Comparison of Treatment Completion Rate Between Conventional and Dose-dense Doxorubicin and Cyclophosphamide (AC) Followed by a Taxane in Patients With Breast Cancer: A Propensity Score-matched Analysis

Abstract

Background/Aim: To maximize the effect of perioperative chemotherapy in breast cancer, it is critical to keep the relative dose intensity (RDI) high. While bi-weekly doxorubicin and cyclophosphamide, dose-dense AC (ddAC), instead of tri-weekly conventional AC (cAC) followed by a taxane has been adopted as standard perioperative chemotherapy, postponement or discontinuation are sometimes experienced during ddAC or subsequent taxane phase. This study aimed at evaluating whether ddAC, compared to cAC, was associated with reduced RDI. Patients and Methods: We compared ddAC and cAC, both followed by a taxane, for perioperative breast cancer regarding the proportion of completion of planned treatment (%completion), defined as an RDI ≥85% for both AC and taxane phases. Results: There was no remarkable difference between the groups in patient characteristics after propensity score matching (n=46 in ddAC, and n=86 in cAC). The %completion was similar between the groups (67.4% vs. 65.1%). Most other endpoints related to RDI were similar between groups. The incidence of pneumonia was higher in the ddAC group (13% vs. 3%) including one Pneumocystis jiroveci pneumonia. Conclusion: ddAC followed by a taxane can be considered with sufficient supportive measures and precautions for pneumonia.Breast cancer is the most common cancer in women worldwide (1). The survival benefit of perioperative, adjuvant or neoadjuvant, chemotherapy has been established in patients with early-stage and locally-advanced breast cancer (2). The standard and one of the most commonly employed perioperative chemotherapy regimens is doxorubicin plus cyclophosphamide (AC) followed by a taxane (docetaxel or paclitaxel) (3,4).The effect of chemotherapy is generally correlated with dose intensity, defined as the total amount of drug given in a fixed unit of time, and most commonly expressed as milligrams per meter squared per week (mg/m 2 /week) (5). Relative dose intensity (RDI) is defined as the ratio of the actual dose intensity over the standard or planned dose intensity. The RDI of perioperative chemotherapy for breast cancer has been reported to affect disease-free survival (DFS) and overall survival (OS) (5). A randomized controlled trial suggested that early-stage breast cancer patients treated with a cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) regimen delivered with an RDI of ≥85% had a significantly better survival than those treated with the same regimen but delivered with an RDI of <85% (6). The survival benefits of receiving a higher RDI have been confirmed subsequently in several observational studies (5, 7), and clinical guidelines recommend keeping an RDI of at least 85% for optimal treatment (8).To increase dose intensity, a dose-dense (dd)AC regimen was developed; it shortens the interval of AC therapy from 6217

The impact of the COVID‐19 pandemic on perioperative chemotherapy for breast cancer

“…This resumption was based on reports that ddAC is safe and well tolerated compared with AC. 18 There was no difference in the selection of taxane, wPTX, or DTX, between the groups.…”

“…Even though an increase in ddAC in the PANDEMIC group was observed (PRE vs. PANDEMIC, 0 patients [0%] vs. 54 patients [14%]), this occurred because we resumed using ddAC in 2021 following an interruption since January 2018 because of concerns regarding its toxicity. This resumption was based on reports that ddAC is safe and well tolerated compared with AC 18 . There was no difference in the selection of taxane, wPTX, or DTX, between the groups.…”

“…Second, we resumed ddAC in 2021 after an interruption since pre‐pandemic 2018, which may have affected the RDI and other chemotherapy‐related data in a COVID‐19‐independent manner. However, the decision to resume ddAC was made based on our own data that the proportion of those who completed perioperative chemotherapy was equivalent between ddAC and conventional AC when both were followed by a taxane 18 . Third, short follow‐up periods and the limited number of patients did not allow us to investigate the impact of the COVID‐19 pandemic on long‐term outcome measures such as disease‐free survival.…”

“…However, the decision to resume ddAC was made based on our own data that the proportion of those who completed perioperative chemotherapy was equivalent between ddAC and conventional AC when both were followed by a taxane. 18 Third, short follow‐up periods and the limited number of patients did not allow us to investigate the impact of the COVID‐19 pandemic on long‐term outcome measures such as disease‐free survival. Despite these limitations, we think that our results are important as a basis for considering breast cancer care under the COVID‐19 pandemic, which is expected to continue for some time.…”

Avaliação da Hipossalivação e Xerostomia em Pacientes Oncológicos em Tratamento Quimioterápico

“…Consequentemente, o protocolo quimioterápico mais observado nos pacientes era para o tratamento do câncer de mama, sendo a combinação "doxorrubicina + ciclofosfamida" a mais utilizada. amplamente utilizado no tratamento do câncer de mama, sobretudo seguido da aplicação de um taxano 20 , cuja combinação pode também ser observada nos resultados deste estudo ocupando o segundo lugar do protocolo mais empregado.…”