PubMed Health⌕ Search

Biomedical subjects

Robert Coleman

Publications and source records attributed to Robert Coleman.

At least 19 recordsLinked to original sources
PubMed2007

2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial.

BACKGROUND: Trastuzumab--a humanised monoclonal antibody against HER2--has been shown to improve disease-free survival after chemotherapy in women with HER2-positive early breast cancer. We investigated the drug's effect on overall survival after a median follow-up of 2 years in the Herceptin Adjuvant (HERA) study. METHODS: HERA is an international multicentre randomised trial that compared 1 or 2 years of trastuzumab treatment with observation alone after standard neoadjuvant or adjuvant chemotherapy in women with HER2-positive node positive or high-risk node negative breast cancer. 5102 women participated in the trial; we analysed data from 1703 women who had been randomised for treatment with trastuzumab for 1 year and 1698 women from the control group, with median follow-up of 23.5 months (range 0-48 months). The primary endpoint of the trial was disease-free survival. Here, we assess overall survival, a secondary endpoint. Analyses were done on an intent-to-treat basis. This trial is registered with the European Clinical Trials Database, number 2005-002385-11. FINDINGS: 97 (5.7%) patients randomised to observation alone and 58 (3.4%) patients randomised to 1 year of treatment with trastuzumab were lost to follow-up. 172 women stopped trastuzumab prematurely. 59 deaths were reported for trastuzumab and 90 in the control group. The unadjusted hazard ratio (HR) for the risk of death with trastuzumab compared with observation alone was 0.66 (95% CI 0.47-0.91; p=0.0115). 218 disease-free survival events were reported with trastuzumab compared with 321 in the control group. The unadjusted HR for the risk of an event with trastuzumab compared with observation alone was 0.64 (0.54-0.76; p<0.0001). INTERPRETATION: Our results show that 1 year of treatment with trastuzumab after adjuvant chemotherapy has a significant overall survival benefit after a median follow-up of 2 years. The emergence of this benefit after only 2 years reinforces the importance of trastuzumab in the treatment of women with HER2-positive early breast cancer.

Adult↗
PubMed2006

Postoperative adjuvant chemotherapy followed by adjuvant tamoxifen versus nil for patients with operable breast cancer: a randomised phase III trial of the European Organisation for Research and Treatment of Cancer Breast Group.

BACKGROUND: The contribution of adjuvant tamoxifen in breast cancer patients after receiving adjuvant chemotherapy is not fully established. We investigated the impact of tamoxifen, given sequentially after completion of adjuvant chemotherapy in patients with operable breast cancer. PATIENTS AND METHODS: Between March 1991 and June 1999, 1863 women with stages I-IIIA operable breast cancer who had undergone surgery and completed six cycles of adjuvant combination chemotherapy with either CMF, CAF, CEF, FAC or FEC were randomised to receive either tamoxifen 20 mg daily for 3 years or no further treatment. Irrespective of menstrual status and hormone receptor content of the primary tumour, patients were stratified by institute, chemotherapy scheme and age (above 50 years or younger). The main end-point was to detect a 5% increase in the 5 year survival (from 80% to 85%) in favour of antioestrogen therapy. Secondary end-points were relapse free survival (RFS), local control, incidence of second primary breast cancer and correlation of results with hormone receptor content. RESULTS: After exclusion of all patients from three sites because of inadequate documentation, a total of 1724 patients (93%) were analysed (Tam 861 and Control 863). At a median follow-up of 6.5 years, 5-year RFS on tamoxifen was 73% versus 67% in controls (p=0.035). No difference was seen in overall survival. The benefit of tamoxifen therapy was mainly seen in the subgroup of patients with histologically documented positive axillary nodes (5-year RFS on tamoxifen 71% versus 64% in the control group, p=0.044) and in patients with tumours expressing the ER and PR positive phenotype (5-year RFS on tamoxifen 77% versus 70% in the control group, p=0.014). CONCLUSIONS: Tamoxifen administered for 3 years after completion of adjuvant chemotherapy in this otherwise unselected group of patients for endocrine sensitivity had a limited impact on relapse and had no detectable effect on overall survival. The beneficial effect of tamoxifen is mainly confined to the subgroup of patients with node-positive disease and to patients with tumours expressing the ER and PR positive phenotype.

Adult↗
PubMed2006

A joined analysis of two European Organization for the Research and Treatment of Cancer (EORTC) studies to evaluate the role of pegylated liposomal doxorubicin (Caelyx) in the treatment of elderly patients with metastatic breast cancer.

We have performed a retrospective analysis to evaluate the impact of age, using a 70 year cutoff, on the safety and efficacy of pegylated liposomal doxorubicin (Caelyx) given at 60 mg/m(2) every 6 weeks (treatment A) or 50 mg/m(2) every 4 weeks (treatment B) to 136 metastatic breast cancer patients in two EORTC trials, of whom 65 were 70 years of age or older. No difference in terms of toxicity was observed between younger and older patients treated with the 4-week schedule, while a higher incidence of hematological toxicity, anorexia, asthenia, and stomatitis was observed in older patients when the 6-week schedule was used. Antitumor activity was not affected by age. In the older cohort of patients, no dependence was found between the incidence of grade 3-4 toxicity or antitumor activity and patients' baseline performance status, number and severity of comorbidities, or number of concomitant medications. The higher therapeutic index of Caelyx 50 mg/m(2) every 4 weeks makes it, of the two dose schedules investigated, the preferred regimen in the elderly.

Adult↗
PubMed2006

Markers of bone metabolism and survival in men with hormone-refractory metastatic prostate cancer.

PURPOSE: To evaluate the relative prognostic value for specific markers of osteoblast and osteoclast activity while controlling for previously reported prognostic variables among men with hormone-refractory metastatic prostate cancer. EXPERIMENTAL DESIGN: The 643 subjects in this report were participants in multicenter randomized controlled trial of zoledronic acid in men with metastatic prostate cancer. All subjects had bone metastases and disease progression despite medical or surgical castration. Relationships between baseline covariates and overall survival were examined by Cox proportional hazard model. Serum bone-specific alkaline phosphatase (BAP) and urinary N-telopeptide were assessed as representative specific markers of osteoblast and osteoclast activity, respectively. Other covariates in the model were age, log prostate-specific antigen, hemoglobin, lactate dehydrogenase, albumin, analgesic use, and Eastern Cooperative Oncology Group performance status. RESULTS: Serum BAP was significantly correlated with urinary N-telopeptide (correlation coefficient = 0.674; 95% confidence interval, 0.628-0.715; P < 0.0001). In univariate analyses, higher levels of serum BAP and urinary N-telopeptide levels were significantly associated with shorter overall survival. After controlling for the other variables, including N-telopeptide, in multivariate models, higher serum BAP levels were consistently associated with shorter survival. In contrast, urinary N-telopeptide levels were not significantly associated with survival in multivariate analyses. Variables retained in the reduced multivariate model were age, log prostate-specific antigen, hemoglobin, lactate dehydrogenase, analgesic use, and BAP. CONCLUSIONS: Serum BAP significantly correlates with urinary N-telopeptide in men with androgen-independent prostate cancer and bone metastases. In multivariate models, higher levels of serum BAP but not urinary N-telopeptide are associated with shorter overall survival.

Aged↗
PubMed2006

Study protocol to investigate the effect of a lifestyle intervention on body weight, psychological health status and risk factors associated with disease recurrence in women recovering from breast cancer treatment [ISRCTN08045231].

BACKGROUND: Breast cancer survivors often encounter physiological and psychological problems related to their diagnosis and treatment that can influence long-term prognosis. The aim of this research is to investigate the effects of a lifestyle intervention on body weight and psychological well-being in women recovering from breast cancer treatment, and to determine the relationship between changes in these variables and biomarkers associated with disease recurrence and survival. METHODS/DESIGN: Following ethical approval, a total of 100 patients will be randomly assigned to a lifestyle intervention (incorporating dietary energy restriction in conjunction with aerobic exercise training) or normal care control group. Patients randomised to the dietary and exercise intervention will be given individualised healthy eating dietary advice and written information and attend moderate intensity aerobic exercise sessions on three to five days per week for a period of 24 weeks. The aim of this strategy is to induce a steady weight loss of up to 0.5 Kg each week. In addition, the overall quality of the diet will be examined with a view to (i) reducing the dietary intake of fat to approximately 25% of the total calories, (ii) eating at least 5 portions of fruit and vegetables a day, (iii) increasing the intake of fibre and reducing refined carbohydrates, and (iv) taking moderate amounts of alcohol. Outcome measures will include body weight and body composition, psychological health status (stress and depression), cardiorespiratory fitness and quality of life. In addition, biomarkers associated with disease recurrence, including stress hormones, estrogen status, inflammatory markers and indices of innate and adaptive immune function will be monitored. DISCUSSION: This research will provide valuable information on the effectiveness of a practical, easily implemented lifestyle intervention for evoking positive effects on body weight and psychological well-being, two important factors that can influence long-term prognosis in breast cancer survivors. However, the added value of the study is that it will also evaluate the effects of the lifestyle intervention on a range of biomarkers associated with disease recurrence and survival. Considered together, the results should improve our understanding of the potential role that lifestyle-modifiable factors could play in saving or prolonging lives.

Aged↗
PubMed2006

Combined arteriovenous fistula and venous aneurysm following knee arthrodesis.

We study a case of a 65-year-old woman who developed popliteal arteriovenous fistula (AVF) and venous aneurysm following left knee arthrodesis. Presenting features included left popliteal and calf pain, a tender pulsatile mass posterior to her left knee, popliteal bruit and a thrill at the popliteal fossa and ankle. Left femoral angiography showed an AVF arising from the right tibioperoneal trunk and an aneurysm at the level of the AVF. Findings at open investigation included AVF between the tibioperoneal trunk and the popliteal vein, and a venous aneurysm arising from the popliteal vein opposite the neck of the arteriovenous communication. The aneurysm and fistula were repaired using prolene suture.

Aged↗
PubMed2005

Placental site trophoblastic tumour: clinical features and management.

OBJECTIVE: To describe the clinical features, treatment and outcome of all consecutive patients with placental site trophoblastic tumour (PSTT) treated at the Sheffield Trophoblast Centre and to compare these findings to other reports. METHOD: All cases of PSTT on the Sheffield Trophoblastic Tumour Centre database from 1984 to 2004 were reviewed. Data obtained included age at diagnosis, antecedent pregnancy (AP), interval from antecedent pregnancy until diagnosis, presenting features, presenting serum human chorionic gonadotrophin hormone (hCG) level, number and sites of metastases, treatment received, outcome and follow-up. RESULTS: Seventeen patients with PSTT were identified from the database which incorporates a total of 7489 cases of trophoblastic disease. Fourteen (70.6%) were more than 30 years old at presentation; 5 were over 40. The median interval from pregnancy to diagnosis was 18 months (range 6 months to 22 years). The outcome of antecedent pregnancy was a female in 11 out of the 13 patients where the sex was known. Eleven (70.6%) of patients presented with irregular vaginal bleeding, with or without a preceding period of amenorrhoea. All 8 patients with non-metastatic (Stage I) disease were alive and well after hysterectomy (6), chemotherapy alone (1) or hysterectomy and chemotherapy (1) whereas only 4 of 9 patients with metastatic (Stage III/IV) disease were alive and well after treatment with chemotherapy and hysterectomy. CONCLUSION: PSTT is rare and accounts for 0.23% cases of gestational trophoblastic disease referred to this centre. It has a variety of presenting features and its course is unpredictable. Metastatic involvement and antecedent pregnancy interval greater than 4 years are poor prognostic factors. Hysterectomy is the primary mode of treatment in the majority of cases. However, chemotherapy can still play a major role when curative surgery is not feasible.

Adult↗
PubMed2005

Adjuvant docetaxel for node-positive breast cancer.

BACKGROUND: We compared docetaxel plus doxorubicin and cyclophosphamide (TAC) with fluorouracil plus doxorubicin and cyclophosphamide (FAC) as adjuvant chemotherapy for operable node-positive breast cancer. METHODS: We randomly assigned 1491 women with axillary node-positive breast cancer to six cycles of treatment with either TAC or FAC as adjuvant chemotherapy after surgery. The primary end point was disease-free survival. RESULTS: At a median follow-up of 55 months, the estimated rates of disease-free survival at five years were 75 percent among the 745 patients randomly assigned to receive TAC and 68 percent among the 746 randomly assigned to receive FAC, representing a 28 percent reduction in the risk of relapse (P=0.001) in the TAC group. The estimated rates of overall survival at five years were 87 percent and 81 percent, respectively. Treatment with TAC resulted in a 30 percent reduction in the risk of death (P=0.008). The incidence of grade 3 or 4 neutropenia was 65.5 percent in the TAC group and 49.3 percent in the FAC group (P<0.001); rates of febrile neutropenia were 24.7 percent and 2.5 percent, respectively (P<0.001). Grade 3 or 4 infections occurred in 3.9 percent of the patients who received TAC and 2.2 percent of those who received FAC (P=0.05); no deaths occurred as a result of infection. Two patients in each group died during treatment. Congestive heart failure and acute myeloid leukemia occurred in less than 2 percent of the patients in each group. Quality-of-life scores decreased during chemotherapy but returned to baseline levels after treatment. CONCLUSIONS: Adjuvant chemotherapy with TAC, as compared with FAC, significantly improves the rates of disease-free and overall survival among women with operable node-positive breast cancer.

Adult↗
PubMed2005

Randomized trial of two intravenous schedules of the topoisomerase I inhibitor liposomal lurtotecan in women with relapsed epithelial ovarian cancer: a trial of the national cancer institute of Canada clinical trials group.

PURPOSE: Liposomal lurtotecan (OSI-211) is a liposomal formulation of the water-soluble topoisomerase I inhibitor lurtotecan (GI147211), which demonstrated superior levels of activity compared with topotecan in preclinical models. We studied two schedules of OSI-211 in a randomized design in relapsed ovarian cancer to identify the more promising of the two schedules for further study. PATIENTS AND METHODS: Eligible patients had measurable epithelial ovarian, fallopian, or primary peritoneal cancer that was recurrent after one or two prior regimens of chemotherapy. Patients were randomly assigned to receive either arm A (OSI-211 1.8 mg/m(2)/d administered by 30-minute intravenous infusion on days 1, 2, and 3 every 3 weeks) or arm B (OSI-211 2.4 mg/m(2)/d administered by 30-minute intravenous infusion on days 1 and 8 every 3 weeks). The primary outcome measure was objective response, which was confirmed by independent radiologic review, and a pick the winner statistical design was used to identify the schedule most likely to be superior. RESULTS: Eighty-one patients were randomized between October 2000 and September 2001. The hematologic toxic effects were greater on arm A than on arm B (grade 4 neutropenia, 51% v 22%, respectively), as was febrile neutropenia (26% v 2.4%, respectively). Of the 80 eligible patients, eight patients (10%) had objective responses; six responders (15.4%; 95% CI, 6% to 30%) were in arm A and two responders (4.9%; 95% CI, 1% to 17%) were in arm B. CONCLUSION: The OSI-211 daily for 3 days intravenous schedule met the statistical criteria to be declared the winner in terms of objective response. This schedule was also associated with more myelosuppression than the schedule of OSI-211 administered in arm B.

Adult↗
PubMed2005

The causes and treatment of bone loss associated with carcinoma of the breast.

Despite an increasing incidence, the outlook for women with early breast cancer has improved considerably over recent years with a steady fall in the death rate in most western countries. This is due, at least in part, to the widespread use of adjuvant systemic therapy. However, some of these treatments have adverse effects on bone metabolism with increased bone loss which may result in osteoporosis and associated fractures. Most of the effects on bone are mediated by endocrine changes, either induction of an early menopause by chemotherapy and ovarian ablation, or further suppression of postmenopausal circulating oestrogens by aromatase inhibitors. There may also be direct effects of chemotherapy on bone cell function. The pathophysiology of osteoporosis in breast cancer patients, the methods of assessment and treatment options are reviewed. Bone health is a highly topical issue in breast cancer with the emergence of data supporting the use of several years of treatment with aromatase inhibitors. Guidelines on who and how to screen for bone loss, and simple, safe strategies for treatment to prevent osteoporosis are presented.

Algorithms↗
PubMed2005

The use of bisphosphonates in breast cancer.

Bisphosphonates will become increasingly important in the management of patients with breast cancer. Currently, bisphosphonates are used to treat bone metastasis because they effectively relieve pain, prevent pathological fractures and treat hypercalcaemia of malignancy. Recent advances in systemic adjuvant therapies for breast cancer are improving survival but many treatments are detrimental to bone and can increase the risk of fracture. The monitoring of breast cancer patients at risk of developing osteoporosis will become increasingly important as survival times improve and more potent treatments are developed. Bisphosphonates may also play a role as an adjuvant therapy for the prevention of bone metastasis in high-risk breast cancer patients.

Antineoplastic Agents↗
PubMed2005

Reducing the global breast cancer burden: the importance of patterns of care research.

Breast cancer treatment guidelines are not uniformly followed in clinical practice, with evidence for substantial variations in treatment patterns, quality of care, and patient outcomes among and within countries. The factors that drive treatment decisions are unclear. Furthermore, the impact of different treatment strategies on survival is poorly understood outside the clinical trial setting. Sources of patterns of care information often have limitations in completeness, quality, timeliness of reporting, and relevance to the larger population. Patterns of care studies frequently lack details on cancer stage at diagnosis, tumor biology, and treatment received. It is difficult to compare data between studies and/or track changes over time because of variations in data sources and collection techniques. Thus, the design and implementation of a global registry is sorely needed in order to prospectively evaluate worldwide patterns of care and outcomes in patients with breast cancer. Components of this registry should include random selection of centers of variable practice settings in multiple countries and accurate and rapid data reporting at prestudy and follow-up timepoints. Data collected would include tumor and demographic factors, staging information, treatment rendered, and survival. Variables that influenced the treatment selected would be assessed. This unique international effort would allow the development of strategies to improve diagnostic and treatment-related standards of care and survival outcomes, thus reducing the breast cancer burden worldwide.

Breast Neoplasms↗
PubMed2005

Improving adherence to guidelines for hypertension drug prescribing: cluster-randomized controlled trial of general versus patient-specific recommendations.

OBJECTIVE: To determine whether an intervention focusing clinician attention on drug choice for hypertension treatment improves concordance between drug regimens and guidelines. STUDY DESIGN: Cluster-randomized controlled trial comparing an individualized intervention with a general guideline implementation in geographically diverse primary care clinics of a university-affiliated Department of Veterans Affairs healthcare system. METHODS: Participants were 36 attending physicians and nurse practitioners (16 in the general group and 20 in the individualized group), with findings based on 4500 hypertensive patients. A general guideline implementation for all clinicians, including education about guideline-based drug recommendations and goals for adequacy of blood pressure control, was compared with addition of a printed individualized advisory sent to clinicians at each patient visit, indicating whether or not the patient's antihypertensive drug regimen was guideline concordant. We measured change from baseline to end point in the proportion of clinicians' patients whose drug therapy was guideline concordant. RESULTS: The individualized intervention resulted in an improvement in guideline concordance more than twice that observed for the general intervention (10.9% vs 3.8%, t = 2.796, P = .008). Bootstrap analysis showed that being in the individualized group increased the odds of concordance 1.5-fold (P = .025). The proportion of patients with adequate blood pressure control increased within each study group; however, the difference between groups was not significant. CONCLUSION: An individualized advisory regarding drug therapy for hypertension given to the clinician at each patient visit was more effective in changing clinician prescribing behavior than implementation of a general guideline.

Aged↗
PubMed2004

Conventional adjuvant chemotherapy versus single-cycle, autograft-supported, high-dose, late-intensification chemotherapy in high-risk breast cancer patients: a randomized trial.

BACKGROUND: Breast cancer patients with four or more positive axillary lymph nodes who are treated with conventional adjuvant therapy have a poor prognosis. In uncontrolled studies, high-dose chemotherapy produced much better results than conventional therapy. We compared the benefits of a single cycle of high-dose chemotherapy and the benefits of conventional chemotherapy in patients with high-risk breast cancer in a prospective, unblinded, randomized trial. METHODS: Between February 23, 1995, and June 29, 1999, 605 patients with breast cancer who had four or more positive lymph nodes were randomly assigned to treatment (307 to high-dose therapy and 298 to conventional therapy). The conventional chemotherapy regimen was four cycles of doxorubicin (75 mg/m2) followed by eight cycles of CMF (cyclophosphamide [600 mg/m2], methotrexate [50 mg/m2], and 5-fluorouracil [600 mg/m2]), all given intravenously on day 1 of a 21-day cycle. The high-dose regimen was four cycles of doxorubicin (75 mg/m2), followed by a single cycle of intermediate-dose cyclophosphamide (4000 mg/m2) supported by filgrastim (300 microg/day) for up to 10 days followed by high-dose cyclophosphamide (6000 mg/m2) and thiotepa (800 mg/m2). Peripheral blood progenitor cells were harvested by leukapheresis after treatment with cyclophosphamide and filgrastim and then re-infused after the high-dose cycle. Log-rank tests were used to compare survival rates. All statistical analyses were two-sided. RESULTS: At a median follow-up of 6 years, no statistically significant differences were detected between the arms in 5-year relapse-free survival (high-dose arm = 57%, 95% confidence interval [CI] = 51% to 63%; conventional-dose arm = 54%, 95% CI = 48% to 61% (P =.73) or in 5-year overall survival (high-dose arm = 62%, 95% CI = 56% to 68%; conventional-dose arm = 64%, 95% CI = 57% to 70%) (P =.38). CONCLUSION: Autograft-supported, high-dose therapy is not superior to conventional chemotherapy in patients with breast cancer who have multiple involved lymph nodes. This conclusion should be viewed in the context of improving the success of conventional chemotherapy.

Adult↗
PubMed2004

Exercise therapy in women who have had breast cancer: design of the Sheffield women's exercise and well-being project.

Recovering from cancer treatment can be a difficult experience, both physically and psychologically. This paper describes a randomized controlled trial that evaluates the effects of exercise therapy upon quality of life in 120 women who have had breast cancer. To facilitate behaviour change, exercise counselling is also included as an integral component in the exercise therapy intervention. Participants are randomized to one of three groups: exercise therapy, body conditioning (placebo control) or a normal care control group. The supervised exercise therapy and body conditioning sessions take place 3 times per week for 8 weeks. Outcome measures include quality of life, physical self-perceptions, depression, satisfaction with life, exercise behaviour, aerobic capacity and percentage body fat. All outcomes are assessed at baseline, 4 weeks during the intervention and at the end of the 8-week intervention. Follow-up assessments of outcomes take place at 3 and 6 months post-intervention. As the number of women surviving breast cancer is increasing and cancer treatment is linked to reduced quality of life, it is critical to evaluate treatments that improve the quality of life of this population or hasten recovery following treatment.

Adolescent↗
PubMed2004

Aberrant p16 methylation is a biomarker for tobacco exposure in cervical squamous cell carcinogenesis.

OBJECTIVE: The purpose of this study was to determine the association between active tobacco exposure and aberrant p16 promoter methylation in primary cervical squamous cell cancer and high-grade squamous cervical dysplasia. STUDY DESIGN: p16 methylation-specific polymerase chain reaction was performed on DNA that was extracted from 60 cervical cancers, 30 high-grade dysplasia specimens, and 78 normal cervical cytologic specimens. Patient data were obtained by medical record review or were collected prospectively. RESULTS: Aberrant p16 methylation was significantly higher in squamous cell cervical cancers (61%) than in squamous high-grade dysplasia (20%) or normal cytologic specimens (7.5%). Approximately one half the women with squamous cancer and one half of the women with high-grade dysplasia were active smokers. Aberrant p16 methylation was associated with active tobacco use in patients with squamous carcinoma (odds ratio, 20.6; 95% CI, 3.6-118; P<.001) and high-grade dysplasia (odds ratio, 4.57; 95% CI, 1.63-12.78; P=.002). CONCLUSION: Aberrant p16 methylation is associated strongly with active tobacco use in squamous cell cervical cancers and high-grade dysplasia.

Carcinoma, Squamous Cell↗