ISSN:0735-7907    

DOI:10.3109/07357909509011683

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

The purpose of this study was to determine whether methotrexate, vinblastine, doxorubicin, and cisplatin, each individually active in metastatic breast cancer (MBC), could, in combination, produce an overall response rate, median survival, and long-term survival sufficiently promising to merit its consideration for phase 111 trials in MBC and as induction therapy prior to autologous bone marrow transplant. From July 1986 through February 1990,30patients with stage IV, measurable breast carcinoma received M-VAC: methotrexate–30 mglm days 1,15, 22; vinblastine–3 mg/m2days 2, 15, 22; doxorubicin–30 mglm day 2; cisplatin–70 mglm day 2. Cycles were repeated at 4-week intervals for up to six courses. Median age was 53 years (range 34–64 years). Prior treatment included adjuvant cyclophosphamide, methotrexate, and 5-Fluorouracil in 12 patients, radiotherapy in 13 patients, and hormonal therapy in 14 patients. Eleven patients were ER (+) at the time of initial diagnosis. Five patients had disease restricted to bone and/or nodes; the other 25 had visceral-dominant sites of metastases, with or without bone involvement, or evidence of rapid, inflammatory chest wall relapse. Twenty-nine of 30 patients were evaluablefor toxicity and response; all were evaluablefor survival. The major overall response rate was 83%, with a 21% complete remission rate. The chief toxicity was bone marrow suppression, with grade 4 granulocytopenia in 20 patients, grade 3 in 7 patients, and grade 3 and 4 thrombocytopenia in 5 patients. Grade 3 stomatitis occurred in 9 patients. Renal insufficiency was clinically insignificant, and neurotoxicity mild, with 7patients sustaining grade I or 2 paresthesias. Median time to progression was 9 months and median survival 19 months (range, 5–84+ months) with 4 patients still alive at least 45 + months or more from the start of treatment and 2 presently free of progressive disease. Although highly toxic, M-VAC produces a response rate and survival duration in visceral-dominant MBC competitive with, if not superior to, conventional regimens such as CAF (Cytoxan, doxorubicin, 5-fluorouracil); it therefore merits further investigation in conjunction with hematopoietic growth factors and as cytoreductive therapy prior to autologous bone marrow transplantation.

ISSN:0735-7907    

DOI:10.3109/07357909509011684

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Twenty-five women with advanced breast carcinoma refractory to first-line chemotherapy entered a phase II trial to evaluate the efficacy of ifosfamide and carboplatin. Additionally the trial assessed the clinical usefulness of oral 2-mercaptoethane sulfonate (mesna) for urothelial protection. Two partial remissions were observed (8%); toxicity was significant but acceptable, with no treatment-related deaths. The combination of ifosfamide and carboplatin had little activity as the second-line treatment in our population of patients with heavily pretreated metastatic breast cancer. Oral mesna was effective for urothelial protection, permitting outpatient administration of ifosfamide.

ISSN:0735-7907    

DOI:10.3109/07357909509011685

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Two groups of patients with disseminated breast carcinomas who had failed radiotherapy, chemotheraphy, and hormonotherapy were treated with natural interferon a (nIFN-α) alone or in combination with nIFN-γdelivered in cycles of 10–12 intralesional (i.l.) injections to recurrent and metastatic lesions. In group, I, 16 skin lesions in 12 patients received nIFN-αalone resulting in 7 complete regressions verified histologically (CR), 7 partial regressions (PR), and no regressions (TV/?J in 2. Group II included 4 patients in whom 7 cutaneous recurrences were treated with nIFN-α/nlFN-γ(5 CR, 2 PR), 2 were injected with nIFN-αalone (1 CR, 1 PR), and I received nIFN-γalone (PR). Two additional patients in group II were given i.l. injections of nIFN-αlnlFN-γto lymph node metastases (I CR, I PR). Clinical toxicity was experienced by 5 of 12 patients in group I and by all the patients in group II and was controlled in most instances by antipyretics. Systemic antitumor effects were not appreciable clinically. Nevertheless, noninjected lesions exposed only to systemic levels of IFNs, when studied immunohistochemically, displayed an immunological response similar to that of IFN-injected lesions, although less intense. Therefore, IFNs can be useful in controlling locoregional recurrences of breast cancer even in patients who are not responding to other forms of therapy. Furthermore, in addition to the local antitumor actions, they appear to be capable of eliciting systemic immunological effects.

ISSN:0735-7907    

DOI:10.3109/07357909509011686

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

We investigated the expression of transforming growth factorsβ1andα(TGF-β1, TGF-α) in hormone-responsive (MPA-R) and unresponsive (MPA-U) tumor lines obtained from medroxyprogesterone acetate (MPA)-induced mammary adenocarcinomas in BALBIc mice. The tumors were transplanted into MPA-treated and untreated mice. TGF-β1gene expression was observed in the MPA-R lines growing in untreated animals, but not in MPA-treated mice. TGF-β1mRNA was not detected in the MPA-U tumor lines growing in either MPA-treated or untreated animals. In MPA-R lines the levels of TGF-β1expression were inversely correlated to growth rate. High-affinity TGF-β1receptors were present in the MPA-R tumors. These results suggest that one of the mechanisms by which MP A exerts its proliferative effect on MPA-R tumor lines is inhibition of the expression of TGF-β1. Thus, the lack of expression of TGF-β1in MPA-U tumors may be related to the acquisition of autonomous growth.

ISSN:0735-7907    

DOI:10.3109/07357909509011687

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Activity of ornithine decarboxylase (ODC), one of the rate-limiting enzymes in the pathway of polyamine biosynthesis, is regulated by various factors. In this study, we examined the role of Ca2+in the regulation of ODC enzyme activity in mouse colon cancer cells (MC-26). KCl, a membrane-depolarizing agent that opens the voltage-dependent Ca -channel to increase intracellular Ca2+, decreased serum-induced ODC enzyme activity in MC-26 cells in a dose-dependent, reversible fashion. Both verapamil and nifedipine, inhibitors of the L-type voltage-dependent Ca2+-channel, decreased serum-induced ODC enzyme activity. W-7, a calmodulin inhibitor, decreased ODC enzyme activity in a dose-dependent, reversible fashion while trifluoperazine, another calmodulin inhibitor, failed to affect ODC enzyme activity in MC-26 cells. Our findings indicate that intracellular Ca participates in the regulatory mechanism of ODC enzyme activity in MC-26 cells, although the exact role of Ca2+is still unclear.

ISSN:0735-7907    

DOI:10.3109/07357909509011688

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

The occurrence of arterial thrombosis reported in other breast cancer series has largely been confined to the upper extremities, ipsilateral to a previous mastectomy site and clinically manifest as cerebral vascular accidents. This case report describes 2 patients who experienced iliac artery thrombosis temporally related to receiving granulocyte-macrophage colony-stimulating factor (GM-CSF) and dose-intensive chemotherapy for metastatic breast cancer. A review of the literature concerning arterial thrombosis as relevant to breast cancer treatment and GM-CSF is included.

ISSN:0735-7907    

DOI:10.3109/07357909509011689

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Limited efficacy of chemotherapy in most solid tumors has revived interest in immunotherapeutic approaches for cancer. One novel form of immunotherapy is the use of cancer vaccines consisting of tumor cells genetically engineered to secrete cytokines. The rationale for this immunization strategy is based on the existence of tumor-specific antigens, on the importance of the cellular arm of the immune system in mediating an effective antitumor response, and on the role of cytokines in regulating the cellular immune response. Such tumor vaccines showed considerable promise in various animal models and induced potent antitumor immunity in the host, which led to regression of established tumors and, moreover, produced immunological memory protecting animals from a subsequent tumor challenge at a distant site. Translated to the human patient, this implies that genetically modified tumor vaccines may be able to eradicate or reduce existing tumor deposits to subclinical levels as well as provide long-term protection from regrowth of tumor cells. This report will review and discuss the concept and rationale for the use of cytokine-secreting tumor vaccines for the treatment of human malignancies.

ISSN:0735-7907    

DOI:10.3109/07357909509011690

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Clinical studies of infusional chemotherapy at The Cancer Center of Boston began in 1980 at the New England Deaconess Hospital and from 1986 to the present have continued under the auspices of a network of free-standing ambulatory cancer treatment centers in Massachusetts. Over 50 peer-reviewed articles on infusional chemotherapy and 3 textbooks on the topic have been published by clinical investigators associated with The Center, including phase I, II, and III trials, multidrug infusion programs, and combined chemolradiotherapy programs. Bringing together the total experience in this review provides a perspective to address those areas that have been inadequately explored and a framework for future development in the field. This paper represents a comprehensive synthesis and analysis of clinical infusional studies carried out at The Center to the present with the goal of achieving those objectives.

ISSN:0735-7907    

DOI:10.3109/07357909509011691

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Among the new tumor markers that have been recently proposed, CA 72-4 is of particular interest, not only for its capabilities in diagnosing and monitoring certain neoplastic diseases, but also for its excellent specificity. Several studies focused on the potential clinical usefulness ofCA 72-4 in gastrointestinal (GI) and gynecological cancer, showing a sensitivity of approximately 40% in colorectal and gastric cancer and 50% in ovarian cancer, with an overall specificity of more than 95%. Longitudinal evaluations of patients with either GI or gynecological malignant diseases demonstrated that significant elevations of CA 72-4 serum levels may be predictive of recurrent disease. Moreover, the combination of CA 72-4 with other known serum markers, such as CEA and CA 19-9 for GI cancer or CA 125 for ovarian cancer, indicated that an increase in the sensitivity can be achieved without substantial changes in the overall specificity, improving the possibility of monitoring these patients. In conclusion, these results provide a strong argument for the use of CA 72-4 in the management of these neoplastic diseases.

ISSN:0735-7907    

DOI:10.3109/07357909509011692

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor