Eugene J. Moylan

Edrecolomab alone or in combination with fluorouracil and folinic acid in the adjuvant treatment of stage III colon cancer: a randomised study

BACKGROUND Edrecolomab is a murine monoclonal antibody to the cell-surface glycoprotein 17-1A, which is expressed on epithelial tissues and on various carcinomas. Preliminary data suggested that it might be of use in the adjuvant treatment of patients with resected stage III colon cancer. We did a randomised trial in 27 countries to determine the effect of adding edrecolomab to the combination of fluorouracil and folinic acid in these patients. METHODS After surgery, 2761 patients were randomly assigned edrecolomab plus fluorouracil-folinic acid (combination therapy [n=912]); fluorouracil-folinic acid alone (chemotherapy [n=927]); or edrecolomab alone (edrecolomab monotherapy [n=922]). Patients were assessed for survival and disease recurrence after surgery. The primary endpoint tested the hypothesis that combination therapy improved overall survival relative to chemotherapy. The key secondary endpoint was to test whether edrecolomab monotherapy was non-inferior to chemotherapy in terms of disease-free survival. Analysis was by intention to treat. FINDINGS Median follow-up time was 26 months (IQR 20-36). 3-year overall survival on combination therapy was no different from that on chemotherapy (74.7% vs 76.1%, hazard ratio 0.94 [95% CI 0.76-1.15], p=0.53). Disease-free survival was significantly lower on edrecolomab monotherapy than on chemotherapy (53.0% vs 65.5%, 0.62 [0.53-0.73], p<0.0001). Hypersensitivity reactions occurred in 452 (25%) patients receiving edrecolomab, causing treatment discontinuation in 71 (4%). The addition of edrecolomab to chemotherapy did not increase neutropenia, diarrhoea, or mucositis. INTERPRETATION The addition of edrecolomab to fluorouracil and folinic acid in the adjuvant treatment of resected stage III colon cancer does not improve overall or disease-free survival, and edrecolomab monotherapy is associated with significantly shorter overall and disease-free survival than fluorouracil and folinic acid and is therefore an inferior treatment option. Edrecolomab is well tolerated and its addition to fluorouracil and folinic acid does not increase the toxicity of chemotherapy.

Multicenter phase II study of combination chemotherapy with capecitabine and intravenous vinorelbine in patients with pretreated metastatic breast cancer

Background:  Capecitabine and i.v. vinorelbine are both active in metastatic breast cancer with non‐overlapping toxicities. This study examined the efficacy and safety of the combination of these agents in patients with pretreated metastatic breast cancer.

Direct comparison of 18F-fluorodeoxyglucose coincidence gamma camera tomography with gallium scanning for the staging of lymphoma.

Abstract

Are Dose-Dense and Triplet Chemotherapy Regimens Optimal Adjuvant Therapy in the Majority of Women With Node-Positive Early Breast Cancer?

ful. The US Food and Drug Administration has similarly proposed expansion of access to data submitted in regulatory applications. Mello et al recently proposed a framework for broad sharing of participant-level data from clinical trials and related documents. Four possible data-sharing models are proposed, varying in who the decision maker would be for releasing these data. As of October 25, 2013, over 154,000 studies have been listed on clinicaltrials.gov. This represents millions of clinical trial participants whose impact on health care is only magnified by the opportunity for additional gains from their efforts. We wholeheartedly agree with the sentiments of Read, although, as the US Food and Drug Administration and EMA outline, these databases will undoubtedly include privately and publicly funded clinical trial data. The devil is in the details.

Herbal Medicine for Hot Flushes Induced by Endocrine Therapy in Women with Breast Cancer: A Systematic Review and Meta-Analysis.

Objective. This systematic review was conducted to evaluate the clinical effectiveness and safety of herbal medicine (HM) as an alternative management for hot flushes induced by endocrine therapy in breast cancer patients. Methods. Key English and Chinese language databases were searched from inception to July 2015. Randomized Controlled Trials (RCTs) evaluating the effects of HM on hot flushes induced by endocrine therapy in women with breast cancer were retrieved. We conducted data collection and analysis in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. Statistical analysis was performed with the software (Review Manager 5.3). Results. 19 articles were selected from the articles retrieved, and 5 articles met the inclusion criteria for analysis. Some included individual studies showed that HM can relieve hot flushes as well as other menopausal symptoms induced by endocrine therapy among women with breast cancer and improve the quality of life. There are minor side effects related to HM which are well tolerated. Conclusion. Given the small number of included studies and relatively poor methodological quality, there is insufficient evidence to draw positive conclusions regarding the objective benefit of HM. Additional high quality studies are needed with more rigorous methodological approach to answer this question.

Patterns of care and outcomes among triple‐negative early breast cancer patients in South Western Sydney

Triple‐negative breast cancer (TNBC) represents 12‐24% of all breast cancer and carries a poor prognosis upon recurrence. Little is known of the treatment, or timing and frequency of recurrences outside of a clinical trial.

Glioblastoma multiforme (GBM) in the elderly: An Irish experience.

e19621 Background: In an aging cancer population treatment decisions become more complex. Treatment options in GBM are increasing and there is a paucity of data in the elderly (>65 years). We sought to review our institutions experience of treating this patient (pt) population. METHODS A prospectively maintained database was evaluated for pts with GBM reviewed at our institution between Aug 2004 and Dec 2009. Pts were divided into: age groups > and <65 years [yrs] (Gp A and Gp B) at diagnosis and treatment received. Optimal treatment was defined as radio-(+/-chemo) therapy followed by adjuvant chemotherapy. Charlson comorbidity score and ECOG performance status (PS) were recorded where possible. Data were analysed with Fishers exact and Mann-Whitney U tests. RESULTS Of 144 pts with GBM, 35 pts were >65 yrs (24.3%) and 4 pts were >75 yrs (2.8%). 132 pts received treatment (92%), which was optimal in 82 pts (57%). In Gp A 34 pts were treated (97%); of these, treatment was optimal in 15 (43%) compared with 61.5% in Gp B (p=0.077). In Gp A the median Charlson score was 6 (range: 6 - 10) and PS was 0 in 10 pts (29%), 1 in 18 pts (53%), 2 in 4 pts (12%) and 3 in 2 pts (6%), comparable to Gp B. Median overall survival (mOS) in Gp A was 5.8 months [mts] (CI: 3.0 - 8.6) compared with 10.1 mts (CI: 7.9 - 12.3) in Gp B (p=0.004). For all treated pts, mOS was 5.8 mts (CI: 3.0 - 8.6) in Gp A compared with 9.7 mts (CI: 8.5 - 11.1) in Gp B (p<0.0005). For pts receiving optimal treatment, mOS was 8.4 mts (CI: 3.2 - 13.5) and 14.2 mts (CI: 11.3 - 17.1) in Gp A and B, respectively (p=0.002). HR for death for age >65 was 3.52 (CI: 2.0 - 6.1). For the 4 pts over age 75 yrs, mOS was 9.8 mts (range 1.7-16.9) compared to 5.4 mts (range 1.5-47.4) in the 65-75 yr age group. Treatment related toxicities were broadly similar between Gps A and B (detailed analysis ongoing). CONCLUSIONS A significant number of pts diagnosed with GBM are elderly. Our data suggest that they have worse overall survival independent of treatment received. A small subset of pts aged >75yrs had improved survival compared with those 65 - 75 yrs, suggesting that careful pt selection may result in improved survival. Prospective trials incorporating comprehensive geriatric assessment and molecular analyses could potentially identify pts who would benefit from treatment.

Clinicopathological analysis of KRAS mutation in an Irish population.

467 Background: Clinical trials have shown that tumor KRAS status predicts response to anti-EGFR monoclonal antibodies in metastatic colorectal cancer (mCRC). We sought to compare distribution of wild-type and mutated KRAS in an Irish population and identify clinicopathologic correlates. METHODS From our prospectively maintained database we retrospectively identified patients with mCRC and documented KRAS status between Jan 2007 to June 2010. Medical notes were examined for patient demographics and disease characteristics. Variables were extracted and compared using unpaired t test and chi2 test. RESULTS 52 patients were identified, 29 (55.8%) with mutated (mt) and 23 (44.2%) with wild type (wt) KRAS from tumor tissue. Males accounted for 61.5% (n=31). Median age at diagnosis of metastatic disease for the KRASmt group was 66.4 years (range 56.7-82.1) and for the KRAS wt group was 64.2 years (40.1-76.8), p= 0.08. 21 (72.4%) of the KRASmt group and 16 (69.6%) of the KRASwt group had metastatic disease at presentation (p=0.81). For patients who presented initially with localised disease, time to development of metastases was 22.5mo (range 14-37.6) for the KRASmt group and 16.7mo (3.2-123.7) for the KRASwt (p=0.30). 21 (72.4%) of KRASmt and 17 (74.1%) of KRASwt tumors had left-sided primary (p = 0.84) with equal numbers of primary tumor resection in both groups. There was no statistical difference in TN-stage or the presence of liver metastases. Numbers of patients with KRASmt tumors with one, two and three or more different sites of metastases was 22 (75.9%), 5 (17.2%), and 2 (6.9%), and in KRASwt tumors there was no significant difference: 18 (78.3%), 4 (17.4%), and 1 (4.3%), respectively (p = 0.93). Median CEA at diagnosis for both groups were 19.7 μg/l (range 1.2-5958) and 6.1 (1.3-696.9; p = 0.11). CONCLUSIONS We found that the ratio of KRASmt to KRASwt tumours in an Irish population is comparable to that in large international trials. Our analysis revealed no association between KRAS status and clinicopathologic variables. The inclusion of BRAF status, not readily available in our institution, may help define poor prognosis tumors. At present there is no validated molecular biomarker that is superior to standard clinicopathologic variables. No significant financial relationships to disclose.

Experience with docetaxel in hormone-refractory prostate cancer (HRPC) at three Australian cancer centers: A retrospective study

Background:  Hormone‐refractory prostate cancer (HRPC) is associated with a poor prognosis and has historically been considered relatively chemoresistant. Emerging data demonstrate clinical benefit with the use of docetaxel in HRPC, culminating in two recent published phase III studies demonstrating survival benefit. Currently, docetaxel is registered but not reimbursed for HRPC in Australia.