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Biomedical subjects

E Quebbeman

Publications and source records attributed to E Quebbeman.

12 recordsLinked to original sources

Phase III study of bolus versus infusion fluorouracil with or without cisplatin in advanced colorectal cancer.

BACKGROUND: Phase II studies of fluorouracil (5-FU) administered by protracted intravenous infusion have suggested an improved response rate and decreased toxicity profile when compared with 5-FU given by bolus injection in patients with metastatic colorectal cancer. Additional studies have suggested further enhancement of infusion 5-FU activity when it is combined with low-dose weekly cisplatin administration. PURPOSE: This phase III study in adults with metastatic colorectal cancer was planned as a comparison of objective response rates, toxicity, and survival in patients receiving bolus versus protracted-infusion 5-FU with or without cisplatin. METHODS: Four hundred ninety-seven previously untreated patients with advanced, measurable metastatic colorectal cancer were randomly assigned to receive treatment A (bolus 5-FU at 500 mg/m2 for 5 days followed in 2 weeks by weekly bolus 5-FU at 600 mg/m2), treatment B (bolus 5-FU at 500 mg/m2 for 5 days followed in 2 weeks by weekly bolus 5-FU at 600 mg/m2, plus weekly cisplatin at 20 mg/m2), treatment C (5-FU at 300 mg/m2 per day by continuous infusion), or treatment D (5-FU at 300 mg/m2 per day by continuous infusion plus weekly cisplatin at 20 mg/m2). All drugs were administered intravenously. Enrollment in the trial occurred from August 1987 through December 1990, and follow-up was through September 1995. The Kaplan-Meier method was used to estimate overall and disease-free survival, and Cox regression models were used to assess the effects of patient characteristics on survival. All P values resulted from two-sided tests. RESULTS: Objective tumor response was observed in 28 (18%) of 153 patients receiving treatment A, in 45 (28%) of 159 patients receiving treatment C (C versus A; P = .045), and in 47 (31%) of 153 patients receiving treatment D (D versus A; P = .016). Because of excessive toxicity, treatment B was discontinued after only 12 patients had begun treatment. Median time to disease progression was 5.1 months for patients in arm A compared with 6.2 and 6.5 months for patients in arms C and D, respectively (C versus A, P = .007; D versus A, P = .017). Patterns of toxic effects differed substantially among the treatment arms. Forty-five percent of the patients receiving bolus 5-FU alone (A) experienced grade 3-4 leukopenia, with two sepsis-related deaths. Hand-foot syndrome and mucositis were the major treatment-limiting toxic effects for patients in the two treatment arms involving infusion. Despite the improvement in response rates and time to disease progression with infusion 5-FU with or without cisplatin (C and D, respectively) (P = .003), the overall survival for the three groups (A, C, and D) was similar (P = .307). This may have been due in part to a longer median survival time of 10.4 months for patients in arm A, compared with an anticipated survival of 7 months. CONCLUSION: 5-FU given as a continuous infusion produced a higher objective response rate, a modest prolongation in time to disease progression, and less life-threatening myelosuppression in patients than bolus 5-FU. Concomitant treatment with low-dose cisplatin caused added toxicity and complexity of treatment and did not provide a major clinical benefit. No statistically significant survival differences were observed among the three treatment groups.

Antimetabolites, Antineoplastic↗

Characteristics of firearms involved in fatalities.

OBJECTIVES: To document the types of firearms associated with firearm fatalities, and to determine the availability of information on firearm characteristics in existing data sources. DESIGN: Review of police, medical examiner, and crime laboratory records for all firearm homicides and review of medical examiner records for all suicides and unintentional and undetermined firearm fatalities. SETTING: City of Milwaukee, Wis, from 1990 through 1994. POPULATION: A total of 175 firearm suicides and 524 firearm homicides. MAIN OUTCOME MEASURES: Source of data; circumstances and means of death; host demographic characteristics; firearm make, model, caliber, barrel length, and serial number. RESULTS: Handguns accounted for 468 (89%) of 524 firearm homicides and 124 (71%) of 175 firearm suicides. Handguns of .25 caliber accounted for 14% (n = 63) of 438 firearm homicides and 12% (n = 15) of all firearm suicides in which caliber was known. The Raven MP-25 was the single most commonly identified firearm and accounted for 10% (n = 15) of 153 handgun homicide cases and 7% (n = 7) of the 76 suicide cases in which the manufacturer of the firearm was identified. From all data sources combined, information on firearm type was available in 681 (97%) of 699 cases, caliber/gauge in 636 cases (91%), manufacturer/model in 309 cases (44%), and serial number in 276 cases (40%). CONCLUSIONS: Inexpensive, short-barreled .25-caliber handguns were the most common weapon type associated with firearm homicides and suicides in Milwaukee during 1990 through 1994. Product-specific information is a crucial part of planning appropriate injury countermeasures for firearms. In combination, police, crime laboratory, and medical examiner data can supply this information with modest changes in data collection procedures.

Data Collection↗

Continuous systemic 5-fluorouracil infusion in refractory prostatic cancer.

Twenty patients with metastatic prostatic cancer were treated on an ambulatory basis with continuous 5-fluorouracil (5-FU) infusion 250-300 mg/M2 per day through a chronic indwelling central venous catheter. All patients had symptomatic, progressive disease despite previous standard therapies. Partial remission was seen in 2 of 20 patients (10%), stable disease in 9 of 20 (45%), and progressive disease in 9 of 20 (45%); mean duration of benefit in responding and stable disease patients was six months. Improvement in pain and ECOG performance status were seen in most of the patients in the responding and stable disease categories. Forty percent of the patients experienced no significant drug toxicity; treatment interruption was necessary for stomatitis in 6 patients (30%), hand/foot syndrome in 3 patients (15%), and diarrhea in 1 patient (5%). No significant myelosuppression or other significant organ toxicities were encountered. Continuous systemic venous infusion of 5-FU may provide significant palliative effect for some patients with symptomatic, refractory carcinoma of the prostate.

Drug Evaluation↗

Continuous systemic 5-fluorouracil infusion in advanced colorectal cancer: results in 91 patients.

Ninety-one patients with metastatic colorectal cancer were treated with continuous ambulatory 5-fluorouracil (5FU) infusion 250-300 mg/m2/day through a chronic indwelling central venous catheter. Twenty-six of the 91 patients (29%) had received previous bolus 5FU. Fifty-eight of the 91 patients (64%) had two or more sites of disease, and 74 of 91 patients (81%) had liver metastases. Results were complete remission in 5 of 91 (6%), partial remission in 25 of 91 (27%), stable disease in 33 of 91 (36%), and progressive disease in 28 of 91 (31%), for an overall response rate of 30 of 91 (33%); median duration of response was 7 months. Twenty-six of 65 previously untreated patients (40%) experienced objective response. Median survival from initiation of treatment for all patients was 11 months. Forty-one percent of patients experienced no significant toxicity and were able to continue therapy without treatment interruption. Toxicities necessitating treatment interruption included stomatitis in 35 patients (39%), hand-foot syndrome in 33 patients (36%), and diarrhea in 10 patients (11%). No significant myelosuppression or serious catheter-related complications were encountered. We conclude that continuous systemic venous infusion of 5FU produces a higher response rate than traditional bolus 5FU schedules, with apparent enhancement of survival and easily managed toxicity.

Adult↗

5-Fluorouracil by protracted venous infusion. A review of current progress.

5-Fluorouracil (5FU) administered by prolonged intravenous infusion may more effectively treat advanced, slow-growing tumors with low growth fractions and long doubling times. Protracted infusion provides continual cancer cell exposure to 5FU; limitations due to cell cycle specificity and a short plasma half-life are theoretically circumvented. Advances in catheter composition and pump technology now make ambulatory infusion therapy widely available. Clinical trials suggest that prolonged infusion may improve the response rate in colorectal cancer. In addition, preliminary results suggest clinical activity against gastric, pancreatic and refractory breast cancers with minimal toxicity. Despite the potential logistic problems of infusion chemotherapy, many patients report improved quality of life. Increased costs incurred from infusion therapy are probably justifiable if survival is prolonged and quality of life maintained.

Catheterization↗

Continuous 5-fluorouracil infusion in advanced gastric carcinoma.

Fourteen patients with advanced gastric adenocarcinoma were treated with continuous 5-fluorouracil (5-FU) infusion, 300 mg/m2/day, through an indwelling central venous catheter; 13 were evaluable for response. The results were as follows; Partial remission was seen in 4 of 13 patients (31%), stable disease in 5 of 13 patients (38%), and progressive disease in 4 of 13 patients (31%). The median duration of response was 19 weeks (range, 10-41), and the median survival for all patients from initiation of infusion was 27 weeks (range, 9-54). Treatment interruption and/or dosage attenuation for toxicity was necessary in 7 of 14 patients (50%); however, myelosuppression, alopecia, and nausea and vomiting were not observed. 5-FU infusion is well-tolerated, palliative therapy for patients with advanced gastric carcinoma and may warrant further investigation in combination with other chemotherapeutic drugs.

Adenocarcinoma↗

Continuous 5-fluorouracil (5FU) infusion in carcinoma of the pancreas: a phase II study.

UNLABELLED: Sixteen patients with metastatic carcinoma of the pancreas were treated with continuous ambulatory 5-Fluorouracil (5FU) infusion (200-300 mg/m2/day) through a chronic indwelling central venous catheter. Twelve of sixteen patients (75%) had two or more sites of disease, and eleven of sixteen (69%) had liver metastases. Five patients had previous chemotherapy. RESULTS: partial remission, 3/16 (19%); stable disease, 8/16 (50%); and progressive disease, 5/16 (31%). Improvement in ECOG performance status was observed in 2/3 responding and 6/8 stable disease patients, respectively. Toxicities included hand-foot syndrome, mucositis, diarrhea, and cerebellar ataxia, which required treatment interruption in 9/16 patients (56%). No myelosuppression or catheter related problems were seen. The authors conclude that continuous infusion 5FU is a potentially efficacious palliative therapy in the management of carcinoma of the pancreas.

Adult↗

Anorectal injuries incident to enema administration. A recurring avoidable problem.

Injuries to the anorectum have been described as having resulted from therapeutic enema use. We report three cases occurring in patients with premorbid perianal pathology. All extended hospitalization although each was managed nonoperatively. These accidents can be prevented by pre-enema rectal examination and attention to perianal anatomy and patient complaints of discomfort during the procedure.

Adult↗

Continuous 5-fluorouracil infusion in refractory carcinoma of the breast.

UNLABELLED: Twenty-five patients with refractory, metastatic carcinoma of the breast were treated with continuous ambulatory 5-fluorouracil (5 FU) infusion (200 to 300 mg/m2/day) through a chronic indwelling central venous catheter. All patients had had extensive previous treatment, including hormonal therapy in 20/25 patients (80%), radiation therapy in 18/25 patients (72%), and an average of 4.6 previous chemotherapy drugs per patient (range 1-10). Twenty-three of 25 patients (92%) had had previous bolus 5 FU. Seventeen of 25 patients (68%) had two or more metastatic sites of involvement and 17/25 patients (68%) had visceral involvement. RESULTS: complete remission-1/25 (4%), partial remission-7/25 (28%), stable disease-6/25 (24%), and progressive disease-11/25 (44%), for an overall response rate of 8/25 (32%). Median duration of response was 6 months. Toxicities included hand-foot syndrome, mucositis, diarrhea, and nausea and vomiting, and required treatment interruption and/or dose attenuation in 9/25 patients (36%). No myelosuppression or serious catheter-related problems were seen. We conclude that continuous 5 FU infusion is a potentially effective salvage treatment that may provide meaningful palliation in some patients with carcinoma of the breast, in spite of extensive previous treatment.

Adult↗

Long-term ambulatory treatment of metastatic colorectal adenocarcinoma by continuous intravenous infusion of 5-fluorouracil.

To delineate the efficacy of continuous intravenous 5-fluorouracil (5-FU) infusion therapy for advanced colorectal adenocarcinoma, a study of 36 patients with measurable metastatic disease was conducted. Patients received a daily intravenous infusion of 300 mg/m2 5-FU over a 24-h period utilizing portable infusion devices and central venous catheters. In a population characterized by substantial pretreatment exposure to radiotherapy, chemotherapy, and other indicators of poor prognosis, 13/36 (36%) patients achieved an objective response. An additional 10/36 (28%) patients manifested stable disease (no change) and experienced survival comparable to that of patients with objective response. Toxicity was minimal; patients were able to continue 5-FU infusions 95% of the total time on protocol. There were no adverse hematologic effects or catheter complications. Because previously untreated patients benefited more frequently (positive response, 50%), continuous intravenous infusion should be evaluated further as a primary modality option when 5-fluorouracil antitumor chemotherapy is contemplated.

Adenocarcinoma↗