Pre-chemotherapy hemoglobin levels and survival in patients with advanced epithelial ovarian cancer who received a first-line taxane/platinum-based regimen: Results of a multicenter retrospective Italian study

Abstract

Objective.

The aim of this retrospective multicenter study was to assess whether the pre-chemotherapy hemoglobin levels have any impact on the clinical outcome of patients with advanced epithelial ovarian cancer who received a first-line taxane/platinum-based regimen.

Methods.

The study was conducted on 315 patients who underwent initial surgery followed by taxane/platinum-based chemotherapy for FIGO stage IIc–IV epithelial ovarian cancer. All the patients had ECOG performance status 0–1 at presentation. The median follow-up of survivors was 36 months (range, 6–120 months).

Results.

The 25%, 50%, and 75% quantiles of hemoglobin levels before starting first-line chemotherapy were 10.2, 11.4, and 12.3 g/dl, respectively. Residual disease after initial surgery (>1 cm versus ≤ 1 cm, P = 0.0013) was the only independent prognostic variable for overall survival. Conversely, hemoglobin levels (<10.2 g/dl versus 10.2–11.4 g/dl versus 11.5–12.3 g/dl versus >12.3 g/dl) were inversely related to overall survival at univariate (P = 0.03) but not at multivariate analysis.

Conclusions.

This investigation showed that hemoglobin levels before starting first-line taxane/platinum-based chemotherapy are not an independent prognostic factor for overall survival in patients with advanced epithelial ovarian cancer.

Introduction

Approximately one third of cancer patients suffer from anemia before any treatment, due to different pathogenetic factors including changes in iron metabolism, endogenous erythropoietin deficiency, or suppression of erythroid progenitor cells by tumor-released cytokines, such as interleukin-1, interferon-gamma, and tumor necrosis factor [1], [2], [3], [4], [5], [6], [7]. Anemia results in a variety of symptoms, including dyspnea, headaches, decline in energy and activity levels, fatigue, and worsening of quality of life [6], [7], [8], [9], [10], [11], [12].

The effects of oxygenation on tumor biology have been long investigated. Some evidences suggest that hypoxia contributes to the malignant behaviour of the disease and that oxygen may play an important role in the response to cancer treatment [13], [14], [15], [16], [17], [18], [19], [20]. In vitro and in vivo experimental studies have shown that hypoxia may provide a selection pressure for tumor cells with higher rates of mutation, which may ultimately result in increased metastatic potential, increased cellular growth, decreased cell response to apoptosis signals, and therapy resistance [13], [17], [18], [20], [21], [22]. Moreover, anemia itself may induce a feedback mechanism that enhances angiogenesis and leads to a higher proliferation rate of tumor cells [21], [23].

Anemia has been found to be a poor prognostic variable in several hematological [24], [25], [26], [27], [28], [29] and non-hematological malignancies [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43]. However, few data are currently available about the clinical relevance of pretreatment hemoglobin levels in patients with primary or recurrent epithelial ovarian cancer [44], [45], [46], [47], [48], [49], [50].

The aim of this retrospective multicenter study was to assess whether the pre-chemotherapy hemoglobin levels have any impact on the clinical outcome of patients with advanced epithelial ovarian cancer who received a first-line taxane/platinum-based regimen.