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Biomedical subjects

G Blumenschein

Publications and source records attributed to G Blumenschein.

18 recordsLinked to original sources
PubMed1995

A marrow harvest procedure under local anesthesia.

This report details a bone marrow harvest procedure performed outside the hospital setting under local anesthesia, thereby avoiding many of the risks associated with the traditional surgical procedure. In approximately 30 minutes, 450 milliliters of marrow can be collected from eight bone punctures, containing a median of 4.18 x 10(9) cells and 33 x 10(6) progenitor cells as defined by CD34 expression. Reinfusion of a median 1.2 x 10(6) CD34+ cells/kg in 10 breast cancer and lung cancer patients after dose-intensive chemotherapy resulted in the recovery of granulocytes > 100/mm3 by day 14 and platelets > 20,000 by day 21. Without progenitor cell support, such recoveries could take 30 and 40 days, respectively. Collection of marrow using this protocol does not compromise the engraftment capability of the progenitor cells, seldom necessitates blood product support, is safer for the patient, and reduces the cost of harvesting by 75% compared to inpatient or day surgery procedures.

Anesthesia, Local↗
PubMed1992

Combination biotherapy utilizing interleukin-2 and alpha interferon in patients with advanced cancer: a National Biotherapy Study Group Trial.

The National Biotherapy Study Group (NBSG) conducted a broad phase II trial using interleukin-2 (IL-2) by continuous infusion and alpha interferon (IFN) subcutaneously in 267 patients with a variety of advanced cancers, including 29 with breast cancer, 89 with renal cancer, and 69 with melanoma. IL-2 [18 million international units (MIU)/m2] was given by continuous infusion for 108 hours with 3 mu/m2 subcutaneous IFN every other day during the IL-2 infusion. The patients were treated for 1 week followed by a 2-week rest. After two cycles of treatment, patients were evaluated for response. Of the 237 patients evaluable for response, 20 (8%) had a complete or partial response and 128 (54%) were stable. Therefore, 62% of the evaluable patients were nonprogressive during the first 90 days of IL-2/IFN therapy. The objective response rate was 11% in melanoma, 7% in renal cancer, 14% in breast cancer, and 3% in patients with a variety of malignancies for an overall response rate of 7% in these patients with advanced cancer. The patients were treated on a general medical ward and tolerated treatment well with fatigue and fever being nearly universal. Dyspnea, pruritus, chills, and elevated creatinines were frequent but less common. This combination biotherapy regimen has minimal activity in a variety of advanced cancers and must be compared with the best existing chemotherapy for each cancer type in randomized, prospective trials.

Adult↗
PubMed1991

Continuous interleukin-2 and lymphokine-activated killer cells for advanced cancer: a National Biotherapy Study Group trial.

We conducted a multicenter, phase II trial of continuous-infusion recombinant interleukin-2 (rIL-2) and lymphokine-activated killer (LAK) cells. Patients had advanced cancer, measurable disease, and a good performance level. Treatment included a 5-day continuous infusion of 18 x 10(6) IU/m2/d of rIL-2 followed by 1 day of rest, 4 days of leukapheresis to collect cells for in vitro augmentation of cellular cytotoxicity, and 5 more days of rIL-2 infusion with reinfusion of LAK cells for 3 successive days. Therapy was repeated after 2 weeks. There were 117 patients enrolled: 63% were males, with a median age of 51 years. Eighty-two percent were managed in oncology units, and 18% were in intensive care units. Six patients died within 1 month of initiating therapy. In renal cell carcinoma, the response rate was one of 31 patients (3%), with a median survival of 10.7 months. In melanoma, the response rate was four of 33 patients (12%), with a median survival of 6.1 months. For all other histologies, response rate was three of 53 patients (5%), with a median survival of 7.4 months. All responders were asymptomatic when therapy was initiated. This trial confirms the feasibility of administering continuous rIL-2 and LAK cells outside the intensive care unit environment. Antitumor activity in melanoma was similar to that seen in multicenter trials of bolus rIL-2 and LAK cells. Activity in renal cell cancer was disappointing.

Adolescent↗
PubMed1985

Five-day continuous-infusion vinblastine in the treatment of breast cancer.

One hundred six evaluable patients with metastatic breast cancer refractory to prior chemotherapy were treated with 5-day intravenous infusions of vinblastine at 1.4 to 2.0 mg/m2/day, through silastic elastomer permanent central venous catheters. Thirty-nine patients achieved objective responses; 5 were considered complete. The overall response rate of 37% was independent of prior exposure to intermittent intravenous vinca alkaloids or prior response to front-line doxorubicin combination chemotherapy. Objective responses were documented in 48% of the patients who received daily doses above 1.7 mg/m2 and in 32% and 29% of those treated with 1.7 mg/m2 or less, respectively (P = 0.10). Myelosuppression was more severe in responders, who received higher average doses, (median average nadir, 850 granulocytes/mm3) than in nonresponders (median, 1300 granulocytes/mm3), but was always rapidly reversible. Infections related to neutropenia were uncommon. Catheter-related toxicities occurred in 13 of 106 patients. Other toxicities were limited. These results confirm that vinblastine given as a continuous 5-day infusion is one of the most effective agents in the treatment of metastatic breast cancer and suggest that its activity is dose-dependent.

Adult↗
PubMed1985

The human tumor stem cell assay revisited.

The human tumor stem cell assay (HTSCA) is a bilayer soft agar system for growing fresh human tumor specimens in vitro to determine drug sensitivity and improve our understanding of tumor biology. Recent clinical correlations of 60% accuracy for predicting a positive clinical response and a 90% accuracy for predicting a lack of response to therapeutic agents suggest promising clinical usefulness. However, the clinician should be aware of the assay's inherent pitfalls, such as heterogeneity of the tumor specimen, inability to obtain pure single-cell suspensions, low cloning efficiency, unusual drug dose-dependent survival curves, uncertain validity of in vitro pharmacology, non-standardized criteria for in vitro sensitivity, and the variability of in vitro results. A brief summary of the concepts, potential, and limitations of this assay are discussed.

Animals↗
PubMed1985

Clonogenic in vitro growth and histologic grading of primary human breast tumors.

We determined the relationship of clonogenic in vitro growth and histopathologic features of 31 primary human breast tumors. Well-differentiated primary tumors formed fewer colonies than poorly differentiated tumors, and the clonogenic in vitro growth of tumors correlated inversely with patient survival. The potential of the clonogenic assay to serve as a predictor of disease course should be explored further.

Breast Neoplasms↗
PubMed1985

Regulation of breast tumor growth by high dose estrogen is independent of the presence of estrogen receptors.

17 beta-estradiol stimulated the clonogenic growth of four established human breast tumor cell lines independent of the estrogen receptor status of the cells. Likewise, tamoxifen citrate, a nonsteroidal antiestrogen, inhibited the in vitro growth of both estrogen receptor-negative and estrogen receptor-positive cell lines to a similar degree. These findings indicate that, at pharmacologic doses, the growth stimulatory and inhibitory effects of estrogen and antiestrogens are not necessarily mediated by hormone-specific receptors.

Breast Neoplasms↗
PubMed1984

The true predictive value of the human tumor stem cell assay: does a workable assay select for treatment responders?

In practice, the human tumor clonogenic assay is workable for less than half of the patient population to which it is applied, since the remainder of the specimens fail to produce sufficient numbers of colonies. Thereby a bias may be introduced which could result in a false predictive value positive of the test. It is therefore necessary to compare the responses to treatment of patients whose tumors could be assayed in vitro to those whose tumors failed to grow adequately, to assure that the prevalence of treatment responders has not changed within the group of patients for which the assay worked. From an analysis of the treatment response of 70 patients with stage III and IV ovarian carcinomas and 70 patients with stage IV breast cancer, no selection bias did occur and no preferential in vitro growth of tumor samples from patients with treatment response was found.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

A phase I-II study of continuous 5-day infusion mitomycin-C.

A phase I-II study was undertaken to establish the maximum-tolerated dose of a continuous 5-day infusion of mitomycin-C and its efficacy in patients with advanced metastatic drug-resistant breast and gastrointestinal malignancies. The dose-limiting toxicity was myelosuppression, predominantly thrombocytopenia, and was severe and cumulative. Nonhematologic toxicity was infrequent, and no renal or cardiac toxicity was seen. For patients with breast cancer who had received extensive prior therapy, 3 mg/m2/day for 5 days repeated every 6-8 weeks were well-tolerated doses; and for patients with gastrointestinal cancer, the maximum-tolerated dose was 4 mg/m2/day. One patient with breast cancer had a partial response lasting 4 months, and no responses were observed in patients with gastrointestinal cancer. The administration of mitomycin-C by continuous infusion did not appear to have improved its therapeutic index.

Aged↗
PubMed1983

Hormonal therapy for metastatic male breast cancer.

Forty-one men with metastatic breast cancer were treated with 70 trials of hormone therapy. These included 25 orchiectomies and 45 additive hormonal treatments. The overall response rate was 31%. The response rate was 32% to orchiectomy, 17% to estrogens, 43% to steroids, 25% to tamoxifen citrate, and 60% to androgens. The response to additive hormonal therapy was 31% and was not affected by prior orchiectomy (33% v 30%). Median overall response duration was 12 months, 17.5 months following orchiectomy, 8.5 months following additive hormonal therapy, five months following estrogens, 11 months following steroids, and eight months following androgens. Median survival from first metastasis was significantly prolonged in patients responding to orchiectomy and additive hormonal therapy. Patients with a disease-free interval (DFI) longer than 12 months had a 59% response rate to hormonal therapy compared with 9% of those with a DFI no more than 12 months. Response to one form of hormonal therapy did not predict later hormonal response. Ablative and additive hormonal therapy offer effective palliation to one third of male breast cancer patients, produce little toxic effects and morbidity, and improve survival duration after metastasis in responders.

Adrenal Cortex Hormones↗
PubMed1982

Ploidy, proliferative activity and estrogen receptor content in human breast cancer.

Tumor samples from 80 patients with breast cancer (43 primary, 37 metastatic) were analyzed for ploidy and proliferative activity using DNA flow cytometry. Sixty-one tumors (40 primary, 21 metastatic) were also analyzed for estrogen receptor content. Eighty-five percent of all tumors had an abnormal DNA content. The majority of tumors were hyperdiploid (65%). Seventy-three tumors had a unimodal ploidy distribution, while in seven cases two distinct aneuploid subpopulations were identified. The degree of ploidy abnormality was not related to extent of disease or menopausal status, but was higher (DNA index greater than 1.5) in poorly differentiated tumors (p = 0.05). ER-positive tumors were more often diploid (7 of 31) than ER-negative tumors (3 of 30, p = 0.16). DNA content was constant in biopsies from multiple sites in 5 patients with metastatic disease and in serial biopsies over the course of the disease. High proliferative activity (percent cells in S-phase) was more often associated with ER-negative tumors than ER-positive tumors (p = 0.03). However, in all subgroups analyzed a wide range of values was noted. We conclude that flow cytometric analysis of cellular DNA content provides a rapid means of quantitating ploidy and proliferative activity in human breast cancer. Ploidy abnormalities were common, stable, and usually unimodal. Proliferative activity was inversely related to estrogen receptor content.

Aneuploidy↗
PubMed1982

Estrogen receptor status in inflammatory breast carcinoma.

Sixteen women with a clinical diagnosis of inflammatory breast carcinoma had estrogen receptor analysis performed. Eleven of 16 were premenopausal. Median age of all patients was 46 years. All patients had estrogen receptor (ER) assay by either dextran charcoal method or by sucrose gradient method. Five patients were ER + ( greater than or equal to 10 fmol/mg cytosol protein) and 11 were ER -, with almost no binding at all. Response to therapy for metastatic disease using either hormones or chemotherapy was disappointing.

Antineoplastic Agents↗
PubMed1982

Potential cardiotoxicity with mitoxantrone.

Mitoxantrone is a promising new agent developed in an attempt to find drugs with a broad spectrum of antitumor activity and devoid of cardiotoxicity. In a phase II clinical trial for refractory metastatic breast cancer, we observed congestive heart failure in four of 31 high-risk patients either during or after treatment with this drug. This report calls attention to that observation, and recommendation is made that further evaluation of this agent include careful cardiac monitoring.

Adult↗
PubMed1980

CSF carcinoembryonic antigen in meningeal carcinomatosis from breast cancer.

Levels of CSF carcinoembryonic antigen (CEA) were determined in 23 patients with breast cancer and meningeal carcinomatosis. Levels greater than 1.5 ng/mL were observed in 16 patients; seven patients had undetectable levels. The meningeal disease of seven patients with elevated CSF CEA levels completely responded to treatment, and their CSF CEA levels concurrently decreased. Two patients whose meningeal disease responded poorly to treatment had persistently elevated levels of CSF CEA. In two other patients, a rising CSF CEA level was detected before there was any other evidence of meningeal relapse. Serial measurement of CSF CEA may play an important role in the clinical management of meningeal carcinomatosis in patients with breast cancer.

Breast Neoplasms↗