Trust in physician in relation to blame, regret, and depressive symptoms among women with a breast cancer experience.

Following a diagnosis of breast cancer women experience considerable distress and often present with elevated symptoms of depression. A woman's relationship with her oncologist, and particularly trust in the physician, might influence depressive symptoms, as well as emotional and cognitive reactions to medical decisions made concerning treatment. To assess these relationships, women currently undergoing treatment for breast cancer (n = 40) and women who had previously been treated for breast cancer (n = 74) were asked about (1) trust in their physician, (2) who they blamed for negative events during treatment, (3) who made the treatment decisions, (4) regret, and (5) depressive symptoms. As well, community participants (n = 146) without breast cancer were asked about trust in their physician, levels of depression, and questions regarding blame if they hypothetically had breast cancer. Depression was greatest among women in treatment, and trust in physician was greatest among women posttreatment. However, trust in physician was neither related to depressive symptoms, decision making, nor responsibility for presence of metastases/relapse. Paradoxically, greater trust in physician was related to increased blame of the doctor for other negative events that had occurred. Furthermore, depressive scores were higher among women who blamed their doctor for negative events in comparison to women who ascribed blame to no one. As well, individuals who blamed themselves for negative events reported greater regret than individuals who blamed no one. Thus, though a woman may not hold her physician directly responsible for health outcomes, this relationship may be important to consider in other aspects of her psychological well-being.

A Phase II Study of Flavopiridol in Patients With Previously Untreated Advanced Soft Tissue Sarcoma.

Purpose. Flavopiridol is a potent cyclin-dependent kinase (CDK) inhibitor that has preclinical activity in many tumours. This synthetic flavonoid was tested in a phase II nonrandomized, nonblinded multicentre clinical trial to determine its activity and toxicity in patients with previously untreated metastatic or locally advanced soft tissue sarcoma. Methods. A total of 18 patients with histologically confirmed nonoperable soft tissue was treated with flavopiridol administered at a dose of 50 mg/m(2) IV over 1 hour daily x3 days every 3 weeks. Results. Eighteen patients were accrued to the study over a period of 6 months. No objective responses were noted in the seventeen evaluable patients. Eight patients (47%) exhibited stable disease after 2 cycles (median duration of 4.3 months (range 1.4-6.9 months). Kaplan-Meier estimates for 3- and 6-month progression-free survivial rates were 44 percent and 22 percent, respectively. The only grade 3 toxicities were diarrhea (N = 2), nausea (N = 2), gastritis (N = 1), and fatigue (N = 1). Ninety-four percent of patients received >/= 90% of the planned dose intensity, during 55 treatment cycles. Conclusions. Flavopiridol was well tolerated at the dose and schedule used in this study, however, no objective treatment responses were seen and thus our results do not support further exploration of flavopiridol as a monotherapy at this dose and schedule in soft tissue sarcomas.

Maximizing clinical benefit with trastuzumab.

To optimize patient management in breast cancer a number of factors are considered, including hormone receptor and HER2 status. A feasible approach for women with less aggressive, estrogen receptor/HER2-positive metastatic breast cancer is to consider trastuzumab (Herceptin; F. Hoffmann-La Roche, Basel, Switzerland) combined with endocrine therapy. Randomized clinical trials are ongoing to assess the combination of trastuzumab with aromatase inhibitors. In patients with aggressive HER2-positive metastatic breast cancer, trastuzumab/chemotherapy combination regimens are warranted. When administered first line in combination with a taxane, trastuzumab improves all clinical outcome parameters, including survival, in such patients. Trastuzumab adds little to the toxicity profile of taxanes, and trastuzumab combination therapy is associated with improvements in quality of life when compared with chemotherapy alone. There is encouraging evidence of improved efficacy when trastuzumab is combined with other cytotoxic agents with proven single-agent activity in breast cancer, including capecitabine (Xeloda; F. Hoffmann-La Roche), gemcitabine, and vinorelbine. Trastuzumab is also being investigated as part of triplet drug regimens. Trastuzumab has good single-agent activity in first-line therapy. This is of relevance to women with HER2-positive disease who are not suitable for, or do not wish to receive, cytotoxic chemotherapy. The benefits noted with trastuzumab-containing regimens were documented in clinical trials where trastuzumab was given until disease progression. A further rationale exists to continue trastuzumab beyond progression. Data from retrospective reviews indicate that this strategy is feasible.

Pharmacokinetics, safety, and efficacy of trastuzumab administered every three weeks in combination with paclitaxel.

PURPOSE: This phase II study evaluated the pharmacokinetics and safety of trastuzumab and paclitaxel given every 3 weeks to women with human epidermal growth factor receptor 2 (HER2)-overexpressing metastatic breast cancer. PATIENTS AND METHODS: Thirty-two patients received a loading dose of trastuzumab 8 mg/kg intravenously (day 1) and paclitaxel 175 mg/m2 (day 0). Thereafter, trastuzumab 6 mg/kg was administered on the same day as paclitaxel 175 mg/m2 every 3 weeks for seven cycles. In responding patients, trastuzumab monotherapy every 3 weeks was then continued until disease progression or patient withdrawal. RESULTS: Trastuzumab trough levels were more than 20 mug/mL by the end of cycle 1. The half-life of trastuzumab was estimated to be 18 to 27 days, although this may be an underestimate. The combination of paclitaxel and trastuzumab was generally well tolerated, with no unexpected toxicities and no pharmacokinetic interaction. The most common adverse events were myalgia, paresthesias, alopecia, arthralgia, and fatigue. Events associated with trastuzumab included infusion-related reactions and cardiac dysfunction. Ten patients had a > or = 15% decrease in ejection fraction, but only one had symptomatic heart failure. The investigator-assessed objective response rate was 59% (four complete and 15 partial responses) and seven patients (22%) had stable disease. The median duration of response was 10.5 months and median time to progression was 12.2 months. CONCLUSION: Additional investigation of trastuzumab administered every 3 weeks is warranted. In combination with paclitaxel, it is generally well tolerated. Plasma trastuzumab trough levels and clinical response rates compare favorably with those achieved with the standard weekly trastuzumab regimen plus chemotherapy. The presence of trastuzumab does not alter exposure to paclitaxel.