Impact of Late Dosing on Testosterone Suppression with 2 Different Leuprolide Acetate Formulations: In Situ Gel and Microsphere. An Analysis of United States Clinical Data.

PURPOSE: Nonadherence to dosing schedules for androgen deprivation therapy increases the risk of testosterone escape for patients with prostate cancer. Two approved formulations of leuprolide acetate, the most commonly prescribed androgen deprivation therapy in the United States, use different extended release delivery technologies: an in situ gel and microspheres. We evaluated the prevalence and impact of late dosing on testosterone suppression for gel and microsphere formulations of leuprolide acetate. MATERIALS AND METHODS: We retrospectively analyzed records of patients with prostate cancer treated with gel or microsphere delivery of leuprolide acetate. Analyses used 2 definitions of "month," "28-day" (late dosing after day 28, 84, 112 or 168) and "extended" (late dosing after day 32, 97, 128 and 194). Frequencies of late dosing and associated testosterone values were calculated. RESULTS: A total of 2,038 patients received gel and 8,360 received microsphere formulations of leuprolide acetate. More than 80% and 27% of injections were late for 28-day and extended month, respectively. For 28-day month late injections 10% (gel delivery) and 14% (microsphere delivery) of testosterone values were above 50 ng/dl, and 25% (gel) vs 33% (microsphere) were above 20 ng/dl. For extended month 18% (gel) vs 25% (microsphere) were above 50 ng/dl, and 34% (gel) vs 44% (microsphere) were above 20 ng/dl. Microsphere leuprolide acetate was 1.5 times more likely to have testosterone above 50/20 ng/dl vs gel. Least square mean testosterone was 34 ng/dl (gel) vs 46 ng/dl (microsphere) for 28-day month, and 48 ng/dl (gel) vs 76 ng/dl (microsphere) for extended month. CONCLUSIONS: Leuprolide acetate therapies were frequently administered late. Gel formulation demonstrated higher rates of testosterone 50 ng/dl or less and 20 ng/dl or less than microsphere formulation. Optimal testosterone suppression can impact prostate cancer progression and patient survival, and differences in extended release technology for androgen deprivation therapy appear relevant.

Impact of race on prostate-specific antigen outcome after radical prostatectomy for clinically localized adenocarcinoma of the prostate.

PURPOSE: To compare prostate-specific antigen (PSA) outcome after radical prostatectomy (RP) for prostate cancer in African-American and white men using previously established risk groups. PATIENTS AND METHODS: Between 1989 and 2000, 2,036 men (n = 162 African-American men, n = 1,874 white men) underwent RP for clinically localized prostate cancer. Using pretreatment PSA, Gleason score, clinical T stage, and percentage of positive biopsy specimens, patients were stratified into low- and high-risk groups. For each risk group, PSA outcome was estimated using the actuarial method of Kaplan and Meier. Comparisons of PSA outcome between African-American and white men were made using the log-rank test. RESULTS: The median age and PSA level for African-American and white men were 60 and 62 years old and 8.8 and 7.0 ng/mL, respectively. African-Americans had a statistically significant increase in PSA (P =.002), Gleason score (P =.003), clinical T stage (P =.004), and percentage of positive biopsy specimens (P =.04) at presentation. However, there was no statistical difference in the distribution of PSA, clinical T stage, or Gleason score between racial groups in the low- and high-risk groups. The 5-year estimate of PSA outcome was 87% in the low-risk group for all patients (P =.70) and 28% versus 32% in African-American and white patients in the high-risk group (P =.28), respectively. Longer follow-up is required to confirm if these results are maintained at 10 years. CONCLUSION: Even though African-American men presented at a younger age and with more advanced disease compared with white men with prostate cancer, PSA outcome after RP when controlled for known clinical predictive factors was not statistically different. This study supports earlier screening in African-American men.

Prospective study of palliative hypofractionated radiotherapy (8.5 Gy x 2) for patients with symptomatic non-small-cell lung cancer.

PURPOSE: Hypofractionated chest radiotherapy regimens have provided excellent palliation of pulmonary symptoms in patients with inoperable non-small-cell lung cancer (NSCLC) and poor performance status in studies from Asia and Europe. We conducted a prospective study of this approach in patients from the United States. METHODS AND MATERIALS: Twenty-three patients with symptomatic NSCLC and an Eastern Cooperative Oncology Group performance status of > or =2 were enrolled between December 1994 and October 2001. Two "involved-field" fractions of 8.5 Gy were delivered 1 week apart. Patients were assessed for efficacy, toxicity, and tumor response at baseline, treatment completion, and 1 week, 1 month, and 4 months after completing radiotherapy. RESULTS: The median follow-up after treatment began was 4.3 months (range, 0.3-38). The median forced expiratory volume in 1 s and Eastern Cooperative Oncology Group performance status as measured at baseline was 1.05 L and 3, respectively. The most common presenting pulmonary symptoms were dyspnea (100%), cough (96%), anorexia/nausea (65%), and chest pain (52%). Between treatment completion and up to 4 months after treatment, dyspnea, cough, anorexia/nausea, chest pain, hoarseness, hemoptysis, and dysphagia had improved in 30%, 60%, 67%, 75%, 25%, 100%, and 100% of patients, respectively. No cases of treatment-related esophagitis, pneumonitis, or radiation myelopathy occurred. Progressive local disease was seen in only 1 (6%) of 18 assessable patients 4 months after treatment. CONCLUSION: For patients with poor performance status and inoperable NSCLC causing pulmonary symptoms, hypofractionated, involved-field radiotherapy, 8.5 Gy in two fractions, offers acceptable palliation with minimal toxicity. A clear advantage of the very short hypofractionated regimen is that it enables patients with a short expected survival time to spend more of their remaining time away from the hospital.

Race, socioeconomic status, and breast carcinoma in the U.S: what have we learned from clinical studies.

BACKGROUND: Whether African-American women have biologically more aggressive breast carcinoma compared with white women and whether race acts as a significant independent prognostic factor for survival have not been determined. Alternatively, race merely may be a surrogate for socioeconomic status (SES). METHODS: A literature review was performed of clinical trials and retrospective studies in the U.S. that compared survival between white women and black women with breast carcinoma after adjustment for known prognostic factors (patient age, disease stage, lymph node status, and estrogen receptor status) to assess the impact of race and SES. RESULTS: Single institutional and clinical studies suggest that, when black patients are treated appropriately and other prognostic variables are controlled, their survival is similar to the survival of white patients. Twelve retrospective studies and 1 analysis of a clinical trial included SES and race as variables for survival. Only three of those studies revealed race as a significant prognostic factor for survival after adjusting for SES. CONCLUSIONS: SES replaces race as a predictor of worse outcome after women are diagnosed with breast carcinoma in many studies. However, black women present with more advanced disease that appear more aggressive biologically, and they present at a younger age compared with white women. Further research should be conducted concerning the precise elements of SES that account for the incidence of breast carcinoma, age at diagnosis, hormone receptor status, and survival to devise better strategies to improve outcome.