An exploratory study of sunitinib plus paclitaxel as first-line treatment for patients with advanced breast cancer.

BACKGROUND: Sunitinib has shown single-agent activity in patients with previously treated metastatic breast cancer (MBC). We investigated the safety of the combination of sunitinib and paclitaxel in an exploratory study of patients with locally advanced or MBC. METHODS: Patients received oral sunitinib 25 mg/day (with escalation to 37.5 mg/day as tolerated) on a continuous daily dosing schedule and paclitaxel 90 mg/m(2) on days 1, 8, and 15 of each 28-day cycle. Study endpoints included safety (primary endpoint), pharmacokinetics, and antitumor activity. RESULTS: Twenty-two patients were enrolled. The most frequent adverse events (AEs) were fatigue/asthenia (77%), dysgeusia (68%), and diarrhea (64%). Grade 3 AEs included neutropenia (43%), fatigue/asthenia (27%), neuropathy (18%), and diarrhea (14%). No drug-drug interaction was observed on the basis of pharmacokinetic analysis. Of 18 patients with measurable disease at baseline, 7 (38.9%) achieved objective responses (including 2 complete and 5 partial responses). Clinical responses were observed in three of nine patients with triple-negative receptor status (estrogen receptor negative, progesterone receptor negative, and human epidermal growth factor receptor-2 negative). CONCLUSIONS: These data indicate that sunitinib and paclitaxel in combination are well tolerated in patients with locally advanced or MBC. No drug-drug interaction was detected and there was preliminary evidence of antitumor activity.

Paradoxical response to a novel influenza virus vaccine strain: the effect of prior immunization.

BACKGROUND: repeated influenza immunization does not appear to adversely affect the serum antibody response to new influenza strains. OBJECTIVE: to determine whether the immune response to a new influenza strain was inferior in persons previously vaccinated compared with persons not previously vaccinated. DESIGN: randomized, double-blind clinical trial. SETTING: university affiliated community teaching hospital. PATIENTS: 139 healthy adult men and women, mean age 38 years. INTERVENTION: subjects were vaccinated as part of another study. They received influenza vaccines containing influenza strains A/Texas/36/91 (H1N1), A/Nanchang/933/95 (H3N2) and B/Beijing/184/93. One group received a licensed influenza vaccine while the other group received a similar vaccine except the A/Nanchang strain had a diminished potency. MEASUREMENTS: serum hemagglutination inhibition (HAI) antibody titers were determined prior to vaccination and two weeks afterward. If patients had a low postvaccination titer, they were revaccinated and HAI titers were determined two weeks later. RESULTS: 68 adults received the licensed vaccine and 70 received the subpotent vaccine. The groups were similar with regards to baseline characteristics. Those previously vaccinated had significantly lower postvaccination HAI geometric mean titers (GMTs) for all three vaccine strains (A/Texas--127 vs. 359, p < 0.001, A/Nanchang--31 vs. 93, p < 0.001 and B/Beijing--140 vs. 205, p < 0.05). The percentage of subjects with a presumed protective HAI titer of > or =40 was significantly lower among the previously vaccinated groups only for the new influenza strain, A/Nanchang (55% vs. 80%, p < 0.05). For the other two vaccine strains, the percentage with an HAI titer > or =40 was greater than 90% for both groups. CONCLUSIONS: the decrease in serologic response to influenza vaccine among healthy, young adults who were previously vaccinated appears to be unique for this year's influenza vaccine. Further studies are required to determine the frequency and clinical significance of this phenomenon observed in younger healthy adults, and whether it is a general one. Based on its proven efficacy, influenza vaccine should continue to be given on an annual basis to high risk children and adults and to all those 65 years or older.

Implementing preventive health measures: a pilot study.

OBJECTIVE: Implementation of preventive services guidelines is performed inconsistently. In an attempt to reduce variation in guideline implementation, we developed a patient questionnaire based on the US Preventive Services Task Force Guide and the Health Plan Employer Data and Information Set 3.0 performance measures of the National Committee on Quality Assurance. SUBJECTS: 100 hospitalized patients of five primary-care physicians. METHODS: In a pilot study, 100 hospitalized patients of five primary-care physicians were questioned about their compliance with evidence-based, preventive healthcare recommendations. Information was requested on blood pressure measurement, cholesterol screening, fecal occult blood testing, smoking-cessation counseling, Pap testing, mammography, postmenopausal hormonal replacement therapy counseling, prostate examination and prostate-specific antigen (PSA) testing, use of aspirin and beta-blockers following an acute myocardial infarction, testing of diabetics for hemoglobin A1c and retinal eye examinations, questioning of the elderly for auditory and visual problems, and receipt of influenza and pneumococcal vaccines. Information on variations from the recommended preventive service was fed back to their physicians. Six months after the initial survey, the patients were requestioned to determine if compliance had improved with the recommendations. RESULTS: We found significant improvement in fecal occult blood testing, smoking cessation, Pap smear testing, mammography use, prostate examinations and PSA testing, hemoglobin A1c testing, seeing or hearing loss follow-up, and the administration of influenza and pneumococcal vaccines. CONCLUSIONS: Improving implementation of preventive services recommendations is a challenge. This pilot study suggests that involving the patient more in the process and informing the physician of the results may improve the process.

Severity adjustment for length of stay: is it always necessary?

OBJECTIVE: Severity adjustment is an oft-cited requirement when comparing physicians or medical delivery systems. Each application of severity adjustment, however, has to be tested to validate the need, the method, and its value. We examined the value of severity adjustment for identifying physician outliers when studying length of stay in the hospital. DESIGN: We compared the placement of physicians in an outlier category using a severity-adjusted average length of stay (SLOS) index with their placement using the unadjusted average length of stay (ALOS). Changes in placement of the list were validated by the utilization review coordinators. SETTING: A 614-bed tertiary-care university teaching hospital. SUBJECTS: We analyzed 11,146 discharges from 138 physicians in 1992. RESULTS: The mean ALOS +/- standard deviation was 9.05 + 4.50 days, and the SLOS Index was 7.56 +/- 3.06. There were 120 inliers, 6 high outliers, and 12 low outliers by the ALOS method. Using the SLOS index, 27 of 138 physicians had their categories changed from inlier to outlier or from outlier to inlier. The difference in group changes was more significant for those going from outlier to inlier status (8/120 vs 6/18; P < .001). The patients of the six physicians whose status changed from outlier to inlier status were sicker, as indicated by the comorbidity, complications, and manifestations of disease processes score. The utilization reviewers validated the status changes in 8 of 14 instances. CONCLUSIONS: Severity-adjusted length of stay by the SLOS index appears to provide a more accurate measure than the unadjusted ALOS. The changes, however, were small. It is not clear that the added effort is worthwhile.

Time to earliest peak serum antibody response to influenza vaccine in the elderly.

The earliest time at which serum antibody levels peak following administration of an influenza virus vaccine in elderly persons is not clearly defined. We compared the time intervals of 1 and 2 weeks after vaccination. A commercial trivalent vaccine containing the hemagglutinins of influenza viruses A/Texas/36/91 (H1N1), A/Johannesburg/33/94 (H3N2), and B/Harbin/7/94 was used. The hemagglutination inhibition (HAI) antibody titers at 1 week after vaccination were significantly lower than the HAI titers at 2 weeks postvaccination for all three vaccine components.

Annual influenza vaccination: immune response in patients over 10 years.

OBJECTIVE: To determine the effect of repeated annual influenza immunization on the host's serum antibody. DESIGN: Ten year observational study with cohort design. SETTING: Cystic Fibrosis Center at St. Vincent's Hospital and Medical Center, New York City, NY. PATIENTS: Thirty-eight children and young adults with cystic fibrosis (CF). MEASUREMENTS: Serum hemagglutination inhibition (HI) antibody titers were determined at the time of vaccination and 4 weeks later each year in the fall before the influenza epidemic. Shwachman scores were determined each year. RESULTS: While the pre-vaccination and post-vaccination geometric mean serum HI antibody titers varied from year to year, no upward or downward trend was evident over the 10 year period. The reciprocal of the post-vaccination geometric mean HI titers ranged annually from 32 to 74 for the influenza A (H3N2) vaccine strains, from 53 to 133 for the influenza A (H1N1) strains, and from 18 to 174 for influenza B strains. In addition, the majority of vaccinees had a presumably protective post-vaccination serum HI titer > or = 1:40 each year for all three vaccine strains. The initial mean Shwachman score of the group was 77. The final score of 76 after 10 years was not significantly different. CONCLUSIONS: Annual influenza vaccination appears to regularly induce presumably protective serum antibody levels in most CF children and young adults studied over a 10 year period.

Time to peak serum antibody response to influenza vaccine in the elderly.

The earliest time at which serum antibody peaks following administration of influenza virus vaccine in elderly persons is not clearly defined. We compared the time intervals of 2 and 4 weeks after vaccination. A commercial trivalent vaccine containing the hemagglutinins of influenza viruses A/Texas/36/91(H1N1), A/Shangdong/9/93(H3N2), and B/Panama/45/90 was used. The hemagglutination inhibition antibody titers at 2 weeks after vaccination were identical to the hemagglutination inhibition antibody titers at 4 weeks for all three vaccine components.

Use of severity-adjusted length of stay to modify physician practice patterns.

OBJECTIVE: To compare inpatient length of stay among physicians by testing a new method for severity adjusting length of stay. DESIGN: A retrospective validation study with prospective follow-up after an intervention. SETTING: A 531-bed community teaching hospital. PATIENTS: Three hundred randomly selected patients from the 30,861 patients discharged in 1990. INTERVENTION: A physician with a significantly prolonged severity-adjusted length of stay was counseled and then monitored for three months. RESULTS: The correlation between the number of comorbidities, complications, and manifestations of disease processes (CCMDPs) was R2 = 0.658, t = 23.96 (p = .001). One physician had an unusually high severity-adjusted length of stay, but lowered it after he was counseled and monitored for three months. CONCLUSIONS: The number of CCMDPs recorded on the hospital discharge abstract can be used as a severity index to adjust a patient's length of stay for illness severity. Using linear regression analysis, a picture of the severity-adjusted length of stay can be derived for physicians. Through counseling and monitoring, individual physicians' lengths of stay patterns may be reduced.