Evaluating the impact of Relative Total Dose Intensity (RTDI) on patients' short and long-term outcome in taxane- and anthracycline-based chemotherapy of metastatic breast cancer- a pooled analysis

Abstract

BackgroundChemotherapy dose delay and/or reduction lower relative total dose intensity (RTDI) and may affect short- and long-term outcome of metastatic breast cancer (MBC) patients.MethodsBased on 933 individual patients' data of from 3 randomized MBC trials using an anthracycline and taxane we examined the impact of RTDI on efficacy and determined the lowest optimal RTDI for MBC patients.ResultsMedian time to disease progression (TTDP) and overall survival (OS) of all patients were 39 and 98 weeks. Overall higher RTDI was correlated with a shorter TTDP (log-rank p = 0.0525 for 85% RTDI cut-off). Proportional hazards assumption was violated, there was an early drop in the TTDP-curve for the high RTDI group. It was explained by the fact that patients with primary disease progression (PDP) do have a high RTDI per definition. Excluding those 114 patients with PDP the negative correlation between RTDI and TTDP vanished. However, non-PDP patients with RTDI-cut-off levels <85% showed a shorter OS than patients with higher RTDI levels (p = 0.0086).ConclusionsOptimizing RTDI above 85% appears to improve long-term outcome of MBC patients receiving first-line chemotherapy. Lowering RTDI had no negative influence on short term outcome like OR and TTDP.

How Effective is the Treatment of Locally Advanced and Metastatic Breast Cancer in Developing Centres?: A Retrospective Review

“…Adisa et al (5) in Southwestern Nigeria noted non-adherence to schedule and the use of less optimal choice of chemotherapy. As mundane as the limitations of breast cancer care in resource poor centres may sound, now we recognize how seriously they may be impacting our care, and this corroborates the statement credited to Loibl (15) et al that the consequences of dose reduction and delays are significant.…”

“…Even though we know that suboptimal therapies are practised in the chemotherapy treatment of breast cancer (5,7,10,13,14,15), the aim of this study was not to determine this. Rather, it was aimed to determine the effectiveness of chemotherapy in a poor resource setting compared to untreated patients.…”

Management of Breast Cancer Patients with Chemotherapy-Induced Neutropenia or Febrile Neutropenia

“…The relative dose intensity is the ratio of the delivered dose intensity to the reference dose intensity for a chemotherapy regimen [4]. A strong relationship exists between the relative dose intensity and the long-term outcome of BC patients diagnosed with chemosensitive tumors (such as cancer with a high proliferative index) [4,5,6]. It is important to maintain the optimal dose intensity in the adjuvant setting since the survival curves of patients treated with a relative dose intensity lower than 85% resemble those of untreated patients [7].…”

Comparison of pegfilgrastim on day 2 vs. day 4 as primary prophylaxis of intense dose-dense chemotherapy in patients with node-positive primary breast cancer within the prospective, multi-center GAIN study: (GBG 33)

“…Fewer patients experienced grades 1 and 2 anemia at baseline in the P4 group (p=0.015; data not shown). For safety reasons after recruiting the first 167 patients, we compared the incidence of leucopenia/neutropenia between the patients before and after the amendment regardless of [14]. All these differences were statistically not significant.…”