Incidence of reduced chemotherapy relative dose intensity among women with early stage breast cancer in US clinical practice

Abstract

Chemotherapy is widely used to treat early stage breast cancer (ESBC). Reductions and delays in dose administered--e.g., due to advanced age or febrile neutropenia (FN)--are generally believed to increase risk of disease progression and reduce survival. Little is known about incidence of reduced chemotherapy dose intensity among women with ESBC in the current era of US clinical practice. This study employed a retrospective cohort design and electronic medical records from > 65 community oncology/hematology clinics in > 35 states (2004-2010). The study population comprised adult women who received myelosuppressive chemotherapy for ESBC (stages I-IIIA). For each such woman, each unique cycle of chemotherapy within their first observed course was identified. Incidence of chemotherapy dose delays (≥ 7 days for any drug in ≥ 1 cycles), chemotherapy dose reductions (≥ 15% for any drug in ≥ 1 cycles), and low chemotherapy relative dose intensity (RDI <85% over the course) relative to published reference standards were descriptively analyzed for the seven most-frequently planned regimens in the study database. A total of 2,228 women (70% of the subjects who received chemotherapy for ESBC and met other selection criteria) initiated 1 of the 7 most-frequently planned regimens. Mean age of subjects was 54 years and 69% received primary prophylaxis against FN with a colony-stimulating factor. Incidence of dose delays, dose reductions, and low RDI was 31, 24, and 26%, respectively; low RDI typically was due to premature treatment discontinuation. For patients (n = 626) receiving the most common regimen (dose-dense AC-T: doxorubicin/cyclophosphamide, Q2 × 4 cycles, paclitaxel or docetaxel, Q2 × 4 cycles), incidence of dose delays, dose reductions, and low RDI was 42, 29, and 32%, respectively. In the current era of US clinical practice, chemotherapy dose delays and dose reductions are common among women with ESBC receiving frequently used myelosuppressive dose-dense, as well as conventional, chemotherapy regimens.

Incidence and Predictors of Febrile Neutropenia among Early-Stage Breast Cancer Patients Receiving Anthracycline-Based Chemotherapy in Korea

“…Widespread screening programs have contributed to its early diagnosis and the current standard treatment for early-stage breast cancer (ESBC) is surgery followed by local radiation therapy and systemic adjuvant treatments using chemotherapy and/or hormonal agents. Advances in systemic adjuvant chemotherapy have shown several convincing roles in preventing relapse and extending survival [3,4]. The dose of adjuvant chemotherapy is known to be one of the important variables that affect the ability of patients with ESBC to achieve maximal benefit [5,6,7,8,9].…”

Prospective cohort study of febrile neutropenia in breast cancer patients with neoadjuvant and adjuvant chemotherapy: CSPOR-BC FN study

“…The outcomes of subjects with doses lower than 85% of RDI were reported to be similar to the outcomes of subjects treated with surgery alone (7,8). In fact, a retrospective cohort study has demonstrated that chemotherapy dose delays and dose reductions are common among breast cancer patients receiving conventional chemotherapy regimens in approximately 20% of cases (9,10).…”

Association of pre-chemotherapy peripheral blood pro-inflammatory and coagulation factors with reduced relative dose intensity in women with breast cancer

“…Nevertheless, RDI reductions are common in clinical practice, and a large nationwide study of community practices identified RDI reductions of 15% or more in over half of patients with early-stage breast cancer [29]. Across several studies, advanced age has consistently been found to be a risk factor for a decreased RDI, and older women with breast cancer are more likely to have a reduced RDI compared with younger women [2, 30–34]. …”