Faculty Bibliography

We examined the proposition that individuals with major depression make predictions about future events relatively automatically and pessimistically, reflecting use of ct future-event schema, white they also ruminate about the future. Depressed participants and nondepressed controls indicated whether or not various positive and negative future events would happen to them or to an average other-either under a concurrent attentional load or no such load-while their response latencies were assessed As hypothesized, depressives showed relatively greater automaticity in their predictions than did nondepressives, and a lack of optimism as well. More specifically, depressives showed a smaller increase in response latency due to the introduction of the attentional load than did nondepressives, suggesting relatively greater processing efficiency, and they also predicted reliably fewer positive events. Indeed, depressives also reported ruminating more about the future based on a recent distressing life event. Overall, the results extend research on future-event schemas and automaticity (Andersen, Spielman, & Bargh, 1992) from moderate to major depression and establish a link with future-event rumination.

PURPOSE: We evaluated the independent response rate of dexamethasone before docetaxel and estramustine administration as measured by changes in serum prostate specific antigen (PSA) in patients with androgen independent prostate cancer. MATERIALS AND METHODS: A total of 12 patients received 20 mg. dexamethasone orally every 6 hours for 3 doses repeated every 3 weeks before starting cytotoxic therapy with estramustine and docetaxel. After progression on dexamethasone 280 mg. estramustine orally 3 times daily on days 1 to 5 and 70 mg./m.2 docetaxel intravenously for 1 hour on day 2 were given. RESULTS: None of the patients initially treated with dexamethasone monotherapy (median 1 cycle, range 1 to 5) had a PSA decline of 50% or greater. Median PSA increase on monotherapy was 47% (range 0% to 22%). On estramustine and docetaxel therapy PSA decreased 50% or greater in 11 patients (92%, 95% confidence intervals [CI] 60 to 99) and 80% or greater in 7 (58%, 95% CI 29 to 84), and normalized in 5 (42%, 95% CI 16 to 71), with a median duration of response of 153 (range 42 to 371), 132 (range 84 to 287) and 84 (range 21 to 174) days, respectively. Median times to reach 50% and 80% decreases in baseline PSA were 21 (range 21 to 209) and 63 (range 21 to 138) days, respectively. In 9 patients (75%, 95% CI 43 to 93) PSA decreased at least 50% by week 9. Of 4 patients with bidimensionally measurable disease 3 had a partial response. Median time to progression was 263 days (range 91 to 378). CONCLUSIONS: Administration of 20. mg. dexamethasone orally every 6 hours for 3 doses every 3 weeks does not significantly contribute to the PSA response rate of estramustine and docetaxel.

Evaluation of the combined regimen of estramustine and docetaxel (Taxotere; Rhone-Poulenc Rorer, Collegeville, PA) in men with hormone-refractory prostate cancer is in its early stages. While this combination is promising in terms of efficacy, adverse events associated with estramustine are a concern. Estramustine has been associated with side effects such as nausea, vomiting, edema, and serious vascular events. Reported here are the results of phase I and phase II trials in which 280 mg estramustine was given three times daily on days I to 5 in 21-day treatment cycles with docetaxel at varying doses. Data from patients evaluable thus far support the efficacy of this combination, both in chemotherapeutically naive patients and in those who have had prior therapy. A survival benefit from this combination appears achievable from these early studies. As significant antitumor activity can be achieved with docetaxel alone, future studies need to define the minimal dose of estramustine for this combination.

Poor insight is a prevalent and clinically significant feature of schizophrenia, but its etiology is still poorly understood. Converging evidence from the literatures on poor insight and on emotional deficits in patients with schizophrenia suggests that emotional factors may play an important role in patients' level of insight, although this idea has not yet been tested empirically. The subjective experience of emotion appears to be particularly relevant to this question, in that both insight and emotional feeling concern subjective phenomena. The main goal of the present study was to examine the relationship between poor insight and diminished emotional experience. We also examined the neuropsychological (frontal, right hemisphere/right parietal, IQ) and clinical correlates (depression, the deficit syndrome, course of illness) of deficits in both insight and subjective emotional experience. The study used a sample of 78 patients with schizophrenia and schizoaffective disorder who were voluntarily admitted inpatients on a research unit. Our results indicate that diminished emotional experience is broadly related to several dimensions of poor insight, including lack of awareness, misattribution, and emotional indifference about the illness. These relationships vary both as a function of the dimension of emotion being assessed and of diagnosis. We replicate previous findings that poor insight is related to frontal lobe dysfunction and extend this work by demonstrating that such impairments are also related to diminished emotional experience. In addition, both poor insight and diminished emotional experience are more strongly associated with impaired verbal/comprehensive skills, as opposed to a general intellectual decline. Our data do not support the idea that poor insight and diminished emotional experience are associated with right hemisphere/right parietal impairment. We also replicate previous findings that poor insight is related to decreased depression, the deficit syndrome, and a poorer course of illness. Diminished emotional experience, however, is not significantly associated with either depression or the deficit syndrome. The research and clinical implications of these findings are discussed.

PURPOSE: To evaluate the toxicity, efficacy, and pharmacokinetics of docetaxel when combined with oral estramustine and dexamethasone in a phase I study in patients with progressive metastatic androgen-independent prostate cancer. PATIENTS AND METHODS: Thirty-four men were stratified into minimally pretreated (MPT) and extensively pretreated (EPT) groups. Estramustine 280 mg PO tid was administered 1 hour before or 2 hours after meals on days 1 through 5, with escalated doses of docetaxel from 40 to 80 mg/m2 on day 2. Treatment was repeated every 21 days. RESULTS: Thirty-four patients were assessable for toxicity and 33 for response. In the MPT patients, dose-limiting myelosuppression was reached at 80 mg/m2, with six patients experiencing grade 3/4 granulocytopenia. In EPT patients, escalation above 70 mg/m2 was not attempted. Fourteen MPT (70%) and six EPT (50%) patients had a > or = 50% decline in serum PSA on two consecutive measurements taken at least 2 weeks apart. The overall 50% PSA response rate was 63% (95% confidence interval [CI], 28% to 81%). Of the 18 patients with bidimensionally measurable disease, five (28%; 95% CI, 11% to 54%) achieved a partial response. At the time of entry onto the study, 15 patients required narcotic analgesics for bone pain; after treatment, eight (53%) discontinued their pain medications. The area under the curve for docetaxel increased linearly from 40 to 70 mg/m2. At 80 mg/m2, the measured area under the curve was 8.37 (standard deviation, 0.724), which was significantly higher than the previously reported values. CONCLUSION: The recommended phase II dose of docetaxel combined with estramustine is 70 mg/m2 in MPT patients and 60 mg/m2 in EPT patients. This combination is active in men with androgen-independent prostate cancer.