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.

Major colorectal cancer resection should not be denied to the elderly.

AIMS: Adjuvant therapy after surgery for colorectal cancer is often denied to the elderly for various reasons. This study was to determine morbidity and mortality risk after surgery in the elderly and whether this is affected by adjuvant therapy. METHODS: Data were collected prospectively and entered on a database for all patients undergoing resection of colorectal cancer between January 1994 and July 2000. A total of 304 patients were included, 65 aged 80 years and over. RESULTS: There were 84 deaths, 21 (30%) in the over 80s, and 63 (26%) in the under 80s (P=0.51). The 'in-hospital' mortality was 10.1% in the over 80s and 3.8% in the under 80s (P=0.056). In the over 80s the colon was more affected than the rectum (P=0.002). The over 80s were less likely to be offered adjuvant therapy, 7.2% vs 42.1% (P<0.001). The 5 year survival (all-cause mortality) in the over 80s was 58.5% and 47.6% in the under 80s (P=0.25). Cox's regression analysis of all patients identified the following factors to be independently related to overall survival: age>80 years, post-operative leak, increasing Dukes stage and distant recurrence of disease. CONCLUSION: This study has demonstrated that surgery should not be denied to elderly patients with colorectal cancer as despite a higher post-operative morbidity and mortality rate and with the absence of adjuvant therapy, favourable long-term outcome can be achieved by resectional surgery alone.