The effect of adjuvant chemotherapy on symptom burden and quality of life over time; a preliminary prospective observational study using individual data of patients aged ≥70 with early stage invasive breast cancer.

OBJECTIVES: We aim to assess short and long term effects of chemotherapy on patient-reported quality of life (QOL) and patient versus clinician symptom reporting in older patients with breast cancer adjusted for tumour and aging parameters. MATERIAL AND METHODS: In this prospective, multicentre, non-interventional, observational study, women aged ≥70years were enrolled after surgery and assigned to a TC chemotherapy (docetaxel and cyclophosphamide) group or a control group depending on their planned adjuvant treatment. Longitudinal multivariate models were used to assess the statistical and minimal clinically important difference (MCID) in the impact of TC chemotherapy over time on QOL and symptom burden adjusted for baseline aging and tumour parameters. Statistical significance was set at 5% and MCID at 10 points. RESULTS: In total, 57 patients were enrolled in the chemotherapy and 52 patients in the control group. Within the chemotherapy group, clinical deterioration was reported at 3months for Fatigue (17.73), Dyspnoea (17.05), Diarrhoea (12.06) and Appetite Loss (17.05) scores (all p<0.001). However, the scores had returned to baseline (or even better for Role Functioning) at year 1. No clinical deterioration was reported in the control group. Symptom scores as reported by patients were significantly (p<0.05) higher than those reported by the clinicians, even more so for Fatigue, Dyspnoea, and Pain. CONCLUSION: Our results show that symptom burden and diminished QOL in an older breast cancer population receiving adjuvant TC chemotherapy are short-lived and disappear after a while with no long-term differences compared to a similar population not receiving chemotherapy.

Guidelines for time-to-event end point definitions in breast cancer trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†.

BACKGROUND: Using surrogate end points for overall survival, such as disease-free survival, is increasingly common in randomized controlled trials. However, the definitions of several of these time-to-event (TTE) end points are imprecisely which limits interpretation and cross-trial comparisons. The estimation of treatment effects may be directly affected by the definitions of end points. The DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for randomized cancer clinical trials (RCTs) in breast cancer. PATIENTS AND METHODS: A literature review was carried out to identify TTE end points (primary or secondary) reported in publications of randomized trials or guidelines. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points based on a validated consensus method that formalize the degree of agreement among experts. RESULTS: Recommended guidelines for the definitions of TTE end points commonly used in RCTs for breast cancer are provided for non-metastatic and metastatic settings. CONCLUSION: The use of standardized definitions should facilitate comparisons of trial results and improve the quality of trial design and reporting. These guidelines could be of particular interest to those involved in the design, conducting, reporting, or assessment of RCT.

Adjuvant chemotherapy in 2005: standards and beyond.

The 2003 St. Gallen consensus panel divided the many available adjuvant chemotherapy (CT) regimens into those with "standard efficacy" (ACx4, CMFx6) and those with "superior efficacy" (FA(E)Cx6, CA(E)Fx6, A(E)-->CMF, TACx6, ACx4--> paclitaxel (P)x4 or docetaxel (D)x4) but also greater complexity, toxicity and cost. This paper will summarize the latest information on long-term side effects of the "superior" regimens and 5-year benefits reported in taxane trials, including those of a "new" sequential regimen, FECx3--> docetaxelx3. Rapidly expanding evidence of marked heterogeneity in the magnitude of CT benefits according to the tumour oestrogen receptor (ER) status, a claim made for many years by IBCSG investigators, will be reviewed; it will lead to the conclusion that a revolution needs to take place in the way oncologists think about the CT added value and design adjuvant clinical trials. The conclusions proposed to the 2005 St. Gallen consensus panel are that: adequately dosed anthracycline-based CT regimens remain an acceptable standard for many women; a lower threshold for using taxanes in sequence or combination with anthracyclines (A) is justified in the presence of an ER-negative or low-ER tumour status, other aggressive biologic features (such as HER-2 overexpression), fear about A-induced cardiotoxicity; no recommendation can yet be made as far as the optimal taxane-A regimen, the best taxane or the best taxane schedule.