Radiofrequency ablation in the management of liver metastases from breast cancer.

OBJECTIVE: Systemic chemotherapy remains the standard treatment for patients with breast cancer hepatic metastases. Resection of metastases has survival advantages in a small percentage of selected patients. Radiofrequency ablation has been used in small numbers of selected patients. This small series was undertaken to review our experience with radiofrequency ablation in the management of patients with breast cancer hepatic metastases. CONCLUSION: Radiofrequency ablation of breast cancer hepatic metastases is safe and may be used to control hepatic deposits in patients with stable or no extrahepatic disease.

Cognitive behavioural therapy for tinnitus.

BACKGROUND: Tinnitus is an auditory perception that can be described as the experience of sound, in the ear or in the head, in the absence of external acoustic stimulation (not usually audible to anyone else). At present no specific therapy for tinnitus is acknowledged to be satisfactory in all patients. Cognitive behavioural therapy (CBT) uses relaxation, cognitive restructuring of the thoughts and exposure to exacerbating situations in order to promote habituation and may benefit tinnitus patients, as may the treatment of associated psychological conditions. OBJECTIVES: To assess whether cognitive behavioural therapy is effective in the management of patients suffering from tinnitus. SEARCH STRATEGY: Our search included the Cochrane ENT Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2006), MEDLINE and EMBASE. The last search date was June 2006. SELECTION CRITERIA: Randomised controlled trials in which patients with unilateral or bilateral tinnitus as main symptom received cognitive behavioural treatment. DATA COLLECTION AND ANALYSIS: One review author (PMD) assessed every report identified by the search strategy. The four review authors assessed the methodological quality, applied inclusion/exclusion criteria and extracted data. MAIN RESULTS: Six trials comprising 285 participants were included. 1. PRIMARY OUTCOME: subjective tinnitus loudness. CBT compared to a waiting list control group: we found no significant difference (Standardised Mean Difference (SMD) 0.06 (95% CI -0.25 to 0.37)). CBT compared to another intervention (Yoga, Education, Minimal Contact - Education and Education): we found no significant difference (SMD 0.1 (95% CI -0.22 to 0.42)).2. SECONDARY OUTCOMES: a) Depression. CBT compared to a waiting list control group: we found no significant difference in either group (SMD 0.29 (95%CI -0.04 to 0.63)). CBT compared to another intervention (Yoga, Education and Minimal Contact - Education): we found no significant difference (SMD 0.01 (95% CI -0.43 to 0.45)). b) Quality of life: CBT compared to a waiting list control group: we found a significant difference in favour of CBT versus the waiting list group (SMD 0.7 (95% CI 0.33 to 1.08)). CBT compared to another intervention (Education, Minimal Contact - Education and Education): we also found a significant difference between CBT and the other intervention control group (SMD 0.64 (95% CI 0.29 to 1.00)). There were no adverse/side effects reported in any trial. AUTHORS' CONCLUSIONS: We did not find a significant difference in the subjective loudness of tinnitus, or in the associated depression. However we found a significant improvement in the quality of life (decrease of global tinnitus severity) of the participants, thus suggesting that cognitive behavioural therapy has an effect on the qualitative aspects of tinnitus and contributes positively to the management of tinnitus.

Dose-dense therapy with weekly 1-hour paclitaxel infusions in the treatment of metastatic breast cancer.

PURPOSE: To evaluate the efficacy and toxicity of paclitaxel administered as a 1-hour infusion on weekly basis, without interruption, to patients with metastatic breast cancer who had received prior therapy. PATIENTS AND METHODS: Thirty patients with metastatic breast cancer received sustained weekly paclitaxel therapy at an initial dose of 100 mg/m2 until disease progression. Prior therapy included adjuvant only (n=17), metastatic only (n=7), or both (n=6). Eighteen patients had received prior anthracycline therapy, 12 of whom had demonstrated progression of disease within 12 months of it. All patients were assessable for efficacy; 29 patients were assessable for toxicity. Pharmacokinetic studies of paclitaxel were also performed. RESULTS: A total of 469 weekly paclitaxel infusions were administered to 30 patients (median, 14 infusions/patient). The median delivered dose-intensity was 91 mg/m2/wk (range, 80 to 108). The overall response rate was 53% (95% confidence interval [CI], 34% to 72%), with 10% complete responses (CRs) and 43% partial responses (PRs). Median response duration was 7.5 months (range, 2 to 11+). Responses were observed in nine of 18 (50%) patients with prior anthracycline therapy, including six of 12 (50%) with disease progression on anthracycline within 1 year (three of four within 6 months). Therapy was well tolerated and remarkable for a lack of overall and cumulative myelosuppression. Grade 3/4 neutropenia occurred in four patients; febrile neutropenia was not observed. Peripheral neuropathy prohibited dose escalation above 100 mg/m2, and grade 3 neuropathy was observed in two of 21 patients at < or = 100 mg/m2. CONCLUSION: Weekly paclitaxel therapy is active and well tolerated in patients with metastatic breast cancer. Weekly therapy should be considered as a current clinical option for these patients and should be incorporated into future comparative clinical trials.

5-year results of dose-intensive sequential adjuvant chemotherapy for women with high-risk node-positive breast cancer: A phase II study.

PURPOSE: We conducted a phase II pilot study of dose-intensive adjuvant chemotherapy with doxorubicin followed sequentially by high-dose cyclophosphamide to determine the safety and feasibility of this dose-dense treatment and to estimate the disease-free and overall survival in breast cancer patients with four or more involved axillary lymph nodes. PATIENTS AND METHODS: Seventy-three patients received adjuvant treatment with four cycles of doxorubicin 75 mg/m(2) as an intravenous bolus every 21 days, followed by three cycles of cyclophosphamide 3,000 mg/m(2) every 14 days with granulocyte colony-stimulating factor support. RESULTS: Seventy-one patients were assessable, and all but two completed all planned chemotherapy. There was no treatment-related mortality. The most common toxicity was neutropenic fever, which occurred in 39% of patients. Median disease-free survival is 66 months (95% confidence interval, 34 to 98 months), and median overall survival has not yet been reached. At 5 years of follow-up, the disease-free survival is 51.7%, and overall survival is 60.0%. There is no long-term treatment-related toxicity, and no cases of acute myelogenous leukemia or myelodysplastic syndrome have been observed. CONCLUSION: Our pilot study of doxorubicin followed by cyclophosphamide demonstrates the safety and feasibility of the sequential dose-dense plan. Long-term follow-up, although noncomparative, is promising. However, this regimen is associated with a higher incidence of toxicity (and also higher costs) than the standard dose and schedule of doxorubicin and cyclophosphamide, and therefore it should not be used as conventional therapy in the absence of demonstrated improvement of outcome. Randomized trials testing the dose-dense approach have been completed but not yet reported. Because the sequential plan can decrease overlapping toxicities, it is an appropriate platform for the addition of newer active agents, such as taxanes or monoclonal antibodies.

Weekly trastuzumab and paclitaxel therapy for metastatic breast cancer with analysis of efficacy by HER2 immunophenotype and gene amplification.

PURPOSE: This phase II study evaluated weekly trastuzumab and paclitaxel therapy in women with HER2-normal and HER2-overexpressing metastatic breast cancer. Efficacy was correlated with immunohistochemical and fluorescent in situ hybridization (FISH) assay results. PATIENTS AND METHODS: Eligible patients had bidimensionally measurable metastatic breast cancer. Up to three prior chemotherapy regimens, including prior anthracycline and taxane therapy, were allowed. Trastuzumab 4 mg/kg and paclitaxel 90 mg/m2 were administered on week 1, with trastuzumab 2 mg/kg and paclitaxel 90 mg/m2 administered on subsequent weeks. HER2 status was evaluated using four different immunohistochemical assays and FISH. RESULTS: Patients received a median of 25 weekly infusions (range, one to 85 infusions). Median delivered paclitaxel dose-intensity was 82 mg/m2/wk (range, 52 to 90 mg/m2/wk). The intent-to-treat response rate for all 95 patients enrolled was 56.8% (95% confidence interval, 47% to 67%). A response rate of 61.4% (4.5% complete response, 56.8% partial response) was observed in 88 fully assessable patients. In patients with HER2-overexpressing tumors, overall response rates ranged from 67% to 81% compared with 41% to 46% in patients with HER2-normal expression (ranges reflect the different assay methods used to assess HER2 status). Differences in response rates between patients with HER2-overexpressing tumors and those with normal HER2 expression were statistically significant for all assay methods, with CB11 and TAB250 antibodies and FISH having the strongest significance. Therapy was generally well tolerated, although three patients had serious cardiac complications. CONCLUSION: Weekly trastuzumab and paclitaxel therapy is active in women with metastatic breast cancer. Therapy was relatively well tolerated; however, attention to cardiac function is necessary.

First cluster of vancomycin-resistant Enterococcus faecalis isolates in Cyprus.

This report describes the first patient in Cyprus to be infected with a vancomycin-resistant enterococcus, as well as the microbiological characteristics of a cluster of vancomycin-resistant enterococcus isolates from the intensive care unit where the index case was hospitalised. All isolates were identified as Enterococcus faecalis, belonged to the same clone, and contained the vanA gene cluster. Transfer of glycopeptide resistance to a susceptible strain of E. faecalis could not be detected.

Phase I study of escalating doses of edatrexate in combination with paclitaxel in patients with metastatic breast cancer.

Motivated by the observation of preclinical synergy, a Phase I dose escalation study of edatrexate in combination with a 3-h paclitaxel infusion was performed in patients with advanced breast cancer to determine the maximum tolerated dose (MTD) of edatrexate and the toxicities associated with this combination and to report preliminary observations of efficacy with this novel combination. Thirty-six patients were enrolled in this Phase I trial. Thirty-five eligible patients were treated every 21 days in cohorts of at least three patients and were assessable for toxicity. One patient was ineligible due to hyperbilirubinemia. Stepwise dose escalations of edatrexate were administered until grade >3 nonhematological dose-limiting toxicities were reported. The initial dose level of edatrexate was 180 mg/m2; subsequent cohorts were treated with escalating doses of edatrexate (210, 240, 270, 300, 350, and 400 mg/m2). Edatrexate was administered by i.v. infusion over 1 h. Paclitaxel was administered 24 h later at a fixed dose of 175 mg/m2 as a 3-h infusion with standard dexamethasone, diphenhydramine, and cimetidine premedication. The MTD of edatrexate was reached at the 350 mg/m2 level in this study. Grade 3 diarrhea was seen in one patient at the 300 and 400 mg/m2 dose levels, requiring dose reductions. Two patients experienced grade 4 stomatitis at the 400 mg/m2 dose level and also required dose reduction, establishing the MTD as 350 mg/m2. Grade 3 nausea and vomiting were noted in two of three patients at the highest dose level. Of 35 patients, 4 patients reported grade 3 myalgias and 1 patient reported grade 3 neurosensory complaints, which were seen mostly at the 350 and 400 mg/m2 dose levels; however, 1 patient reported grade 3 myalgias at 180 mg/m2. No cumulative neurotoxicity was observed, and no patient experienced an allergic reaction to paclitaxel. In 23 patients with bidimensionally measurable disease, there were four complete (17%) and seven partial responses, with an overall response rate of 48% (95% confidence interval, 27-69%). All of the responses were seen in patients who had not received prior chemotherapy for stage IV disease. The median duration of response was not assessable because many responding patients went on to receive high-dose chemotherapy treatment with stem cell support. The combination of edatrexate and paclitaxel for treatment of metastatic breast cancer is a feasible and safe regimen. The MTD of edatrexate was 350 mg/m2 when combined with a 3-h infusion of paclitaxel (175 mg/m2) given 24 h later. Activity was noted even among patients who had relapsed shortly after receiving methotrexate- and/or doxorubicin-containing adjuvant regimens. Additional studies evaluating the sequences and dosing schema for this combination are warranted to improve the response proportion and define the duration of the response.

Doxorubicin followed by sequential paclitaxel and cyclophosphamide versus concurrent paclitaxel and cyclophosphamide: 5-year results of a phase II randomized trial of adjuvant dose-dense chemotherapy for women with node-positive breast carcinoma.

PURPOSE: We conducted a randomized Phase II trial to directly compare toxicity, feasibility, and delivered dose intensities of two adjuvant dose-intensive regimens containing doxorubicin, paclitaxel, and cyclophosphamide for patients with node-positive breast carcinoma. EXPERIMENTAL DESIGN: Forty-two patients with resected breast carcinoma involving one or more ipsilateral axillary lymph nodes, were randomized to receive two different schedules of adjuvant chemotherapy using 14-day dosing intervals: either (a) three cycles of doxorubicin 80 mg/m(2) as i.v. bolus followed sequentially by three cycles of paclitaxel 200 mg/m(2) as a 24-h infusion and then by three cycles of cyclophosphamide 3.0 g/m(2) as a 1-h infusion (arm A); or (b) the same schedule of doxorubicin followed by three cycles of concurrent cyclophosphamide and paclitaxel at the same doses (arm B). All cycles were supported by granulocyte colony-stimulating factor administration. RESULTS: Forty-one patients were assessable for toxicity and feasibility; 37 (90%) completed all planned chemotherapy. There was no treatment-related mortality; however, increased toxicity was observed on arm B compared with arm A, manifested by an increase in hospitalization for toxicity, mainly neutropenic fever, and an increased incidence of transfusion of packed RBCs transfusions for anemia. The mean delivered dose intensities for paclitaxel and cyclophosphamide were significantly greater for arm A compared with arm B (P =.01 and P =.05, respectively). There is no long-term, treatment-related toxicity, and no cases of acute myelogenous leukemia or myelodysplastic syndrome have been observed. CONCLUSIONS: Dose-dense sequential single-agent chemotherapy is more feasible than doxorubicin with subsequent concurrent paclitaxel and cyclophosphamide.

Dose-dense therapy with paclitaxel via weekly 1-hour infusion: preliminary experience in the treatment of metastatic breast cancer.

In an ongoing effort to establish the most appropriate dose and administration schedule for paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), the feasibility and safety of weekly 1-hour infusions were evaluated in 16 women with metastatic breast cancer previously treated with at least one chemotherapy regimen. Paclitaxel was administered on an outpatient basis at a starting dose of 100 mg/m2/wk for 4 consecutive weeks, with 4-week cycles continued until disease progression or the onset of intolerable toxicity. With 215 weekly infusions administered so far (median, 13 per patient), no episodes of febrile neutropenia have occurred, and no hematopoietic growth factors have been used. Plans for dose escalation were abandoned after grade 3 sensorimotor neuropathy developed in five of nine patients treated at paclitaxel 110 to 120 mg/m2. With dose escalation eliminated, further severe neurotoxicities were rare, but some degree of cumulative peripheral neuropathy was noted in all but three patients. No acute hypersensitivity reactions were noted. To date, six of 15 evaluable patients have achieved a major response to therapy, with one complete response and five partial responses. Four other patients had a minor response to therapy, one patient had an early death due to autopsy-proven extensive pulmonary microvascular carcinomatosis, and five patients have stable disease. Although the potential neurotoxicity of this regimen merits attention, the overall profile of a high therapeutic index, manageable toxicity, and convenient administration schedule makes this an attractive treatment alternative for patients with metastatic breast cancer.

Sequential adjuvant therapy: the Memorial Sloan-Kettering Cancer Center experience.

Adjuvant chemotherapy has a real but modest impact on the disease-free and overall survival of patients with breast cancer. Recent attempts to improve its effectiveness have focused on dose intensity and new agents. Sequential therapy maximized dose intensity while limiting overlapping toxicity. Sequential therapy using doxorubicin followed by cyclophosphamide/methotrexate/5-fluorouracil (CMF) has been found superior in patients with high-risk resectable breast cancer. The novel chemotherapy agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is now known to be highly active in advanced breast cancer and appears to be clinically non-cross-resistant with doxorubicin. Therefore, this drug is being studied as a component of the next generation of adjuvant chemotherapy regimens. The most appropriate way to incorporate paclitaxel has not yet been defined, but its concurrent administration with other agents has, in some cases, been troublesome. Based on the demonstrated advantage of the sequential plan for doxorubicin and CMF, we conducted a series of pilot trials testing sequential high-dose therapy. Initially, we studied multiple cycles of doxorubicin followed by cyclophosphamide; we later added paclitaxel to this regimen. These phase II studies demonstrate the feasibility of sequential therapy with doxorubicin, paclitaxel, and cyclophosphamide, and early disease-free survival results are promising. Cooperative group projects are under way or planned to further define the activity of these regimens.

Long-standing reaction to a hemi-silastic implant.

The complications associated with the hemi-silicone implants of the foot have been well documented. Reasons for their failure are many. In the past, there has been an overuse of these devices without strict adherence to their proper indications. Today, these implant failures are being manifested by extremely unusual pathology. Although silicone has not been shown to be carcinogenic, the florid reaction seen in this case demonstrated a degree of "malignancy" that may have incapacitated the patient.

Screening for anxiety and depression in women with breast cancer. Psychiatry and medical oncology gear up for managed care.

In this study, 275 women with breast cancer attending ambulatory breast cancer clinics in two sites were evaluated for psychological distress by using three self-report instruments: a visual analogue scale for psychological distress, the Hospital Anxiety and Depression Scale, and the Brief Symptom Inventory. Results suggest that significant psychological distress exists in ambulatory women with breast cancer; all three instruments effectively measured that level of distress. Implications for the use of these instruments in educating oncological staff members, documenting need for psychiatric services in a period of capitation, and providing quality assurance evaluations of psychiatric services are discussed.