A Multicentre Retrospective Study of Fulvestrant Use and Efficacy in Advanced/Metastatic Breast Cancer.

AIMS: Fulvestrant is a selective oestrogen receptor (ER) degrader used in postmenopausal women with hormone receptor-positive advanced breast cancer. The study aim was to analyse demographics and outcomes of UK patients treated with fulvestrant monotherapy at nine representative centres. MATERIALS AND METHODS: Medical records of 459 patients with locally advanced or metastatic ER-positive, HER2-negative breast cancer treated with fulvestrant between August 2011 and November 2018 at nine UK centres were reviewed. Data were collated on demographics, progression-free survival, overall survival and disease response at first radiological assessment following fulvestrant initiation. Patients still alive by December 2018 were censored. RESULTS: Data from 429 of the 459 patients identified were eligible for inclusion in the analysis. The median age was 69 (range 21-95) and 64% (n = 275) had Eastern Cooperative Oncology Group performance status 0-1. Bone was the most commonly involved metastatic site (72%, n = 306). However, 295 (69%) patients had visceral involvement. Patients had received a median 2 (range 0-5) prior lines of endocrine therapy and median 0 (range 0-6) prior chemotherapies. Fulvestrant was first-line therapy in 43 patients (10%). The median duration of treatment was 5 months (range 1-88). The median progression-free survival was 5.5 months. In 51% of 350 patients radiologically assessed, there was evidence of disease response to fulvestrant. Fifteen per cent of these had a complete/partial response. Fulvestrant was discontinued predominantly due to disease progression, with 3% discontinued solely due to adverse events. The median overall survival for the whole cohort was 22.5 months (range 0-88). CONCLUSIONS: This is one of the largest studied cohorts of breast cancer patients treated with fulvestrant. This heavily endocrine-pretreated population reflects real-life use in the UK. Within this context, our retrospective data show that patients can experience maintained disease response when treated with fulvestrant, supporting the importance of equitable availability for all UK patients.

Epithelial ovarian cancer: a review of current management.

Epithelial ovarian cancer is the most lethal gynaecological cancer among women worldwide, with 6000 new cases diagnosed in the UK each year. Most women present with advanced disease, but, despite a good initial response to treatment, most relapse. The overall 5-year survival rate is 46%, although this drops to about 13% in women with advanced disease. Transvaginal ultrasound and the tumour marker CA125 are being investigated for screening in ongoing randomised trials. Treatment of ovarian cancer is dependent on clinical stage, and should always be managed within a multidisciplinary team. Most cases will require a pelvic clearance and adjuvant chemotherapy. Current guidelines by the National Institute of Clinical Excellence (NICE) recommend that first-line chemotherapy should include a platinum-based regimen with or without paclitaxel. Relapsed ovarian cancer is incurable; however, chemotherapy can improve quality of life and survival. Gene therapy, immunotherapy and signal transduction inhibitors are all potential future therapies, and are being investigated in ongoing clinical research. In this paper we review the literature on the epidemiology, pathology, clinical features and the current treatment options in epithelial ovarian cancer.

A phase II study of sequential carboplatin, paclitaxel and topotecan in patients with previously untreated advanced ovarian cancer.

We evaluated the sequential use of carboplatin, paclitaxel and topotecan in patients with advanced, previously untreated ovarian cancer. In total, 43 patients with advanced ovarian cancer and >1 cm residual disease were treated with sequential carboplatin (area-under-the-curve (AUC) 5 days 1 and 22), paclitaxel (175 mg m(-2) days 43 and 64) and topotecan (1.5 mg m(-2) daily for 5 days from days 85, 106, 127 and 148). Median age of patients was 61 years. Median follow-up was 22.2 months (range 0.76-50.6 months). In all, 34 (79%) patients received all eight cycles of treatment and nine (21%) withdrew. Of the 29 evaluable patients, 19 (66%) responded according to WHO and 30 of 36 (83%) patients according to CA125. The best overall response (CA125 and/or WHO) was 77% (33 of 43 patients). The response rates to sequential drugs based on >50% fall in CA125 were as follows: carboplatin, 77% (30 of 39 patients); paclitaxel, 65% (15 of 23 patients); topotecan, 38% (five of 13 patients). Two patients responded to paclitaxel and one to topotecan after failure to respond to preceding chemotherapy. Median survival and time to progression was 22.24 and 10.61 months, respectively. This study demonstrates that sequential chemotherapy with just two initial courses of carboplatin is a reasonable way to introduce new agents into first-line therapy for poor prognostic ovarian cancer patients.

The role of surveillance CT scans in patients with diffuse large B-cell non-Hodgkin's lymphoma.

The use of routine surveillance computed tomography (CT) scans in the follow-up of patients with diffuse large B-cell lymphoma may allow the detection of early asymptomatic relapse. On this basis, CT scans are frequently included in follow-up schedules, but the utility of this investigation in this setting has never been determined. This study evaluated the effectiveness of routine surveillance CT scans performed 3 and 12 months after completion of chemotherapy in patients with diffuse large B-cell lymphoma who had achieved a complete response. One hundred and seventeen patients with diffuse large B-cell lymphoma achieved complete remission at the Royal Marsden Hospital using first line combination chemotherapy between January 1992 and January 2000. The median follow-up was 4.6 years and 35 patients subsequently relapsed. Relapse was associated with the development of new symptoms and/or signs in 86% of cases. Only 5.7% of relapses were detected in asymptomatic patients using surveillance CT scans. Routine surveillance CT scans are of limited value in detecting asymptomatic early relapse and other approaches are required in order to identify patients destined to relapse at an earlier stage.

CA125 response: can it replace the traditional response criteria in ovarian cancer?

CA125 is well established as an accurate and reliable means of monitoring response to treatment and confirming relapse in ovarian cancer patients. Its role in follow-up after initial treatment is less certain and the subject of a current clinical trial. Measuring response with computerized tomography scans is futile in the majority of patients, as disease is often nonmeasurable at presentation, e.g., ascites or peritoneal deposits, or all measurable disease has been removed at the time of surgery. Serial changes in CA125 can be used as a reliable indicator of disease response or progression so that patients can be classified as responding or progressing according to either standard or CA125 criteria. These precise definitions are currently being prospectively validated in conjunction with the new response evaluation criteria in solid tumor response guidelines and are being incorporated into all future clinical trials.