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Biomedical subjects

Eric Vallieres

Publications and source records attributed to Eric Vallieres.

7 recordsLinked to original sources
PubMed2006

Phase I Trial of sequential administration of recombinant DNA and adenovirus expressing L523S protein in early stage non-small-cell lung cancer.

L523S is an immunogenic lung cancer antigen that has demonstrated preclinical safety when the gene is injected intramuscularly as an expressive plasmid (pVAX/L523S) and when delivered following incorporation into an E1B-deleted adenovirus (Ad/L523S). We performed a phase I clinical trial in 13 stage IB, IIA, and IIB non-small-cell lung cancer patients. pVAX/L523S (8 mg on days 0 and 14 in all cohorts) and Ad/L523S (1, 20, 400 x 10(9) vp on days 28 and 56, cohorts 1, 2, and 3, respectively) were administered to 3 patients in each of three cohorts. No significant toxic effect was identified. All but 1 patient demonstrated greater than or equal to twofold elevation in anti-adenovirus antibodies. One of 10 evaluable patients demonstrated L523S-specific antibody by direct IgG ELISA. Two patients developed disease recurrence and all remain alive after a median of 290 days follow-up. Results suggest a high level of safety but evidence of L523S-directed immune activation was limited, suggesting a need for modification of dose, schedule, and site of vaccination (i.e., intradermal) with further clinical testing.

Adenoviridae↗
PubMed2005

Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer.

BACKGROUND: We undertook to determine whether adjuvant vinorelbine plus cisplatin prolongs overall survival among patients with completely resected early-stage non-small-cell lung cancer. METHODS: We randomly assigned patients with completely resected stage IB or stage II non-small-cell lung cancer to vinorelbine plus cisplatin or to observation. The primary end point was overall survival; principal secondary end points were recurrence-free survival and the toxicity and safety of the regimen. RESULTS: A total of 482 patients underwent randomization to vinorelbine plus cisplatin (242 patients) or observation (240); 45 percent of the patients had pathological stage IB disease and 55 percent had stage II, and all had an Eastern Cooperative Oncology Group performance status score of 0 or 1. In both groups, the median age was 61 years, 65 percent were men, and 53 percent had adenocarcinomas. Chemotherapy caused neutropenia in 88 percent of patients (including grade 3 febrile neutropenia in 7 percent) and death from toxic effects in two patients (0.8 percent). Nonhematologic toxic effects of chemotherapy were fatigue (81 percent of patients), nausea (80 percent), anorexia (55 percent), vomiting (48 percent), neuropathy (48 percent), and constipation (47 percent), but severe (grade 3 or greater) toxic effects were uncommon (<10 percent). Overall survival was significantly prolonged in the chemotherapy group as compared with the observation group (94 vs. 73 months; hazard ratio for death, 0.69; P=0.04), as was relapse-free survival (not reached vs. 46.7 months; hazard ratio for recurrence, 0.60; P<0.001). Five-year survival rates were 69 percent and 54 percent, respectively (P=0.03). CONCLUSIONS: Adjuvant vinorelbine plus cisplatin has an acceptable level of toxicity and prolongs disease-free and overall survival among patients with completely resected early-stage non-small-cell lung cancer.

Adult↗
PubMed2005

Time from treatment to subsequent diagnosis of brain metastases in stage III non-small-cell lung cancer: a retrospective review by the Southwest Oncology Group.

PURPOSE A retrospective review of the Southwest Oncology Group (SWOG) database was undertaken to review the incidence and timing of diagnosis of brain metastases in patients undergoing combined-modality therapy for stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Four hundred twenty-two eligible, assessable patients with stage IIIA/B NSCLC were treated on four SWOG protocols. Treatment varied with protocol but consisted of concurrent cisplatin-etoposide and radiation in all patients, with a surgery arm in two of the four protocols. Results Of the 422 total patients, 268 (64%) have experienced disease progression; 54 relapses (20%) were in brain only, 17 (6.5%) were in brain and other sites simultaneously, and 197 (63.5%) were in sites other than brain. Of the 268 patients with disease progression, progression in the brain only, in the brain and other sites, and not in the brain occurred in 20%, 6%, and 74% of patients, respectively. Time from treatment to diagnosis of disease progression in the brain in 71 patients was as follows: during treatment, 16 relapses (22.5%); 0 to 16 weeks after treatment, 17 relapses (24%); 16 weeks to 6 months after treatment, 10 relapses (14%); 6 to 12 months after treatment, 16 relapses (22.5%); and more than 12 months after treatment, 12 relapses (17%). Nonsquamous histology and young patient age were the only significant predictors for increased risk of early relapse with brain metastases. CONCLUSION Brain metastases often develop early in the course of treatment for stage IIIA/B NSCLC. The statistical designs of ongoing trials of prophylactic cranial irradiation in stage III NSCLC have taken this into account.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Escape from therapy-induced accelerated cellular senescence in p53-null lung cancer cells and in human lung cancers.

Accelerated cellular senescence (ACS) has been described for tumor cells treated with chemotherapy and radiation. Following exposure to genotoxins, tumor cells undergo terminal growth arrest and adopt morphologic and marker features suggestive of cellular senescence. ACS is elicited by a variety of chemotherapeutic agents in the p53-null, p16-deficient human non-small cell H1299 carcinoma cells. After 10 to 21 days, infrequent ACS cells (1 in 10(6)) can bypass replicative arrest and reenter cell cycle. These cells express senescence markers and resemble the parental cells in their transcription profile. We show that these escaped H1299 cells overexpress the cyclin-dependent kinase Cdc2/Cdk1. The escape from ACS can be disrupted by Cdc2/Cdk1 kinase inhibitors or by knockdown of Cdc2/Cdk1 with small interfering RNA and can be promoted by expression of exogenous Cdc2/Cdk1. We also present evidence that ACS occurs in vivo in human lung cancer following induction chemotherapy. Viable tumors following chemotherapy also overexpress Cdc2/Cdk1. We propose that ACS is a mechanism of in vivo tumor response and that mechanisms aberrantly up-regulate Cdc2/Cdk1 promotes escape from the senescence pathway may be involved in a subset of tumors and likely accounts for tumor recurrence/progression.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Prospective randomized study evaluating a biodegradable polymeric sealant for sealing intraoperative air leaks that occur during pulmonary resection.

BACKGROUND: To evaluate the safety and effectiveness of a new biodegradable polymeric sealant to close intraoperative air leaks after pulmonary resection. METHODS: In a multicenter prospective randomized trial, 161 patients with a median age of 67 years old (range 18-85 years old), were randomized in a 2:1 ratio to receive sealant or control for at least one significant air leak (> or = 2.0 mm in size) after pulmonary resection. In the sealant group, all significant air leaks underwent attempted repair by standard methods (sutures, staples, or cautery) prior to the application of sealant. The control group underwent only standard methods. Blood was analyzed for immunologic response. Patients were followed up 1 month after surgery. RESULTS: Intraoperative air leaks were sealed in 77% of the sealant group compared with 16% in the control group (p < 0.001). The sealant group had significantly fewer patients with postoperative air leaks compared with the control group (65% vs 86%, p = 0.005). Median length of hospitalization was 6 days (range, 3-23 days) for the sealant group compared with 7 days (range 4-38 days) for controls (p = 0.028). There was no difference in mortality, morbidity, duration of chest tubes, or immune responses between the two groups. CONCLUSIONS: This study demonstrates the effectiveness of a biodegradable polymer when used as an adjunct to standard closure methods for sealing significant intraoperative air leaks that develop from pulmonary surgery. Use of the sealant led to a reduction in postoperative air leaks, which may have decreased the length of hospitalization.

Adolescent↗
PubMedDate not supplied

Chronic traumatic and congenital diaphragmatic hernias: presentation and surgical management.

BACKGROUND: The diagnosis of chronic diaphragmatic hernias, whether due to congenital defects or trauma, may be difficult to make and may rely on clinical suspicion in the setting of persistent nondiagnostic radiographic findings. Repair is indicated to avoid catastrophic cardiopulmonary compromise and/or incarceration of abdominal organs. STUDY OBJECTIVES: To review the varied presentations and treatment of chronic diaphragmatic hernia. DESIGN: Retrospective review. SETTING: University of Washington and Harborview Medical Center, Seattle, Washington. PATIENTS: Between 1997 and 2001, nine patients presented with chronic diaphragmatic hernia (two congenital cases, seven post-traumatic cases). Four cases involved the right diaphragm. The following clinical features were noted: asymptomatic, chest radiograph showing bowel herniation (n=1); chest wall mass (n=1); asymptomatic with the chest radiograph showing marked elevation of hemidiaphragm (n=1); dyspnea with the chest radiograph showing marked elevation of hemidiaphragm (n=1); diarrhea and heartburn (n=1); generalized gastrointestinal upset (n=1); recurrent pneumonia (n=2); recurring effusions (n=4); and dyspnea on exertion (n=5). INTERVENTIONS: Diagnosis was confirmed by chest radiograph in two patients, chest computed tomography scan in one patient, barium studies in three patients and thoracoscopy in three patients. All hernias were repaired via thoracotomy, and two hernias were repaired with artificial patch. CONCLUSIONS: Patients with chronic diaphragmatic hernias present with a variety of symptoms and radiographic findings. When radiology or symptoms suggest bowel involvement, barium studies are appropriate. In other cases, chest computed tomography scans and/or thoracoscopy are useful. Repair is accomplished through the ipsilateral chest, with primary repair of the diaphragm preferred over patch repair.

Adolescent↗