl)-1-nitrosurea (BCNU)] is an antitumour agent, however, its usefulness has been limited by a side effect; which involves pericholangitis and intrahepatic cholestasis. The primary effects of cholestasis is well known; bile flow retention, intracellular Ca++ accumulation and acidosis although it may lead to hepatotoxicity by dose-dependent manner. Recent studies provide evidence that lipoperoxidation (LPO) and alterations in the antioxidant system may significantly contribute to BCNU induced hepatotoxicity. Trimetazidine, (1-[2,3,4-Trimethoxy-benzyl] piperazine HCl; TMZ) introduced as an antianginal compound, is found to exhibit various cytoprotective features by preserving cellular ATP levels, limiting intracellular acidosis and inorganic phosphate as well as Na+ and Ca++ accumulation in ischemic cardiac injury. No study was undertaken to investigate the cytoprotective role of TMZ in cholestatic injury till today; therefore we initiated this study to investigate if its cytoprotective features also exhibit in the liver and to characterize further the cholestatic response to BCNU administration. Male rats were randomly seperated to control (CONT) (n = 15), BCNU administered (BCNU) (n = 16) and BCNU+TMZ administered (BCNU+TMZ) (n = 12) groups. The control rats received a single dosage of 2 ml/kg of corn oil (i.p.) while the BCNU group received a single dosage of BCNU (20 mg/kg, i.p.) in corn oil. In the BCNU + TMZ group 2,5 mg/kg/day (i.p.) of TMZ was administered for three days. This group also received BCNU (20 mg/kg, i.p.) in corn oil, 12 hours after the initial dose of TMZ. The cholestatic effect of BCNU was monitored by stasis markers such as ALP, GGT and total bilirubin levels. Hepatic TBARS analysis was determined with the modified method of OKHAWA et al. based on the reaction of lipid peroxides with thiobarbituric acid. Oxidized (GSSG) and reduced (GSH) glutathione levels were measured by the modified enzymatic recycling method of TEARE et al. Statistical tests were performed using Kruskal Wallis one-way Anova test and posthoc analysis by Newman-Keuls test. The BCNU group and the BCNU + TMZ group showed significant increases (p = 0.029) in hepatic TBARS levels compared to the CONT group; however the difference between the BCNU and BCNU + TMZ groups in regard to TBARS was not significant. BCNU and BCNU + TMZ groups manifested a significant decrease (p = 0.0005) in GSH levels as compared to controls. GSH/GSSG ratios in the BCNU and BCNU + TMZ group also manifested a significant decrease (p = 0.0013) as compared to the CONT group. TMZ administration caused a significant increase in total GSH levels (p = 0.0026) in BCNU + TMZ group when compared to the BCNU group. Our results support the hypothesis that BCNU induced cholestasis partly involves LPO revealed by the distinct increase in the content of TBARS in the liver after BCNU administration. BCNU is a potent inhibitor of GSSG reductase altering the preservation of the thiol redox balance in the system. As a result, supranormal concentrations of intracellular GSSG would accumulate in the hepatocyte and the extrusion of this oxidized compound would require active transport leading to ATP hydrolysis. This would deplete the energy stores of the cell which would accelerate further the possible prooxidant status. Although administration of TMZ did not provoke any significant alterations in LPO, it preserved the total GSH levels of the cell probably by improving the energy status of the cell by protection of ATP-producing processes at the mitochondrial level and provision of the necessary substrates for GSH synthesis. This protective role in the antioxidant system normalizes the altered GSH levels by BCNU and hence proposes TMZ to be a promising agent in the cholestatic injury.

Animals↗
PubMed2004

Interstitial infusion of carmustine in the rat brain stem with systemic administration of O6-benzylguanine.

Interstitial infusion of carmustine (BCNU) into the rat brain stem in conjunction with systemic administration of O6-benzylguanine (O6-BG) was performed in an effort to assess clinical tolerance. A total of 12 rats underwent stereotactic cannula placement into the pontine segment of the brain stem. Six of the rats underwent a 24-h infusion of BCNU (Volume of infusion [Vi] 200 microl) at its maximal concentrated dose (3.3 mg/ml) in 5% dextrose water. Six additional rats underwent 24-h infusion of BCNU preceded by an intraperitoneal injection of O6-BG at a dose of 50 mg/kg. Serial neurological examinations were performed on all animals. Histologic analyses were performed immediately or 2 weeks following sacrifice. Postoperatively, there were no neurological changes in any of the animals. Postmortem histological examination of the brains showed small pontine cavitary lesions (ranging from 20 to 250 microm) containing variable numbers of macrophages or neutrophils consistent with an inflammatory response. No changes beyond these findings indicated any histological evidence of injury. These finding were limited only to the cannula site and no changes beyond region of the cannula tract were found. These findings indicate that interstitial infusion of BCNU into the brain stem in conjunction with systemic administration of O6-BG is safe in a small animal and may serve as a potential investigative strategy for children with diffuse pontine gliomas.

Animals↗
PubMed2001

Comparison of vincristine, carmustine, melphalan, cyclophosphamide, prednisone (VBMCP) and interferon-alpha with melphalan and prednisone (MP) and interferon-alpha (IFN-alpha) in patients with good-prognosis multiple myeloma: a prospective randomized study. Greek Myeloma Study Group.

OBJECTIVES: The purpose of the study was to evaluate, in a selected group of myeloma patients with favorable prognosis, the effect, on response and survival, of polychymotherapy compared with melphalan prednisone, plus interferon in both arms. METHODS: Eighty-nine previously untreated patients with multiple myeloma and prognostic factors indicating a good prognosis were randomized to either oral melphalan plus prednisone (MP) in combination with recombinant interferon-alpha (rIFN-alpha) or combination chemotherapy with vincristine, carmustine, melphalan, cyclophosphamide, and prednisone (VBMCP) alternating with rIFN-alpha. The two treatment groups were comparable in terms of pretreatment characteristics. RESULTS: The overall response rate was 67.4% (2.3% complete remission, 65.1% partial response) in the MP/IFN-alpha group and 69.1% (14.3% complete remission, 54.8% partial response) in the VBMCP/IFN-alpha group (p=0.59). There were no differences also in response duration and overall survival between the two treatment groups. The median response duration was 39.1 months in the MP/IFN-alpha group and was not reached in the VBMCP/IFN-alpha group (p = 0.6). Overall survival was long in both treatment groups. The estimated 5-yr survival was 66% and 62% in the MP/IFN-alpha and VBMCP/IFN-alpha group, respectively (p=0.8). Toxicity was modest and treatments were well tolerated. Neutropenia (WHO grade 3 or 4) was higher, but not statistically significant, in the VBMCP/IFN-alpha group. CONCLUSIONS: The results of the study show that in myeloma patients with good prognosis, combination chemotherapy alternating with interferon-alpha has no advantage over conventional MP plus interferon-alpha, in regard to response rate, response duration, and overall survival of patients.

Aged↗
PubMed1990

Enhanced anti-tumour activity of carmustine (BCNU) with tumour necrosis factor in vitro and in vivo.

The effects on experimental melanoma of a combination of recombinant human tumour necrosis factor alpha (rhTNF alpha) and carmustine (BCNU) were studied in vitro and in vivo. In vitro, BCNU alone was cytotoxic to murine B16 melanoma cells, and at all concentrations of BCNU this toxicity was increased by the addition of TNF. In vivo, BCNU and TNF, when given separately, caused tumour growth delay of B16 melanoma and of human melanoma xenografts in immune-deprived mice. The combination of TNF at low dose 2.5 x 10(5) U kg-1 = 122 ng kg-1) with BCNU (35 mg kg-1) resulted in significant growth delay (compared with either drug alone) in B16 melanoma (P = 0.005). There was no significant increase in toxicity as assessed by weight loss and peripheral blood counts. Experiments with human melanoma xenografts yielded similar results (P = 0.001) but only at higher doses of TNF (1 x 10(6) U kg-1 = 489 ng kg-1). The enhancement of BCNU cytotoxicity by TNF may be important if it can be translated into patients with melanoma. A randomised study is now underway to investigate the clinical potential of this observation.

Animals↗
PubMed1997

Headache, circumoral paresthesia, and facial flushing associated with high-dose carmustine infusion.

We describe seven patients who developed symptoms including severe headache, circumoral paresthesia, and facial flushing during high-dose carmustine (BCNU) infusion as part of the preparative regimen for autologous peripheral blood stem cell (PBSC) transplantation for metastatic breast cancer. Five patients responded to pain medications, including partial and complete opiate receptor agonists. Premedication of subsequent doses of BCNU with corticosteroids, pain medications, or benzodiazepines lessened, but did not prevent the same symptoms from recurring. The incidence and mechanism of this toxicity are unknown, but this adverse syndrome should be considered when administering high-dose BCNU infusions.

Antineoplastic Agents, Alkylating↗
PubMed1999

Regimen-related toxicity and non-relapse mortality with high-dose cyclophosphamide, carmustine (BCNU) and etoposide (VP16-213) (CBV) and CBV plus cisplatin (CBVP) followed by autologous stem cell transplantation in patients with Hodgkin's disease.

This analysis compares the regimen-related toxicity (RRT) and overall non-relapse mortality (NRM) in Hodgkin's disease patients conditioned with either CBV (cyclophosphamide, BCNU (carmustine), and VP16-213 (etoposide)) (26 patients) or CBVP (CBV + cisplatin) (68 patients) followed by autologous stem cell transplantation (ASCT). CBVP included a continuous infusion rather than intermittent doses of etoposide, a lower BCNU dose and the addition of cisplatin. RRT and NRM were determined for each regimen and compared; risk factors for each were examined by multivariate analysis. Grade IV (fatal) RRT occurred in five patients (pulmonary in two, cardiac in two, and central nervous system in one). Eighteen patients experienced grade II-III pulmonary RRT, consistent with BCNU damage in 15. Prior nitrosourea exposure was the main risk factor for pulmonary RRT. Grade II mucosal and hepatic RRT occurred less often after CBVP vs CBV (P = 0.031 and 0.0003, respectively). In addition, three other early and eight late non-relapse deaths were seen. Median follow-up of the entire group is 5.1 (range 2.8-10.2) years. The probability of overall NRM was 26% (95% confidence interval (CI) 13-50%) with CBV vs 23% (95% CI 12-41%) with CBVP (P = 0.40). The progression-free survival and relapse rates were similar. Although the rates of fatal RRT, pulmonary RRT and overall NRM were similar with CBV or CBVP, CBVP produced less mucosal and liver RRT with a comparable antitumor effect. As many autografted patients are cured, future efforts should include measures to decrease NRM.

Adult↗
PubMed2000

Rapid achievement of complete donor chimerism and low regimen-related toxicity after reduced conditioning with fludarabine, carmustine, melphalan and allogeneic transplantation.

Between August 1998 and July 1999, 21 patients received a novel protocol of reduced conditioning with fludarabine, carmustine and melphalan (FBM) followed by matched-related allogeneic peripheral blood stem cell transplantation (PBSCT) in a prospective multi-center phase I/II study. Cyclosporin A and 'mini-methotrexate' were used for GVHD prophylaxis. Patients were included because of age, advanced disease, previous transplantation or co-morbidity. Hematopoietic engraftment after allogeneic transplantation was rapid with a median white blood count (WBC) >1 x 10(9)/l on day +11 (range 10-17) and a median platelet count >20 x 10(9)/l on day +13 (range 9-36). Donor chimerism was complete in 16/21 (76%) patients at all time points during follow-up and mixed at least on one occasion in 5/21 (24%) patients. The conditioning regimen was well tolerated with low toxicity even in previously transplanted patients. Thirteen patients (62%) developed acute GVHD grades II-IV. Nineteen out of 21 patients achieved complete (CR, n = 15) or partial remission (PR, n = 4) with a median patient follow-up of 354+ days (range 258-577) for patients alive. The reduced intensity protocol FBM is feasible with rapid engraftment, early achievement of complete donor chimerism, low toxicity, especially in heavily pretreated patients, and good response rates in advanced disease patients.

Adult↗
PubMed1984

[Prospective randomized study in advanced stomach cancer. Comparison between combinations of 5-fluorouracil and carmustine without and with adriamycin].

In a multi-center study of 77 patients with gastric carcinoma and metastases, the effects of combined 5-fluorouracil and carmustine with or without adriamycin (FB vs FAB) were compared. There was no significant difference between the two treatment groups as to rate of response or survival time, response to treatment was 20% (FB) and 24% (FAB), including "no change" 52% and 56%, respectively. But median survival time among the responders (partial remission and clinical improvement) and of the patients with unchanged findings was significantly longer (8.4 or 7.4 months, respectively) than that among patients with progression (4.5 months). Analysis of prognostic factors in terms of survival curves revealed no difference between patients with or without measurable tumor parameters, with or without local recurrences or liver metastases. However, there was a statistically significant worsening of prognosis for patients whose initial general state was reduced, who had lung metastases or increased WBC counts. Side effects were relatively mild with both therapy regimens, except for alopecia with FAB. After the second treatment cycle myelosuppression was more marked with FAB than FB.

Adult↗
PubMed2005

Augmented high-dose regimen of cyclophosphamide, carmustine, and etoposide with autologous hematopoietic stem cell transplantation for relapsed and refractory aggressive non-Hodgkin's lymphoma.

Progressive disease is the major cause of treatment failure after autologous hematopoietic stem cell transplantation for relapsed or refractory non-Hodgkin's lymphoma. An augmented high-dose regimen of cyclophosphamide 7,200 mg/m2, carmustine 300 - 400 mg/m2, and etoposide 2,400 mg/m2 (CBV) was developed in an attempt to improve disease control post-transplant. Sixty-seven adult patients received augmented CBV followed by infusion of unpurged autologous peripheral blood stem cells. Thirty seven patients had relapsed after standard chemotherapy, 28 patients had primary refractory disease, and 2 patients had transformed lymphoma in first partial response. Treatment-related mortality was 4%. Actuarial four year overall survival and progression-free survival were 46+/-8% and 36+/-6%, respectively. Risk factors for disease progression were histologic involvement of marrow by lymphoma and infusion of increased numbers of CD34 + cells per kg in the stem cell autograft. The outcome for patients with relatively chemorefractory disease (defined as 25 - 49% reduction in tumor volume after salvage chemotherapy) was no different than that for patients with chemosensitive disease. Compared to standard high-dose CBV regimens, augmented CBV does not appear to have substantially improved disease control. Prospective study of the association between inferior progression-free survival and infusion of higher CD34 + cell doses in stem cell autografts is warranted.

Adult↗
PubMed2002

Chemosensitization of carmustine with maitake beta-glucan on androgen-independent prostatic cancer cells: involvement of glyoxalase I.

OBJECTIVE: To improve the poor efficacy (< 10%) of chemotherapy for patients with hormone-refractory prostate cancer, we investigated a possible cytotoxic effect of carmustine/beta-glucan combination on prostatic cancer PC-3 cells, focusing on a glutathione-dependent detoxifying enzyme, glyoxalase I (Gly-I). METHODS: Carmustine (BCNU) is an anticancer agent and a putative inhibitor of Gly-I, while beta-glucan is a unique, nontoxic polysaccharide extracted from maitake mushrooms. The cytotoxic effects of BCNU or other anticancer agents with beta-glucan on PC-3 cells were assessed by cell-viability testing and Gly-I activity was measured using the spectrophotometric method. RESULTS: BCNU, 5-fluorouracil (5-FU), and methotrexate (MTX) were capable of inducing approximately a 50% reduction in cell viability at 72 hours, while etoposide, cisplatin, and mitomycin C were all ineffective. Only the combination of BCNU (50 micro ;mol) and beta-glucan (60 micro g/mL) exhibited an enhanced cytotoxicity with an approximate 90% cell viability reduction, but little improvement was seen with any combinations of 5-FU, MTX, or beta-glucon. Gly-I assays revealed that such a profound (approximately 90%) cell death was accompanied by an approximate 80% reduction in Gly-I activity by 6 hours. CONCLUSION: This study demonstrates a sensitized cytotoxic effect of BCNU with beta-glucan in PC-3 cells, which was associated with a drastic (approximately 80%) inactivation of Gly-I. Therefore, the BCNU/beta-glucan combination may help to improve current treatment efficacy by targeting Gly-I, which appears to be critically involved in prostate cancer viability.

Agaricales↗
PubMed1992

Phase I study of streptozocin- and carmustine-sequenced administration in patients with advanced cancer.

BACKGROUND: Fewer than 20% of patients with nonhematologic malignancies treated with chloroethylnitrosoureas (CENUs) respond, but streptozocin (STZ), which depletes O6-methylguanine-DNA-methyltransferase (MGMT), has been shown to reverse resistance to CENUs in vitro. PURPOSE: The purpose of this phase I study was to determine (a) the maximum tolerated dose (MTD) of carmustine (BCNU), a CENU, plus a fixed dose of STZ; (b) the toxic effects of the drugs; and (c) the effects on peripheral blood mononuclear cells (PBMC). METHODS: A clinical phase I study of STZ followed by BCNU was designed to simulate conditions that produce maximal sensitization of CENU-resistant HT-29 cells in vitro. Patients received a 20-minute infusion of the MTD of STZ (2 g/m2) followed 1 hour later with a 60-minute infusion of BCNU (100, 125, 137.5, or 150 mg/m2). Treatment was repeated after 6 weeks. Twenty-four patients with advanced malignancies received 32 courses of therapy (range, 1-2 courses). RESULTS: The MTD of BCNU was 125 mg/m2. The dose-limiting toxic effect was thrombocytopenia occurring about 22 days after treatment, with recovery between days 28 and 35. Transient hypophosphatemia and proteinuria were common, and serum creatinine was elevated in 9% of the courses. Two patients who received therapy died--one due to pulmonary toxic effects and one due to hepatic toxic effects. Two patients with previously untreated carcinoid achieved partial response. In three patients, MGMT levels in PBMC were more than 85% depleted after STZ administration and more than 90% depleted after BCNU infusion. CONCLUSIONS: These results show that the magnitude of MGMT depletion by STZ in PBMC is in the range necessary to produce sensitivity to CENUs in resistant cell lines but also that, when BCNU is combined with STZ, the MTD of BCNU is about 50% that of BCNU as a single agent and that platelet count suppression occurs earlier. IMPLICATIONS: We plan to conduct phase II studies of STZ plus BCNU in tumor types with low response to CENUs. One of the major goals will be to demonstrate that depletion of MGMT is greater in tumor cells than in normal cells.

Adult↗
PubMed1992

Adjuvant chemotherapy in malignant melanoma using dacarbazine, carmustine, cisplatin, and tamoxifen: a University of South Florida and H. Lee Moffitt Melanoma Center Study.

A prospective, nonrandomized trial was performed of the four-drug chemotherapy protocol consisting of dacarbazine, carmustine, cisplatin, and tamoxifen citrate given to high-risk patients for recurrence of melanoma after local regional treatment. The treated patients were consecutively registered and 6 patients who did not elect to be treated served as the control population. Criteria for inclusion in the trial were the presence of four or more lymph nodes positive for metastatic melanoma on regional modal dissection, the presence of metastatic disease in second station lymph node areas such as the iliac basin, greater than 5 cm in maximal diameter tumor burden in the nodal basin, and patients who had resected stage 4 (systemic metastases) disease with clear margins and were rendered free of disease. Actuarial survival curves for the treated group and the control subjects were similar (p = 0.91). There was a definite trend toward an increased disease-free survival for the group receiving adjuvant chemotherapy (p = 0.09). The mean disease-free survival for the control population was 200 days and for the treated group, 600 days. The study suggests a therapeutic benefit for adjuvant chemotherapy treatment of patients with metastatic melanoma who have been rendered free of disease but are at high risk for recurrence.

Adult↗
PubMed1992

Treatment of stage IV malignant melanoma with dacarbazine, carmustine, cisplatin, and tamoxifen regimens: a University of South Florida and H. Lee Moffitt Melanoma Center Study.

Fourteen consecutive patients with stage IV metastatic melanoma with measurable disease were treated between January 1989 and August 1990 with combination chemotherapy. The chemotherapy regimen (DBPT) included dacarbazine (DTIC) 200 mg/m2/i.v. on days 1 through 3, carmustine (BCNU) 150 mg/m2/i.v. on day 1, cisplatin 25 mg/m2/i.v. on days 1 through 3, and tamoxifen citrate 10 mg p.o. twice daily. This cycle was repeated every 4 weeks. BCNU was given every other cycle. A total of six cycles of chemotherapy were delivered. Patients were then restaged to assess the response. Six concurrent patients during the study period did not elect to undergo chemotherapeutic approach and served as control subjects. When evaluated at 300 days of follow-up, 4 patients had response (3 complete response and 1 partial response), 3 had stable disease, and 7 showed progression. At 300 days of evaluation after chemotherapy, survival appeared significantly increased between treated and nontreated groups, that is, 48% in the chemotherapy group versus 27% in the control group (p = 0.03). Actuarial survival was significantly increased between those who responded to chemotherapy versus the nonresponders. At 300 days follow-up, survival was at 83% in the responders and 22% in nonresponders (p = 0.0002). This study shows that in stage IV disease, systemic chemotherapy appears to make a difference in survival. Attempts to discover better chemotherapy regimens to improve response in patients with stage IV malignant melanoma should continue to be rewarded.

Adult↗
PubMed1999

Phase I evaluation of preirradiation chemotherapy with carmustine and cisplatin and accelerated radiation therapy in patients with high-grade gliomas.

OBJECTIVE: A Phase I study was conducted to determine the safety, toxicity, and maximum tolerated dose of preirradiation chemotherapy using carmustine (BCNU) and cisplatin in the treatment of high-grade gliomas. METHODS: Patients with newly diagnosed high-grade gliomas received BCNU and cisplatin after surgery, both before and during definitive radiation therapy. Preirradiation chemotherapy consisted of an administration of 40 mg/m2 BCNU on Days 1 through 3 and 30 mg/m2 cisplatin on Days 1 through 3 and 29 through 31 and repeated at 8 weeks to coincide with the start of radiation therapy. Postradiation chemotherapy consisted of an administration of 200 mg/m2 BCNU once every 8 weeks for four cycles. Radiation therapy consisted of 160-cGy fractions administered twice daily for 15 days, yielding a total dose of 4800 cGy. Dose escalation of BCNU was planned. If hematological toxicity was mild, the dose of cisplatin was to be held constant and BCNU dose escalated to 50 mg/m2 on Days 1 through 3. RESULTS: Eighteen patients were studied. The hematological toxicity was dose-limiting. Grade 3 or 4 leukopenia occurred in each of 10 patients (56%), and Grade 3 or 4 thrombocytopenia occurred in each of 9 patients (50%). Other toxicities included anorexia (94%), nausea (83%), emesis (33%), alopecia (94%), mild ototoxicity (50%), and, in one patient, death as a result of BCNU pulmonary toxicity. The median survival time was 14 months. Objective responses occurred in 45% of the patients evaluable for response. The maximum tolerated dose of this combination was 50 mg/m2 BCNU on Days 1 through 3 and 30 mg/m2 cisplatin on Days 1 through 3 and 29 through 31 before radiation and repeated in 8 weeks to coincide with the start of radiation. CONCLUSION: This schedule of the preirradiation administration of BCNU and cisplatin with accelerated hyper-fractionated radiation therapy for the treatment of high-grade gliomas provides a less toxic alternative to that of previous studies of preirradiation chemotherapy with these agents and merits further investigation.

Adult↗
PubMed1995

Dacarbazine, cisplatin and carmustine, with or without tamoxifen, for metastatic melanoma: 5-year follow-up.

Metastatic melanoma has a grim prognosis. Response rates and survival of patients treated with combination chemotherapy are not superior to single-agent chemotherapy. This study seeks to evaluate the objective response rate and survival of patients with metastatic melanoma treated with multiagent chemotherapy, with or without tamoxifen. Forty-two patients with metastatic melanoma were treated from March 1982 to February 1988 with dacarbazine, cisplatin and carmustine, with or without tamoxifen. An overall objective response rate of 43% was seen (complete response rate 17%; partial response rate, 26%). The response rate was 54% for patients treated with tamoxifen and 25% for patients treated without tamoxifen, but the results did not achieve statistical significance. Median overall survival was 412 days, and was significantly longer in the tamoxifen-treated group. Combination chemotherapy as described in this study is well-tolerated. The observation that tamoxifen appears to impact on survival should be interpreted with great caution due to the deficiencies in the design of the trial and small patient numbers. A randomized trial of this regimen vs single-agent chemotherapy is indicated and is currently being conducted.

Adult↗
PubMed1997

A phase II study of interferon-alpha 2b with dacarbazine, carmustine, cisplatin and tamoxifen in metastatic melanoma.

A phase II trial was conducted to determine the efficacy and toxicity of the addition of interferon-alpha 2b (IFN-alpha) to the chemotherapy combination of dacarbazine (DTIC), carmustine (BCNU), cisplatin and tamoxifen (DBCT), in patients with stage III or IV melanoma. Treatment consisted of DTIC 220 mg/m2 and cisplatin 25 mg/m2 intravenously on days 1-3, BCNU 100 mg/m2 IV on day 1 only, tamoxifen 20 mg orally twice daily and IFN-alpha 5 x 10(6) units/m2 subcutaneously on days 1-5. Cycles were repeated every 4 weeks. All patients received a loading dose of tamoxifen 100 mg orally twice daily for 5 days before the first course of therapy. Of the 24 patients treated, three (13%) achieved a complete response (CR) and six (25%) a partial response (PR), for an overall response rate of 38% (95% confidence interval, 17-58%). Two patients, one who achieved a clinical CR and one a PR, had pathologically confirmed complete responses. Severe myelosuppression occurred in 47% of cycles and constitutional symptoms were common. Overall, the addition of IFN-alpha to the DBCT regimen did not appear to enhance the response rate and may have increased toxicity.

Adolescent↗