Biomedical subjects

Lance K Heilbrun

Publications and source records attributed to Lance K Heilbrun.

At least 19 recordsLinked to original sources

PubMed2007

Pilot study of intraoperative chemotherapy with cisplatin and 5-fluorouracil in patients with advanced squamous cell carcinoma of the head and neck.

BACKGROUND: Intraoperative manipulation of the tumor during cancer surgery has long been recognized as a source of metastasis and contamination of the surgical wound during tumor removal. We explored the use of intraoperative chemotherapy to minimize the risk of tumor cell implantation and metastasis during head and neck cancer surgery and conducted a dose escalating intraoperative chemotherapy clinical trial designed to assess the feasibility of this approach and associated toxicities in patients with advanced squamous cell carcinoma of the head and neck. METHODS: Fourteen patients were treated with 5-fluorouracil at a dose of 1000 mg/m(2) administered intravenously over an 8-hour period during the surgery with simultaneous cisplatin. The cisplatin dose was escalated and toxicity observed. Cisplatin at 75 mg/m(2) was chosen as the maximum tolerated dose level. RESULTS: One patient experienced a grade 3 nephrotoxicity, 1 patient a grade 1 neuropathy, and 5 patients grade 2 nausea (36%). There were no grade 4 toxicities. CONCLUSION: Intraoperative chemotherapy is feasible, and the combination of cisplatin at 75 mg/m(2) and 5-fluorouracil at 1000 mg/m(2) can be administered during surgery without significant toxicity.

Aged↗

PubMed2006

A phase 1 trial of XK469: toxicity profile of a selective topoisomerase IIbeta inhibitor.

PURPOSE: XK469, a member of the quinoxaline family of antitumor agents, is believed to be unique in its ability to selectively target topoisomerase IIbeta. Based on encouraging pre-clinical data, a phase I trial was conducted to determine the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD). METHODS: A 2B accelerated titration schema was employed. XK469 was administered as a 5 or 20 min IV infusion on days 1-5 every 21 days. The starting dose was 9 mg/m(2). Pharmacokinetics (PK) were conducted in cycles 1-3. RESULTS: 22 patients (21 evaluable, mean age: 56 years, median performance status: 1) were enrolled. At dose level 11 (260 mg/m(2)/daily X 5), 1/6 patients experienced a DLT of grade 4 neutropenia. At 346 mg/m(2)/daily X 5, 2/2 patients experienced DLT's with one episode of febrile neutropenia and one grade 3 infection. The MTD was identified as 260 mg/m(2)/day. XK469 peak plasma levels and systemic exposure were proportional to dose indicating linear pharmacokinetics. However, secondary peaks in the PK profiles and a rapid decline in drug level from 23 to 24 h occurred in some patients. Drug infusion in the afternoon followed by dense sampling of levels during the elimination phase supported the hypothesis that the drug was being sequestered. No anti-tumor activity was identified. CONCLUSIONS: Traditional PK sampling designs were inadequate to describe XK469 disposition. XK469 and related structures work through a unique mechanism of action. A further understanding of the specific mechanism of these compounds might uncover a unique avenue for future drug development.

Adolescent↗

PubMed2006

Phase II trial of interferon and thalidomide in metastatic renal cell carcinoma.

OBJECTIVES: To evaluate the toxicity and efficacy of interferon and thalidomide combination in a phase II clinical trial. PATIENTS AND METHODS: Eligibility included metastatic renal cancer with a maximum of two prior regimens, performance status of 0-2 and adequate renal, hepatic and bone marrow function. RESULTS: Twenty patients were enrolled on this phase II trial. Median age was 60.5 years (Range: 39-75 years). 17 patients had visceral metastases (lung/liver/both) and 3 patients had lymph node only metastases. A total of 26 cycles of 4 weeks each were administered; median of 1 cycle and range from 0-9 cycles. The therapy was poorly tolerated with grade 3 adverse events noted in 12 (60%) of the 20 patients. No objective responses were noted. Of the 14 response evaluable patients, one had an unconfirmed response (38% decrease in size) and one had prolonged disease stabilization for 10 months. The median time to progression was 1.0 month and median survival was 2.8 months. Pre and post therapy PET scans were performed nine weeks apart on one patient. The mean standardized uptake values (SUV) declined from 1.45 (SUV min-max 0.89-1.76) to 1.12 (SUV min-max 0.55-1.47), denoting anti vascular effect. The patient did not have an objective response but had a disease stabilization sustained for 10 months. CONCLUSION: The combination of interferon and thalidomide has minimal efficacy and considerable toxicity which makes this combination unworthy of future investigation in metastatic renal cancer.

Administration, Oral↗

PubMed2006

Benefit of postoperative chemoradiotherapy for patients with unknown primary squamous cell carcinoma of the head and neck.

BACKGROUND: Postopertative adjuvant chemoradiotherapy recently became an established modality for patients with selected high-risk locally advanced head and neck cancers. The optimal treatment of unknown primary squamous cell cancer of the head and neck (SCCHN) continues to be controversial, since major randomized studies excluded those patients. METHODS: We conducted a retrospective review of patients treated during 1995 to 2002 for unknown primary SCCHN. All patients were treated with a neck dissection followed by concurrent high-dose cisplatin (100 mg/m(2)) and bilateral neck radiotherapy. RESULTS: Thirty-seven patients were identified with nodal disease distribution of N1 (5%), N2a (22%), N2b (41%), N2c (8%), N3 (22%), and Nx (3%). Modified neck dissection was done on the majority (30/37 = 81%) of patients. With a median follow-up of 42 months among the survivors, very few patients had regional recurrence (5%) or distant failure (11%), and 89% of patients were alive. The actuarial 5-year overall survival rate could not be estimated because there were no deaths beyond 20 months after surgery. Substantial yet acceptable acute and late morbidities were demonstrated in this cohort of patients. CONCLUSIONS: Postoperative chemoradiotherapy is of potential benefit to patients with unknown primary SCCHN by improving survival and reducing failures. This treatment warrants further prospective evaluation.

Adult↗

PubMed2006

Racial disparity in outcomes of a clinical trial population with metastatic renal cell carcinoma.

OBJECTIVES: Population studies have revealed that black Americans with renal cell carcinoma (RCC) have a shorter survival than do white Americans. Differences in socioeconomic status and treatment are frequently cited as the reasons for this disparity. The effect of these social obstacles may be reduced by studying a patient population with advanced RCC enrolled in clinical trials, because patients in these trials are likely to be similar in terms of their access to care, compliance, and performance status. METHODS: A retrospective review of all patients with metastatic RCC enrolled in clinical trials at Wayne State University from 1992 to 2002 was conducted. Log-rank survival analysis by age, sex, race, smoking history, nephrectomy history, prior therapy, type of protocol therapy (immunotherapy versus other), performance status (0 versus 1 to 2), and number of metastatic sites was conducted. Univariate and multivariate comparisons by race were performed for overall survival and time to progression. RESULTS: A total of 122 patients (median age 57 years) were enrolled; 21 (17%) were black and 101 (83%) were white. Overall survival was significantly shorter for the black Americans (P = 0.0027). The median survival for black Americans and white Americans was 6.9 and 11.5 months, respectively. On multivariate analysis, black race and performance status of 0 versus 1 and 2 were significant predictors of shorter survival. The presence of liver metastases and/or the absence of prior nephrectomy also influenced the length of overall survival through an interaction effect. CONCLUSIONS: Within a clinical trial patient population with RCC, race was a significant predictor of overall survival.

Adult↗

PubMed2006

Effects of high fruit-vegetable and/or low-fat intervention on plasma micronutrient levels.

OBJECTIVES: Higher plasma micronutrient levels have been associated with decreased cancer risks. The objective of this study was to determine the relative effects of reduced fat and/or increased fruit-vegetable (FV) intakes on plasma micronutrient levels. METHODS: Healthy, premenopausal women with a family history of breast cancer (n = 122) were randomized across four diet arms for one year in a 2 x 2 factorial design study: control, low-fat, high fruit-vegetable and combination low-fat/high FV diets. Levels of plasma micronutrients were measured in plasma at 0, 3, 6 and 12 months. RESULTS: The high FV intervention, regardless of fat intake, significantly increased alpha-carotene, beta-carotene and vitamin C levels in plasma. Only the combination high FV, low-fat intervention significantly increased plasma beta-cryptoxanthin and zeaxanthin levels over time. Although alpha-tocopherol was not affected, a potential concern is that the low-fat intervention resulted in significantly decreased both gamma-tocopherol dietary intakes and plasma levels, regardless of whether or not FV intakes were concomitantly increased. CONCLUSIONS: Unlike alpha-tocopherol, gamma-tocopherol plasma levels were decreased by a low fat diet, perhaps because gamma-tocopherol is not generally added to foods nor widely used in vitamin E supplements. The decreased dietary intakes and plasma levels of gamma-tocopherol with a low-fat diet may have implications for health risks since the biological functions of the different tocopherol isomers have been reported to be distinct.

Adult↗

PubMed2006

Relationships of psychosocial factors to dietary intakes of preadolescent girls from diverse backgrounds.

Family and personal factors that might be related to the development of food selection and eating patterns have not been well studied in children. The aim of this study was to examine whether such psychosocial factors differ in girls from four culturally diverse Girl Scout troops and how these factors are associated with dietary intakes. The social measures and dietary assessments were all obtained at baseline on subjects who were participating in a small nutrition education programme. The programme enrolled girls and one parent for each girl from four Girl Scout troops in Detroit, Michigan. The social factors assessed included girls' emotionality and use of food to regulate emotions, their general attitudes about health, eating and body image, and self-perceptions of their competence. Dietary intakes also were assessed in both the girls and their parents. There were large differences between troops in ethnicity and parent education level, and there were differences in dietary intakes as well. The psychosocial factors assessed in this study, however, did not differ significantly by troop. When the psychosocial factors were examined for their relationships to dietary factors, there was an indication that families which reported higher self-competence and academic competence in their daughters also had healthier eating patterns in their daughters. This was a small study, but the data suggest that simple comparisons between ethnic groups may not adequately capture the complexity of family and psychosocial factors contributing to good dietary practices.

Adult↗

PubMed2006

Women participating in a dietary intervention trial maintain dietary changes without much effect on household members.

This study examined whether subjects who participated in a 12-mo intervention would maintain their diets 1 yr after the study ended and whether the diets of household members were affected. Premenopausal women, who had at least one first-degree relative with breast cancer (n = 122), were randomized to one of four diets: control, low fat (15% of energy), high fruit and vegetable (FV, nine servings per day), and combination low fat, high FV. Study subjects and one household member were asked to complete the Block '95 food-frequency questionnaire (FFQ) at baseline, 1 yr, and 2 yr. Study subjects also completed 24-h recalls and 4-day food records at baseline and Year 1. Fat and FV intakes by all three assessment methods compared reasonably well except that fat intakes by FFQ were somewhat higher. FV intakes by FFQ in the high-FV and combination arms increased significantly from 4 servings per day to about 10 servings per day at Year 1 and 7 servings per day at Year 2. FV intakes increased much more modestly in the low-fat and control arms. Fat intakes in the low-fat and combination arms were lower at Year 1 than Year 2, but mean Year 2 fat intakes of 26-28% were still significantly lower than those at baseline. In household members, the only significant change was a small decrease in energy from fat at Year 1 in the household members of subjects who were in the combination arm. These results indicate that study subjects were making large dietary changes independently of their household members and that fat and FV intakes in study subjects 1 yr after intervention stopped were still substantially different from intakes at baseline.

Adult↗

PubMed2005

Phase I clinical trial of BMS-247550, a derivative of epothilone B, using accelerated titration 2B design.

PURPOSE: BMS-247550 is a semisynthetic derivative of epothilone B with mechanism of action analogous to paclitaxel. It has shown impressive antitumor activity in preclinical studies including in taxane-resistant models. We conducted a phase I trial, based on accelerated titration "2B" design, of BMS-247550 given as a 1-hour infusion every 3 weeks. EXPERIMENTAL DESIGN: Seventeen patients (M:F, 10:7; median age, 54 years; performance status, 0-2) were treated on the trial. Forty-five cycles (1-9 cycles) of BMS-247550 were given at dosages ranging from 7.4 to 56 mg/m2. All patients received prophylaxis for hypersensitivity reactions, related to Cremophor-EL, with steroids and histamine antagonists. RESULTS: First-course dose-limiting toxicity (DLT) was observed in two of three patients at 56 mg/m2 (neutropenic sepsis, prolonged grade 4 neutropenia) and in one of six patients at 40 mg/m2. Nonhematologic grade 3 to 4 toxicities observed were emesis and fatigue and they occurred only at 56 mg/m2. Grade 1 to 2 peripheral neuropathy was also observed. Other grade 1 to 2 toxicities were myalgias, arthralgias, rash, hand/foot syndrome, and mucositis. AUC and C(max) seemed proportional to the dose and the DLT. Development of neutropenia with BMS-247550 is related to the duration of drug exposure above a threshold. CONCLUSIONS: The maximum tolerated dose (MTD) of BMS-247550 is 40 mg/m2 given every 3 weeks. Neutropenia is the DLT. The accelerated titration "2B" design may help in determining MTD with fewer patients enrolled and more being treated closer to the MTD. However, the accelerated titration design did not seem to shorten the study duration.

Adult↗

PubMed2005

A simplified analysis of [18F]3'-deoxy-3'-fluorothymidine metabolism and retention.

PURPOSE: [18F]3'-deoxy-3'-fluorothymidine (FLT) is a thymidine analog developed for imaging tumor proliferation with positron emission tomography (PET). To quantitatively assess images, the blood activities of FLT and its glucuronidated metabolite were measured and its kinetics analyzed. This study sought to limit the number of blood samples needed to measure FLT retention. METHODS: Total FLT activity was measured from 18 venous samples obtained over the first hour and dynamic imaging performed on 33 patients (average dose 350 MBq/mmol). The 5-, 10-, 30- and 60-min samples were analyzed to measure the fraction of activity in FLT and its glucuronide. HPLC analysis was compared against a two-step column (Sep-Pak) and metabolic rates measured using full and limited sampling. Probenecid (2 g, oral) was given to two patients to determine whether imaging of the liver improved. RESULTS: At 60 min, 74% of the blood activity was unmetabolized (range 57-85%). HPLC and Sep-Pak gave comparable results (r=0.97; average difference 2.1%). For kinetic analysis, eight venous samples were sufficient to accurately measure total activity; for metabolite analysis, a single sample at 60 min yielded data with mean errors of 2.2%. The metabolic rate correlated with average SUV (r2=0.85; p=0.0002). An aorta input function gave kinetic results comparable to venous blood (r2=0.82). Probenecid did not improve imaging of the liver. CONCLUSION: Dynamic measurements of FLT retention can be used to calculate metabolic rates using a limited set of samples and correction for metabolites measured in a single sample obtained at 60 min.

Computer Simulation↗

PubMed2005

The impact of CAG repeats in exon 1 of the androgen receptor on disease progression after prostatectomy.

BACKGROUND: The authors examined the impact of the number of CAG repeats in exon 1 of the androgen receptor on disease progression among men with prostate carcinoma after prostatectomy. This polymorphism has been associated with alterations in activity of the androgen receptor in in vitro systems and with the risk of clinically diagnosed prostate carcinoma in some epidemiologic studies. An earlier series found that, among men at low risk of progressive disease, a small number of CAG repeats predicted a high risk of recurrence, and the impact of CAG repeats varied among men with different risks of progressive disease. METHODS: The authors analyzed specimens from a large clinical series of fixed tissue specimens from men who underwent prostatectomy at a single institution, including 413 American white men (WM) and 298 African-American men (AAM), with 5-10 years of available clinical follow-up. RESULTS: There was little association between the number of CAG repeats and extent of disease, Gleason score, and preoperative PSA level at diagnosis. Overall, patients who had > 18 CAG repeats had a greater risk of recurrence compared with patients who had </= 18 CAG repeats (hazard ratio [HR] = 1.52; P = 0.03). Excess risk was not found among men who were at low risk of recurrence (HR = 0.93; P = 0.96); however, among men who were at high risk of recurrence, the risk elevated for WM (HR = 1.75; P = 0.28), AAM (HR = 1.49; P = 0.06), and both races combined (HR = 1.53; P = 0.03). CONCLUSIONS: Overall, men with prostate carcinoma who had > 18 CAG repeats had an estimated 52% increased risk of disease recurrence. The increased risk could be attributed to men who were at high risk of recurrence.

Adenine↗

PubMed2005

A phase II study of celecoxib, gemcitabine, and cisplatin in advanced pancreatic cancer.

BACKGROUND: Pancreatic cancer is amongst the most chemoresistant malignancies. Expression of the cyclooxygenase-2 (COX-2) enzyme plays a major role in tumor progression and resistance to therapy. A Phase II study was undertaken to determine the effect of gemcitabine by fixed-dose rate infusion (FDR), cisplatin and the COX-2 inhibitor, celecoxib, on the 6-month survival rate in patients with metastatic pancreatic cancer. METHODS: The eligibility criteria included a pathologically or cytologically confirmed diagnosis of adenocarcinoma of the pancreas. No prior gemcitabine therapy was allowed. Patients received a combination of gemcitabine 1,000 mg/m(2) over 100 minutes, cisplatin 35 mg/m(2) I.V. on days 1 and 8, and celecoxib continuously at a daily dose of 800 mg. Cycles were repeated every 21 days. RESULTS: Twenty-two patients with metastatic pancreas cancer were enrolled (median age, 59.5 years; M:F, 13:9). The median number of cycles was 2 per patient. The median survival time was 5.8 months (90% CI, 3.6-7.6 months). The probability of survival at 6 months was 46% (90% CI, 27-62%). The major toxicity was neutropenia with grade 3 or 4 toxicities seen in 65% of patients. CONCLUSIONS: The addition of celecoxib to gemcitabine (by FDR) and cisplatin did not appear to increase activity of the chemotherapy doublet in patients with advanced pancreatic cancer. Celecoxib alone may not be sufficient to sensitize pancreatic cancer to the effects of conventional cytotoxic therapy.

Adenocarcinoma↗

PubMed2005

Phase II trial of fenretinide in advanced renal carcinoma.

PURPOSE: Fenretinide, a synthetic form of retinoid, induced apoptosis even in chemotherapy resistant cell lines. A phase II study was hence conducted to evaluate toxicity and efficacy of fenretinide in metastatic renal cancer. METHODS: Eligibility included unresectable or metastatic renal cell carcinoma (RCC), adequate organ function and Zubrod performance status < or =2. Prior immunotherapy and a maximum of one prior chemotherapy regimen were allowed. Fenretinide was administered at a dose of 900 mg/m(2) twice daily orally for 7 days in a 21-day cycle. Toxicity was assessed at the start of each cycle, and response every 2 cycles. RESULTS: Nineteen eligible patients enrolled of which fifteen had visceral/bone metastases. Seventeen patients had prior nephrectomy and 11 had prior immunotherapy. 76 cycles of therapy were delivered. Therapy was very well tolerated with few severe toxicities consisting of thrombosis in 1 individual and grade 3 fatigue, nausea and diarrhea in 1 patient. 5 patients had grade 2 nyctalopia and 3 patients had transient grade 2 visual toxicity. No objective responses were noted. Stable disease was seen in seven of nineteen cases (37%, 90% C.I. 0.21-0.59). Median time to progression was 1.5 months and median duration of stable disease was 5.8 months (90% C.I. 3.0-8.4). Median survival was 10 months. Tumor fenretinide levels were obtained in three patients and were in the lower end of the therapeutic range. CONCLUSION: Fenretinide was well tolerated but demonstrated minimal activity that was consistent with results of intratumoral drug measurements. Strategies are needed that will increase systemic and tumor levels of fenretinide.

Administration, Oral↗

PubMed2005

A phase II study of carboplatin and paclitaxel in adenocarcinoma of unknown primary.

BACKGROUND: Cisplatin-based combination chemotherapy is commonly used in the treatment of carcinoma of unknown primary site. Paclitaxel has shown promising activity as a single agent in a number of malignancies. This study was conducted to evaluate the efficacy and toxicity of combination carboplatin and paclitaxel in patients with adenocarcinoma of unknown primary site (ACUP). METHODS: Twenty-two patients with ACUP were enrolled in the study. Patients were treated with 200 mg/m2 paclitaxel intravenously (IV) over 3 hours followed by carboplatin IV with a targeted plasma area under the curve (AUC) of 5 mg/h/mL. RESULTS: A total of 73 treatment courses were administered with a median of 5 courses per patient. Five of the 22 registered patients had a major response for an objective response rate of 23% (90% confidence interval [CI], 0.11-0.40) by intention-to-treat analysis. The median response duration was 4.1 months (90% CI, 3.6-7.1). The median survival time was 6.5 months (90% CI, 5.5-10.1) and the 1-year survival rate was 27% (90% CI, 0.11-0.42). The major toxicity observed was neutropenia, with grade 3-4 neutropenia occurring in 3 patients (14%). There were no treatment-related deaths. CONCLUSIONS: The combination of carboplatin and paclitaxel is a tolerable and moderately active regimen in ACUP.

Adenocarcinoma↗

PubMed2004

Vitamin D receptor gene polymorphisms and disease free survival after radical prostatectomy.

BACKGROUND: Vitamin D has been linked with prostate cancer risk in epidemiologic studies and has antiproliferative, prodifferentiation, and antimetastatic properties in experimental systems. Its hormonal activity is mediated by the vitamin D receptor. We investigated whether germ-line genetic variation in the vitamin D receptor impacts progression of prostate cancer after radical prostatectomy. METHODS: We analyzed BsmI and TaqI polymorphisms using archived specimens from a large series of radical prostatectomy patients at a single institution. Our series included 428 white men (WM) and 310 African-American men (AAM) who were carefully and uniformly staged and followed for 5-10 years. RESULTS: The distribution of polymorphisms varied between WM and AAM. There was little association between genotype and extent of disease at diagnosis, Gleason score, preoperative PSA, or recurrence overall. Among WM with locally advanced disease, however, the BsmI B allele protected against recurrence in models examining gene dose (P = 0.04) and dominant effects (P = 0.05). CONCLUSIONS: Overall vitamin D receptor polymorphisms did not predict pathologic features of prostate cancer but may impact on risk of recurrence among men in certain risk groups. Analysis of polymorphisms may provide clues about the mechanisms through which vitamin D exerts its inhibitory effects on prostate cancer in vivo in men.

Black or African American↗

PubMed2004

Cytochrome p450 and glutathione transferase expression in squamous cell cancer.

PURPOSE: The cytochrome P-450 (CYP) and glutathione S-transferase (GST) enzyme systems modulate the carcinogenic effects of tobacco. Therefore, the expression of these enzymes may be in part responsible for the observed interindividual and inter-racial differences in the risk of development of squamous cell carcinoma of the head and neck (SCCHN). The first aim of this study was to evaluate the feasibility of measuring the expression of the CYP and GST in target tissue from the head and neck. The second aim was to compare the expression of CYPs 1A1, 2E1, and 3A4 in squamous epithelium from African-American and Caucasian pediatric patients. The third aim was to compare the expression of CYPs 1A1, 2E1, 3A4, and GST-pi on the p16 expression in patients with SCCHN. EXPERIMENTAL DESIGN: The expression of CYP 1A1, 2E1, 3A4, GST-pi, and p16 was quantified by immunoblotting. Expression of CYPs 1A1, 2E1, and 3A4 was quantified in tissue from 160 pediatric patients undergoing tonsillectomy. Expression of CYPs 1A1, 2E1, 3A4, GST-pi, and p16 was determined in 46 resected SCCHN patients. RESULTS: Large interindividual variability in the expression of these enzymes was observed in the pediatric and adult populations. No significant difference was observed in CYP 1A1, 2E1, and 3A4 expression of Caucasian and African-American patients. There was no correlation between p16 and enzyme expression in patients with SCCHN. CONCLUSION: Evaluation of CYP expression in the target tissue of interest is feasible. The clinical significance of CYPs and GST-pi alterations in the risk of developing SCCHN will need to be investigated in larger trials.

Blotting, Western↗

PubMed2004

CYP3A4 genetic variant and disease-free survival among white and black men after radical prostatectomy.

PURPOSE: Prostate cancer is an androgen sensitive disease. Cytochrome P450 3A4 (CYP3A4) oxidatively deactivates testosterone by converting it to biologically less active metabolites. Previous studies suggest that a germline genetic variant in the 5' regulatory region of the gene may interfere with deactivation and increase the risk of clinically advanced prostate cancer. We investigated the impact of this polymorphism on the risk of recurrence after prostatectomy. MATERIALS AND METHODS: We assembled clinical data and analyzed specimens from a large series of patients who underwent prostatectomy who were carefully staged at a single institution and had 5 to 10 years of prospective clinical followup. The series included 428 white men and 309 black men. RESULTS: Stage, Gleason score or preoperative prostate specific antigen strongly predicted progression-free survival (PFS) but were not associated with CYP3A4 genotypes. There was a strong association between race and genotype (p = 0.00002) in that 8% of white men and 83% of black men had 1 or more copies of the G allele. When both races were included genotype was associated with PFS (hazard ratio [HR] 1.27, CI 1.08-1.27, p = 0.005). In race specific analyses increasing copies of the G allele were associated with poorer PFS among white men (HR 1.98, CI 1.06-3.70, p = 0.03) but had little impact on PFS among black men (HR 1.004, CI 0.77-1.32, p = 0.97). CONCLUSIONS: The CYP3A4 genotype studied was not associated with pathological features of prostate cancer for men of either race. Unstratified analyses of men of both races and stratified analyses of white men demonstrated poorer PFS after prostatectomy for those with the G allele, but the G allele did not predict PFS among black men.

Aged↗

PubMed2004

Efficacy and safety of reteplase for central venous catheter occlusion in patients with cancer.

PURPOSE: To evaluate the efficacy and safety of reteplase for central venous catheter (CVC) occlusion in patients with cancer. MATERIALS AND METHODS: An open-label, single-arm, prospective study was conducted. Reteplase (0.4 U) was instilled into each catheter lumen with a dwell time of 30 minutes in patients with cancer with a dysfunctional CVC. If the function of the catheter was not restored in 30 minutes, an additional dwell time of 30 minutes was allowed (a total of 60 minutes possible dwell time for the first dose). A second dose was repeated at 60 minutes after the first dose if catheter function was not restored (a total of 120 minutes for up to two doses). The primary efficacy outcome was the restoration of CVC function. RESULTS: Of 139 patients who received reteplase, the first-attempt success rate after a 30-minute dwell time was 66.9%. The cumulative success rates at 60, 90, and 120 minutes were 88.5%, 94.7%, and 94.7%, respectively. The variation of patient age, catheter age, CVC occlusion age, CVC type, number of lumen, or occlusion type was not associated with the efficacy of reteplase. There were no treatment-associated adverse events reported during the study period. CONCLUSION: Reteplase at 0.4-U dosing per catheter lumen is an effective and safe alternative that rapidly restores the patency of occluded CVCs in patients with cancer.

Adult↗