Effect of intravenously administered iron sucrose on the prevention of anemia in the cervical cancer patients treated with concurrent chemoradiotherapy
Introduction
Cervical carcinoma is second only to breast cancer worldwide as the most common malignancy in women with respect to both incidence and mortality [1]. It is also the most prevalent gynecologic malignancy in South Korea. According to the 2003 annual report of the Korean Ministry of Health and Welfare, approximately 4000 women annually are newly diagnosed with invasive disease, suggesting the importance in public health welfare [2].
Concurrent chemoradiotherapy has been used as the standard therapeutic modality for locally advanced cervical cancer since 1999 [3], [4], [5]. Using cisplatin-based chemotherapy, five prospective randomized clinical studies documented a reduction of 30–50% for the risk of death for patients treated with concurrent chemoradiotherapy when compared with radiotherapy alone [3], [6], [7], [8], [9]. However, in the cases treated with chemoradiotherapy, more severe anemia could be developed than with the cases treated with radiotherapy alone, because of the myelosuppressive effect of chemotherapeutic drugs on bone marrow. Anemia is one of the most common complications in cancer patients receiving chemoradiotherapy. If hemoglobin value lower than 12.0 g/dl were defined as anemia, retrospective studies indicate that the incidence of anemia in colorectal cancer, lung cancer and cervical cancer treated with radiation was 67%, 63%, and 82%, respectively, at the endpoint of treatment [10]. Anemia was induced in over 50% of cervical cancer patients treated with concurrent chemoradiotherapy, and thus it is an important clinical issue which could not be overlooked [3].
Many studies have reported a correlation between anemia and poor disease-free and overall survival in patients undergoing radiation for cervical cancer [11], [12], [13]. The mechanism of such negative effects on the prognosis of anemic cervical cancer patients who received radiation therapy has not yet been clearly elucidated, nevertheless, it has been suggested that oxygen supply is impaired due to anemia, resulting in the decrease of sensitivity of tumors to radiation: cells under hypoxic condition show 2–3 times higher resistance to radiation than cells under normal oxygen condition [4], [14], [15]. In addition, a couple of studies have shown an adverse relationship between anemia and the prognosis in patients receiving concurrent chemoradiotherapy for cervical carcinoma [16], [17].
Patients with anemia can be treated with blood transfusion or the administration of erythropoietin or the administration of iron. However, there are some concerns regarding cost-effectiveness, the risk of transfusion-related infection and the stimulatory or antiapoptotic effect of erythropoietin on cancer cells [18], [19], [20]. Furthermore, the Southwest Oncology Group (SWOG) recommended that recombinant human erythropoietin not be used routinely in women with cervical cancer during chemoradiotherapy due to a high rate of deep vein thrombosis [21].
Recently, it has been reported that intravenous administration of iron could ameliorate anemia more rapidly than oral iron in cancer patients treated with concurrent chemoradiotherapy and that it could be of help to patients who suffer from the malabsorption of iron or cannot withstand it [22]. Generally, three types of non-oral iron substances including iron dextran, ferric gluconate and iron sucrose have been used, and administration of iron sucrose among them has been reported to induce least hypersensitivity [23].
To the best of our knowledge, there has been no report to investigate the potential that the intravenous administration of iron sucrose could decrease the transfusion frequency and its amount in cervical cancer patients treated with concurrent chemoradiotherapy.
Therefore, we examined in the present study whether the administration of iron sucrose to cervical cancer patients who were treated with concurrent chemoradiotherapy and under mild anemic condition could prevent the exacerbation of anemia and reduce the transfusion volume.
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Materials and methods
The present study was conducted prospectively on 75 patients who were diagnosed as having cervical cancer from October 2003 to December 2005 and treated with concurrent chemoradiotherapy. All study participants gave written informed consent. The general characteristics of patients, such as age, stage, tumor size, cell type, chemotherapeutic drugs and initial hemoglobin, the initial hematocrit, the hematocrit and hemoglobin volume in each chemotherapy cycle were examined. In addition, among the
Results
The mean age of patients in the study group was 55.1 years (range, 41–77 years) and the control group was 50.1 years (range, 38–75 years). The mean value of the initial serum hemoglobin value in the study group was 11.27 ± 1.94 g/dl, and 11.33 ± 2.14 g/dl in the control group, and a significant difference was not detected (P = 0.90). Other patient characteristics between the study and control groups were not significantly different (Table 1).
A similar hemoglobin distribution was shown in both the
Discussion
Anemia, whether it is present at baseline or develops with treatment, is prevalent among cervical cancer patients. A number of factors contribute to the high incidence of cancer-associated anemia. These include not only chemoradiotherapy-induced myelosuppression, but also bleeding, hemolysis, bone marrow infiltration by tumor, nutritional deficiencies, and cytokine-mediated anemia of chronic disease [10], [24], [25], [26]. In addition, Birgegard et al. reported that anemia pertinent to cancer
Acknowledgments
This study was supported by the Brain Korea (BK) 21 Project for Medical Sciences, Yonsei University and a grant of the Korean Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (0412-CR01-0704-0001). We thank H.K.Park (Choongwae Pharma. Corp.) for his assistance in preparing this work.
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