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Ronald Feld

Publications and source records attributed to Ronald Feld.

16 recordsLinked to original sources
PubMed2006

Natural history and chemotherapy effectiveness for advanced adenocarcinoma of the small bowel: a retrospective review of 113 cases.

BACKGROUND: Small bowel adenocarcinoma is a rare cancer that has generally been considered resistant to chemotherapy, although little has been published on the role of chemotherapy. A retrospective analysis was conducted of patients with advanced small bowel adenocarcinoma to explore chemotherapy use, and gain knowledge for ongoing management and future clinical trials. PATIENTS AND METHODS: All patients with advanced adenocarcinoma of the small bowel treated at Princess Margaret Hospital (PMH) between 1986 and 2004 were identified through the cancer registry. The medical records were reviewed for patient characteristics, treatment and outcome data. Survival statistics were estimated using the Kaplan Meier survival curves and Cox proportional regression model. RESULTS: Data on 113 patients was reviewed. Forty-four patients received palliative chemotherapy with an overall response rate (ORR) of 36% during a first or second line regimen (9% complete responses and 27% partial responses). Newer chemotherapy regimens including gemcitabine and irinotecan combinations appeared to have higher ORR, than older fluorouracil-based regimens. Some patients responded to more than one line of chemotherapy. Palliative chemotherapy predicted for overall survival (OS) in a multivariate analysis (HR 0.47, P = 0.035). CONCLUSION: Chemotherapy appears to have activity in adenocarcinoma of the small bowel. Prospective trials evaluating patient benefit are required to confirm this activity using newer systemic therapies, until such time retrospective reviews such as this will continue to guide treatment decisions.

Adenocarcinoma↗
PubMed2005

Platinum-based versus non-platinum-based chemotherapy in advanced non-small-cell lung cancer: a meta-analysis of the published literature.

PURPOSE: This meta-analysis was performed to compare the activity, efficacy and toxicity of platinum-based versus non-platinum-based chemotherapy in patients with advanced non-small-cell lung cancer. METHODS: Randomized phase II and III clinical trials comparing first-line palliative platinum-based chemotherapy with the same regimen without platinum or with platinum replaced by a nonplatinum agent were identified by electronic searches of Medline, Embase, and Cancerlit, and hand searches of relevant abstract books and reference lists. Response rates, 1-year survival, and toxicity were analyzed. Subgroups of trials using third-generation agents were compared. RESULTS: Thirty-seven assessable trials were identified including 7,633 patients. A 62% increase in the odds ratio (OR) for response was attributable to platinum-based therapy (OR, 1.62; 95% CI, 1.46 to 1.8; P < .0001). The 1-year survival rate was increased by 5% with platinum-based regimens (34% v 29%; OR, 1.21; 95% CI, 1.09 to 1.35; P = .0003). No statistically significant increase in 1-year survival was found when platinum therapies were compared to third-generation-based combination regimens (OR, 1.11; 95% CI, 0.96 to 1.28; P = .17). The toxicity of platinum-based regimens was significantly higher for hematologic toxicity, nephrotoxicity, and nausea and vomiting, but not for neurotoxicity, febrile neutropenia rate, or toxic death rate. CONCLUSION: Response is significantly higher with platinum-containing regimens. One-year survival was not significantly prolonged when platinum-based therapies were compared with third-generation-based combination regimens. Toxicity is generally higher for platinum-based regimens.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Does the incidence and outcome of brain metastases in locally advanced non-small cell lung cancer justify prophylactic cranial irradiation or early detection?

OBJECTIVE: The radical treatment of locally advanced non-small cell lung cancer (LA-NSCLC) currently involves combined modality therapy (CMT) with the use of chemotherapy in addition to radiation therapy and/or surgery. Chemotherapy has been shown to improve survival, but does not alter brain relapse. We reviewed the outcomes of Stage IIIA and IIIB LA-NSCLC patients treated with CMT at our institution. We assessed the incidence of brain metastases and the management and outcome of these patients. METHODS: Using our radiation-planning database (RSTS), we identified 230 consecutive patients from the years 1999 and 2000 who received radical radiation therapy to the lung. Extracting data from the chart, we identified 83 patients who were treated radically with chemotherapy, radiation and possibly surgery. These patients form the basis of this study. RESULTS: At 2 years, the actuarial rates for any brain failure, first failure in the brain and sole failure in the brain were 34.2%, 24.6% and 11.0%, respectively. Age was the only factor among sex, histology, stage, weight loss and the timing of chemotherapy and radiation that predicted for an increased risk of first failure in the brain. Patients less than age 60 had a risk of 25.6% versus 11.4% for those greater than 60 (p = 0.022). Among the patients who failed first in the brain, those who had aggressive management of their brain metastases with surgical resection in addition to whole brain radiotherapy had a median survival of 26.3 months compared with 3.3 months for those treated with palliative whole brain radiotherapy alone. CONCLUSION: Brain metastases are common in patients with LA-NSCLC treated with CMT. These patients may benefit from either prophylactic cranial irradiation or early detection and aggressive treatment of brain metastases.

Aged↗
PubMed2005

Influence of sex on toxicity and treatment outcome in small-cell lung cancer.

PURPOSE: Female sex has been shown consistently to be a favorable prognostic factor in small-cell lung cancer (SCLC). Studies have shown that women with other tumor types experience greater treatment toxicity, but there have been few studies of sex-related toxicity in SCLC. PATIENTS AND METHODS: This was a sex-based retrospective analysis of four SCLC trials conducted by the National Cancer Institute of Canada Clinical Trials Group between 1987 and 1999. The 1,006 patients (648 males and 358 females) received similar chemotherapy consisting of cyclophosphamide-doxorubicin-vincristine and etoposide-cisplatin. Toxicities examined included myelosuppression, stomatitis, vomiting, and infection. Other end points included dose reductions and omissions, response, and survival. RESULTS: Women experienced significantly more hematologic toxicity than men (grade 3 and 4 anemia, 16.3% v 7.6%, respectively, P < .001; grade 3 and 4 leukopenia, 80.4% v 69.2%, respectively, P = .0001). However, toxic death rates were similar for men and women (1.5% v 1.1%, respectively, P = .58). Women also had significantly more stomatitis and vomiting of all grades. Despite increased toxicity, 76% of females versus 73.4% of males received all six treatment cycles (P = .38), but 52% of females versus 43.4% of males had treatment delayed for 2 weeks or more (P = .022). Only 31.8% of females and 28.2% of males had at least one cycle of chemotherapy dose reduction (P = .23). The overall response rate was 80.3% for females and 66.9% for males (P < .0001), and the median survival time was 1.31 years for females compared with only 0.91 year for males (P < .0001). CONCLUSION: Women experience more chemotherapy-related toxicity in the treatment of SCLC, but they also have increased response rates and survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Adjuvant Chemotherapy for Early-Stage Non-small Cell Lung Cancer.

Lung cancer is the leading cause of cancer-related mortality in the developed world. Non-small cell lung cancer (NSCLC) represents 85% of cases of lung cancer, and patients have a poor 5-year survival rate. Approximately one third of NSCLC patients present with early-stage disease that is amenable to potentially curative resection and multimodality therapy. Several randomized trials now have confirmed the survival benefit with adjuvant platinum-based chemotherapy, as seen in the 1995 meta-analysis from the NSCLC Collaborative Group. The International Adjuvant Lung Cancer Collaborative Group Trial demonstrated a 4.5% improvement in survival for patients with stage I to III NSCLC. Studies from Japan have reported an improvement of 15.4% in the 5-year survival rate among patients with T1N0 disease after they had received adjuvant therapy with a combination of platinum and uracil-tegafur, and an improvement in the 5-year survival of 11% rate favoring chemotherapy with uracil-tegafur in a subgroup analysis of patients with T2N0 disease. Two recently published meta-analyses have estimated a relative risk reduction in mortality of 11 to 13% at 5 years. Significant improvement in the long-term survival rate has been demonstrated for patients with stage IB and II disease by the Cancer and Leukemia Group B 9633 trial (4-year survival rate, 12%) and the The National Cancer Institute of Canada Clinical Trials Group BR.10 trial (5-year survival rate, 15%; risk reduction for recurrence, 40%). Thus, there is compelling evidence to now recommend adjuvant platinum-based combination chemotherapy for patients after resection of early-stage NSCLC.

Carcinoma, Non-Small-Cell Lung↗
PubMed2005

Chemotherapy-induced oral mucositis: new approaches to prevention and management.

Oral mucositis is a common and significant toxicity of cancer chemotherapy. It is under-reported and not well treated, particularly in patients that receive high-dose therapy with an autologous or allogenic stem cell transplant. Two recently published retrospective analyses of patient complaints following stem cell transplantation have identified oral mucositis as the worst toxicity reported by patients, and what is more important is that patients indicated that oncology healthcare team members do a poor job of managing and providing methods of symptom relief. Twenty percent of patients surveyed indicated they received no symptom relief at all.

Anti-Inflammatory Agents↗
PubMed2005

A simple, focused, computerized query to detect overutilization of laboratory tests.

CONTEXT: Although there is nearly universal agreement that laboratory tests are overutilized, the degree of overutilization in a given institution is difficult to quantify and monitor across time. OBJECTIVE: To detect and clearly document repetitive daily ordering of a commonly ordered laboratory test (serum sodium) by employing a simple, focused, computerized query of a test result database followed by chart review and validation. DESIGN: A retrospective computerized query of our clinical data repository was performed to find inpatients who displayed normal serum sodium test results on 4 or more consecutive days, without any abnormal values during the same admission. The search was limited to a 1-month period. A subset of these patients was selected for chart review. RESULTS: One hundred sixteen patients met our criteria, and the tests ordered for those patients comprised 5.1% of the monthly volume of serum sodium tests ordered in our institution. Chart review revealed a consistent lack of documentation of medical necessity for repeat testing as well as persistence of repeat serum sodium orders until the end of the patients' hospital course. CONCLUSIONS: We conclude that a focused query of data derived from a clinical data repository can detect and document overutilization of a common laboratory test in a convincing fashion within a given institution.

Clinical Laboratory Techniques↗
PubMed2004

Phase II study of activated charcoal to prevent irinotecan-induced diarrhea.

PURPOSE: The dose-limiting toxicity of irinotecan (CPT-11; Camptosar) is delayed-onset diarrhea, with an incidence at the grade 3 to 4 level of 20% to 35%. SN38, its active moiety, is responsible by a direct effect on mucosal topoisomerase-I. The aim of this study was to assess whether activated charcoal (AC), possibly by adsorbing free lumenal SN38, can reduce irinotecan-induced diarrhea (CID) and optimize its dose-intensity. PATIENTS AND METHODS: Patients with advanced colorectal cancer receiving irinotecan 125 mg/m(2) intravenously once a week for 4 weeks every 6 weeks were studied. In cycle 1, patients received irinotecan plus AC (5 mL aqueous Charcodote [1,000 mg AC] plus 25 mL water) given the evening before the irinotecan dose and then tid for 48 hours after the dose. In cycle 2, no AC was given. National Cancer Institute Common Toxicity Criteria diarrhea grade, irinotecan dose-intensity, and loperamide consumption were recorded prospectively in both cycles. RESULTS: Twenty-eight patients had completed cycle 1 with AC; 24 subsequently completed cycle 2 without AC. Grade 3 to 4 diarrhea was 7.1% v 25%, and grade 0 diarrhea was 46.4% v 20.8% in cycles 1 and 2, respectively. Median percent planned dose delivered was 98% v 70% in cycles 1 and 2, respectively. In cycles 1 and 2, respectively, 25% v 54% patients took more than 10 loperamide tablets. AC was well tolerated with excellent compliance. CONCLUSION: The administration of AC with irinotecan reduced the incidence of grade 3 to 4 diarrhea and antidiarrheal medication consumption and increased irinotecan dose-intensity. Prophylactic AC may have a role in reducing dose-limiting CID and optimizing irinotecan therapy.

Adult↗
PubMed2004

Appraising and applying evidence about a diagnostic test during a performance-based assessment.

BACKGROUND: The practice of Evidence-based Medicine requires that clinicians assess the validity of published research and then apply the results to patient care. We wanted to assess whether our soon-to-graduate medical students could appraise and apply research about a diagnostic test within a clinical context and to compare our students with peers trained at other institutions. METHODS: 4th year medical students who previously had demonstrated competency at probability revision and just starting first-year Internal Medicine residents were used for this research. Following an encounter with a simulated patient, subjects critically appraised a paper about an applicable diagnostic test and revised the patient's pretest probability given the test result. RESULTS: The medical students and residents demonstrated similar skills at critical appraisal, correctly answering 4.7 and 4.9, respectively, of 6 questions (p = 0.67). Only one out of 28 (3%) medical students and none of the 15 residents were able to correctly complete the probability revision task (p = 1.00). CONCLUSIONS: This study found that most students completing medical school are able to appraise an article about a diagnostic test but few are able to apply the information from the article to a patient. These findings raise questions about the clinical usefulness of the EBM skills possessed by graduating medical students within the area of diagnostic testing.

Bayes Theorem↗
PubMed2004

Evaluation of two-dimensional cytometric lamellar body counts on the ADVIA 120 hematology system for estimation of fetal lung maturation.

BACKGROUND: We sought to determine if the ADVIA 120 hematology system (Bayer HealthCare LLC, Diagnostics Division, Tarrytown, NY), which employs a unique two-dimensional cytometric analysis approach for platelet (PLT) counting, might also be useful for estimation of LB lamellar body counts in amniotic fluid. METHODS: ADVIA 120 LB counts were performed on 217 amniotic fluid specimens, 88 of which were obtained within 72 h of infant delivery. The ADVIA 120 LB count (ADVIA LB count) results were compared with results from other FLM tests, including the TDx-FLM II (FLM II) test (Abbott Diagnostics, Abbott Park, IL) and the A(650) estimate of lamellar body density using the refractive-index-matched anomalous diffraction (RIMAD) technique. RESULTS: Use of an ADVIA LB count referent value of > or =35,400/microl to indicate maturity, yielded sensitivity, specificity, PV(RDS) and PV(maturity) of 100%, 67.6%, 36.8% and 100%, respectively, in our study population (prevalence of RDS=15.9%). The clinical performance of the ADVIA LB count assay was compared to that of the FLM II and RIMAD assays by predictive value and receiver operating characteristic (ROC) curve analysis. CONCLUSIONS: These data suggest that the ADVIA 120-derived LB counts on amniotic fluid can be useful in predicting fetal lung maturity.

Amniotic Fluid↗
PubMed2003

Expression and prognostic significance of kit, protein kinase B, and mitogen-activated protein kinase in patients with small cell lung cancer.

PURPOSE: The Kit receptor has been proposed as a key molecular target for the treatment of small cell lung cancer (SCLC). Protein kinase B (PKB/Akt) and mitogen-activated protein kinase (MAPK) are intracellular kinases that regulate cell survival and proliferation and may play a role in Kit signal transduction. This study was designed to examine the expression and importance of Kit, PKB/Akt, and MAPK relative to standard clinical prognostic factors in SCLC. EXPERIMENTAL DESIGN: Kit, PKB/Akt, and MAPK expression was assessed by immunohistochemistry in SCLC biopsies. Clinical data were collected on tumor stage, weight loss, hematology, biochemistry, response to treatment, and survival. Univariate and multivariate analyses were performed to evaluate prognostic significance. RESULTS: Biopsies from 42 patients were evaluable, and significant Kit expression (>/=35% cells) was detected in 51% of the tumors, phosphorylated PKB/Akt was detected in 62% of the tumors, and phosphorylated MAPK was detected in 48% of the tumors. Neither Kit nor PKB/Akt expression predicted for survival. Only increased expression of cytoplasmic MAPK was prognostic for survival (median, 1 year for negative staining versus 1.8 years for positive staining; P = 0.0054). CONCLUSIONS: Kit, PKB/Akt, and MAPK are expressed in a high percentage of SCLCs, and our data suggest that MAPK is an independent positive predictive factor in this malignancy.

Adult↗
PubMed2002

Methodology for clinical trials involving patients with cancer who have febrile neutropenia: updated guidelines of the Immunocompromised Host Society/Multinational Association for Supportive Care in Cancer, with emphasis on outpatient studies.

Two multinational organizations, the Immunocompromised Host Society and the Multinational Association for Supportive Care in Cancer, have produced for investigators and regulatory bodies a set of guidelines on methodology for clinical trials involving patients with febrile neutropenia. The guidelines suggest that response (i.e., success of initial empirical antibiotic therapy without any modification) be determined at 72 h and again on day 5, and the reasons for modification should be stated. Blinding and stratification are to be encouraged, as should statistical consideration of trials specifically designed for showing equivalence. Patients enrolled in outpatient studies should be selected by use of a validated risk model, and patients should be carefully monitored after discharge from the hospital. Response and safety parameters should be recorded along with readmission rates. If studies use these guidelines, comparisons between studies will be simpler and will lead to further improvements in patient therapy.

Anti-Bacterial Agents↗
PubMed2002

Sucralfate mouthwash for prevention and treatment of 5-fluorouracil-induced mucositis: a randomized, placebo-controlled trial.

A randomized, double-blind, placebo-controlled trial was conducted to evaluate the effectiveness of a sucralfate mouthwash in preventing and alleviating oral mucositis induced by 5-fluorouracil (5FU). A total of 81 patients with colorectal cancer were enrolled. Patients were studied during their first cycle of chemotherapy with 5FU and leucovorin (LV) daily for 5 days every 4 weeks (Mayo Clinic schedule). Patients were randomly allocated to receive either a sucralfate suspension or a placebo suspension that was identical in appearance. Patients were instructed to use the suspension as a mouthwash four times daily from the beginning of the chemotherapy cycle. All patients received oral cryotherapy. Patients graded the severity of their own symptoms on a daily basis, and this was the primary outcome measure. There was no difference in the frequency or severity of oral mucositis between the sucralfate- and the placebo-treated group. Some mucositis was reported by 79% of the patient group. Assessment of mucositis by trial staff underestimated the incidence of this problem. Results of this trial do not support the hypothesis that a sucralfate mouthwash can prevent or alleviate oral mucositis induced by 5FU. Patient reporting of mucositis is a more sensitive instrument for assessment of mucositis than review by medical staff.

Administration, Oral↗
PubMed2002

Economic analysis of the TAX 317 trial: docetaxel versus best supportive care as second-line therapy of advanced non-small-cell lung cancer.

PURPOSE: To determine the cost-effectiveness (CE) of second-line docetaxel compared with best supportive care (BSC) in the TAX 317 trial, a randomized clinical trial of second-line chemotherapy in non-small-cell lung cancer. METHODS: A retrospective CE analysis of the TAX 317 trial was undertaken, evaluating direct medical costs of therapy from the viewpoint of Canada's public health care system. Costs were derived in 1999 Canadian dollars, and resource use was determined through prospective trial data. RESULTS: The incremental survival benefit in the docetaxel arm over BSC was 2 months (P =.047). The CE of docetaxel was $57,749 per year of life gained. For patients treated with docetaxel 75 mg/m(2), the CE was $31,776 per year of life gained. In univariate sensitivity analyses, CE estimates were most sensitive to changes in survival, ranging from $18,374 to $117,434 with 20% variation in survival at the recommended dose. The largest cost center in both arms was hospitalization, followed by the cost of drugs, investigations, radiotherapy, and community care. BSC patients had fewer hospitalizations than patients in the chemotherapy arm and were more often palliated at home. CONCLUSION: Although the decision to treat should not be based on economic considerations alone, our CE estimate of $31,776 per year of life gained (at the currently recommended dose of docetaxel) is within an acceptable range of health care expenditures, and the total costs of therapy are similar to those of second-line palliative chemotherapy for other solid tumors.

Antineoplastic Agents, Phytogenic↗
PubMed2002

Radiofrequency ablation of malignant hepatic neoplasms.

OBJECTIVE: To assess the safety and efficacy of radiofrequency ablation (RFA) in the treatment of malignant neoplasms of the liver. METHODS: Sixty-seven patients received RFA for primary or secondary hepatic malignancies. Patients were followed prospectively with computed tomography (CT) scanning to assess for therapeutic response, disease progression and complications. RESULTS: Eighty-eight lesions were treated, including 57 hepatocellular carcinomas, 28 metastases, 2 cholangiocarcinomas and 1 hepatic plasmacytoma. Mean tumour size was 2.7 cm (range 0.5-6.9 cm). A total of 101 ablations were performed (66 percutaneously, 35 intraoperatively). Over a mean follow-up period of 142 days, results were available for 85 lesions. Local tumour control was achieved for 61 (72%) lesions, but new distant lesions developed in 6 of these cases. Residual disease was present in 20 (23%) lesions, and 4 (5%) lesions developed local recurrence. There were 10 complications, including 1 death in a patient who developed a liver abscess and subsequently died from hepatic failure. CONCLUSIONS: RFA is safe and effective in the treatment of hepatic malignancies. Local tumour control can be achieved in most cases; however, careful surveillance is important for detecting recurrent disease, as well as new lesions distant from the treated site.

Adult↗