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Biomedical subjects

B Levin

Publications and source records attributed to B Levin.

At least 145 records · Page 8Linked to original sources
PubMed1993

Intensive preoperative chemotherapy with colony-stimulating factor for resectable adenocarcinoma of the esophagus or gastroesophageal junction.

PURPOSE: The curative resection rate in patients with potentially resectable carcinoma of the esophagus is approximately 55% and their median survival time is 11 months. Preoperative chemotherapy with high doses of chemotherapeutic agents was used to evaluate clinical and pathologic responses, curative resection rate, toxicity, and survival. Colony-stimulating factor (CSF) was added to reduce the severity of myelosuppression. PATIENTS AND METHODS: Twenty-six consecutive assessable patients with potentially resectable adenocarcinoma of the esophagus or gastroesophageal junction were treated with two preoperative courses of intensive chemotherapy (etoposide, doxorubicin, and cisplatin [EAP]) with granulocyte-macrophage CSF (GM-CSF). Additional three conventional-dose postoperative chemotherapy courses without GM-CSF were given to patients who responded to preoperative chemotherapy. RESULTS: A median of three courses (range, one to six), were administered. Of 27 patients, 26 were assessable for response to preoperative EAP; 13 (50%) achieved a major response. Among 23 patients who underwent surgery, 15 (65%) had a curative resection (58% of 26 assessable patients); none of the patients had a pathologic complete response, but two patients had only microscopic carcinoma in the resected specimen. Six patients had carcinoma present at the resection margins and received postoperative radiotherapy. Two patients were found to have liver metastases at exploration. At a median follow-up of 22 months, the median survival of 26 patients was 12.5 months (range, 2 to 32 +). Fourteen patients died of their carcinoma; two patients died of treatment-related causes; one died of an unrelated CNS arterial malformation; and the causes of death in two patients remain unknown. Seven patients are alive with no evidence of relapse. Major toxicities of this regimen included severe myelosuppression, nausea and vomiting, infections, and severe constitutional symptoms related to GM-CSF. However, subcutaneous injection of GM-CSF was well tolerated. CONCLUSION: High-dose EAP is active against locoregional adenocarcinoma of the esophagus and gastroesophageal junction but can be associated with significant toxicity. Although this strategy remains attractive and needs to be developed further, less toxic and more effective regimens need to be identified.

Adenocarcinoma↗
PubMed1993

A phase II study of merbarone in patients with adenocarcinoma of the pancreas.

Merbarone, a nonsedating derivative of thiobarbituric acid that has demonstrated antineoplastic activity against a variety of murine tumors, was evaluated in a phase II trial in patients with advanced, measurable adenocarcinoma of the pancreas. Seventeen patients were treated at a starting dose of 1000 mg/m2/day for 5 days by continuous intravenous infusion; the dose was escalated in accordance with the toxicity experienced, and no dosage reductions owing to toxicity were required. No complete or partial responses were observed, and only one minor response was documented, suggesting that merbarone is ineffective against pancreatic cancer at the doses and schedule in which it was administered in this trial.

Adenocarcinoma↗
PubMed1992

Phase II evaluation of fluorouracil and recombinant alpha-2a-interferon in previously untreated patients with pancreatic adenocarcinoma.

BACKGROUND: Based on initial encouraging results of the combination of 5-fluorouracil (5-FU) with recombinant alpha-2a-interferon (r alpha-2a-IFN) in the treatment of advanced colorectal carcinomas, a clinical trial was conducted using 5-FU with r alpha-2a-IFN in 49 patients with advanced pancreatic adenocarcinoma. METHODS: Forty-nine patients who had bidimensionally measurable disease and had not been treated previously with chemotherapy were entered in the trial. Starting on day 1, 5-FU was administered as a continuous infusion at a dose of 750 mg/m2/day for 5 consecutive days. Starting on day 12, it was administered as an intravenous bolus of 750 mg/m2 a week for 7 weeks. The r alpha-2a-IFN was administered subcutaneously at a dose of 9 x 10(6) units three times a week during weeks 1-8. RESULTS: Of the 46 patients evaluable for response, none had a complete response, and two had partial responses that lasted 14 and 28 weeks. The overall response rate was 4% (95% confidence interval, 1-15%). Fourteen patients had minor responses (median duration of response, 12 weeks). The median length of survival of all patients enrolled in this trial was 22 weeks. Grade 3-4 toxicities included oral mucositis in 19 patients, granulocytopenia in 16, fatigue in 8, and diarrhea in 3. One patient had severe ataxia and leg weakness. Another died of neutropenic sepsis. CONCLUSIONS: This regimen had significant toxicity and little evidence of therapeutic activity against advanced pancreatic carcinoma.

Adult↗
PubMed1992

Nutrition and colorectal cancer.

Environmental and genetic factors play an important role in the cause and pathogenesis of colorectal cancer. In addition to nutritional aspects, other environmental factors include physical exercise, energy intake, obesity, and parity. Dietary components currently under study are dietary fiber, fat, fruits, vegetables, and calcium. Intermediate markers of colonic proliferation, including bromodeoxyuridine and proliferating cell nuclear antigen incorporation, are being used to evaluate the response of the colonic epithelium to putative chemopreventative agents.

Animals↗
PubMed1992

Inflammatory bowel disease and colon cancer.

Patients who have had extensive colitis for more than 10 years are at increased risk for colorectal cancer. The risk may be greatest for those whose onset of illness is in childhood. Management options for patients at increased risk include prophylactic colectomy or endoscopic surveillance. The object of surveillance is prevention of cancer by detecting premalignant lesions that predispose to cancer. A less desirable objective is the diagnosis of cancer at an early curable stage. Patients must be well informed about their risk for cancer, the limitations of endoscopic surveillance, and the availability of surgical alternatives. Current endoscopic and pathologic techniques focus on the detection of dysplasia, but newer biomarkers may offer greater sensitivity and specificity in the future.

Adolescent↗
PubMed1992

Quantitation of human tumor-reactive monoclonal antibody 16.88 in the circulation and localization of 16.88 in colorectal metastatic tumor tissue using murine antiidiotypic antibodies.

Detection of administered human monoclonal antibodies in the tissues and circulation of patients requires special reagents to overcome interference by normal endogenous immunoglobulin. A practical approach is the development of antiidiotypic antibodies to the human monoclonal antibody and their application in immunoassays specific for the human monoclonal antibody. Accordingly, antiidiotypic antibodies were made to the monoclonal antibody 16.88, a human IgM class anti-colon carcinoma antibody being developed for applications in antibody-targeted immunotherapy of cancer. Three stable clones were obtained that produced antiidiotypic antibodies reactive with 16.88 but nonreactive with human polyclonal IgM or 16.52, a patient-matched IgM monoclonal antibody with different specificity than 16.88. One antiidiotypic antibody, MID 65, was used in a capture format radioimmunoassay to detect 16.88 in the sera of patients who had received 108-mg doses of unlabeled 16.88 coadministered with trace doses of 131I-16.88. Using this assay it was demonstrated that unlabeled 16.88 antibody and 131I-labeled 16.88 antibody did not differ significantly in blood retention for up to 24 h after administration, the period during which the immunoreactivity of the administered antibody remained over 90%. Indirect microautoradiography using exogenously applied 125I-MID 65 to localize 16.88 in frozen metastatic tumor tissue from patients given 16.88 8 days prior to surgery demonstrated the accumulation of 16.88 in areas of apparently healthy tumor cells. Much less 16.88 was detected in stroma or areas of tumor cell necrosis. The accumulation of antibody in nonnecrotic tumor sites encourages the further development of 16.88 for radioimmunotherapy of colon cancer and provides support for further development of human anticytokeratin monoclonal antibodies for cancer therapy.

Animals↗
PubMed1992

Identification of ras oncogene mutations in the stool of patients with curable colorectal tumors.

Colorectal (CR) tumors are usually curable if detected before metastasis. Because genetic alterations are associated with the development of these tumors, mutant genes may be found in the stool of individuals with CR neoplasms. The stools of nine patients whose tumors contained mutations of K-ras were analyzed. In eight of the nine cases, the ras mutations were detectable in DNA purified from the stool. These patients included those with benign and malignant neoplasms from proximal and distal colonic epithelium. Thus, colorectal tumors can be detected by a noninvasive method based on the molecular pathogenesis of the disease.

Adult↗
PubMed1992

A phase II trial of 5-fluorouracil and recombinant alpha-2a-interferon in previously untreated metastatic gastric carcinoma.

A Phase II clinical trial of the combination of 5-fluorouracil (5-FU) and recombinant alpha-2a-interferon (alpha-2a-IFN) was conducted in 44 patients. Patients had not received chemotherapy previously and had measurable metastatic gastric carcinoma. 5-FU was administered as a continuous infusion at a dose of 750 mg/m2/d for 5 consecutive days and as an intravenous bolus at a dose of 750 mg/m2 weekly for 7 weeks beginning on day 12. Recombinant alpha-2a-IFN was administered subcutaneously at a dose of 9 x 10(6) U three times a week during weeks 1 to 8. Patients were examined for response during week 9. Of 44 patients entered, 40 could be examined for response. Nine patients experienced a partial clinical response and one achieved a complete response, for an overall response rate of 25% (95% confidence interval, 13% to 41%). The median duration of response was 13 weeks (range, 9 to 67 weeks) and the median survival time was 29 weeks. Grade 3 to 4 toxicities included granulocytopenia (nine patients), diarrhea (three patients), oral mucositis (seven patients), skin rash (one patient), and fatigue (four patients). One patient died of neutropenic sepsis. This regimen had modest activity with significant toxicity and produced responses of short duration. It did not appear to be superior to existing treatments of metastatic gastric carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Evaluation of random digit dialing as a method of control selection in case-control studies.

Control groups selected by random digit dialing are frequently used in case-control studies. Concern about the potential for bias in these control groups has been expressed, primarily because of low response rates. This study compares the characteristics of a hypothetical control group consisting of 341 men and women aged 40-74 years, selected by random digit dialing and participating in an interview in 1990, with the characteristics of 15,563 men and women aged 40-74 years who participated in a privately conducted census in the same upstate New York county in 1989. For most measures, no differences were seen between the random digit dialing sample and the census population. However, the hypothetical control group was more likely to have had their cholesterol checked in the past 2 years and was somewhat more likely to have had other screening tests as well. In addition, the hypothetical control group was somewhat better educated. The results suggest that, at least in this setting, control groups selected by random digit dialing are representative of the general population in most respects; however, caution should be used when studying the relation between screening tests and disease occurrence by means of case-control studies using controls selected by random digit dialing.

Adult↗
PubMed1992

Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas.

Chemoradiation prior to pancreaticoduodenectomy ensures that all patients who undergo resection complete multimodality therapy, avoids resection in patients with rapidly progressive disease, and allows radiation therapy to be delivered to well-oxygenated cells before surgical devascularization. Twenty-eight patients with cytologic or histologic proof of localized adenocarcinoma of the pancreatic head received preoperative chemoradiation (fluorouracil, 300 mg/m2 per day, and 50.4 Gy) with the intent of proceeding to resection; all 28 completed this preoperative therapy. Hospital admission because of gastrointestinal toxic effects was required in nine patients, yet no patient experienced a delay in operation. Restaging was performed 4 to 5 weeks after completion of chemoradiation, and five patients were found to have metastatic disease; the 23 patients without evidence of progressive disease underwent laparotomy. At laparotomy, three patients were found to have unsuspected metastatic disease, three patients had unresectable locally advanced disease, and 17 patients were able to undergo pancreaticoduodenectomy. One perioperative death resulted from myocardial infarction, and perioperative complications occurred in three patients. Histologic evidence of tumor cell injury was present in all resected specimens. Our results suggest that pancreaticoduodenectomy can be performed with a low incidence of complications after chemoradiation for localized adenocarcinoma of the pancreas.

Adenocarcinoma↗
PubMed1992

Antihypertensive and metabolic effects of single and combined atenolol regimens.

The antihypertensive and metabolic effects of placebo (PL), a fixed combination of hydrochlorothiazide (25 mg) and triamterene (50 mg) (HCTZ/TRI), atenolol (25 mg) (Atc-25), atenolol (50 mg) (Ate-50) and their combination with HCTZ/TRI given once daily, were tested on 256 patients with mild-to-moderate essential-hypertension. After 3 weeks of PL monotherapy, 43 patients were randomized to PL (group 1), 41 patients to HCTZ/TRI (group 2), 44 patients to Ate-25 (group 3), 42 patients to Ate-50 (group 4), 43 patients to Ate-25/HCTZ/TRI (group 5), and 43 patients to Ate-50/HCTZ/TRI (group 6) in a double-blind parallel design study and were followed for 4 weeks. At the end of week 7, those patients who were randomized to groups 5 and 6 were allowed to continue for an additional 12 weeks, if their arterial pressure was satisfactorily controlled. Complete blood counts, blood chemistries, urinalyses, and electrocardiograms were done initially and during the study. Monotherapy with HCTZ/TRI, Ate-25, and Ate-50 had significant and equal antihypertensive effects compared with placebo. (P less than .01). However, the combination of Ate-25/HCTZ/TRI and Ate-50/HCTZ/TRI resulted in further reduction of arterial pressure with the effect being greatest with Ate-50/HCTZ/TRI (P less than .001). Patient groups 3 through 6 had also slower heart rates compared with groups 1 and 2 (P less than .01). Mild, but statistically significant, increases in BUN, glucose, triglycerides, and uric acid were noted in groups 2, 5, and 6 (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Atenolol↗
PubMed1992

Ulcerative colitis and colon cancer: biology and surveillance.

The risk of colorectal carcinoma is increased among patients with longstanding ulcerative colitis and Crohn's disease. The development of cancer in inflammatory bowel disease is hypothesized to evolve by a multistep process involving genetic instability, clonal expansion and the development of a malignant phenotype. The contribution of nutritional factors such as folate deficiency is of great interest; molecular genetic mechanisms are under study. In contrast to sporadic colorectal carcinoma, carcinomas in ulcerative colitis are associated with a long prior history of chronic inflammation and the subsequent development of epithelial dysplasia. Dysplasia is defined as an unequivocal neoplastic alteration of the colonic mucosa. The object of surveillance is prevention of death from cancer by detection at a premalignant or early curable stage. Patients at greatest risk of cancer who customarily undergo endoscopic surveillance are those with extensive colitis of more than 8 years duration. Dysplastic epithelium may occur in flat mucosa, and may produce a plaque or a nodular/villiform appearance. Dysplasia is not present in all patients with cancer in colitis. It is important to develop more sensitive and specific markers for the presence of precancer or cancer in colitis. Under study are proliferation-associated markers detected by immunohistochemistry, lectin binding, flow cytometry and laser-induced fluorescence coupled with endoscopy.

Carcinoma↗
PubMed1992

Phase II study of didemnin B in advanced colorectal cancer.

Didemnin B is a depsipeptide derived from a Caribbean tunicate (sea squirt) that has demonstrated antineoplastic activity against a variety of murine tumor models, including the L1210 and P388 leukemia, the B16 melanoma, and M5076 sarcoma cell lines. Based on these data, we designed a phase II trial in which 15 patients with measurable, unresectable colorectal cancer were treated with Didemnin B at an initial dosage of 3.47 mg/m2 over 30 minutes administered by intravenous infusion every 28 days; the dosage was altered in accordance with the toxicity observed, with only one patient requiring a dosage reduction for pronounced nausea and vomiting. No hematologic or nonhematologic toxicity developed. No complete or partial responses were observed. These results do not compare favorably with results of treatments using other single agents or combinations that are currently available for the treatment of advanced colorectal cancers. However, because of the tolerable levels of toxicity experienced by in our patients, it is possible that an insufficient dose of the medication was delivered. We concluded that Didemnin B is not active against of colorectal cancers at the dosage and schedule at which it was administered in this study.

Adenocarcinoma↗
PubMed1992

Phase II trial of fazarabine in advanced colorectal carcinoma.

A total of 15 patients with measurable advanced colorectal adenocarcinoma were prospectively treated with fazarabine (Ara-AC), reconstituted in dimethyl sulfoxide, and administered at a starting dose of 48 mg/m2/day as a continuous intravenous infusion for three days. The dose was repeated every 21 days and dose escalations or reductions were made on the basis of toxicities encountered in the preceding course. No patient achieved either a complete or partial response. Major toxicities encountered were granulocytopenia, thrombocytopenia, nausea, vomiting, anemia, and headache. All toxicities were reversible upon discontinuation of the drug and no life-threatening toxicities occurred. These data indicate that further clinical trials in colorectal carcinoma with this agent and schedule of administration are not warranted.

Adult↗
PubMed1992

Calcium supplementation decreases rectal epithelial cell proliferation in subjects with sporadic adenoma.

The results of three small clinical trials examining the effect of calcium carbonate supplementation on the proliferation cytokinetics of the rectal epithelium in subjects with a current history of sporadic adenoma are reported. In six subjects, a daily administration of 1500 mg of calcium carbonate for 90 days failed to significantly suppress thymidine labeling in normal-appearing mucosa of the rectum. However, a daily dose of 2000 mg of calcium significantly (P = 0.008) altered mucosal proliferation in a second set of six subjects after a 30-day trial. Finally, a placebo-controlled trial of calcium (2000 mg) was conducted in which 20 subjects were randomized to groups receiving a 4-week intervention with calcium (or placebo), followed by the alternative treatment (placebo or calcium). The results of the study show a marked suppression of rectal proliferation during the calcium phase of the study but not during the placebo phase. This study adds to accumulating evidence showing that calcium supplementation regulates the proliferative behavior of colonic epithelium in the individual at high risk for colon cancer. Longer term trials of calcium supplementation will ascertain whether a continuing benefit from increasing dietary calcium translates into inhibition of adenoma recurrence.

Adenoma↗