Mount Vernon, United Kingdom
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Beresford M.,Bristol Oncology and Haematology Center | Tumur I.,Pfizer | Chakrabarti J.,Pfizer | Barden J.,Abacus International | And 2 more authors.
Clinical Oncology | Year: 2011

Aims: The most effective sequence of tamoxifen and both steroidal (SAIs) and non-steroidal aromatase inhibitors (NSAIs) has been extensively studied in the adjuvant setting. However, treatments for women who have failed initial aromatase inhibitor therapy in the metastatic setting have received relatively little attention. A systematic review was undertaken to assess the use of SAIs and NSAIs in metastatic breast cancer. Materials and methods: Medline, Embase and the Cochrane library were searched using free text and MeSH terms. Studies assessing the cross-resistance, efficacy and safety of SAIs and NSAIs for postmenopausal women with advanced metastatic breast cancer confirmed by histology/cytology were included. Patients had progressed/relapsed from previous adjuvant, first- or second-line aromatase inhibitor treatment and had undergone treatment with at least two regimens consisting of aminoglutethimide, anastrozole, letrozole and/or exemestane. Results: Nine studies reported results for patients treated with an SAI after treatment failure with an NSAI. For SAI after NSAI, clinical benefit was the most frequently reported outcome. The clinical benefit for exemestane (SAI) after any NSAI failure or before treatment ranged from 12% (complete response not recorded, partial response 2%, stable disease 10%) to 55% (complete response 6%, partial response 13%, stable disease 35%) Survival outcomes were infrequently reported; four studies reported disease progression. The time to progression ranged from 3.7 to 5.2 months. Only one study reported a median overall survival with exemestane at 15.2 months. Only one study reported information for an NSAI after SAI and an NSAI followed by another NSAI. Discussion: This review suggests that switching from an NSAI to an SAI is a reasonable option. This would be particularly important for patients who would probably respond to further endocrine manoeuvres; strongly oestrogen receptor-positive disease, non-visceral disease, a good prior response or a long duration of response. Further research to optimise the sequence of endocrine therapies in metastatic breast cancer is needed. © 2010 The Royal College of Radiologists.


Banerjee S.,Foundation Medicine | Rusti G.,Mount Vernon Hospital Northwood | Paul J.,Cancer Research UK Clinical Trials Unit | Williams C.,University of Bristol | And 14 more authors.
Annals of Oncology | Year: 2013

Background: The aim of the study is to demonstrate that intrapatient dose escalation of carboplatin would improve the outcome in ovarian cancer compared with flat dosing. Patients and methods: Patients with untreated stage IC-IV ovarian cancer received six cycles of carboplatin area under the curve 6 (AUC 6) 3 weekly either with no dose modification except for toxicity (Arm A) or with dose escalations in cycles 2-6 based on nadir neutrophil and platelet counts (Arm B). The primary end-point was progression-free survival (PFS). Results: Nine hundred and sixty-four patients were recruited from 71 centers. Dose escalation was achieved in 77% of patients who had =1 cycle. The median AUCs (cycle 2-6) received were 6.0 (Arm A) and 7.2 (Arm B) (P <0.001). Grade 3/4 non-hematological toxicity was higher in Arm B (31% versus 22% P = 0.001). The median PFS was 12.1 months in Arm A and B [hazard ratio (HR) 0.99; 95% confidence interval (CI) 0.85-1.15; P = 0.93]. The median overall survival (OS) was 34.1 and 30.7 months in Arms A and B, respectively (HR 0.98; 95% CI 0.81-1.18, P = 0.82). In multivariate analysis, baseline neutrophil (P <0.001), baseline platelet counts (P < 0.001) and the difference between white blood cell (WBC) and neutrophil count (P = 0.009) had a significant adverse prognostic value. Conclusions: Intrapatient dose escalation of carboplatin based on nadir blood counts is feasible and safe. However, it provided no improvement in PFS or OS compared with flat dosing. Baseline neutrophils over-ride nadir counts in prognostic significance. These data may have wider implications particularly in respect of the management of chemotherapy-induced neutropenia. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Papamichael D.,Cyprus Oncology Center | Glynne-Jones R.,Mount Vernon Hospital Northwood
Current Colorectal Cancer Reports | Year: 2013

Colorectal cancer is the commonest malignancy in patients aged 75 years or older. The incidence is likely to rise further over the next two decades as the population ages and survival increases. Robust data on the adherence to guidelines for the elderly and the uptake of treatment in the elderly are limited - particularly with regard to rectal cancer. However, the evidence available suggests that clinical attitudes observed regarding age and cancer treatment are consistent. Older people with colorectal cancer tend to be offered either less intensive treatment or no treatment at all. Population data confirm that treatment rates for surgery, chemotherapy and radiotherapy in patients with colorectal cancer all decline for those over 70 years old, and continue to decline exponentially with increasing age. So should new, more tolerable strategies which may avoid radical surgery be more widely available (short-course preoperative radiotherapy, chemoradiotherapy, transanal excision microsurgery, brachytherapy, contact therapy)? It is not clear if oncologists are always making the most appropriate management decisions. So how do oncologists and surgeons balance chronological age, comorbidity, social isolation and other influences in their clinical decision-making? We need to recognise that this is a difficult issue and will be an increasing issue for multidisciplinary teams. © 2013 Springer Science+Business Media New York.

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