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At least 199 records · Page 11Linked to original sources

Addition of cisplatin and bleomycin to vincristine-carmustine-doxorubicin-prednisone (VBAP) combination in the treatment of relapsing or resistant multiple myeloma: a Southwest Oncology Group study.

Fifty-five patients with myeloma who had relapsed on or were resistant to melphalan and/or cyclophosphamide with prednisone received vincristine, carmustine, doxorubicin, and prednisone (VBAP) plus cisplatin and bleomycin at 21-day intervals. Eighteen (32.7%) patients responded. The response rate was 38.5% (15 responses among 39 patients) in relapsing patients. Three (18.8%) of 16 patients with resistant myeloma responded. Granulocytopenia was the most frequent toxic effect, and was severe in 12 (22%) patients. Severe thrombocytopenia occurred in seven (13%) patients and severe nausea and vomiting occurred in eight (15%). One patient with previously normal renal function developed renal failure on this regimen. The median survival (100 weeks) in those patients responding to treatment was significantly longer than that in patients not responding (25 weeks; P = 0.001). VBAP plus cisplatin and bleomycin was at least as effective as VBAP but had greater toxicity, expense, and inconvenience; it therefore is not preferable to VBAP.

Antineoplastic Combined Chemotherapy Protocols↗

Pathology of the liver with bone marrow transplantation. Effects of busulfan, carmustine, acute graft-versus-host disease, and cytomegalovirus infection.

The morphologic changes in the livers of autopsy specimens from recipients of 62 allogeneic bone marrow transplants were reviewed and characterized in specimens from patients who had had apparent drug toxicity, graft-versus-host disease (GVHD), and disseminated cytomegalovirus (CMV) infection. Two conditioning protocols were associated with significant hepatic toxicity. Two of 3 recipients on whom autopsies were performed who had been prepared with high doses of carmustine, cyclophosphamide, and total body irradiation had undergone acute hepatic failure and submassive necrosis with periportal sparing. Seven of 9 patients prepared with busulfan (16 or 20 mg/kg) and cyclophosphamide had moderate to marked centrilobular sinusoidal fibrosis and associated hepatocellular atrophy and necrosis. Twenty of the patients had acute cutaneous GVHD with associated hepatic dysfunction, including 8 with disseminated CMV infection. Of the 12 patients without concomitant CMV infection, 5 had an early onset of GVHD and had predominantly periportal and focal midzonal hepatocellular necrosis, and 7 had acute GVHD with later onset with predominantly bile duct injury. Fifteen patients had evidence of disseminated CMV infection. Whereas CMV infection alone was associated with both hepatocellular and bile duct injury, detectable virus infection was not a requirement for hepatocellular or bile duct injury associated with GVHD.

Anemia, Aplastic↗

Comparisons of carmustine, procarbazine, and high-dose methylprednisolone as additions to surgery and radiotherapy for the treatment of malignant glioma.

Within 3 weeks of definitive surgery, 609 patients with histologically demonstrated, supratentorial malignant glioma were randomized to receive, in addition to 6000 rads of radiotherapy, one of four treatment regimens: carmustine (BCNU), high-dose methylprednisolone, procarbazine, or BCNU plus high-dose methylprednisolone. We analyzed the data for the total randomized population and for the 527 patients (87% with glioblastoma multiforme) in whom the initial protocol specifications were met (the valid study group). Significantly longer survival was experienced by patients receiving procarbazine or BCNU alone compared to those receiving only high-dose methylprednisolone. No other pairwise comparisons demonstrated differences significant at the 0.05 level. However, the combination of BCNU plus high-dose methylprednisolone tended to be less effective than BCNU alone in patients with poor prognosis. This study indicates that BCNU and procarbazine are moderately useful agents in conjunction with radiotherapy for patients with malignant glioma. In addition, future protocols may allow use of corticosteroids in conventional dosages for treating cerebral edema and controlling symptoms; conclusions based on survival as the endpoint are unlikely to be affected by administering steroids at somewhat greater than the usual dose. More effective regimens for the treatment of malignant glioma should be sought.

Adolescent↗

Combination chemotherapy for multiple myeloma with melphalan, prednisone, cyclophosphamide, vincristine, and carmustine (BCNU) (M-2 protocol).

From January 1975 to May 1981, 25 consecutive patients with multiple myeloma (MM) were entered in a prospective study and treated with the M-2 protocol (melphalan, prednisone, cyclophosphamide, vincristine, and carmustine [BCNU]). The Karnofsky performance status was less than 70 in 62% of the patients. Nineteen patients were classified as being in stage III, three were in stage II, and three were in stage I. All patients had symptomatic and previously untreated MM. In 17 of 21 (80.9%) evaluable patients, an objective response according to Myeloma Task Force criteria was obtained. There was no difference in response rate among patients in the various stages of the disease or according to types of proteins secreted. The median time to obtain an objective response was 2 months and the median duration of the remission is 18+ months. The actuarial median survival was 42 months. In the first 15 months of follow-up, 20% of the patients died. Toxicity was not negligible and was mainly hematologic. One treatment-related death occurred. Our study confirms the efficacy of the M-2 protocol in MM and supports the data reported by the Memorial Hospital group.

Adult↗

Phase III study of intermittent carmustine (BCNU), cyclophosphamide, and prednisone versus intermittent melphalan and prednisone in myeloma.

A prospective randomized trial in patients with previously untreated multiple myeloma was performed comparing carmustine (BCNU), cyclophosphamide, and prednisone (BCP) to melphalan (Alkeran) and prednisone (AP). Induction response rates, remission duration, and survival were similar with both regimens. Hematologic toxicity was greater with AP. Crossover studies in patients who relapsed did not illustrate any significant activity with either drug treatment program. Therefore, BCP can be utilized as initial therapy in myeloma because of comparable remission rates and less hematologic toxicity.

Aged↗

Multiple myeloma resistant to melphalan: treatment with doxorubicin, cyclophosphamide, carmustine (BCNU), and prednisone.

Sixty-five patients with multiple myeloma resistant to melphalan were randomized to receive cyclophosphamide, doxorubicin (Adriamycin), and prednisone (CAP) (30 patients) or carmustine (BCNU), doxorubicin, and prednisone (BAP) (35 patients). Objective responses occurred in two patients in the CAP group and in seven in the BAP group. Indirect responses were noted in seven additional patients in the CAP group and in six additional patients in the BAP group. Toxic effects consisted mainly of leukopenia and thrombocytopenia. Median survival did not differ between the two treatment groups (CAP, 8.4 months; BAP, 7.7). Objective responders had a longer survival than nonresponders (14.5 vs 7.7 months).

Aged↗

High-dose cyclophosphamide, carmustine (BCNU), and etoposide (VP16-213) with or without cisplatin (CBV +/- P) and autologous transplantation for patients with Hodgkin's disease who fail to enter a complete remission after combination chemotherapy.

Patients with Hodgkin's disease (HD) who fail to enter a complete remission after an initial course of combination chemotherapy are usually considered to have an induction failure (IF); this subset of patients has an extremely poor outcome with further conventional therapy. Since 1985, we have entered 30 IF patients into protocols using conditioning with high-dose cyclophosphamide, carmustine (BCNU), and etoposide (VP16-213) with or without cisplatin (CBV +/- P) followed by autologous stem cell transplantation (ASCT) with bone marrow (19 patients), peripheral blood stem cells (PBSCs; 8 patients), or both (3 patients). All except 2 patients had previously received chemotherapy regimens for HD that contained at least 7 drugs, and 9 had received prior radiotherapy (RT). After documentation of IF, the majority of patients received some cytoreductive therapy as specified by protocol (local RT in 9, two cycles of conventional chemotherapy in 2, both modalities in 2, or high-dose cyclophosphamide to enhance PBSC collection in 11) before CBV +/- P. Five treatment-related deaths occurred, all before day 150 posttransplant. Eleven patients have had progressive HD at a median of 6 months (range, 0.1 to 45 months) after ASCT. The actuarial progression-free survival (PFS) at a median follow-up of 3.6 years (range, 0.2 to 8.2 years) is 42% (95% confidence intervals, 21% to 61%). The statistical analysis identified only prior clinical bleomycin lung toxicity as an adverse risk factor for PFS, mainly because of the increased nonrelapse mortality seen in these patients. CBV +/- P and ASCT can produce durable remission in a substantial proportion of IF HD patients who otherwise have a poor survival, and we believed ASCT approaches represent the best therapy currently available for these patients. Additional measures are needed to reduce the primary problem of disease progression despite high-dose chemotherapy and stem cell transplantation.

Actuarial Analysis↗

Randomized, comparative study of high-dose (with autologous bone marrow support) versus low-dose cyclophosphamide, cisplatin, and carmustine as consolidation to adjuvant cyclophosphamide, doxorubicin, and fluorouracil for patients with operable stage II or III breast cancer involving 10 or more axillary lymph nodes (CALGB Protocol 9082). Cancer and Leukemia Group B.

The prognosis for patients with primary breast cancer involving multiple axillary lymph nodes is poor. Only about 30% of patients remain disease-free at 5 years from diagnosis despite surgery, conventional-dose chemotherapy, and radiation therapy. In nonrandomized studies, the use of high-dose chemotherapy as consolidation therapy after standard-dose induction chemotherapy has resulted in an apparent improvement in disease-free survival rates to over 70%. These results have prompted the National Cancer Institute to sponsor large-scale, multicenter, randomized comparative trials of this strategy. This Intergroup Study (Cancer and Leukemia Group B 9082, Southwest Oncology Group 9114, and National Cancer Institute of Canada MA13) compares two treatment strategies in women with primary breast cancer involving 10 or more axillary lymph nodes. Arms A and B are identical in the use of four cycles of conventional therapy with cyclophosphamide and doxorubicin and fluorouracil, radiation therapy, and tamoxifen. The only difference between the two arms is the dose intensity of the cyclophosphamide, cisplatin, and carmustine given following conventional adjuvant treatment. Arm A dictates bone marrow, peripheral blood stem cell, and hematopoietic growth factor support and frequently requires a prolonged hospital stay with high resource utilization. Arm B, with its less dose-intensive therapy, requires considerably less support to apply the treatment. Because of the high cost of this therapy and the requirement for technology-intensive support, there has been considerable interest in economic outcome assessments.

Antineoplastic Combined Chemotherapy Protocols↗

In vivo enhanced antitumor activity of carmustine [N,N'-bis(2-chloroethyl)-N-nitrosourea] by simvastatin.

The effects of a combination of simvastatin, a cholesterol-lowering agent, and carmustine (BCNU; N,N'-bis(2-chloroethyl)-N-nitrosourea) on experimental C6 glioma were studied in vitro and in vivo. In vitro simvastatin and BCNU alone inhibited cell proliferation in a dose-dependent fashion. A subliminal concentration of simvastatin (0.1 microM) markedly and synergistically increased the BCNU toxicity to C6 glioma cells. The cytofluorimetric analysis of DNA from simvastatin-treated C6 glioma cells showed, besides the already described arrest in G1, an arrest/retardation in G2-M. Mitotic index from C6 cells incubated with simvastatin (10 microM) decreased by about 90%, indicating a specific C6 arrest/retardation in G2. The drug effects could be completely reversed by simvastatin withdrawal or mevalonate addition to the cultured cells. The combination of simvastatin and BCNU resulted predominantly from the profound retardation of cells in the G2-M compartment of the cell cycle. In vivo simvastatin (administered daily mixed with food) and BCNU (single i.p. injection), when given separately, caused a dose-dependent inhibition of labeling index in C6 glioma homografts (ID50, 61 mg/kg/day and 8.7 mg/kg, respectively). The combination of the lowest doses tested (simvastatin, 25 mg/kg/day and BCNU 0.3 mg/kg) resulted in a significant growth delay (compared to either drug alone) in C6 glioma (P < 0.05). There was no significant increase in toxicity as assessed by myelosuppression (WBC counts and bone marrow labeling index) and body weight. The results provide in vivo support for the combined use of simvastatin, a cholesterol-lowering agent, and BCNU in brain tumor treatment.

Animals↗

Ocular toxicity of systemic chemotherapy with megadoses of carmustine and mitomycin.

The use of chemotherapeutic agents in high doses in the treatment of advanced-stage cancer enhances drug toxicity, and ocular complications are not uncommon. In this article, we discuss the ocular toxicity in six patients with advanced nonpretreated colorectal cancer who received megadoses of carmustine and mitomycin with the support of autologous bone marrow transplantation. The results obtained did not reveal any subjective or objective pathologic conditions of the ocular apparatus with particular attention to orthoptic examinations, the anterior segment, and the fundus. No patient had changes in visual acuity. Tonometry did not demonstrate significant variations. There were, however, qualitative and quantitative changes in the tear films of all patients, leading to damage to the corneal and conjunctival epithelium.

Antineoplastic Combined Chemotherapy Protocols↗

Topical carmustine (BCNU) for patch/plaque mycosis fungoides.

This article summarizes experience with topical carmustine (BCNU) solution in 172 patients with patch/plaque stage mycosis fungoides. At 36 months 92% of stage-T1 (less than 10% skin involvement) and 64% of stage-T2 (10% or more skin involvement) patients were either in complete or partial remission. The most frequent side effect was an erythematous reaction which was followed by a benign-type telangiectasia in some patients. No secondary skin cancers were seen. Bone marrow depression was uncommon. Topical BCNU is an effective treatment for patch/plaque stage mycosis fungoides.

Administration, Topical↗

Intensive therapy with cyclophosphamide, carmustine, etoposide +/- cisplatin, and autologous bone marrow transplantation for Hodgkin's disease in first relapse after combination chemotherapy.

The optimal timing in which to use intensive chemotherapy and autologous bone marrow transplantation (BMT) in Hodgkin's disease (HD) is uncertain. In 1985, we initiated a program in which this modality was used as the initial salvage therapy in patients relapsing after combination chemotherapy. Fifty-eight patients with HD in first relapse after primary chemotherapy received conditioning with high-dose cyclophosphamide, carmustine, etoposide (VP16-213) +/- cisplatin (CBV +/- P) followed by autologous BMT. All but six of these patients were given a median of two cycles of conventional chemotherapy +/- involved field radiation therapy before CBV +/- P and autologous BMT. These measures were not used as a means for patients selection; all patients receiving such therapy ultimately were transplanted. The probability of nonrelapse mortality, progression of HD, and progression-free survival post-BMT were calculated, and prognostic factors for progression-free survival were evaluated using the Cox proportional hazards method. Treatment-related deaths occurred in only three patients. Thirteen patients have relapsed at a median 0.7 years (range 0.1 to 3.5) post-BMT. At a median follow-up of 2.3 years (range 0.4 to 7.2), the actuarial progression-free survival is 64% (95% confidence interval, 46% to 78%). In the statistical analysis, three similarly weighted but independent prognostic factors were identified: "B" symptoms at relapse, extranodal disease at relapse, and initial remission duration of less than 1 year. Patients with no risk factors had a 3-year progression-free survival of 100%, compared with 81% in patients with one factor, 40% in those with two factors, and 0% in patients with all three factors. CBV +/- P and autologous BMT is highly effective salvage therapy for HD patients in a first relapse, particularly in the subset of patients with less than two adverse factors. Therapy must be improved in the future for patients with > or = 2 adverse factors.

Adolescent↗

Degradable starch microspheres in cytostatic treatment of a liver carcinoma; experimental studies in rats with 5-fluorouracil, tauromustine, carmustine, doxorubicin and RSU-1069.

The degradable starch microspheres (DSM) used have a size of 45 microns and are dissolved by amylase in blood. After intraarterial administration of a mixture of DSM and cytostatic drugs the coinjected drugs remain for a longer time in the target tissue/tumor. A transient hypoxia occurs. Systemic exposure of drugs is decreased. Rats with a carcinoma implanted into the liver were given DSM and drugs via the hepatic artery. DSM did not significantly increase the incorporation of 5-fluorouracil (5-FU) into liver tumor RNA. The incorporation of 5-FU into intestinal and bone marrow RNA increased. DSM increased the antitumor effect of doxorubicin, tauromustine, carmustine and RSU-1069 (aziridine 2-nitroimidazole). Side effects, such as liver and gastric necroses and body weight loss, appeared in some rats. The toxic overspill to the stomach seemed to be reduced by giving the DSM in two parts, with all the cytotoxic drug in the first part. The effect on liver and tumor was not decreased by this procedure. DSM alone had no anti-tumor effect. DSM alone decreased liver UDP-glucuronic acid in tumor-free rats, given either by the hepatic artery or, in the double dose, by the portal vein. DSM alone did not increase liver NADPH-cytochrome c reductase activity or serum ASAT (aspartate-aminotransferase) or ALAT (alanine-aminotransferase), indicating that the DSM are inert to the liver, when infused into the tributary vessels.

Adenosine Triphosphate↗

Therapy for metastatic melanoma: effective combination of dacarbazine, carmustine, cisplatin and tamoxifen.

Thirty-two patients with metastatic melanoma received combination chemotherapy and hormonal therapy. Treatment included Carmustine, Cisplatin, Dacarbazine and Tamoxifen (BCDT). The overall response rate was 47%: five patients had a complete response (16%), 10 patients had a partial response (31%) and two had no response (6%). The median survival for responders was 10 months (range 2-20). The BCDT regimen was equally effective against soft tissue and visceral metastases. Neither survival or response rate was modified by pretreatment with alpha-interferon (alpha-IFN). In agreement with the results of a recent randomized trial comparing the efficacy of Dacarbazine with that of Dacarbazine plus Tamoxifen, a better survival was found in women than in men: although the response rate was identical (47%), the median duration of response was higher for women. A fall in serum soluble IL-2 receptor (sIL-2R) levels after therapy was seen in responding patients, confirming the usefulness of this parameter in monitoring disease evolution.

Adult↗

A mononuclear cell dose of 3 x 10(8)/kg predicts early multilineage recovery in patients with malignant lymphoma treated with carmustine, etoposide, Ara-C and melphalan (BEAM) and peripheral blood progenitor cell transplantation.

We have assessed the potential use of the mononuclear cell (MNC) content as the sole assessment of graft quality in 35 patients receiving BEAM (carmustine, etoposide, cytosine arabinoside, melphalan) chemotherapy and autologous peripheral blood progenitor cell (PBPC) transplantation for malignant lymphoma. PBPCs were mobilized with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), and each patient underwent two (n = 20) or three (n = 15) apheresis procedures. Median cell yields were 5.08 x 10(8) MNC/kg (range 1.59-15.70 x 10(8)) and 73.10 x 10(4) CFU-GM/kg (range 0.09-346.72 x 10(4)). All patients achieved hematologic recovery. Median days to neutrophils > or = 0.1 x 10(9)/L, neutrophils > or = 0.5 x 10(9)/L, and platelets > or = 25 x 10(9)/L were 11 (range 8-15), 13 (range 10-37), and 11 (range 7-41), respectively. A close correlation was observed between the MNC and CFU-GM dose (r = 0.79, p < 0.0001). We have previously defined a minimum threshold CFU-GM dose of 20 x 10(4)/kg for patients undergoing high-dose therapy. This corresponds with an MNC dose of 3 x 10(8)/kg. Comparison of engraftment in patients receiving 3 x 10(8) MNC/kg with those receiving lower doses demonstrated significantly longer times to recovery of neutrophils to > or = 0.5 x 10(9)/L and platelets to > or = 25 x 10(9)/L. All patients receiving an MNC dose of > or = 3 x 10(8)/kg achieved neutrophil and platelet recovery by days 12 and 24, respectively. These preliminary data demonstrate that for patients with lymphoma undergoing PBPC mobilization according to this protocol and treatment with BEAM chemotherapy, assessment of MNC dose alone is sufficient to predict early hematologic recovery. Additional assays such as CFU-GM or CD34+ cell counts may not be necessary if this MNC dose is reinfused.

Antineoplastic Combined Chemotherapy Protocols↗

Retrospective study of the correlation between the DNA repair protein alkyltransferase and survival of brain tumor patients treated with carmustine.

We tested the hypothesis that the level of the DNA repair protein O6-alkylguanine-DNA alkyltransferase in brain tumors was correlated with resistance to carmustine (BCNU) chemotherapy. Alkyltransferase levels in individual cells in sections from 167 primary brain tumors treated with BCNU were quantitated with an immunofluorescence assay using monoclonal antibodies against human alkyltransferase. Patients with high levels of alkyltransferase had shorter time to treatment failure (P = 0.05) and death (P = 0.004) and a death rate 1.7 times greater than patients with low alkyltransferase levels. Furthermore, the size of the subpopulation of cells with high levels of alkyltransferase was correlated directly with drug resistance. For all tumors the variables most closely correlated with survival, in order of importance, were age, tumor grade, and alkyltransferase levels. For glioblastoma multiforme, survival was more strongly correlated with alkyltransferase levels than with age. These results should encourage prospective studies to evaluate alkyltransferase levels as a method, for identifying brain tumor patients with the best likelihood of response to BCNU chemotherapy.

Antibodies, Monoclonal↗

Combination chemotherapy (dacarbazine, carmustine, cisplastin, and tamoxifen) in advanced melanoma.

Melanoma is rare in Singapore with an age-standardised rate (ASR) of 0.4-0.8 per 100,000 per year. Thirteen patients with metastatic or locally advanced melanoma were referred to the Department of Medical Oncology, Singapore General Hospital between Feb 1991 and Nov 1993. Ten patients were given combination chemotherapy comprising carmustine (BCNU), cisplatin, dacarbazine (DTIC) and tamoxifen. The remaining 3 patients either rejected chemotherapy or were too ill to receive chemotherapy. Patient characteristics were as follows: there were 6 males and 4 females; age range 29-75 years; all were Chinese; sites of primary disease: extremities 8, retroorbital 1, vagina 1; sites of metastases: lymph nodes 6, skin 2, pulmonary 3, liver 1. All received the same combination chemotherapy comprising iv BCNU 150 mg/m2 q8wk, iv DTIC 220 mg/m2 x 3 days q4 wk, iv cisplatin 25 mg/m2 x 3 days q4 wk and tab tamoxifen 40 mg daily. There were 6 partial responses and no complete responses, giving a response rate of 60% with a median survival of 11.5 months. Three patients with sites of disease in the vagina, retroorbital region and metastatic liver disease had progressive disease despite chemotherapy and one died of treatment related sepsis. The 6 responders include those with metastases to the skin, nodes and/or lung. Treatment was generally tolerable. Two patients experienced delays of their subsequent cycles of treatment by 1-2 weeks due either to neutropenia and/or thrombocytopenia. This regimen is a fairly active combination against metastatic melanoma, particularly those with metastases to the nodes, skin and the lung. Those with involvement of other sites tend to respond poorly.

Adult↗

Comparison of melphalan and prednisone with vincristine, carmustine, melphalan, cyclophosphamide, and prednisone in the treatment of multiple myeloma: results of Eastern Cooperative Oncology Group Study E2479.

BACKGROUND: The Eastern Cooperative Oncology Group (ECOG) performed a Phase III comparison of melphalan and prednisone (MP) with vincristine, carmustine (BCNU), melphalan, cyclophosphamide, and prednisone (VBMCP) in an attempt to determine which of these regimens should be the standard treatment for multiple myeloma. METHODS: Four hundred seventy-nine previously untreated patients with multiple myeloma from 23 ECOG institutions were enrolled. Treatment, assigned by randomization, consisted of either 4-week cycles of MP or 5-week cycles of VBCMP. After 1 year of induction therapy, patients received MP or VBMCP maintenance therapy at 6- and 8- week intervals, respectively, until relapse. Patients who experienced treatment failure with MP were eligible for crossover therapy with VBMCP. RESULTS: Objective responses were obtained for 51% of patients receiving MP, as compared with 72% of patients receiving VBMCP (P < 0.001). Response duration was also longer with VBMCP (median, 18 months with MP vs. 24 months with VBMCP; P = 0.007). Overall survival was not significantly different between MP and VBMCP (P = 0.30). The 5-year survival for VBMCP was 26%, as compared with 19% for MP. VBMCP was associated with more nausea, peripheral nerve toxicity, alopecia, and neutropenia, but the infection rate was equal to that observed with MP. Both regimens were generally well tolerated. The main exception was that elderly patients who were confined to bed had a higher risk of death with VBMCP. The two regimens produced a similar incidence of late secondary myelodysplastic syndrome and acute leukemia. Crossover VBMCP for patients failing with MP was only minimally effective, with an objective response rate of 20% and median survival of 11 months after crossover. CONCLUSIONS: VBMCP is more effective than MP in producing and sustaining remission of multiple myeloma. It is associated with a marginal survival advantage and an apparently greater chance of surviving 5 years for patients who can tolerate moderately intensive combination chemotherapy. Cancer 1997;79:1561-7. 1997 American Cancer Society.

Adult↗