Leucocyte nadir as a marker for chemotherapy efficacy in node-positive breast cancer treated with adjuvant CMF

Abstract

SummaryThe purpose of this study was to examine the association between the leucocyte nadir and prognosis in breast cancer patients receiving adjuvant chemotherapy consisting of cyclophosphamide, methotrexate and fluorouracil (CMF). Three hundred and sixty-eight patients with node-positive breast cancer without distant metastases were treated with six cycles of adjuvant CMF. Some patients (n = 60) also received tamoxifen. All patients underwent surgery and received radiotherapy to the axillary and supraclavicular lymph nodes and the chest wall. The effect of leucopenia caused by CMF on distant disease-free survival (DDFS) and overall survival (OS) was assessed. A low leucocyte nadir during the chemotherapy was associated with a long DDFS in univariate analysis when tested as a continuous variable (the relative risk (RR) 1.3, 95% confidence interval (CI) 1.04-1.06, P = 0.02). Similarly, when the leucocyte nadir count was divided into tertiles, the patients who had the highest nadir values during the six-cycle treatment had worst outcome (RR 1.6, 95% CI 1.07-2.5, P = 0.02). However, in a multivariate analysis only the number of affected lymph nodes, tumour size, progesterone receptor status, surgical procedure, age and adjuvant tamoxifen therapy retained prognostic significance, whereas the leucocyte nadir count did not. A low leucocyte nadir during the adjuvant CMF chemotherapy is associated with favourable DDFS and it may be a useful biological marker for chemotherapy efficacy.

Predictive value of chemotherapy-induced neutropenia for the efficacy of oral fluoropyrimidine S-1 in advanced gastric carcinoma

“…Since the late 1990s, several studies have linked myelosuppression induced by adjuvant chemotherapy to a better outcome in patients with breast cancer (Saarto et al, 1997;Poikonen et al, 1999;Mayers et al, 2001;Cameron et al, 2003). Recently, Di Maio et al (2005) reported the first evidence regarding the relationship between chemotherapy-induced neutropenia and longer survival time in patients with an advanced stage of cancer.…”

“…The survival curves of the four categories were estimated by the Kaplan -Meier method and compared by the log-rank test. This approach, considering the occurrence of myelosuppression during chemotherapy to be a baseline feature, has been used in many studies (Saarto et al, 1997;Poikonen et al, 1999;Cameron et al, 2003;Nakata et al, 2006) and is appropriate in an adjuvant setting, as the number of patients who die during the chemotherapy treatment period is usually negligible. In advanced cancer, however, considering myelosuppression to be a baseline feature can lead to a large bias because fewer cycles of chemotherapy can be administered due to poorer outcomes, consequently leading to a lower chance of neutropenia.…”

“…Therefore, many oncologists may consider that the absence of haematological toxicity will raise the hope of an adequate tumour response without myelosuppression. Since the late 1990s, however, several studies have reported that neutropenia or leucopenia occurring during chemotherapy is a sign of patient's response to adjuvant chemotherapy in women with breast cancer; a significantly longer survival results in patients who have those haematological toxic effects (Saarto et al, 1997;Poikonen et al, 1999;Mayers et al, 2001;Cameron et al, 2003). A recent study by Di Maio et al (2005) confirmed the positive correlation between chemotherapy-induced neutropenia and increased survival in a pooled analysis of three randomised trials that included a total of 1265 patients with advanced non-small-cell lung cancer (NSCLC).…”

Does chemotherapy-induced neutropaenia result in a postponement of adjuvant or neoadjuvant regimens in breast cancer patients? Results of a retrospective analysis

“…This has been confirmed by other retrospective studies using either CMF (Mayers et al, 2001) or anthracyclinebased regimens (Chirivella et al, 2006). Moreover, numerous retrospective studies suggested that early breast cancer patients who experienced the greater myelosuppression related to adjuvant chemotherapy have a trend towards a better outcome (Saarto et al, 1997;Colleoni et al, 1998;Poikonen et al, 1999;Mayers et al, 2001;Cameron et al, 2003). Additionally, prospective studies demonstrated that an increase in chemotherapy RDI resulted in an improvement of DFS and OS (Budman et al, 1998;Citron et al, 2003;Bonneterre et al, 2005).…”

Association of Chemotherapy-induced Leucopenia with Treatment Outcomes in Advanced Non-small-cell lung Cancer Cases Receiving the NP Regimen

“…Chemotherapy induced leucopenia (CIL) is a common and significant adverse effect of chemotherapy, defined as a leucopenia count of <4.00×10 9 /L, and it can put patients at risk for severe infection (Lyman et al, 2010;Lyman and Kleiner, 2011). It is also the major dose-limiting toxicity, and it is frequently managed by reducing or delaying the chemotherapy (Delbaldo et al, 2004;Hangaishi, 2011;Saloustros et al, 2011), which can result in lower diseasefree and overall survival (Kvinnsland et al, 1999;Gurney Schiller et al, 2002;Pfister et al, 2004), However, research (Shitara et al, 2011) on breast cancer (Saarto et al, 1997;Poikonen et al, 1999;Cameron et al, 2003;Shitara et al, 2010;Han et al, 2012), small-cell lung cancer (Banerji et al, 2006), osteosarcoma (Ratain, 1998), ovarian cancer (Sawyer and Ratain., 2001) have shown the association between chemotherapy-induced neutropenia and better clinical outcome for patients. It is not associated with increased risk for death (Souza-Dantas et al, 2011).…”