Biomedical subjects

S Lipsitz

Publications and source records attributed to S Lipsitz.

17 recordsLinked to original sources

PubMed2000

Treatment of squamous cell esophageal cancer with topotecan: an Eastern Cooperative Oncology Group Study (E2293).

Seventeen patients with enhanced measurable squamous cell carcinoma of the esophagus were treated with topotecan 1.5 mg/m2 daily for 5 days repeated every 21 days. Toxicity was severe, with 1 death from myelotoxicity and 10 patients with life-threatening myelotoxicity. Severe gastrointestinal toxicity consisting of vomiting was also seen in three patients. No response was seen in any of the patients in the study. Topotecan given in this manner has no activity in squamous cell carcinoma of the esophagus.

Antineoplastic Agents↗

PubMed1999

Phase II trial of trimetrexate for patients with advanced gastric carcinoma: an Eastern Cooperative Oncology Group study (E1287).

BACKGROUND: A Phase II study was conducted to evaluate the response, duration of response, and duration of survival of patients with measurable gastric carcinoma treated with trimetrexate (TMTX) who had not had prior chemotherapy. METHODS: Thirty-three patients with unresectable or metastatic gastric adenocarcinoma who had not received previous chemotherapy were treated with intravenous TMTX 12 mg/m(2) daily for 5 days. The dosage of TMTX was reduced to 8 mg/m(2) daily for 5 days for those who had received prior radiotherapy. The cycle was repeated every 3 weeks until disease progression or unacceptable toxicity occurred. RESULTS: Thirty-three patients could be analyzed with follow-up data. There was one Grade 5 (lethal) toxicity and four Grade 4 toxicities. Hematologic toxicity was the most common. The overall response rate was 21%, the overall median progression free survival was 2.7 months, and the overall median survival was 5.9 months for the entire cohort. No patients were alive at last follow-up. CONCLUSIONS: Though TMTX as a single agent has activity in gastric carcinoma with manageable toxicity, it cannot be recommended for routine use as a single agent due to the brief duration of response and median survival.

Adenocarcinoma↗

PubMed1999

A phase II study of 5-fluorouracil, leucovorin, and interferon-alpha in the treatment of patients with metastatic or recurrent gastric carcinoma: an Eastern Cooperative Oncology Group study (E5292).

BACKGROUND: Chemotherapy has a limited impact on adenocarcinoma of the stomach. Although biochemical modulation of 5-fluorouracil (5-FU) by leucovorin (LV) and interferon-alpha (IFN-alpha) has improved the outcomes of patients with metastatic colorectal carcinoma compared with 5-FU alone, this approach has not been extensively evaluated in the treatment of advanced gastric carcinoma. METHODS: Twenty-seven patients with bidimensionally measurable, metastatic gastric carcinoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 received the combination of IFN-alpha (5 million U/m2 administered subcutaneously daily on Days 1-7), LV (500 mg/m2 administered intravenously over 30 minutes immediately after IFN-alpha on Days 2-6), and 5-FU (370 mg/m2 given as an intravenous bolus 60 minutes after LV on Days 2-6), with treatment repeated every 4 weeks. Oral cryotherapy was administered routinely before each dose of 5-FU to reduce the incidence of severe stomatitis. RESULTS: The median age of the patients was 58 years (range, 20-76), and 22 patients had residual, unresectable primary lesions. The median number of cycles received was 3 (range, 1-11). Of 24 patients who received at least 2 cycles of treatment, 15 (62.5%) did not require dose reduction for toxicity during the initial 2 cycles. The predominant toxicities were gastrointestinal: diarrhea and stomatitis of Grade 3-4 occurred in 28.6% and 35.7% of patients, respectively. Other severe (Grade 3-4) toxicities were granulocytopenia (which occurred in 21.4% of patients) and fatigue (in 10.7%). Fever and flu-like symptoms were common but usually mild. Of 24 patients who were evaluable for response, 3 had partial responses (PR) of 16, 23, and 33 weeks' duration, respectively, for a response rate of 12.5% (95% confidence interval = 2.7-32.4%). Two additional patients had reductions in tumor size sufficient for PR, but scans to document the minimum required response duration of 4 weeks were not obtained before progressive disease occurred. The median progression-free and overall survivals were 2.5 and 7.8 months, respectively. CONCLUSIONS: Although this regimen can be administered safely with appropriate supportive care to patients with good performance status, it has limited therapeutic activity in patients with advanced gastric carcinoma.

Adult↗

PubMed1999

A phase II trial of homoharringtonine and caracemide in the treatment of patients with advanced large bowel cancer.

Twenty-four previously untreated, ambulatory patients with advanced colorectal carcinoma were treated with either caracemide (11 patients) or homoharringtonine (13 patients). No objective responses were observed in any of the treatment cohorts. Caracemide was well tolerated with the exception of one death due to sepsis. On the homoharringtonine arm one patient died of pulmonary sepsis, one patient experienced grade 4 leukopenia requiring more than 4 weeks of recovery, and an additional patient developed grade 4 renal failure. These severe and unexpected complications caused early termination of accrual to the homoharringtonine arm of the study. These agents have no activity in the treatment of advanced colorectal carcinoma.

Adult↗

PubMed1998

Using a hypothetical case to measure differences in treatment aggressiveness among physicians in Canada, Germany and the United States.

Variations in physician practice style, within and between countries, account for much of the differences in the utilization of scarce health care resources. Practice style differences are particularly important at the end of life, when a substantial amount of resources are consumed. We use a hypothetical case of a severely ill elderly patient to identify factors associated with aggressive treatment and to test whether physicians in the US practice differently from their counterparts in other countries. Data come from a random sample of practicing physicians in three industrialized countries, the United States, Canada and Germany (N = 1369). Although the case stated that the chance of survival of the patient was low, 73% of all physicians selected the aggressive treatment. Physicians from the United States were the most aggressive (86%), followed by Germany (68%) and Canada (61%). Practicing in the United States was the strongest predictor of aggressiveness in the multiple linear logistic regression; German and Canadian physicians were one fourth as likely to use aggressive treatment. Specialty training, older age and being a resident all increased the likelihood of selecting the more aggressive treatment. The fear of being sued for malpractice and income did not have an effect on treatment decisions.

Adult↗

PubMed1998

Phase II trial of preoperative radiation therapy and chemotherapy for patients with localized, resectable adenocarcinoma of the pancreas: an Eastern Cooperative Oncology Group Study.

PURPOSE: A prospective, multiinstitutional trial was initiated in 1991 to examine the tolerance to and efficacy of a program of preoperative chemoradiotherapy (CTRT) and surgical resection for patients with localized adenocarcinoma of the pancreas. PATIENTS AND METHODS: Fifty-three patients were assessable for analysis, with a median follow-up of 52 months for survivors. Radiation therapy (RT) totaling 5,040 cGy in 180 cGy fractions with mitomycin 10 mg/m2 day 2 and fluorouracil (5-FU) 1,000 mg/m2/d continuous infusion days 2 through 5 and 29 through 32 were given as preoperative adjuvant therapy. Twelve patients did not proceed to surgery (one death, one toxicity, three local progression, six distant metastases, one intercurrent illness), whereas 41 patients underwent surgery. Of these, 17 patients did not have resection (11, hepatic and/or peritoneal metastases and six local extension that precluded resection). Twenty-four patients had tumor resection (19 Whipple, four total pancreatectomy, one distal pancreatectomy). RESULTS: Treatment toxicity was primarily hematologic, although a comparable number suffered biliary tract complications, either from obstruction or cholangitis as a result of an occluded stent or the primary tumor. There was one postoperative death. Median survival for the entire group and for the 24 patients with resection was 9.7 and 15.7 months. This survival rate reflected the advanced state of most resected cancers (positive peritoneal cytology, three patients; margins within 2 mm, 13 patients; involved lymph nodes, four patients; and need for superior mesenteric vein (SMV) resection, four patients). Tumor progression was most frequent at metastatic sites. CONCLUSION: This preoperative CTRT protocol was feasible and safe in a cooperative group setting. Entry of patients with advanced tumors probably accounted for the suboptimal resectability and survival results.

Adenocarcinoma↗

PubMed1996

Long-term pulmonary toxicity of multiagent chemotherapy including bleomycin and cyclophosphamide in osteosarcoma survivors.

PURPOSE: To assess long-term pulmonary effects of multiagent chemotherapy, we studied serial pulmonary function tests (PFTs) of 35 children with osteosarcoma up to 12 years after diagnosis. PATIENTS AND METHODS: We analyzed 84 sets of PFTs from 35 patients diagnosed with osteosarcoma between 1981 and 1991. They received bleomycin, cyclophosphamide, methotrexate, doxorubicin, cisplatin, and actinomycin D over 9-12 months and we performed PFTs from 3 days to 152 months after diagnosis. Time period I included 36 PFTs (43%) performed between 1 and 5 months from diagnosis, time period II included 20 PFTs (24%) performed between 8 and 12 months from diagnosis, and time period III included 28 PFTs (33%) performed between 12 and 119 months from diagnosis. Total lung capacity (TLC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and carbon monoxide diffusing capacity (DLCO) were analyzed. Maximal respiratory pressures and arterial blood gases were measured to assess muscle weakness and gas exchange, respectively. Mean differences in PFTs were compared among the three time periods and between time period pairs. RESULTS: All mean PFT values showed significant differences among time periods. Significant decline in DLCO; (P=.012), TLC (P=.020), and FEV1 (P=.028) between time periods I and II were noted followed by a trend towards recovery between time periods II and III. Time periods I and III were not significantly different from one another. Mean PFTs performed after 2 years of diagnosis were not different from mean PFTs performed from diagnosis at 2 years. CONCLUSION: This dosage regimen of multi-agent chemotherapy for osteosarcoma patients caused a transient, but significant, decline in PFTs within 8-12 months after administration but appears to cause no significant long-term pulmonary function abnormalities.

Adolescent↗

PubMed1996

Phase II trial of prolonged continuous infusion of 5-fluorouracil and interferon-alpha in patients with advanced pancreatic cancer. Eastern Cooperative Oncology Group Protocol 3292.

Evidence suggests that interferon-alpha (IFN-alpha) augments the antineoplastic activity of 5-fluorouracil (5-FU) in human adenocarcinoma cell lines in vitro and may enhance the efficacy of 5-FU in patients with advanced colorectal carcinoma. In addition, 5-FU may be more effective when given as a prolonged, continuous i.v. infusion (PCI). The Eastern Cooperative Oncology Group performed a Phase II trial of PCI 5-FU plus IFN-alpha in patients with advanced pancreatic carcinoma. Twenty-six patients with advanced, surgically incurable adenocarcinoma of the pancreas received PCI 5-FU (250 mg/m2 daily for 28 days) in combination with IFN-alpha (5 x 10(6) IU/m2 s.c. thrice weekly). Treatment cycles were repeated 14 days or longer after completion of the previous cycle. Treatment was interrupted prior to day 28 if intolerable toxicity developed, and the dose of 5-FU was reduced in subsequent cycles. Partial response occurred in two of 24 evaluable patients (8%; 95% confidence interval, 0-19%). The majority of the study group (88%) had liver metastases. Patients whose serum lactate dehydrogenase (LDH) was more than twofold elevated developed 5-FU-related toxicity significantly sooner than patients with smaller elevations in serum LDH (9 vs. 22 days; p = 0.003). A similar trend was observed for patients with a more than twofold elevation in serum glutamic-oxaloacetic transaminase (SGOT; 9 vs. 15 days; p = 0.07). In conclusion, PCI 5-FU plus IFN-alpha has minimal activity in patients with advanced pancreatic carcinoma, and elevated serum LDH and/or SGOT may be useful for predicting greater toxicity from 5-FU-based therapy in patients with liver metastases.

Adenocarcinoma↗

PubMed1996

Regression analysis with missing covariate data using estimating equations.

In regression analysis, missing covariate data has been among the most common problems. Frequently, practitioners adopt the so-called complete-case analysis, i.e., performing the analysis on only a complete dataset after excluding records with missing covariates. Performing a complete-case analysis is convenient with existing statistical packages, but it may be inefficient since the observed outcomes and covariates on those records with missing covariates are not used. It can even give misleading statistical inference if missing is not completely at random. This paper introduces a joint estimating equation (JEE) for regression analysis in the presence of missing observations on one covariate, which may be thought of as a method in a general framework for the missing covariate data problem proposed by Robins, Rotnitzky, and Zhao (1994, Journal of the American Statistical Association 89, 846-866). A generalization of JEE to more than one such covariate is discussed. The JEE is generally applicable to estimating regression coefficients from a regression model, including linear and logistic regression. Provided that the missing covariate data is either missing completely at random or missing at random (in addition to mild regularity conditions), estimates of regression coefficients from the JEE are consistent and have an asymptotic normal distribution. Simulation results show that the asymptotic distribution of estimated coefficients performs well in finite samples. Also shown through the simulation study is that the validity of JEE estimates depends on the correct specification of the probability function that characterizes the missing mechanism, suggesting a need for further research on how to robustify the estimation from making this nuisance assumption. Finally, the JEE is illustrated with an application from a case-control study of diet and thyroid cancer.

Biometry↗

PubMed1995

Phase II trial of taxol in patients with adenocarcinoma of the upper gastrointestinal tract (UGIT). The Eastern Cooperative Oncology group (ECOG) results.

Taxol was administered as a 24-hour continuous infusion at 250 mg/m2 in this Phase II trial in patients with adenocarcinomas of the upper gastrointestinal tract (UGIT). Twenty-five patients were entered between July 1991 and June 1992, twenty-three were eligible and were evaluated for toxicity and twenty-two were assessable for response. There was one partial response (4.5%) in a patient with liver metastases, with a duration of 6 months. Toxicity was primarily neutropenia. Taxol as a single agent appears to have little activity in adenocarcinoma of the UGIT.

Adenocarcinoma↗

PubMed1995

Hepatocellular carcinoma. An ECOG randomized phase II study of beta-interferon and menogaril.

This study was undertaken to investigate the response rate, time to treatment failure and survival time of patients with hepatocellular cancer (HCC) treated with beta-interferon or menogaril. Sixty-nine patients with histologically confirmed, advanced, measurable hepatocellular carcinoma were randomized to receive beta-interferon or menogaril. Eligibility criteria included an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2, or 3, as well as adequate kidney and liver function and hematologic reserve. The number of patients with lethal, life-threatening, and severe toxicities on beta-interferon were 1, 3, and 12 and on menogaril 2, 5, and 10, respectively. No objective responses were documented among the 61 patients who had HCC, histologically reviewed and confirmed. The time to treatment failure was 6.7 weeks on beta-interferon and 8.6 weeks on menogaril. The median survival time was 11.1 weeks on beta-interferon and 23.1 weeks on menogaril (South African patients 10.1 weeks). The difference is not significant. Poor prognostic factors were jaundice, age, and associated hepatitis. After controlling for other covariates, beta-interferon appears to increase the relative risk of dying by 2.7. This trial reconfirms the importance, previously reported by ECOG of jaundice and age in the prognosis of patients with HCC. It shows that further trials with neither beta-interferon nor menogaril are warranted.

Aged↗

PubMed1994

Dietary vitamin A intake and the risk of mortality among children.

Increased consumption of dietary vitamin A is advocated as a long-term solution to vitamin A deficiency. We prospectively examined the relationship of dietary vitamin A intake and child mortality among 28,753 Sudanese children aged 6 mo to 6 y, who participated in a trial of vitamin A supplementation. After 18 mo of follow-up, 232 children died. Total dietary vitamin A intake was strongly and inversely associated with risk of mortality. The age- and sex-adjusted relative risk (RR) of mortality for a comparison of children in extreme quintiles was 0.35 (95% CIs 0.21-0.60; P for trend over quintiles < 0.0001). Even after possible confounding by socioeconomic variables was adjusted for, vitamin A intake was significantly protective (multi-variate relative risk 0.53). Dietary vitamin A intake was especially protective among children who were wasted and stunted or who had diarrhea or cough. These prospective data support an important role of dietary vitamin A in reducing childhood mortality in developing countries.

Age Factors↗

PubMed1993

Vitamin A supplementation and dietary vitamin A in relation to the risk of xerophthalmia.

We examined the effect of 60-mg (200,000-IU) supplements of vitamin A administered every 6 mo on the incidence of xerophthalmia among preschool children who were free of eye symptoms and signs of vitamin A deficiency. We also prospectively studied the relationship of dietary vitamin A intake with the same endpoint. After 18 mo of follow-up, 400 children developed xerophthalmia during 80,104 child-periods of follow-up. Vitamin A supplementation only modestly reduced the risk of xerophthalmia (relative risk 0.88, 95% confidence interval 0.72-1.07, P = 0.19). On the other hand, total dietary vitamin A intake was strongly associated with reduced risk of xerophthalmia; the multivariate relative risk when children in extreme quintiles were compared was 0.38 (95% confidence interval 0.19-0.74; P for trend over quintiles = 0.002). These results emphasize the need for further data on factors that modify the bioavailability of large-dose vitamin A supplements. Increased consumption of inexpensive vegetables and fruits is highly likely to reduce significantly the risks of vitamin A deficiency, including nutritional blindness in developing countries.

Child↗

PubMed1992

Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma.

BACKGROUND: The combination of streptozocin and fluorouracil has become the standard therapy for advanced islet-cell carcinoma. However, doxorubicin has also been shown to be active against this type of tumor, as has chlorozotocin, a drug that is structurally similar to streptozocin but less frequently causes vomiting. METHODS: In this multicenter trial, we randomly assigned 105 patients with advanced islet-cell carcinoma to receive one of three treatment regimens: streptozocin plus fluorouracil, streptozocin plus doxorubicin, or chlorozotocin alone. The 31 patients in whom the disease did not respond to treatment were crossed over to chlorozotocin alone or to one of the combination regimens. RESULTS: Streptozocin plus doxorubicin was superior to streptozocin plus fluorouracil in terms of the rate of tumor regression, measured objectively (69 percent vs. 45 percent, P = 0.05), and the length of time to tumor progression (median, 20 vs. 6.9 months; P = 0.001). Streptozocin plus doxorubicin also had a significant advantage in terms of survival (median, 2.2 vs. 1.4 years; P = 0.004) that was accentuated when we considered long-term survival (greater than 2 years). Chlorozotocin alone produced a 30 percent regression rate, with the length of time to tumor progression and the survival time equivalent to those observed with streptozocin plus fluorouracil. Crossover therapy after the failure of either chlorozotocin alone or one of the combination regimens produced an overall response rate of only 17 percent, and the responses were transient. Toxic reactions to all regimens included vomiting, which was least severe with chlorozotocin; hematologic depression; and, with long-term therapy, renal insufficiency. CONCLUSIONS: The combination of streptozocin and doxorubicin is superior to the current standard regimen of streptozocin plus fluorouracil in the treatment of advanced islet-cell carcinoma. Chlorozotocin alone is similar in efficacy to streptozocin plus fluorouracil, but it produces fewer gastrointestinal side effects than the regimens containing streptozocin. It therefore merits study as a constituent of combination drug regimens.

Adenoma, Islet Cell↗

PubMed1992

Designs and analysis of two-stage studies.

This paper concerns the design and analysis of two-stage studies, where, at the first stage, the response and the exposure variables are available among a large group of subjects. The other covariables, however, are available in only a subset of the large group, obtained in a second-stage sample. This paper introduces a class of twelve such two-stage designs, including two-stage case-control and case-cohort designs as special cases. In analysing such two-stage data, one objective is to extract information about the relationship between the exposure variable and the response after controlling for other covariables. We discuss three statistical methods to analyse the data and report results of Monte Carlo stimulation to study the efficiency of the three methods.

Case-Control Studies↗

PubMed1992

Physicians' perceptions of the risk of being sued.

We explore the deterrent effect of the tort system by assessing physician perceptions of the risk of being sued and the impact of those perceptions on their own practice. The data are from a mailed survey conducted in 1989 of a random sample of physicians who were practicing in New York State in 1984. The survey results were compared to the actual risk of suit using the between-group (Wald) test and logistic regression methods. We also surveyed physicians about practice changes undertaken in the last ten years, factors influencing practice standards, and the costs of being sued and included these in the analysis. On average, physicians estimate that 19.5 out of one hundred of their colleagues will be sued in a given year, approximately three times the actual rate, with significant differences by specialty, location, and suit history. Perceived risk is associated with self-reported changes in test-ordering frequency and reduction in practice scope. The median number of days lost from practice to defend a malpractice suit was three to five, and 6 percent of the physicians surveyed incurred some out-of-pocket expenses. These findings suggest that physicians respond to the messages sent by litigation in a manner consistent with the deterrent theory of tort litigation.

Age Factors↗

PubMedDate not supplied

Issues in the analysis of repeated categorical outcomes.

This paper discusses statistical methods for the analysis of repeated observations of categorical variables as they might arise in longitudinal studies. Two general types of models are described: marginal models that give representations for the marginal distribution of response at each occasion, and transitional models that give representations for the transition probabilities between outcome states at successive occasions. The conceptual and technical differences are discussed and recent work advancing both approaches is reviewed. The two approaches are illustrated through analysis of repeated observations on interval history of the respiratory symptom 'persistent wheeze' in preadolescent children.

Asthma↗