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PubMed1994

Plasma cell dyscrasia with marrow fibrosis. A reversible syndrome mimicking agnogenic myeloid metaplasia.

BACKGROUND: The interrelation between plasma cell dyscrasia and myelofibrosis or agnogenic myeloid metaplasia (AMM) is unclear. The existence of two distinct syndromes has been proposed: (1) plasma cell dyscrasia associated with simple marrow fibrosis caused by the secretion of lymphokines and (2) myeloma coexisting with AMM representing two distinct clonal diseases. METHODS: The authors report the case of a 68 year-old man seen initially with severe anemia, massive splenomegaly, a leuko-erythroblastic blood morphology, and myelofibrosis coexisting with massive bone marrow infiltration with IgA lambda-producing plasmacytoid cells. RESULTS: Cyclic therapy with vincristine, carmustine, cyclophosphamide, melphalan, and prednisone resulted in clinical remission of the myeloma lasting for 2 years and complete resolution of all the clinical features resembling AMM. CONCLUSIONS: The authors' observations and the report of two other patients in whom remission of AMM has been observed after myeloma treatment underline the broad spectrum of secondary abnormalities ranging from moderate bone marrow fibrosis to the full clinical expression of a syndrome closely mimicking AMM. These secondary abnormalities are potentially reversible even in the presence of advanced bone marrow fibrosis and massive splenomegaly.

Aged↗

PubMed1995

Central pathology review in clinical trials for patients with malignant glioma. A Report of Radiation Therapy Oncology Group 83-02.

BACKGROUND: Confounding biologic factors, including histologic grade, may influence the outcome of adult patients with malignant gliomas more than may modifications in therapeutic approach. Any clinical trial design for malignant gliomas in adults must account for such biologic factors, including the accurate identification of the two histologic subgroups astrocytoma with anaplastic foci (AAF) or glioblastoma multiforme (GBM), which are associated with distinctly different survival outcomes. This paper examines the need for a central pathology review before entry of patients in cooperative group clinical trials stratified by histologic grade. METHODS: Pathology slides from Radiation Therapy Oncology Group (RTOG) trial 83-02, a randomized Phase II study of hyperfractionated and accelerated hyperfractionated radiation therapy and carmustine for malignant gliomas, provided 747 analyzable cases, with 680 (91%) available for central pathology review. This review was performed by a single pathologist according to RTOG/Eastern Cooperative Oncology Group histopathologic criteria. The kappa statistic was used to measure agreement between the institutional and central classification of AAF and GBM. The influence of misclassification was examined using computer simulation of varying clinical trial sizes (n = 25, 50, or 200). The effect on the statistical power of trials (n = 200) with varying mixtures of AAF and GBM tumors was investigated using computer simulations. RESULTS: Of 159 tumors classified as AAF by institutional pathology review, only 66% (105) were classified as AAF (AAF/AAF) by central review, and 54 of these cases (34%) were classified as GBM (GBM/AAF), whereas 96% (501) of 521 institutionally classified as GBM (GBM/GBM) were similarly classified by central review. Computer simulations demonstrated a 59% underestimation in the median survival (1.82 vs. 4.49 years) for trials of patients with institutionally defined AAF compared to patients with centrally defined AAF in studies of 200 patients, resulting from the addition of poor prognosis of GBM in the trial. Misclassification can also substantially reduce the statistical power of a clinical trial. In one of the simulation studies, statistical power was reduced from 65% to 14% if 50% of the patients were to receive an inaccurate histologic classification. Even greater losses in power are possible in many plausible clinical settings. CONCLUSIONS: This examination of a central versus an institutional pathology review demonstrates a low level of agreement on AAF classification and a high level of concordance on GBM classification. The results indicate the need to adjust sample size for trials of both AAF and GBM tumors to have adequate statistical power. A central pathology review remains essential for trial entry for patients with AAF and could be omitted for trials enrolling patients with GBM only.

Adult↗

PubMed1995

Hemolytic uremic syndrome after high dose chemotherapy with autologous stem cell support.

BACKGROUND: Chemotherapy intensification may lead to new forms of toxicity such as hemolytic uremic syndrome. METHODS: Three patients are described who developed this complication 4 to 6 months after high dose chemotherapy followed by autologous stem cell support. The literature on this subject is reviewed. RESULTS: One patient was conditioned with BEAC (carmustine, etoposide, cytosine arabinoside, and cyclophosphamide) and received autologous bone marrow. The other two underwent triple peripheral stem cell transplantation after conditioning with CTC (carboplatin, cyclophosphamide, and thiotepa). Symptoms were hypertension, microangiopathic hemolytic anemia, thrombocytopenia, and renal insufficiency. One patient had a retinal vein thrombosis. One patient died of a cardiac arrest shortly after the diagnosis was made. The remaining two achieved a partial remission: one with fresh frozen plasma without plasmapheresis and fresh frozen plasma, but improved on high dose intravenous immunoglobulin and vincristine. CONCLUSIONS: Hemolytic uremic syndrome is a serious complication of the more intensive chemotherapy made possible by stem cell support. Because of the rapidly growing indications for this approach, an increase in this type of vascular complication is expected.

Adult↗

PubMed1988

Successful chemotherapy for recurrent malignant oligodendroglioma.

Eight consecutive patients with recurrent malignant oligodendroglioma were treated with systemic chemotherapy. Six patients received a combination of procarbazine, lomustine (CCNU), and vincristine; 1 received carmustine (BCNU), and 1 diaziquone. All responded by clinical and computed tomographic scan criteria. One patient had a complete response for 78 weeks, and 7 patients had unequivocal partial responses lasting 30+ to 68+ weeks. Two partial responders had complete control of systemic metastases. Malignant oligodendroglioma is a uniquely chemosensitive glial tumor.

Adult↗

PubMed2002

Evaluation of the efficiency of chemotherapy in in vivo orthotopic models of human glioma cells with and without 1p19q deletions and in C6 rat orthotopic allografts serving for the evaluation of surgery combined with chemotherapy.

BACKGROUND: Malignant gliomas of the central nervous system remain associated with dismal prognoses because of their diffuse invasion of the brain parenchyma. Very few experimental models that mimic clinical reality are available today to test potentially new therapies. The authors set up experimental in vivo glioma models of anaplastic astrocytomas of human and rat origins and anaplastic oligodendroglioma of human origin. Standard hospital chemotherapies were employed to test the validity of these models. METHODS: Three glioma cells lines obtained from the American Type Culture Collection (i.e., human Hs683 and U373 cells and rat C6 cells) were implanted into nude mouse brains (Hs683 and U373 cells) and rat brains (C6 cells). The astrocytic nature, as opposed to the oligodendrocytic nature, of the Hs683 and U373 models was investigated by using quantitative (computer-assisted microscopy) immunohistochemical characterizations of nestin, vimentin, glutathione-S-transferase alpha (GSTalpha), GSTmu, GSTpi, and p53 expression. Comparative genomic hybridization (CGH) was employed to investigate 1p19q losses. Chronic administrations of carmustine (BCNU), fotemustin, or temozolomide were assayed in the xenografted U373 and Hs683 models. Both BCNU-related chemotherapy and surgery were assayed in the C6 model. RESULTS: The quantitative phenotypic analyses pointed to the oligodendroglial nature of the Hs683 cell line and the astrocytic nature of the U373 cell line. The Hs683 cells exhibited 1p19q losses, whereas the U373 cells did not. BCNU, fotemustin, and temozolomide dramatically increased the time of survival of the Hs683 oligodendroglioma-bearing mice, whereas temozolomide only induced a weak but nevertheless statistically significant increase in the U373 glioma-bearing mice. In the C6 rat glioma model, surgery and BCNU chemotherapy were more efficient than either treatment alone. CONCLUSIONS: The in vivo models of gliomas of the central nervous system developed in the current work best mimicked clinical reality. They can be used either to identify new therapies against human gliomas or to optimize existing therapies.

Animals↗

PubMed2005

Quality of life among patients with Stage II and III breast carcinoma randomized to receive high-dose chemotherapy with autologous bone marrow support or intermediate-dose chemotherapy: results from Cancer and Leukemia Group B 9066.

BACKGROUND: The objective of this study was to compare the quality of life (QOL) after treatment among patients who had breast carcinoma with multiple positive lymph nodes. The patients were randomized to receive either high-dose chemotherapy with autologous stem cell support (HDC) or intermediate-dose chemotherapy (IDC) in the adjuvant setting. METHODS: Two hundred forty-six patients with AJCC Stage IIA, IIB, or IIIA breast carcinoma who had > or = 10 positive lymph nodes and who were participants in Cancer and Leukemia Group B (CALGB) 9082 were enrolled in this companion study, CALGB 9066. Patients were randomized to receive either high-dose cyclophosphamide, carmustine, and cisplatin (CPA/cDDP/BCNU) and autologous bone marrow transplantation (the HDC arm) or intermediate-dose CPA/cDDP/BCNU as consolidation to adjuvant chemotherapy (the IDC arm). QOL was assessed at baseline and at 3 months, 12 months, 24 months, and 36 months using the Functional Living Index-Cancer (FLIC), the Psychosocial Adjustment to Illness Scale (PAIS)-Self Report, and the McCorkle Symptom Distress Scale (SDS). RESULTS: At the 3-month assessment, patients in the HDC arm demonstrated significant worsening of QOL compared with the IDC arm in terms of their physical well being (FLIC, P = 0.023), social functioning (FLIC, P = 0.026; PAIS, P < 0.0001), symptom distress (SDS, P = 0.0002), and total QOL scores (FLIC, P = 0.042). At 12 months, the differences in QOL scores between the HDC arm and the IDC arm had resolved. CONCLUSIONS: Patients who received more intensive adjuvant therapy experienced transient declines in QOL. By 12 months after therapy, QOL was comparable between the 2 arms, regardless of therapy intensity, and many QOL areas were improved from baseline.

Adolescent↗

PubMed2006

Complete response in multiple myeloma: clinical trial E9486, an Eastern Cooperative Oncology Group study not involving stem cell transplantation.

BACKGROUND: The importance of obtaining a complete response (CR) in multiple myeloma (MM) treated with chemotherapy is unclear. METHODS: The Eastern Cooperative Oncology Group evaluated 653 previously untreated patients with active MM randomized to vincristine, carmustine (BCNU), melphalan, cyclophosphamide, and prednisone (VBMCP), to VBMCP and recombinant interferon alfa-2 (INFalpha-2), or to VBMCP and high-dose cyclophosphamide. RESULTS: Objective response was achieved in 420 (67%) of the 628 eligible patients, and 85 (14%) achieved a CR. Patients receiving VBMCP and recombinant INFalpha-2 had a significantly higher CR (18%) than those receiving VBMCP alone (10%) (P = .02). The CR rate for VBMCP and high-dose cyclophosphamide was 12%. Median duration of survival was 3.5 years for all eligible patients, and the estimated 5-year survival rate was 31%. The median duration of survival from the date of objective response was 5.1 years for those who achieved a CR and 3.3 years for those with a partial response (P < .0001). The median postresponse survival was 6.6 years in the 21 patients in CR with nonclonal disease and 4.4 years in the 11 patients in CR who had persistent clonal disease. All patients with negative immunofixation results and nonclonal plasma cells in whom polymerase chain reaction was performed had a positive result (presence of tumor DNA). CONCLUSION: Patients in whom a CR was achieved had a longer survival than those who had a partial response.

Adult↗

PubMed2005

Involvement of the immune response in the cure of metastatic murine CT-26 colon carcinoma by low electric field-enhanced chemotherapy.

Low electric field cancer treatment-enhanced chemotherapy (LEFCT-EC) is a new treatment modality that combines chemotherapeutic agents and low electric field stimulation. LEFCT-EC was found to destroy malignant mouse tumors and cause massive death of tumor cells. This may enable the immune system cells to efficiently recognize and eliminate tumor cells at the primary tumor site and at metastatic foci. Mice with 15 mm diameter intracutaneous colon carcinomas (CT-26) were injected with BCNU (35 mg/kg), and 2 min later the tumors were exposed to low electric fields (intensity 40 V/cm, pulse duration 180 micros, frequency 500 Hz) for 12 min (LEFCT-EC). We found that treatment with LEFCT-EC achieved complete cure of 93% of the animals. In comparison, electric fields alone (13% cure), chemotherapy alone (0%), surgery (15%) or a combination of surgery and bis-chloroethyl-nitrosurea, carmustine (BCNU; 84%) treatments resulted in lower cure rates. After treatment and cure with LEFCT-EC, 50% of the cured mice developed resistance to a tumor challenge (surgery + BCNU only 15%). Furthermore, splenocytes from cured animals protected naive animals from a tumorigenic dose of tumor cells. Separation of spleen cells into lymphocyte subpopulations indicated a major role for CD4 and CD8 T cells in this protection. FACS analysis revealed restoration of normal splenocyte subpopulation proportions impaired by cytotoxic chemotherapy. Our results suggest that LEFCT-EC can directly destroy primary tumors and facilitate the destruction of metastatic disease by enforcement of antitumor immune responses.

Animals↗

PubMed1989

Ovarian function following chemotherapy for childhood brain tumours.

Pubertal development, basal gonadotrophin, and oestradiol levels were assessed in 21 girls who had received neuroaxis irradiation for a brain tumour followed by adjuvant chemotherapy with carmustine (BCNU) or lomustine (CCNU) and procarbazine. Thirteen received chemotherapy before the age of 11 years. Ten remained prepubertal at their last assessment, nine of whom showed biochemical evidence of primary ovarian failure. The remaining three were pubertal or adult, and although basal follicle-stimulating hormone (FSH) and luteinising hormone (LH) levels were normal, all had shown abnormalities of gonadotrophin secretion previously. Eight girls received chemotherapy after 11 years of age. Only three girls exhibited an elevated basal FSH level or exaggerated FSH response to GnRH. Elevated basal FSH values had been noted previously in two of the other five girls. All girls entered or progressed through puberty spontaneously. Seven experienced menarche at an appropriate age. However in four, gonadotrophin levels, which had been elevated, were now within the normal range. In two, menses had continued throughout with normal midfollicular oestradiol levels, whilst the other two developed secondary amenorrhoea associated with radiation-induced gonadotrophin deficiency. The majority of girls showed evidence of primary ovarian dysfunction. This did not prejudice pubertal development or the timing of menarche. Ovarian function may return to normal in the years after treatment, indicating a potential for fertility.

Adolescent↗

PubMed1991

Late BCNU lung: a light and ultrastructural study on the delayed effect of BCNU on the lung parenchyma.

We describe eight patients who developed interstitial pulmonary fibrosis following BCNU (carmustine) therapy for cerebral tumours. The fibrosis presented 12-17 (mean 14) years after exposure to the drug. A distinctive pattern of pulmonary fibrosis with involvement of the apices and subpleural areas was seen in one patient dying of the disease. Light microscopy showed interstitial elastosis and intra-alveolar fibrosis which was often focal with an associated mild lymphoplasmacytic infiltrate, intra-alveolar oedema, macrophages, and some neutrophils. Ultrastructural studies showed electron lucency of type I pneumocytes, with breaks in the cytoplasmic membranes leaving a bare basement membrane. Degenerative change was also seen in endothelial cell cytoplasm along with lipofuscin deposition. While BCNU pulmonary fibrosis has been described up to 2 years after treatment, this complication so late after therapy, though rare, has important implications for the follow-up of patients receiving this drug.

Astrocytoma↗

PubMed1988

Hematopoiesis on cellulose ester membranes (CEM). IX. Enrichment of membranes with adherent layers from long-term marrow culture from normal or drug-treated mice (hematopoietic microenvironment study II).

Cellulose ester membranes (Millipore) or polytetrafluoroethylene (Mitex) membranes were coated with adherent layers taken from Dexter-type long-term cultures, 4-5, 8 or 12 weeks after initiation of culture. The cultures were established with marrow taken from untreated mice or, in some cases, from mice treated with a single lethal dose (LD10) of carmustine (BCNU) or cyclophosphamide. In the studies using untreated mice, the cultures went for 8 or 12 weeks and in the drug studies, for 4-5 weeks. The 8 and 12 week cultures were reseeded at 4 weeks. The membranes were implanted into the peritoneal cavities of mice for 3-12 months after which they were removed, fixed, sectioned and stained for histologic study. After 6 months of implantation, about 40% of the membranes coated with cells from non-drug-treated mice and 60% of the membranes coated with cells from drug-treated mice contained hematopoietic elements; often there were foci of trilineal hematopoiesis. Hematopoiesis never occurred without bone formation, but the reverse was not true. Membranes coated with adherent layers established from marrow of mice treated with cyclophosphamide or BCNU showed two main characteristics: 1) they supported hematopoiesis normally, and 2) the regeneration of stroma and hematopoiesis occurred earlier than in membranes coated with stroma derived from normal mice, perhaps because the cells from the drug-treated mice spent a shorter time in culture. In vitro culture may damage cells required to condition the membrane for hematopoiesis.

Animals↗

PubMed1990

Use of recombinant human hematopoietic growth factors and autologous bone marrow transplantation to attenuate the neutropenic trough of high-dose therapy.

This manuscript summarizes our experience with recombinant human granulocyte colony-stimulating factor (rhG-CSF) with high-dose Cytoxan, carmustine and etoposide (CBV in Hodgkin's disease). rhG-CSF regularly shortened the neutropenic phase following autologous bone marrow transplantation. However, this effect was more marked on the latter part of neutrophil recovery than the early part of granulocyte recovery to 100 granulocytes/microliters. The frequency of afebrile episodes was not reduced by rhG-CSF administration, but there was a tendency for the duration of fever to be shortened. Increasing doses and continuous infusion did not hasten the early part of neutrophil recovery needed to prevent the onset of infection, but was more effective than bolus infusion in increasing the rate of late neutrophil recovery. If fevers are to be prevented in this patient population, the duration of an absolute granulocyte count of less than 100/microliters will have to last only a few days. Recombinant hematopoietic growth factors alone do not hasten recovery fast enough to prevent the onset of afebrile episodes. Studies are described using both recombinant growth factor and peripheral blood and bone marrow cells to see if the neutropenic trough can be further shortened over that achievable with growth factor and autologous transplant alone.

Agranulocytosis↗

PubMed2002

Development of an in vitro chemo-radiation response assay for cervical carcinoma.

PURPOSE: To determine if synergistic effects of radiation (RT) and chemotherapy (chemo) on human cervical carcinoma cell lines and fresh tumor explants could be determined using an in vitro assay. EXPERIMENTAL DESIGN: In vitro radiation response was determined for 4 cell lines and 26 fresh tumor explants in an agar-based assay. Cells were exposed to increasing doses of RT with or without cisplatin (CDDP), carmustine (BCNU), buthionine sulfoximine (BSO), or paclitaxel (Tax). Cell suspensions were cultured for 5 days, with [(3)H]thymidine added on day 3 and proliferation was measured. Results were reported as the fraction of proliferation compared to control (FC). For each combination of irradiation and drug, synergy was tested using the Chou analysis, where a combination index (CI) <1 indicated synergistic interaction. In simple correlation analysis, an R value of >0.7 indicated cross-resistance. RESULTS: RT dose-dependent proliferation inhibition was observed for 2 of the 4 cell lines, and for all but 1 of the fresh specimens. Significant heterogeneity of tumor response to RT was seen. Four specimens that were 1 standard deviation below the median FC response after exposure to 300 cGy were classified as extremely radiation resistant. Twenty-one tumors were evaluated for synergistic response using the combination of chemo and RT with a median FC of 0.27 (+/-0.27) for 6.0 Gy of RT alone, 0.22 (+/-0.21) for CDDP alone, and 0.05 (+/-0.08) for the combination. A CI of 0.35 and an R value of 0.09 demonstrated synergy between chemo and RT without cross-resistance. Similar synergy without cross-resistance was found for RT in combination with BCNU, BSO, and TAX. CONCLUSIONS: Heterogeneous RT dose-response relationships in the in vitro assay were demonstrated. Explants were more sensitive to RT than cell lines. Unlike cell lines, fresh tumor cells consistently displayed synergy with RT and chemo. The synergy between RT and BSO suggests that glutathione depletion may enhance the effect of RT. The assay was feasible for examining fresh tumors and may be an important tool for studying RT or drug resistance. Clinical trials to evaluate this assay are indicated.

Antineoplastic Agents↗

PubMed1991

Autologous bone marrow transplantation for refractory or relapsed Hodgkin's disease: the Memorial Sloan-Kettering Cancer Center experience using high-dose chemotherapy with or without hyperfractionated accelerated total lymphoid irradiation.

Fifty patients with advanced-stage Hodgkin's disease (HD) who relapsed or failed to respond to multiple regimens of combination chemotherapy were entered onto two autologous bone marrow transplantation (AuBMT) protocols. Twenty-eight patients who did not have prior radiation therapy were treated with protocol A. Protocol A consisted of reinduction with conventional doses of combination chemotherapy followed by boost local-field irradiation to areas of residual disease and hyperfractionated accelerated total lymphoid irradiation (TLI). Chemotherapy consisted of high-dose etoposide (VP-16) and cyclophosphamide followed by infusion of cryopreserved, unpurged autologous bone marrow. Twenty-two patients who have had prior radiation therapy were treated with protocol B. Protocol B consisted of reinduction with conventional doses of chemotherapy followed by involved field radiation therapy (when tolerance to residual disease has not been previously reached). High-dose chemotherapy regimen consisted of cyclophosphamide, carmustine (BCNU), and VP-16 (CBV) followed by autologous bone marrow transplantation. Of the 28 patients in protocol A, 5 patients died during the immediate peritransplant period, 5 patients progressed within six months, and 2 of them died. Two patients relapsed 13 and 39 months post transplant; 1 of them was reinduced into a complete remission (CR). Seventeen patients (61%) are disease free (16 patients in continuous complete remission), 12-54+ months (median 25+ months) following completion of therapy. Of the 22 patients in protocol B, 1 died of cytomegalovirus pneumonitis, and 11 relapsed. Ten patients (45%) are alive and disease free 16-42+ months (median 23+ months) after therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed2003

Intracavitary chemotherapy for glioblastoma: present status and future directions.

Considerable efforts have been invested to improve local control of the glioma disease although its infiltrative nature leading to whole brain involvement is a fundamental characteristic and antagonistic to this endeavour. The typically local recurrence of glioblastoma in about 80% of the cases has prompted intracavitary treatments of which presently only a biodegradable wafer containing carmustine has shown statistically significant benefit regarding survival in three phase III trials. Based on that proof of principle, many new developments are attempting to improve on this concept, introducing different agents with otherwise high systemic toxicity and poor penetration. New pharmacological formulations offer longer sustained release, better adaptation to the geometry of the resection cavity, and allow repeated administration. Should local recurrence become effectively controlled, significant progress can be made to increase survival with very limited local and virtually no systemic side effects. Since all agents so far show only limited activity against solid tumor, complete resection seems to be the prerequisite for effective local therapies.

Antineoplastic Agents↗

PubMed1986

Nalbuphine and droperidol in combination for sedation and prevention of nausea and vomiting during intra-carotid BCNU infusion.

A therapeutic regimen is described for sedative, analgesic, and anti-emetic effect in patients receiving intra-arterial carmustine (BCNU) for malignant gliomas. This regimen consists of nalbuphine, 30 mg, i.v., and droperidol, 2.5 mg, i.v., given immediately prior to intra-carotid BCNU infusion. Droperidol, 2.5 mg, i.v., is then administered on four hour intervals for sixteen hours post-procedure. This combination provided excellent effect in nine patients treated for twelve intra-carotid infusions. None of the nine patients experienced vomiting, one experienced mild nausea several hours post-infusion, and non complained of severe pain or discomfort. Thirteen additional patients received diazepam, 10 mg, P.O., prior to the intra-carotid BCNU infusion, with fentanyl, 100 mcg, i.v., and prochlorperazine, 10 mg, i.m. at the onset of infusion. All thirteen patients suffered from severe nausea, vomiting, and orbital pain. The nalbuphine/droperidol combination is thought to provide a superior alternative to the traditional narcotic/pheonothiazine/benzodiazepine combination for carotid BCNU infusion. This combination has theoretical advantages for the patient with intracranial mass lesions by providing analgesia and sedation with minimal potential for respiratory depression and carbon dioxide retention.

Adult↗

PubMed1991

Thermal enhancement of ACNU and potentiation of thermochemotherapy with ACNU by hypertonic glucose in the BT4An rat glioma.

Hyperthermia increases the cytotoxicity of the nitrosourea BCNU (carmustine). Glucose given before treatment may further increase the value of thermochemotherapy, presumably by lowering tumour pH through blood flow reduction. The water-soluble ACNU (nimustine) is an alternative to other nitrosoureas in the treatment of gliomas. The drug is soluble without use of ethanol, and the eye complications when given intra-arterially are reduced compared with similar use of BCNU. The influence of simultaneous hyperthermia on treatment with ACNU, and the value of glucose administered before thermochemotherapy therefore were investigated in the malignant rat glioma BT4An. BD IX rats with subcutaneous BT4An tumours on the hind leg were treated with ACNU (i.p.), or ACNU and locally applied waterbath hyperthermia (44 degrees C for 45 min), with or without previous glucose (6 g/kg i.p. 2 hours before treatment). ACNU (10 or 20 mg/kg) alone and ACNU (20 mg/kg) after previous glucose did not influence tumour growth, compared to the controls. Simultaneous ACNU (10 mg/kg) and hyperthermia clearly was more effective than treatment with hyperthermia alone. Glucose load before treatment further enhanced the effect of combined ACNU and hyperthermia. Glucose before treatment did not change local toxicity or weight profiles of treatment with ACNU alone, or simultaneous ACNU and hyperthermia. Glucose load therefore represented a therapeutic gain when administered before thermochemotherapy with ACNU.

Animals↗

PubMed1984

Efficacy of the M-2 protocol in previously untreated patients with advanced multiple myeloma.

37 consecutive, previously untreated patients with advanced multiple myeloma (16 patients Stage II, 21 patients Stage III) were treated with a five drug regimen consisting of carmustine, melphalan, vincristine, cyclophosphamide and prednisolone (M-2-protocol) in a prospective manner. Remission was achieved in 24 patients (65%). The median time to remission was 10 weeks, the median duration of remission 15,3 months. Median survival time from the onset of treatment was 24 months for all patients. Responding patients have a projected 65% three year survival. Median survival in non-responders was 10 months. 8 patients died during the first year of treatment. These results do not confirm the favourable results with this drug combination obtained in a previous trial. The discrepancy may be explained by a higher proportion of poor risk patients in the present study.

Aged↗