Showing papers by "David Cameron published in 2004"

First line hormonal treatment (HT) for metastatic breast cancer (MBC) with exemestane (E) or tamoxifen (T) in postmenopausal patients (pts) - A randomized phase III trial of the EORTC Breast Group

Abstract: 515 Background: E is an aromatase inactivator, with demonstrated efficacy in MBC progressing under T, which remained standard 1st line HT over decades. The randomized EORTC phase II trial of E vs T, which showed promising activity in 1st line MBC (Ann. Oncol. 2003, 14: 1391–8) was extended in a phase III reported here, aiming at a true comparison of efficacy and tolerability of both drugs. Methods: Postmenopausal MBC pts with ECOG PS ≤2 and measurable, hormone responsive disease (ER &/or PgR + or unknown with disease free interval >2y) previously untreated with HT for MBC, were randomized to receive open label E 25mg or T 20mg daily. One prior chemotherapy (CT) for MBC was permitted. Prior adjuvant T was allowed if treatment free interval exceeded 6 mo. The trial was powered to detect an increase in median progression free survival (PFS, primary endpoint) of 3 mo in favor of E. Secondary endpoints were survival and tolerability. All analyses were intent to treat. Results: 382 pts accrued by 81 centers rec...

Conventional Adjuvant Chemotherapy Versus Single-Cycle, Autograft-Supported, High-Dose, Late-Intensification Chemotherapy in High-Risk Breast Cancer Patients: A Randomized Trial

Abstract: 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/m(2)) followed by eight cycles of CMF (cyclophosphamide [600 mg/m(2)], methotrexate [50 mg/m(2)], and 5-fluorouracil [600 mg/m(2)]), all given intravenously on day 1 of a 21-day cycle. The high-dose regimen was four cycles of doxorubicin (75 mg/m(2)), followed by a single cycle of intermediate-dose cyclophosphamide (4000 mg/m(2)) sup- ported by filgrastim (300 mug/day) for up to 10 days followed by high-dose cyclophosphamide (6000 mg/m(2)) and thiotepa (800 mg/m(2)). 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 (highdose 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.

A prognostic index for operable, node-negative breast cancer

Abstract: There is long-standing controversy over the management of small, node-negative breast cancers. Surgical excision, with or without local radiotherapy, plus adjuvant tamoxifen will result in long-term disease-free survival for some 80% of patients. On the other hand, around 20% will develop distant metastases and this figure can be reduced by adjuvant chemotherapy (Early Breast Trialists, 1998). The issue is whether it is justifiable to expose all patients with early disease to the side effects of cytotoxic therapy for the benefit of the minority. If those at greatest risk of relapse could be identified at the time of diagnosis, treatment decisions would be simplified. Many attempts have been made to categorise patients with operable node-negative tumours according to their individual prognoses (Merkl and Osborne, 1989; Leonard, 1999; Isaacs et al, 2001; Mirza et al, 2002; Niu et al, 2002) but no single marker or combination of markers has gained widespread acceptance and authoritative guidelines achieve only very broad selection of ‘higher risk’ patients for adjuvant cytotoxic chemotherapy (Eifel et al, 2001; Goldhirsch et al, 2001). Most recently, a prognostic ‘gene-expression signature’ has been described, based on microarray analysis of 70 genes (van't Veer et al, 2002; van de Vijver et al, 2002). However, it will be some time before such sophisticated technology can be applied in routine diagnostic practice (Schubert, 2003). Meanwhile, the range of possible predictive indicators, identifiable by long-established techniques, continues to grow and the potential benefits of a simple and reliable prognostic index justify further assessment.

Organizational and occupational commitment : exploring chefs from a cultural perspective

Abstract: A central research theme in commitment theory is the use of attitudinal surveys, which for the most part, are designed to measure organizational commitment (Mathews et al, 2002). As an alternative to a unitary concept (i. e. organizational culture and organizational commitment), this thesis has explored both the commitment and cultural concept of occupation and organization to a self-percept of chefs working for 4-and 5-star hotels in the UK. Methodologically, the research followed a dualistic-approach using a 'nomothetic method' for quantitative-deductive inquiry and an 'ideographic method' for qualitative-inductive inquiry. The results of the nomothetic inquiry (n=135), revealed behavioural consistencies recurrent to commitment. It provided cues to chefs' cultural practices and norms. Drawing from these findings, the quantitative constructs were converted to qualitative constructs addressing the issue of why things happen. The data elicited from multiple-case studies: 6 hotels, a total of 30 participants, was analysed in a number of ways. These were: 'strength of association', 'consistency', and 'specificity' for attitudinal and behavioural commitment in talk. This was followed by commitment analysis to phenomenon and the ad-hoc in 'talk'. Essentially, chefs gave their perceptual thoughts on commitment through narrative based on a series of cognitive maps. As mutual-equivalence, chefs described cognitive schemas, which were attitudinally 'valuable' to their occupation (Becker 1960). In contrast to occupation commitment, chefs' commitment to organization was, in most cases, behavioural. Enactments of commitment revealed behavioural 'side-bets' (Becker 1960) to themes of discourse. Conversational 'talk' revealed discourse markers depicting 'well', 'actually, 'in fact' and 'oh'. As a result, the chef self-percept reveals cognitive schema attributable to five operational themes: opportunity, occupation, reputation, hard work and skills. This revealed rich data, which showed that chefs are, in many cases, highly committed to their occupation. This is mainly because they seek opportunity for occupational development: gaining professional experience is a key factor. Chefs aspire to be inspired by their occupation and not by their organization. In addition, the research reveals that chefs display a mutual-equivalence without necessarily enacting cognitive sharing with their organization.

A comparative study of exemestane versus anastrozole in post-menopausal breast cancer subjects with visceral disease

Abstract: 628 Background: A pilot, open-label, multicenter, multinational, randomized, parallel group, comparative study was conducted in post-menopausal women with advanced ER/PgR + breast cancer (BC) and at least one visceral lesion (liver or lung) measurable using RECIST criteria Methods: Subjects had progressed during prior antiestrogen treatment, or ≤ 12 months since adjuvant antiestrogen treatment. Subjects were randomized 1:1 to either exemestane (E) (25 mg po qd) or anastrozole (A) (1 mg po qd). Prior treatment with ≤ chemotherapy (CT) regimen for metastatic BC was permitted. ECOG performance status of 0 –2. Primary efficacy end-point was objective response rate in visceral disease using modified RECIST Guidelines. Stable disease required documentation over 24 weeks. Secondary end-points included tolerability (absence of NCI CTC grade 2 –4 AEs), TTP, and survival. Results: The last patient was enrolled 20Dec2002. 28 patients remained on study drug as of 1Nov2003. Data are shown in the Table. There are no si...

A phase II trial of gemcitabine (gem) & cisplatin (cis) in advanced esophageal cancer (AEC)

Abstract: 4034 Background: Current cisplatin based regimens for the treatment of AEC are disappointing with response rates between 25 and 45% and median survival of around 9 months. Gemcitabine (Gem) is active against a range of tumour types. Preclinical models suggest synergistic cytotoxic activity for Gem and Cisplatin (Cis), and in phase II trials this combination is active in NSCLC, head & neck cancer and bladder cancer. Methods: This non-randomised open label phase II study evaluated the efficacy and safety of Gem 1250 mg/m2 on days 1, 8, and Cis 75 mg/m2 on day 1 every 21 days in AEC. Patients with; histologically proven, bidimensionally measurable, locally advanced or metastatic oesophageal carcinoma (squamous or adenocarcinoma), aged >18yrs, with a performance status 0–2 and life expectancy >3 months, and able to give informed consent were eligible. Interim review after 19 patients were enrolled suggested that this was unacceptably toxic, subsequent patients were treated with Gem 1000mg/m2 and Cis 75mg/m2. ...

A double blind, parallel, placebo controlled, dose ranging study on efficacy and safety of oral clodronate in cancer induced osteolysis measured by biochemical markers of bone resorption

Abstract: 8056 Background: The bisphosphonate clodronate is effective in the treatment of osteolytic bone metastases at an oral dose of 1600 mg per day. However other doses such as 2400 mg and 3200 mg have also been used. Using bone markers as surrogate biomarkers for osteolysis, the purpose of the study was to investigate the efficacy of oral clodronate (BONEFOS®) across a range of doses in patients with tumour induced osteolysis. Methods: 125 patients with metastatic bone disease (87 breast, 33 prostate and 5 other tumour types) were randomized to oral clodronate (800, 1600, 2400 and 3200 mg) or placebo in a phase II double blind, dose ranging, multicentre study with ethical approval. During 6 weeks of treatment, bone markers were assessed weekly. Results: Doses of 1600 mg or above were all effective in producing a mean fall in both urinary N-telopeptide (NTX, see table for breast data) and C-telopeptide of over 40 % from baseline values. Moreover, effects of clodronate were seen by 1 week. The 800mg dose gave a ...

Phase III randomised trial of doxorubicin (A) and docetaxel (D) versus A and cyclophosphamide (C) as primary medical therapy (PMT) in women with breast cancer

Abstract: 521 Background: Use of PMT as pre-operative therapy for large primary, or locally advanced inoperable, breast cancer (BC)is increasing. Such regimens usually contain A,in combination with C (AC). D is among the most active single agents in metastatic BC and is increasingly used with A in advanced BC. Methods: Patients suitable for PMT (n=363) were randomised to receive up to 6 cycles of either (a) A (50mg/m2) and D (75mg/m2) i/v every 3 weeks, or (b) A (60mg/m2) and C (600mg/m2) i/v every 3 weeks. Patients with operable disease after completing chemotherapy had surgery followed by radiotherapy if indicated, and tamoxifen if ER+. We compared the response rates (clinical and pathological), relapse-free survival (RFS) after subsequent surgery, and overall survival (OS) of patients treated with AC and AD as PMT. Results: Patients with locally advanced inoperable (8%), inflammatory (15%) or large, operable (77%) primary BC, and with no evidence of metastatic disease, were randomised to AC (n=180) or AD (n=183)...

Time for a change in breast cancer therapy

Abstract: Taken together, recent studies make a powerful case for the licensing of aromatase inhibitors in the adjuvant setting, offering an alternative to tamoxifen which has long been the gold standard in breast cancer therapy in the prevention of recurrence.