摘要:

A total of 248 analyzable patients with Stages III-IV ovarian epithelial cancer (114 with and 134 without prior chemotherapy) were randomized to one of four cisplatin (DDP)-hexamethylmelamine (HMM) regimens. In each, HMM, 200 mg/m2was given orally daily on days 8-21 of each 21-day cycle. DDP was given i.v. on Day 1 at a dose of 37.5 mg/m2(regimens A and B) or 75 mg/m2(regimens C and D). In addition, since pyridoxine administration has been reported to reduce the neurotoxicity of HMM, that agent was given at a dose of 300 mg/m2orally on Days 1-21 in regimens B and D. Randomization was stratified for performance status (0-1, 2-3) and largest tumor diameter at entry (>2-≤10 cm,>10 cm) for previously untreated patients, and for performance status and time from initial diagnosis to entry on study (1 year) for previously treated patients. The overall response rate (PR + CR) was 54%, with 25% of patients achieving a complete response. The 61 % response rate with the higher dose DDP regimens was significantly greater than the 47% response rate with the lower dose regimens (p = 0.031). Multivariate analysis identified higher DDP dose, age<60 years, no prior chemotherapy, small tumor bulk and favorable tumor grade as significant prognosticators for response. The overall median response duration was 8.3 months (range 1-70 months). Prior chemotherapy, pyridoxine administration, recent diagnosis, and large tumor size were identified by multivariate analysis as factors adversely affecting response duration. Patients treated with the higher dose DDP regimens had more severe nausea, vomiting, and neurotoxicity. This study demonstrates that the combination of DDP + HMM is an effective regimen for advanced ovarian carcinoma that yields response rates comparable to other more complex regimens, and that there is a dose-response relationship for DDP in ovarian cancer. Although pyridoxine administration significantly reduced neurotoxicity, its adverse effect on response duration suggests that the agent should not be administered with DDP or HMM. The mechanism by which pyridoxine may unfavorably affect response duration deserves further investigation.

ISSN:0735-7907    

DOI:10.3109/07357909209032783

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

To study the efficiency of high-dose melphalan in previously untreated patients with advanced myeloma, we performed a Phase I-U trial. Twenty-eight patients were treated at dose level of 60-140 mg/m2. Each patient was first treated with a priming dose of cyclophosphamide (300 mg) followed by high-dose melphalen 1 week later. One course of therapy was given. Patients were then followed without further therapy until relapse. Clinical and laboratory features of the 28 patients in this study included: median age 63, performance status 0-2, hypercalcemia 21%, bone pain 82%, paraprotein types: IgG 76%, Iga 20%, and paraproteinuria 71%. Because none of the patients acheived complete remission (CR) at 60 mg/m2, despite life-threatening toxicity in all patients, the dose level was rapidly increased to 140 mg/m2, a dose previously reported to induce a high percentage of CR. At this dose, CR was achieved in only 1 of 11 patients (9%). This patient had multiple plasmacytomas without generalized bone marrow involvement. One additional patient at 100 mg/m2achieved CR Of the whole group, 12 achieved PR. Durations of remissions were generally short: CR 6.3 and 18+ months and PR 2.3-18 month, median 6.9 months. Life-threatening myelosuppression was universal with prolonged pancytopenia. Treatment-related deaths from sepsis were observed in 29% of patients. The median survival of the entire group was 15.6 months. Older patients in this trial did not tolerate high-dose melphalen therapy well; this resulted in a high proportion of toxic deaths and poor overall survival.

ISSN:0735-7907    

DOI:10.3109/07357909209032784

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Immunotherapy with recombinant human interleukin-2 (IL-2) and allogeneic spleen cells has led to significant antitumor effects in B-cell leukemia- (BCL1) bearing mice following transplantation with T-lymphocyte-depleted allogeneic bone marrow cells. Graft versus leukemia (GVL) effects were studied in a model mimicking minimal residual disease following bone marrow transplantation (BMT). Lethally irradiated (BALB/c X C57BL/6)F1 recipients were reconstituted with 20 X 105T-lymphocyte-depleted C57BL/6 bone marrow cells mixed with 104to 106BCL1 cells followed by administration of sequential increments of allogeneic C57BL/6 spleen cells; 106cells on Day +1, 107cells on Day +5, and 5 X 107cells on Day +9, with or without concomitant IL-2 treatment (intraperitoneal injections of 20,000 U twice daily for 3 days) together with each spleen cell administration. All mice receiving 10t-106BCL1 cells developed marked splenomegaly by Day +21 and all adoptive recipients of 10sspleen cells obtained from these mice developed leukemia within 21-36 days. Treatment of mice which received 104BCL1 cells by either three courses of low dose IL-2 or three increments of allogeneic spleen cells alone and certainly by a combination of both resulted in normalization of splenomegaly on Day +21, but only adoptive recipients of 105spleen cells obtained from mice treated by both allogeneic spleen cells and IL-2 (10/10) or allogeneic spleen cells alone (8/10) were disease free (>100 days). Mice inoculated with 105BCL1 cells developed mild splenomegaly on Day +21 after R2 treatment alone, but showed no clinical evidence of disease following administration of allogeneic spleen cells or both allogeneic spleen cells and IL-2. Following adoptive transfer of 10sspleen cells obtained from each treated group no leukemia (>100 days) was evident in recipients of spleen cells obtained from mice treated with both, allogeneic spleen cells and IL-2 (10/10) whereas a partial effect was observed in mice treated by allogeneic spleen cells only (4/10). Mice inoculated with a high dose ofBCLl cells (106) showed some delay in onset of splenomegaly, but no curative antileukemic effects could be observed even following a synergistic combination of IL-2 and allogeneic spleen cells. Our data suggest that immunocompetent allogeneic lymphocytes may play an important role against leukemic relapse and thus cell therapy may be used therapeutically to treat minimal residual disease after BMT even following initial reconstitution with T-cell-depleted bone marrow cells. Moreover, GVL effected mediated by allogeneic lymphocytes may be further augmented by concomitant administration of suboptimal doses of IL-2. A similar approach may prove beneficial in conjunction with autologous and allogeneic BMT in humans as long as graft versus host disease can be prevented or controlled.

ISSN:0735-7907    

DOI:10.3109/07357909209032785

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

ISSN:0735-7907    

DOI:10.3109/07357909209032786

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

ISSN:0735-7907    

DOI:10.3109/07357909209032787

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

ISSN:0735-7907    

DOI:10.3109/07357909209032788

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

The most significant advancements in techniques and methods for protein purification and analysis have been made in liquid chromatography and in electrophoresis. In the area of chromatography, adsorbents based on new affinity principles have been prepared. New packing materials have facilitated the rapid progress of high-performance techniques. A great many new techniques in the field of electrophoresis have emerged. On an analytical scale, electrophoretic methods in two dimensions or in capillaries are unsurpassed in resolution power. Development of techniques for protein transfer between different media is a prerequisite for a full exploitation of the new methods. Modern techniques for analysis of submicrogram quantities facilitate the separation, detection, and characterization of complex protein mixtures.

ISSN:0735-7907    

DOI:10.3109/07357909209032789

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

ISSN:0735-7907    

DOI:10.3109/07357909209032790

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

ISSN:0735-7907    

DOI:10.3109/07357909209032791

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

ISSN:0735-7907    

DOI:10.3109/07357909209032792

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor