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PubMed1995

Malignant gliomas in older adults with poor prognostic signs. Getting nowhere, and taking a long time to do it.

The median survival time of adults with supratentorial malignant glioma treated in clinical studies with surgery, 6 weeks of external-beam radiotherapy, and carmustine (BiCNU) is approximately 1 year. This poor survival time is almost certainly optimistic, since only a select subgroup of patients end up participating in clinical trials--ie, those with a better prognosis. For elderly patients and/or those with poor functional status, median survival time ranges from 16 to 40 weeks. A regimen of surgery plus 2 to 3 weeks of radiotherapy appears to achieve a survival duration equivalent to that of long courses of chemoradiotherapy at less cost in time and money, and perhaps with less caregiver stress. Since the incidence of brain tumors in the elderly is rising and the size of the elderly population is increasing, it is appropriate to investigate the role of less aggressive therapy for what will be a growing number of malignant glioma patients with a poor prognosis.

Age Factors↗
PubMed1993

Characterization of endogenous cytokine concentrations after high-dose chemotherapy with autologous bone marrow support.

Endogenous cytokines are thought to mediate numerous biologic processes and may account for some adverse effects experienced following the administration of recombinant proteins. This study describes the pattern of endogenous cytokine exposure following high-dose chemotherapy. Blood concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), macrophage colony-stimulating factor (M-CSF), and erythropoietin (EPO) were measured by enzyme-linked immunosorbent assay (ELISA) methods in 68 patients receiving the same ablative chemotherapy regimen (cyclophosphamide, cisplatin, carmustine). Patients were grouped according to cellular support (autologous bone marrow [BM] CSF-primed peripheral blood progenitor cells [PBPCs]) and prescribed growth factor (recombinant human granulocyte or granulocyte-macrophage colony-stimulating factor [rHuG-CSF or rHuGM-CSF]). Leukocyte reconstitution was most accelerated in the groups treated with PBPCs and rHuG-CSF. IL-6, M-CSF, and TNF-alpha concentrations were higher in the groups treated with rHuGM-CSF and without PBPCs. Maximal endogenous cytokine concentrations occurred approximately 12 days after BM reinfusion. High concentrations of EPO occurred in patients experiencing significant hypotension despite routine transfusions for hematocrit < 42%. High M-CSF and IL-6 levels were associated with increased platelet transfusion requirements. Concentrations of all four cytokines were significantly higher in patients experiencing renal or hepatic toxicity, with elevations occurring in a predictable sequence and M-CSF elevations occurring first. This report shows that endogenous cytokine concentrations may be influenced by either cellular or CSF support and are associated with differences in platelet reconstitution and organ toxicity.

Adult↗
PubMed1995

Retrovirus-mediated expression of a DNA repair protein in bone marrow protects hematopoietic cells from nitrosourea-induced toxicity in vitro and in vivo.

Severe and delayed myelosuppression is a major side effect encountered with the clinical use of nitrosourea-type chemotherapeutic drugs. The DNA repair protein O6-methylguanine DNA methyltransferase (MGMT) has been shown to repair nitrosourea-induced DNA damage. We therefore investigated the effect of expressing MGMT in hematopoietic cells (via retrovirus-mediated gene transfer) on nitrosourea-induced toxicity. A retroviral vector (N2/ZipPGK-MGMT) expressing the human MGMT cDNA from the phosphoglycerate kinase promoter was constructed. Infection of murine bone marrow with the N2/ZipPGK-MGMT retrovirus significantly increased the survival of murine bone marrow-committed progenitor cells following in vitro exposure to N-N'-bis(2-chloroethyl)-N-nitrosourea (BCNU, carmustine). MGMT gene transfer also protected murine hematopoietic cells in vivo in a murine model of BCNU-induced myelosuppression. The infusion of 4-6 x 10(6) N2/ZipPGK-MGMT-transduced bone marrow cells into mice every 2 weeks significantly increased peripheral leukocyte counts, platelet counts, and hematocrits compared to infusions of mock-infected bone marrow cells. In addition, bone marrow-committed progenitor cells from some recipient animals demonstrated increased resistance to BCNU in vitro when analyzed 2.5 months after initial treatment. The integration of the N2/ZipPGK-MGMT provirus in the spleen DNA from these animals correlated with committed progenitor cell resistance to BCNU. These data suggest that MGMT expression in hematopoietic progenitor and precursor cells protects against nitrosourea-induced toxicity and that gene transfer may prove useful in attempts to reduce nitrosourea-induced myelosuppression in the clinical setting.

3T3 Cells↗
PubMedDate not supplied

Effect of doxorubicin on glutathione and glutathione-dependent enzymes in cultured rat heart cells.

The effect of doxorubicin (DOX) on heart cell glutathione (GSH)-based enzyme systems was investigated in a rat heart myocyte model. Cellular levels of GSH decreased commensurate with viability following exposure to DOX or to the unrelated alkaloidal cardiotoxin emetine. GSH depletion by L-buthionine sulfoximine (L-BSO) did not alter myocyte viability nor doxorubicin (DOX) dose-response. The nitrosourea carmustine (BCNU), which impairs GSH reductase activity, also did not alter DOX cardiotoxicity. Doxorubicin significantly increased glutathione-S-transferase (GST) activity in a time-dependent fashion. In contrast, selenium-dependent glutathione peroxidase activity was reduced by 50%. These findings demonstrate that lowered GSH or GSH reductase levels do not enhance DOX cardiotoxicity in vitro and suggest that DOX may be a substrate for GST.

Adenosine Triphosphate↗
PubMedDate not supplied

Synthesis and preliminary in vitro cytotoxicity evaluation of 1,3-bis-(2-propynyl)-1-nitrosourea (BPNU) and derivatives.

The in vitro cytotoxicity and differential cellular sensitivity of a series of new N1-(propargyl) nitrosourea derivatives, including 1,3-bis-(2-propynyl)-1-nitrosourea (BPNU), a carmustine (BCNU) analog, were determined in the National Cancer Institute's primary antitumor drug screen. BPNU has a level of cytotoxic activity comparable to BCNU, CCNU and Methyl-CCNU. Unexpectedly, the bi-substitution of BPNU at the amino N3 position produced an inactive compound. Compared to BCNU, BPNU has a marked specificity towards leukemic cells and could potentially be useful as an anti-leukemic agent. In this series, the N1-(propargyl) group seems to induce cell line specificity.

Antineoplastic Agents↗
PubMed1994

[Excretion of beta-2-microglobulin and Tamm-Horsfall protein in patients undergoing a conditioning regimen before bone marrow transplantation].

UNLABELLED: This study aimed assess function of renal tubules in patients undergoing conditioning regimen before bone marrow transplantation. The examined group comprised 19 patients. 13 of them underwent autologuous bone marrow transplantation (ABMT), or autologuous peripheral blood stem cells transplantation (APBSCT). These patients were treated with Cyclophosphamide (Cy) (120 mg/kg), Etoposide (1.6-1.8 g/m2) and Carmustine (400-450 mg/m2). The remaining 6 patients underwent allogenic bone marrow transplantation (BMT). They were treated with Cy 200 mg/kg or with Cy 120 mg/kg and Busulfan 16 mg/kg (doses given are the total amount or respective drugs were administered during the whole conditioning regimen). Urinary excretion of beta-2MB and THP was assessed a) before the conditioning regimen was started, b) one day before completion of it, and c) one day before bone marrow transplantation. In ABMT/APBSCT patients urinary excretion of beta-2-MG was significantly higher before and during conditioning regimen as compared with baseline value (3309 +/- 1123.7 vs 3919 +/- 1417.8 vs 246.7 +/- 50.3 mg/24h, respectively, p < 0.05). Urinary excretion of THP in these patients was significantly higher only during the conditioning regimen (90.6 +/- 14.3 vs. 30.4 +/- 6.24 mg/24h, p < 0.0002). In BMT patients conditioning regimen was followed by similar but less marked changes of urinary excretion of beta-2-MG and THP as compared with ABMT/APBSCT patients. CONCLUSIONS: 1. Conditioning regimen do influence significantly function of proximal and distal renal tubules. 2. The extent of disturbed function of renal tubules seems to depend on kind of medication that is given during the conditioning regimen.

Adjuvants, Immunologic↗
PubMed1994

Total body irradiation and high-dose cyclophosphamide, BCNU and VP-16 (CBV) as a new preparatory regimen for allogeneic bone marrow transplantation in patients with advanced hematologic malignancies.

To increase the cure rate of advanced hematologic malignancies following allogeneic bone marrow transplantation we sequentially evaluated two intensified conditioning regimens. Eleven patients with acute myeloblastic leukemia (AML) beyond the first complete remission or chronic myelogenous leukemia (CML) not in first chronic phase received an association of 13.5 Gy of fractionated total body irradiation (TBI) followed by cyclophosphamide (CY) 120 mg/kg. Following this regimen, the probability of relapse was 47% at 3 years and the non-relapse mortality rate was 27%. Given the acceptable tolerance of this regimen, 13.5 Gy fractionated TBI was associated with intensified chemotherapy consisting of a combination of CY 120 mg/kg, carmustine 300 mg/m2 and etoposide 600 mg/m2 (CBV). This regimen was administered to 22 patients with comparable diseases. Of these patients, 7 received a transplant from a matched unrelated donor and 2 other patients received a second transplant from the original genoidentical donor. For 15 patients with a genoidentical donor, including the 2 second transplant, the 3 year probability of survival, disease-free survival and relapse are 40%, 40% and 14%, respectively. No regimen-related toxic deaths were recorded during the first 100 days. Of 7 patients with matched unrelated donors, 3 died before day 100, one death being directly attributable to the regimen. Early non-fatal regimen-related toxicity consisted mainly in grade II mucositis with no grade III or IV toxicity in recipients of genoidentical marrow. The late deaths were mainly due to chronic GVH-related complications. In conclusion, the association of fractionated 13.5 Gy TBI and CBV carries a high antileukemic activity and an acceptable toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Autologous bone marrow transplantation using TBI and CBV for disseminated high/intermediate grade cutaneous non-epidermotropic non-Hodgkin's lymphoma.

Patients with stage IV high/intermediate grade cutaneous non-epidermotropic lymphoma of skin as first localization of the disease have a poor prognosis. In this setting, autologous bone marrow transplantation (BMT) has rarely been evaluated. We report here on the treatment of four patients with such lymphomas with autologous BMT using 12 Gy total body irradiation (TBI) and CBV (cyclophosphamide, carmustine and etoposide). Using a plexiglass screen, TBI delivered an homogenized dose to the skin. With this conditioning regimen, all patients are still in complete remission 22, 44, 46 and 51, respectively, months after high-dose chemotherapy, TBI and autologous BMT.

Adult↗
PubMed1994

White matter changes in patients with breast cancer treated with high-dose chemotherapy and autologous bone marrow support.

PURPOSE: To study MR changes in the white matter of the brain in patients with breast cancer treated with a widely used protocol of high-dose chemotherapy and autologous bone marrow support. METHODS: Thirteen patients with high-risk stage II or stage IV breast cancer treated with high-dose cyclophosphamide, cisplatin, carmustine, and bone marrow support underwent posttransplant MR examination of the brain. Serial posttransplant MR examinations were performed in 5 of the 13 patients and single MR examinations in 8. The severity of the white matter change was evaluated by two neuroradiologists and rated mild, moderate, or severe. RESULTS: In 9 of the 13 patients, central and peripheral cerebral white matter changes were observed. Four patients had severe changes, extending from the ependyma of the lateral ventricles to the gyri. An additional 4 patients had moderate white matter change at the last observation. One had mild change, and 4 had no white matter change. In all patients, there was sparing of inferior frontal, posterior inferior occipital, and anterior temporal lobes, and of the centrosylvian brain. CONCLUSIONS: White matter change occurred in patients treated with a high-dose chemotherapy and bone marrow support protocol. Most of the changes, and the more severe ones, occurred 5 or more months after the transplants. There was no apparent relationship between these changes and central nervous system function. Because of the increased longevity with this treatment, it is important to appreciate these white matter changes, recognizing however that their expression may be subclinical.

Adult↗
PubMed1994

Treatment of cutaneous T-cell lymphoma.

A review of current therapy for cutaneous T-cell lymphoma (CTCL) (mycosis fungoides and erythrodermic CTCL) is presented. Treatments for mycosis fungoides limited to the skin include topical steroids, mechlorethamine (nitrogen mustard) and carmustine (BCNU), electron beam radiation, low-dose methotrexate, and interferon-alpha (IFN). Treatments for erythrodermic CTCL include low-dose methotrexate, IFN, extracorporeal photopheresis, and single agent or combination chemotherapy. Treatment for systemic CTCL includes IFN, single or combination chemotherapy, and combined modalities. Newer therapies are reviewed. Whereas prognosis for patients with disease limited to the skin is generally good, that for those with nodal or visceral lymphoma is mostly unfavorable. Controversial issues relating to total skin versus local treatment, prolonged maintenance versus intermittent therapy, and aggressive versus conservative treatment of early stage disease are discussed. The UCSF approach to treatment of CTCL and lymphomatoid papulosis is presented.

Carmustine↗
PubMed1993

[Specific curative effects of nitrosourea drugs on tumor cells with Mer--phenotype in Chinese].

O6-Methylguanine DNA methyltransferase (O6-MT) activity and cellular sensitivity to nitrosourea drugs of 10 kinds of tumor cell strains derived from Chinese patients were measured by 3H radioactivity and colony-forming ability, respectively. The results in vitro showed that nimustine (Nim) 25 micrograms.ml-1 and carmustine (Car) 20 micrograms.ml-1 exhibited specific killing effects on Mer-phenotype tumor cells characterized by low O6-MT activity. In vivo both Nim and Car (25 mg.kg-1.wk-1 x 4 wk, ip) had specific curative ability to Mer- tumor cells implanted in nude mice. These findings suggested that assay of O6- MT activity in tumor biopsy could be used as a predictable guide to human tumor chemotherapy with nitrosourea compounds.

Animals↗
PubMed1993

Comparison of preparative transplantation regimens using carmustine/etoposide/cisplatin or busulfan/etoposide/cyclophosphamide in lymphoid malignancies.

Most bone marrow transplantation preparative regimens use total body irradiation as one component. Recently, however, two non-total body irradiation containing autologous bone marrow transplantation preparative regimens have been evaluated in patients with lymphoid malignancies. The first regimen consisted of carmustine, etoposide, and cisplatin; some patients also received involved-field radiotherapy to sites of prior disease. Of the 79 patients with relapsed or refractory lymphoma who participated in this study, 57 (72%) achieved a complete remission and 40 (51%) remain in complete remission. Treatment-related deaths occurred in five patients (6%). The second preparative regimen evaluated consisted of busulfan, etoposide, and cyclophosphamide and included 21 patients with Hodgkin's lymphoma, non-Hodgkin's lymphoma, or acute lymphocytic leukemia. Sixteen patients (76%) achieved complete remission and 12 (57%) remain disease free. The regimen-related mortality rate in this study was 14%. The three treatment-related deaths were all due to pulmonary toxicity. The results of these clinical trials indicate that both the carmustine/etoposide/cisplatin regimen and the busulfan/etoposide/cyclophosphamide regimen are effective in treating lymphoid malignancies. Treatment-related toxicities and deaths are significant, but not prohibitive. Accordingly, these new preparative regimens deserve further evaluation in the treatment of patients with lymphoma or leukemia.

Adolescent↗
PubMed1993

Post-5-fluorouracil human marrow: stem cell characteristics and renewal properties after autologous marrow transplantation.

The effect of 5-fluorouracil (5-FU) pretreatment on human bone marrow (BM) progenitor/stem cells and recovery of hematopoiesis after autologous marrow transplant was studied. Twenty-one patients were treated with 5-FU (15 mg/kg to 45 mg/kg) intravenously (IV) for 1 to 3 days administered 6 to 22 days before BM harvest. Post-FU marrow was infused into 15 patients after high-dose cyclophosphamide, carmustine (BCNU), and VP-16 (CBV). Seventeen patients (historical controls) were treated with CBV and autologous BM transplantation but did not receive 5-FU before marrow harvest. The groups were comparable for diagnosis and prior therapy. In the 5-FU-treated group and control group, median recovery times for platelet count to 50,000/mm3 were 20 and 30 days, respectively (P = .007), and for platelet count to 100,000/mm3, 23 and 38 days, respectively (P = .007), while neutrophil recovery was not significantly altered. In vitro cultures with 1 to 7 growth factors (interleukin-1 [IL-1], IL-3, IL-4, IL-6, colony-stimulating factor-1 [CSF-1], granulocyte-macrophage colony-stimulating factor [GM-CSF], and G-CSF) were performed. In 8 of 10 patients whose marrow was studied before and after 5-FU treatment, the numbers of CFU-C responsive to the combination of GM-CSF and IL-3 was increased 6.15-fold by 5-FU pretreatment. In 4 of these patients, thymidine suicide of GM-CSF- and IL-3-stimulated CFU-C ranged from 17% to 42%. High proliferative potential colony-forming cell (HPP-CFC) was observed in low frequency in normal marrow and patient's marrow before 5-FU treatment. In 11 of 16 patients pretreated with 5-FU, increased numbers of HPP-CFC were noted. GM-CSF and IL-3 interacted synergistically to stimulate HPP-CFC. Multifactor combinations, especially GM-CSF + G-CSF + IL-3 + IL-6 + IL-1 + CSF-1 did not increase total colony count or classic HPP-CFC but did result in altered morphology, producing huge, loose colonies. The marrow from patients pretreated with 5-FU is enriched with multifactor-responsive HPP-CFC, renews in vivo granulopoiesis in a manner comparable with marrow harvests without 5-FU pretreatment, and provides accelerated in vivo platelet recovery. This marrow may be an appropriate target marrow for gene insertion in gene-therapy protocols.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Topical treatment of early cutaneous T-cell lymphoma.

The two major topical treatment modalities for cutaneous T-cell lymphoma (CTCL) are mechlorethamine (nitrogen mustard) and topical carmustine (BCNU). Topical mechorethamine hydrochloride has been used since the late 1950s as therapy for CTCL. Topical BCNU solution is a highly effective treatment for early stage mycosis fungoides. This article describes these two modalities.

Administration, Topical↗
PubMed1996

[Chemo-/immunotherapy in advanced malignant melanoma: carboplatin and DTIC or cisplatin, dtic, bcnu and tamoxifen followed by immunotherapy with interleukin 2 and interferon alpha-2a].

BACKGROUND: Polychemotherapy and immunomodulating treatment using IL-2 and/or IFN-alpha produce objective responses in a proportion of advanced malignant melanoma patients. PATIENTS AND METHODS: In 2 consecutive phase II trials in a total of 85 patients, we assessed the potential synergism between both modalities i.e., chemo- and immunotherapy. Treatment consisted of intravenous carboplatin (CBDCA, 400 mg/m2) and dacarbazine (DTIC, 750 mg/m2) given twice at a 3-week interval, or 4 cycles of DTIC (220 mg/m2 i.v. x 3 days), cisplatin (DDP 35 mg/m2 i.v. x 3 days), carmustine (BCNU 150 mg/m2 i.v., cycles 1 and 3) and tamoxifen (TAM 20 mg/per os x 5 days) at a 3-week interval. Chemotherapy was followed by immunotherapy with combined subcutaneous interleukin-2 and (rIL-2) and s.c. interferon-alpha 2a (rIFN-alpha). RESULTS: Among 40 patients who received a full cycle of chemotherapy with CBDCA/DTIC and sequential immunotherapy, there were 3 (7.5%) complete remissions (CR) with durations of 13 to 26+ months. Partial remissions (PR) were noted in 11 (27.5%) patients with a median response duration of 8 (range 5 to 14) months. Among 45 patients who received DTIC/DDC/DDP/BCNU and TAM and sequential rIL-2/rIFN-alpha 2a there were 5 (11%) complete remissions and 17 (38%) partial remissions. Duration of complete and partial remissions ranged from 8+ to 24+ months (median 12+) and 5+ to 17 months (median 8+), respectively. Chemotherapy produced mostly moderate toxicity. Thrombocytopenia was common with the nadir after a median time of 17 days following start of the chemotherapy. 19 patients required transfusion of thrombocytes. Nausea and vomiting due to chemotherapy were well tolerated using concomitant ondansetrone (8 mg i.v.). Immunotherapy was self-administered at home with mild to moderate side-effects; malaise, fever, chills, nausea/vomiting, diarrhea, anorexia and arthralgias were most frequent (70% to 100%), but spontaneously reversible after ending the immunotherapy. A mean of 87% (trial I) to 89% (trial II) of the projected doses of rIL-2 and rIFN-alpha were administered on either protocol. There were no life-threatening complications and no treatment-related deaths. CONCLUSION: The sequential combination of chemotherapy and immunotherapy had at least additive therapeutic activity against metastatic malignant melanoma. Both schedules produced long-lasting remissions and were overall well tolerated. These trials substantiate a potential role for low to intermediate dose immunotherapy in maintaining and consolidating therapeutic effects of chemotherapy in metastatic melanoma.

Adult↗
PubMed1996

High-dose chemotherapy and autologous peripheral blood progenitor cell transplant for the treatment of Hodgkin's disease.

This paper evaluates a comprehensive strategy of chemotherapy mobilization of peripheral blood progenitor cells (PBPCs) followed by high-dose chemotherapy for the treatment of refractory or relapsed Hodgkin's disease (HD). Patients with relapsed or refractory HD were enrolled to receive cyclophosphamide, etoposide +/- cisplatin (CE +/- P) and rhG-CSF mobilization of PBPCs. Patients achieving < or = 2.5 x 10(6) CD34+ cells/kg following initial mobilization were eligible to receive a second course of CE +/- P. Unmanipulated PBPCs alone were infused following administration of high-dose carmustine, etoposide, cytarabine arabinoside and cyclophosphamide (BEAC). Thirty-eight consecutive patients with relapsed or refractory HD were initially enrolled to receive CE +/- P. Analysis was performed on an intent-to-treat basis. A median of 6.4 x 10(6) CD34+ cells/kg (range 0.66-62.3) were collected with a median of 3 (range 2-9) leukaphereses. Twenty-eight of 38 (74%) patients achieved > or = 2.5 x 10(6) CD34+ cells/kg. Analysis of variables potentially effecting mobilization of CD34+ cells revealed that only the amount of prior chemotherapy statistically influenced collecting CD34+ cells (P = 0.005). Two of six patients undergoing a second mobilization procedure achieved > or = 2.5 x 10(6) CD34+ cells/kg for a total of 30 patients eligible to proceed with high-dose BEAC. The 3-year Kaplan-Meier estimate of overall survival (OS) and progression-free survival (PFS) for all 38 patients is 65 and 53%, respectively. The 3-year OS and PFS for the 28 patients receiving BEAC is 77 and 64% respectively vs 33 and 30% for the 10 patients not receiving BEAC. The strategy of CE +/- P and BEAC was well tolerated with a 100-day treatment-related mortality of 3.6%. All patients experienced rapid and sustained hematologic recovery with PBPCs alone. The median time to an ANC > or = 5 x 10(9)/1 and platelet transfusion independence was 10 days. Although development of better strategies to mobilize PBPCs may benefit additional patients, currently the best strategy to collect PBPCs is early before patients have received extensive chemotherapy treatment. Collection of PBPCs immediately following initial relapse or induction failure using CE +/- P for PBPC mobilization allows sufficient PBPCs to be collected in greater than 90% of patients. Treatment of refractory or relapsed HD utilizing a strategy of CE +/- P PBPC mobilization for hematopoietic reconstitution following high-dose BEAC is associated with acceptable toxicity and rapid engraftment. A 3-year PFS greater than 60% can be achieved in the community hospital setting.

Adolescent↗
PubMed1996

High-dose BCNU and autologous progenitor cell transplantation given with intra-arterial cisplatinum and simultaneous radiotherapy in the treatment of high-grade gliomas: benefit for selected patients.

A phase II study of postoperative high-dose carmustine (HDBCNU), intracarotid cisplatin (CDDP), and radical radiotherapy in patients with high-grade glioma was performed. Patients underwent 4-6 consecutive days of blood hematopoietic progenitor cell (HPC) apheresis without prior mobilization. Chemotherapy included intracarotid CDDP, 60 mg/m2, and BCNU, 900 mg/m2. HPC were infused 48 h after HDBCNU. Whole brain irradiation, up to 50 Gy, was started on the 8th day after HPC infusion. With a median follow-up time of 44 months, median overall survival was 15.5 months. Eight patients (23.5%) are alive free of disease 2-6 years after treatment (seven out of 25 patients with glioblastoma multiforme and one out of nine patients with anaplastic astrocytoma). Survival was influenced by young age, good performance and complete surgical resection. Two patients (5.8%) died of therapy-related complications. Acute hematological toxicity of HDBCNU was moderate, with a full recovery on day 26. No acute pulmonary or hepatic toxicity was found. Late severe neurological toxicity was observed in one third of patients surviving beyond 2 years. We conclude that HDBCNU, 900 mg/m2, intracarotid CDDP and radical radiotherapy appear to benefit some patients with high-grade gliomas, and phase III studies should preferentially select young patients with resectable tumors.

Adult↗
PubMed1997

Outpatient chemoimmunotherapy for the treatment of metastatic melanoma.

The prognosis for most patients with metastatic melanoma is poor, as the median survival is only 7 months. Phase II trials of chemoimmunotherapy have, however, reported response rates of 40% to 70% and prolonged disease-free survival in small subgroups of patients. Most chemoimmunotherapy trials have used high doses of recombinant interleukin-2 (rIL-2) and recombinant interferon alpha (rIFN-alpha) that produce significant toxicity and require prolonged hospitalization to manage side effects. To develop a treatment regimen for metastatic melanoma that would minimize costly hospitalization, we initiated a phase II trial of outpatient chemoimmunotherapy. Patients were treated with monthly cycles of intravenous carmustine, dacarbazine, cisplatin, and tamoxifen plus self-administered subcutaneous rIL-2 and rIFN-alpha as outpatients. To date, 32 patients have received 94 cycles of therapy. The most common toxicity was nausea and vomiting. Hospitalization for the management of toxicity was required in only seven cycles (7%). Thirty patients have been assessed for clinical response. The overall response rate was 43% (13% complete and 30% partial response). This phase II trial has established a tolerable regimen of outpatient chemoimmunotherapy, which has shown significant antitumor activity.

Adult↗