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R Feld

Publications and source records attributed to R Feld.

At least 19 recordsLinked to original sources
PubMed2000

Differential expression of matrix metalloproteinases and their inhibitors in non-small cell lung cancer.

In a comprehensive immunohistochemical study of the expression of ten metalloproteinases (MMPs) and their four inhibitors (TIMPs) in 115 non-small cell lung carcinomas (NSCLCs), the findings have been correlated with the histological and clinical features of the tumours. All MMPs and TIMPs were expressed in tumours, with frequencies ranging from 41% for MMP-2 to 68% for MMP-13. Stromal immunoreactivity ranged from 6% for TIMP-4 to 87% for MMP-13. In some tumours, an overexpression of these proteins, as revealed by stronger staining in cancer cells than in adjacent normal bronchial epithelium, was also observed. The frequency ranged from 1% for MMP-3 to 28% for MMP-13. Compared with squamous cell carcinoma (SqCC), adenocarcinoma (AdC) more frequently overexpressed MMP-1, -11, -13, -14, and TIMP-2, and TIMP-1 and/or TIMP-2 overexpression positively correlated with more advanced stage disease. None of the MMP or TIMP expression correlated with the ras genotype of the tumours. The higher frequency of MMP overexpression in AdC than in SqCC may relate to the greater tendency of the former for systemic metastasis. The association of TIMP-1 overexpression with more advanced disease may suggest a role in prognosis.

Adult↗
PubMed2000

The Multinational Association for Supportive Care in Cancer risk index: A multinational scoring system for identifying low-risk febrile neutropenic cancer patients.

PURPOSE: Febrile neutropenia remains a potentially life-threatening complication of anticancer chemotherapy, but some patients are at low risk for serious medical complications. The purpose of this study was to develop an internationally validated scoring system to identify these patients. MATERIALS AND METHODS: Febrile neutropenic cancer patients were observed in a prospective multinational study. Independent factors assessable at fever onset, predicting low risk of complications, on a randomly selected derivation set, were assigned integer weights to develop a risk-index score, which was subsequently tested on a validation set. RESULTS: On the derivation set (756 patients), predictive factors were a burden of illness indicating absence of symptoms or mild symptoms (weight, 5; odds ratio [OR], 8.21; 95% confidence interval [CI], 4.15 to 16.38) or moderate symptoms (weight, 3; OR, 3.70; 95% CI, 2.18 to 6.29); absence of hypotension (weight, 5; OR, 7.62; 95% CI, 2.91 to 19.89); absence of chronic obstructive pulmonary disease (weight, 4; OR, 5. 35; 95% CI, 1.86 to 15.46); presence of solid tumor or absence of previous fungal infection in patients with hematologic malignancies (weight, 4; OR, 5.07; 95% CI, 1.97 to 12.95); outpatient status (weight, 3; OR, 3.51; 95% CI, 2.02 to 6.04); absence of dehydration (weight, 3; OR, 3.81; 95% CI, 1.89 to 7.73); and age less than 60 years (weight, 2; OR, 2.45; 95% CI, 1.51 to 4.01). On the validation set, a Multinational Association for Supportive Care in Cancer risk-index score >/= 21 identified low-risk patients with a positive predictive value of 91%, specificity of 68%, and sensitivity of 71%. CONCLUSION: The risk index accurately identifies patients at low risk for complications and may be used to select patients for testing therapeutic strategies that may be more convenient or cost-effective.

Anti-Bacterial Agents↗
PubMed1999

The influence of age on the delivery, tolerance, and efficacy of thoracic irradiation in the combined modality treatment of limited stage small cell lung cancer.

PURPOSE: To assess the impact of age on the delivery, tolerance, and efficacy of thoracic irradiation (TI) for limited small cell lung cancer (L-SCLC). METHODS AND MATERIALS: This is a retrospective review of data from 608 patients 80 years or less with L-SCLC, who participated in two previously reported randomized trials (BR3 and BR.6) of the National Cancer Institute of Canada. All patients received the same chemotherapy, consisting of cyclophosphamide, doxorubicin, vincristine (CAV), and etoposide cisplatin (EP) delivered either in sequential or alternating sequence. In BR.3, TI was given after chemotherapy with randomization to 25 Gy in 10 fractions or 37.5 Gy in 15 fractions. In BR.6, TI (40 Gy in 15 fractions) was given concurrently with EP with randomization to either the early (with cycle 2, week 4) or late (with cycle 6, week 16) arm. RESULTS: A total of 665 patients entered these two trials. Of these, 608 patients were eligible for analysis, 300 in BR.3 and 308 in BR.6. Five hundred and twenty patients were under age 70 and 88 patients were 70 years or older. Baseline characteristics between the two groups were comparable. In BR3, 179 patients (60%) participated in radiotherapy randomization (61% young, 52% elderly), and 176 patients actually received TI. In BR.6, randomization occurred at study entry for all patients, and 282 (91.6%) patients received TI (92% young, 88% elderly). More patients of both age groups randomized to receive late TI did not receive TI (13% and 14%) than those randomized to the early TI arm (3%) of BR.6. We could identify no tendency to reduce field sizes to minimize toxicity in either age group at higher doses of TI. Once TI was started, there was no difference between the two age groups with regards to the proportion of patients who completed TI, although elderly patients were less likely to complete high dose TI. Of those who completed TI, there was no difference in the time to complete TI, mean dose delivered or in the incidence of acute and late TI-related toxicities. No statistical difference in response rate, local relapse rate, or overall survival was seen between young and older age groups. CONCLUSION: In summary, in the dose range examined, age does not appear to impact on the delivery, tolerance or efficacy of TI in the combined modality management of L-SCLC. Potentially curative combined modality treatment should not be withheld on the basis of age.

Age Factors↗
PubMed1999

Vancomycin as part of initial empirical antibiotic therapy for febrile neutropenia in patients with cancer: pros and cons.

Gram-positive organisms predominate as the bacterial pathogens identified in episodes of febrile neutropenia. This has led to increased use of antibiotics with efficacy against gram-positive organisms (often vancomycin) as part of empirical antibiotic regimens for treating febrile neutropenia. Among 101 children randomized to receive amikacin, ticarcillin, and vancomycin or ticarcillin/clavulanate and amikacin along with vancomycin placebo, treatment success in those treated with vancomycin was higher (85% vs. 62%). In 1990, the European Organization for Research and Treatment of Cancer-National Cancer Institute of Canada Clinical Trials Group compared amikacin and ceftazidime with and without vancomycin and concluded that there was no need to include vancomycin in initial empirical antibiotic therapy. Results from another study and a retrospective review of a large clinical trial also support the previous conclusion. In 1999, most experts in the field recommend vancomycin not be part of the initial empirical therapy regimen for treating febrile neutropenia in patients with cancer.

Anti-Bacterial Agents↗
PubMed1999

Clinical impact of sonographically guided biopsy of salivary gland masses and surrounding lymph nodes.

Although fine-needle aspiration biopsy of salivary gland masses has been reported in the otolaryngology literature, the use of sonography to guide the biopsy of nonpalpable masses and masses seen on other cross-sectional imaging studies has not been described. Our goal was to evaluate sonographically guided biopsy of masses and lymph nodes related to the salivary glands. We analyzed the records of 18 patients who had undergone fine-needle aspiration biopsy of a salivary gland mass or lymph node with a 25-, 22-, or 20-gauge needle. A definitive cytologic diagnosis was made for 13 of the 18 patients (72%); cytology was suggestive but not definitive in three patients (17%) and insufficient in two (11%). Definitive diagnoses were made in three cases of reactive lymph node, in two cases each of lymph node metastasis and Warthin's tumor, and in one case each of pleomorphic adenoma, adenoid-cystic carcinoma, schwannoma-neurofibroma, parotid metastasis, parotid lymphoma, and Sjögren's-related lymphoid-epithelial lesion. Sonographically guided biopsy allows for confident needle placement in masses seen on computed tomography and magnetic resonance imaging. Sonography can usually distinguish a perisalivary lymph node from true intrasalivary masses, and it can help the surgeon avoid the pitfall of a nondiagnostic aspiration of the cystic component of masses. We conclude that sonographically guided biopsy of salivary gland masses can provide a tissue diagnosis that can have a direct impact on clinical decision making.

Adenoma, Pleomorphic↗
PubMed1998

Criteria for response in patients in clinical trials of empiric antibiotic regimens for febrile neutropenia. Is there agreement?

A review of the literature on the criteria of response in patients on clinical trials of empiric antibiotic therapy revealed that there are at least three definitions utilized worldwide along with individual investigator definitions. The main definitions include definitions by Pizzo from the NCI, by the EORTC Antimicrobial group and by the Immunocompromised Host Society. The outcome in clinical trials can be affected by the definition used if the major endpoint in the study compares response rates of two or more initial empiric antimicrobial regimens for febrile neutropenia. Survival based definitions (Pizzo) are very useful but may not identify which regimen required the least number of modifications during the critical initial 3-5 days of trial. Evaluations later in the course of the febrile episode will not likely be influenced by these definitions as most patients with prolonged and severe neutropenia will eventually require modifications of therapy. A consensus to use a single response definition is necessary to allow comparisons and meta-analysis of results with specific antibiotic regimens for febrile neutropenia. These must be enforced by editors of major medical journals to truly allow this to happen.

Anti-Bacterial Agents↗
PubMed1998

A phase II study of temozolomide in advanced untreated pancreatic cancer.

Temozolomide (SCH 52365) is an imidazotetrazine derivative which exhibits broad spectrum activity against murine tumors and is structurally related to dacarbazine (DTIC). Temozolomide cytotoxicity is schedule dependent in vivo with a daily x 5 schedule showing the highest activity. Oral temozolomide is rapidly and completely absorbed with minimal interpatient and intrapatient variability in pharmacokinetics. Clinical studies have demonstrated activity against melanoma and glioma. The present study examined the activity of oral temozolomide against patients with pancreatic cancer. Patients with advanced pancreatic adenocarcinoma previously untreated with chemotherapy received temozolomide 200 mg/m2/day once daily orally for 5 days with cycles repeated every 28 days. There were 16 patients entered on study with 15 evaluable for response and toxicity. There were no responses seen in 15 evaluable patients with 14 manifesting progressive disease within 2 months of starting therapy. Toxicity was primarily hematological with 3 patients experiencing > or = grade 3 neutropenia and thrombocytopenia respectively. Other toxicities were relatively modest. In conclusion, temozolomide in the once daily x 5 schedule is inactive against adenocarcinoma of the pancreas.

Adenocarcinoma↗
PubMed1998

Phase I and pharmacologic study of 9-aminocamptothecin colloidal dispersion formulation given as a 24-hour continuous infusion weekly times four every 5 weeks.

PURPOSE: 9-Aminocamptothecin (9-AC) is a water-insoluble camptothecin (CMP) derivative that inhibits normal topoisomerase I function. Schedule dependency was noted, with the greatest activity seen in the setting of greater than 24 hours exposure to lactone (L) concentrations > or = 10 nmol/L. In this phase I study, 9-AC was given by a continuous intravenous infusion over 24 hours once weekly times four every 5 weeks. PATIENTS AND METHODS: Twenty patients, of whom 16 had fluorouracil-refractory colorectal cancer (CRC), entered the study. Dose levels were 0.7 mg/m2 (n = 4), 1.4 mg/m2 (n = 3), 1.9 mg/m2 (n = 6), and 1.65 mg/m2 (n = 7). Detailed pharmacokinetic (PK) measurements of 9-AC L and carboxylate (C) were performed on day 1 of cycles 1 and 2. RESULTS: At 1.9 mg/m2, dose-limiting toxicity (DLT) was reached, with three of six patients having grade 4 neutropenia. At 1.65 mg/m2, one of seven patients had grade 4 neutropenia. Nonhematologic toxicity was modest, with diarrhea > or = grade 3 in two patients and lethargy > or = grade 3 in eight. PK/pharmacodynamic (PD) analyses showed marked interpatient variability. Steady-state concentrations (Css) of 9-AC L > or = 10 nmol/L (3.6 microg/L) were seen in five of seven patients at 1.65 mg/m2 and five of six patients at 1.9 mg/m2. Using the sigmoidal maximal effect (Emax) model, 9-AC L area under the concentration-time curve (AUC) and Css correlated with day 15 decrease in neutrophils (R2 = .47), but not platelets. CONCLUSION: The recommended phase II dose of 9-AC colloidal dispersion (CD) given as a 24-hour continuous infusion weekly for 4 of every 5 weeks is 1.65 mg/m2.

Adult↗
PubMed1997

Second primary cancers related to smoking and treatment of small-cell lung cancer. Lung Cancer Working Cadre.

BACKGROUND: An increased risk of second primary cancers has been reported in patients who survive small-cell carcinoma of the lung. The treatment's contribution to the development of second cancers is difficult to assess, in part because the number of long-term survivors seen at any one institution is small. We designed a multi-institution study to investigate the risk among survivors of developing second primary cancers other than small-cell lung carcinoma. METHODS: Demographic, smoking, and treatment information were obtained from the medical records of 611 patients who had been cancer free for more than 2 years after therapy for histologically proven small-cell lung cancer, and person-years of follow-up were cumulated. Population-based rates of cancer incidence and mortality were used to estimate the expected number of cancers or deaths. The actuarial risk of second cancers was estimated by the Kaplan-Meier method. RESULTS: Relative to the general population, the risk of all second cancers among these patients (mostly non-small-cell cancers of the lung) was increased 3.5-fold. Second lung cancer risk was increased 13-fold among those who received chest irradiation in comparison to a sevenfold increase among nonirradiated patients. It was higher in those who continued smoking, with evidence of an interaction between chest irradiation and continued smoking (relative risk = 21). Patients treated with various forms of combination chemotherapy had comparable increases in risk (9.4- to 13-fold, overall), except for a 19-fold risk increase among those treated with alkylating agents who continued smoking. IMPLICATIONS: Because of their substantially increased risk, survivors should stop smoking and may consider entering trials of secondary chemoprevention.

Actuarial Analysis↗
PubMed1997

The role of surveillance cultures in patients likely to develop chemotherapy-induced mucositis.

Mucositis can be the major dose-limiting toxicity during the adminstration of certain types of chemotherapy, especially 5-fluorouracil, methotrexate and doxorubicin. Infection probably plays a role after initial inflammatory changes occurs in the mucous membranes of the mouth after chemotherapy, especially if the patient becomes neutropenic. The issues addressed in this paper following a review of the literature are whether surveillance cultures can be helpful to avoid mucositis or at least predict who will be at risk for its development and whether this will be a help in decisions on the antimicrobial treatment that should be given if mucositis develops. Bacterial, fungal and viral causes of mucositis have been identified. The simplest to deal with is viral, since if herpes simplex is identified it should be treated with acyclovir; in the case of allogeneic bone marrow transplants acyclovir is usually given prophylactically. Fungal organisms almost certainly play a part; especially if a Candida species, particularly Candida tropicalis, is identified in surveillance cultures, it is probably important. The significance of bacterial pathogens in surveillance cultures is more difficult to sort out except for Pseudomonas aeruginosa, which almost always predicts for eventual systemic infection, especially bacteraemia. The poor overall predictive value (both positive and negative) for surveillance cultures and their significant expense do not support their routine use in 1997.

Anti-Bacterial Agents↗
PubMed1997

1997 guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever. Infectious Diseases Society of America.

This is the first in a series of practice guidelines commissioned by the Infectious Diseases Society of America through its Practice Guidelines Committee. The purpose of these guidelines is to provide assistance to clinicians when making decisions on treating the conditions specified in each guideline. The targeted providers are internists, pediatricians, and family practitioners. The targeted patients and setting for the fever and neutropenia guideline are hospitalized individuals with neutropenia secondary to cancer chemotherapy. Panel members represented experts in adult and pediatric infectious diseases and oncology. The guidelines are evidence-based. A standard ranking system was used for the strength of the recommendations and the quality of the evidence cited in the literature reviewed. The document has been subjected to external review by peer reviewers as well as by the Practice Guidelines Committee and was approved by the IDSA Council. An executive summary, algorithms, and tables highlight the major recommendations. The guideline will be listed on the IDSA home page at http://www.idsociety.org.

Adult↗
PubMed1997

Biliary-pleural fistulas without biliary obstruction: percutaneous catheter management.

OBJECTIVE: Our purpose was to report the use of percutaneous catheter drainage as a therapeutic option in the management of three patients with biliary-pleural fistulas without biliary obstructions. CONCLUSION: In the proper clinical setting, the CT findings of liver dome laceration or abscess, diaphragm disruption, and pleural effusion should suggest biliary-pleural fistula. Percutaneous catheter management can be curative or serve a temporizing function before surgery.

Adult↗
PubMed1997

Phase II trial of gemcitabine and weekly cisplatin for advanced non-small cell lung cancer.

Single-agent gemcitabine, when given in doses of > or = 1,250 mg/m2 weekly x 3 with a 1-week break, induces responses in approximately 20% of untreated patients with non-small cell lung cancer. This phase II study was undertaken to determine the efficacy of weekly administration of gemcitabine 1,500 mg/m2 combined with cisplatin 30 mg/m2 x 3 with a rest period of 1 week. Patients younger than 75 years were eligible if they had stage III/IV non-small cell lung cancer, a life expectancy > or = 12 weeks, hemoglobin > or = 10 g/dL, absolute granulocyte count > or = 10(9)/L, platelets > or = 100 x 10(9)/L, hepatic enzymes no more than three times the upper limit of normal, and serum creatinine < or = 130 micromol/L. There were 22 men and 18 women, with a median age of 60 years; 35 had a performance status of 0 or 1. Pathology included adenocarcinoma in 22 patients, squamous cell carcinoma in nine, large cell carcinoma in seven, and mixed non-small cell lung cancer in two. Six patients had stage III and 34 had stage IV tumors. Of the 39 patients eligible for response evaluation, partial remission was seen in 10, for an overall response rate of 26% (95% confidence interval, 12% to 41%). The median duration of response was 19 weeks (range, 7 to 32+ weeks). Grade 3/4 anemia was seen in 11 patients, and 21 patients required red blood cell transfusions. Grade 3/4 neutropenia occurred in 22 patients and grade 3/4 thrombocytopenia in 21 patients. One patient experienced febrile neutropenia Hematologic toxicity, particularly thrombocytopenia, was cumulative over time. Nonhematologic toxicity was modest, but one patient stopped therapy because of a grade 2 skin rash and one stopped because of a grade 4 pulmonary toxicity, both of which were thought to be related to gemcitabine. The modest activity of weekly gemcitabine and weekly cisplatin seen in this trial does not suggest in vivo synergy for these two agents as administered using this schedule and these doses.

Adult↗
PubMed1996

Quinolone-based antibacterial chemoprophylaxis in neutropenic patients: effect of augmented gram-positive activity on infectious morbidity. National Cancer Institute of Canada Clinical Trials Group.

OBJECTIVE: To determine whether augmented quinolone-based antibacterial prophylaxis in neutropenic patients with cancer reduces infections caused by gram-positive cocci and preserves the protective effect against aerobic gram-negative bacilli. DESIGN: Open, randomized, controlled, multicenter clinical trial. SETTING: Centers participating in the National Cancer Institute of Canada Clinical Trials Group. PATIENTS: 111 eligible and evaluable patients hospitalized for severe neutropenia (neutrophil count < 0.5 x 10(9)/L lasting at least 14 days) who were receiving cytotoxic therapy for acute leukemia or bone marrow autografting. INTERVENTION: One of three oral antibacterial prophylactic regimens (norfloxacin, 400 mg every 12 hours; ofloxacin, 400 mg every 12 hours; or ofloxacin, 400 mg, plus rifampin, 300 mg every 12 hours) beginning with cytotoxic therapy. MEASUREMENTS: Incidence and cause of suspected or proven infection. RESULTS: Microbiologically documented overall infection rates for norfloxacin, ofloxacin, and ofloxacin plus rifampin were 47%, 24%, and 9%, respectively (P < 0.001). Corresponding rates were 24%, 13%, and 3%, respectively for staphylococcal bacteremia (P = 0.03) and, 21%, 3%, and 3%, respectively for streptococcal bacteremia (P < 0.01). The pattern of bacteremia suggested that rifampin played a role in suppressing staphylococcal infection. Both ofloxacin alone and ofloxacin plus rifampin had a clinically significant antistreptococcal effect. Aerobic gram-negative rods were cleared from rectal surveillance cultures in all patients after a median of 5.5 days and caused infection in only one patient (0.9%). The reductions in the number of microbiologically documented infections among ofloxacin recipients and ofloxacin plus rifampin recipients were offset by concomitant increases in the number of unexplained fevers (24% of norfloxacin recipients, 53% of ofloxacin recipients, and 49% of ofloxacin plus rifampin recipients; P = 0.02). No statistically significant difference was found among the treatment arms with respect to the overall incidence of febrile neutropenic episodes as defined for this trial (79% for the norfloxacin group, 82% for the ofloxacin group, and 77% for the ofloxacin plus rifampin group). CONCLUSIONS: Quinolone-based antibacterial chemoprophylaxis protected patients from aerobic gram-negative bacillary infections. Augmentation of the gram-positive activity reduced the incidence of gram-positive infections but did not influence the overall incidence of febrile neutropenic episodes.

Adult↗