An open-label study of lapatinib in women with HER-2-negative early breast cancer: the lapatinib pre-surgical study (LPS study).

BACKGROUND: This phase II, open-label, multicentre study aimed to evaluate changes in cell proliferation and biomarkers, as well as efficacy of lapatinib in treatment-naïve patients with HER-2-negative primary breast cancer. PATIENTS AND METHODS: Patients received 1500 mg lapatinib for 28-42 days before surgery with repeat biopsies and measurements. The primary end point was inhibition of cell proliferation measured by Ki67; the secondary end points included clinical response, adverse events and changes in FOXO3a, FOXM1, p-AKT and HER-3. RESULTS: Overall, there was no significant reduction in Ki67 with treatment (assessment carried out in 28 of 31 subjects enrolled). However, four patients (14%) showed a reduction in Ki67 ≥50%. Four of 25 patients (16%) had a partial response to treatment judged by sequential ultrasound measurements. Response, in terms of either Ki67 or ultrasound, did not relate to changes in any biomarker assessed at baseline, including the estrogen receptor (ER) and epidermal growth factor receptor (EGFR). However, all four clinical responders were HER-3 positive, as were three of four Ki67 responders. CONCLUSIONS: Overall, a pre-surgical course of lapatinib monotherapy had little effect on this group of patients; however, in subsets of patients, especially those with HER-3-positive tumors, we observed either reduction in proliferation (Ki67) or tumor size; EGFR/ER status had no impact.

Patient preference for surgical method of abdominal aortic aneurysm repair: postal survey.

OBJECTIVES: To determine whether men with small abdominal aortic aneurysm have a preference between either endovascular or open aneurysm repair for future treatment. DESIGN: Prospective study of self-declared treatment preference following receipt of a validated patient information pack. PARTICIPANTS: Men aged 65-84 years (n=237) with asymptomatic aneurysm (4.0-5.4 cm) detected by population-based screening. METHODS: An unbiased, validated patient information pack and questionnaire were developed to conduct a postal survey. RESULTS: One hundred sixty seven participants (70%) returned a completed questionnaire; 24 (10%) did not respond at all. Initially, only 38 (23%) declared a treatment preference. After reading the information pack, 130 participants (80%) declared a treatment preference: 30 preferred open repair (18%), 77 endovascular repair (46%), 23 were happy with either option (14%) and only 34 remained without any preference (20%). Nearly all (92%) thought that the information pack had prepared them well for future discussions with clinicians and with no single feature identified as influencing the preference-making process, 66 respondents (40%) still opted to 'take the advice of the doctor'. CONCLUSION: The patient information pack facilitated the development of treatment preferences with endovascular repair being preferred to open repair. Nevertheless for patient-centred care, vascular centres must continue to safely provide both open and endovascular repair.

The adjuvant benefit of angioplasty in patients with mild to moderate intermittent claudication (MIMIC) managed by supervised exercise, smoking cessation advice and best medical therapy: results from two randomised trials for stenotic femoropopliteal and aortoiliac arterial disease.

BACKGROUND: Uncertainty exists on whether there is adjuvant benefit of percutaneous transluminal angioplasty (PTA) over supervised exercise and best medical therapy in the treatment of intermittent claudication. METHODS: Patients with symptoms of stable mild to moderate intermittent claudication (MIMIC) were randomised in two multi-centre trials, for femoropopliteal and aortoiliac arterial disease, to receive either PTA or no PTA against a background of supervised exercise and best medical therapy and followed up for 24 months. Initial claudication distance (ICD) and absolute walking distance (AWD) on treadmill were compared between randomised groups adjusting for the corresponding measure at baseline. Secondary outcomes included ankle-brachial pressure index (ABPI) and quality of life. FINDINGS: A total of 93 patients were randomised into the femoropopliteal trial (48 into PTA) and 34 into the aortoiliac trial (19 to PTA). The mean (standard deviation, SD) age was 66(9) years for the femoropopliteal trial (63% male) and 63(9) for the aortoiliac trial (65% male). At 24 months, there were significant improvements in both AWD and ICD in the PTA groups for both trials. The adjusted AWD was 38% greater in the PTA group for the femoropopliteal trial (95%; CI 1-90) (p=0.04) and 78% greater in the PTA group for the aortoiliac trial (95%; CI 0-216) (p=0.05). Further benefits were demonstrated for ABPI but not for quality of life. INTERPRETATION: PTA confers adjuvant benefit over supervised exercise and best medical therapy in terms of walking distances and ABPI 24 months after PTA in patients with stable mild to moderate intermittent claudication.

Glutathione and neonatal lung disease.

Glutathione (GSH) was measured using HPLC-electrochemical detection in bronchoalveolar lavage fluid from 28 neonates for up to 21 days after birth. GSH levels varied from 0.1-11.2 mumol l-1 (with a geometric mean concentration of 1.3 mumol l-1). GSH in epithelial lining fluid was estimated using the urea dilution method at 15.0 mumol l-1 (range 0.5-196 mumol l-1), which is significantly lower than observed in adult subjects. There was an L shaped relationship between GSH and the two markers of oxygen therapy, oxygen index and FiO2. The lowest GSH levels were associated with the group of infants with the most severe airways problems who required high oxygen.