ISI Impact Factor (2004): 1.096

Editor-in-Chief
Prof. Yi-Fei WANG,

Anemia in patients on combined androgen block therapy for prostate cancer

Li-Xin Qian, Li-Xin Hua, Hong-Fei Wu, Yuan-Geng Sui, Shuang-Guan Cheng, Wei Zhang, Jie Li, ¹Xin-Ru Wang

Asian J Androl  2004 Dec; 6: 383-384       

Keywords: prostate cancer; androgen block; anemia

Abstract

Aim: To study the effect of combined androgen block therapy on hemoglobin and hematocrit values in patients with prostate cancer. Methods: One hundred and thirty-six patients with adenocarcinoma of prostate were treated with combined androgen block (orchiectomy and flutamide 250 mg, tid). Complete blood counts were determined before and after 1, 2, 3, 6, 9 and 12 months of therapy. Results: The hemoglobin and hematocrit levels declined significantly in all patients and at all the time points after treatment (P<0.05). Conclusion: Prostate cancer patients treated with combined androgen block would develop obvious anemia. Recombinant human erythropoietin can be used to treat patients with severe anemia.

1 Introduction

From March 1996 to October 2001, 136 patients with adenocarcinoma of the prostate were treated with combined androgen blockade (CAB). The levels of hemoglobin and hematocrit value were determined.

2 Patients and methods

The mean age of the 136 cases is 70.1 (54 to 85) years. Pathological gradings of the adenocarcinoma were as follows: high grade in 38 cases, medium in 74 cases and low in 24 cases. The clinical staging (UICC staging) included 12 cases with T1N0M0, 21 with T2N0M0, 33 with T3N0M0 and 70 with T1-4N1-4M0-1. They were all treated with CAB, bilateral orchiectomy plus flutamide 250 mg tid. The levels of hemoglobin and hematocrit were determined before and 1, 2, 3, 6, 9 and 12 months after therapy. Six patients with severe anemia were treated with recombinant human erythropoietin (RHE), 3000 units subcutaneously every 2 days. Hemoglobin and hematocrit recovered to normal after 6 - 8 doses of RHE.

The clinical data is studied with mean±SD, paired t-test and c² test and the P values determined.

3 Results

In 136 patients, 120 patients completed the study and 16 cases not, including 6 patients with serum PSA elevated and 10 patients with abnormal liver function. After CAB treatment, the levels of hemoglobin and hematocrit decline significantly (P<0.05) (Table 1). The levels of hemoglobin and hematocrit declined more than 10 % in 108 patients (90.0 %) and more than 25 % in 18 patients (15.0 %) with 14 cases (11.7%) complained of weakness and dyspnea after exertion. There was no significant difference in lowering the levels of hemoglobin and hematocrit among the patients with different pathological grading and clinical staging (P>0.05). Six serious cases recovered after RHE treatment.

Table 1. Changes in hemoglobin and hematocrit after combined androgen blockade therapy (mean±SD, n=136).

Androgens activate haematopoietic stem cells and stimulate the production of erythropoietin [1]. It was indicated that testosterone and 5b-dihydrotestosterone stimulate the maturation of early erythroid precursors and testosterone and 5b-dihydrotestosterone stimulate erythropoietin production in laboratory animals [2]. Before the discovery of recombinant erythropoietin, androgens were used clinically to improve haematocrit levels in anaemic patients [1].

Ornstein et al [1] indicated that the serum level of testosterone decreased after castration within 10 days and haemoglobin levels declined to a mean level 1.0 g/dL 40 days following orchidectomy in six men with prostate cancer who underwent castration. In recent years the anaemic effects of hormonal therapy in patients with prostate cancer were studied. Weber et al [3] documented that six months of androgen deprivation with drugs (luteinizing hormone-releasing hormone agonists) might lead to a decrease in hemoglobin level within the normal range by 3.7 % in seven patients with BPH (benign prostate hyperplasia). Fonseca et al [4] performed orchidectomy in 64 patients with adenocarcinoma of the prostate. They found that the hemoglobin level decreased below the normal range in 37 cases (57 %) four years after the operation. It was believed that the result was caused by the androgen deprivation which was not due to disease progressing or other possible factors.

CAB or maximal androgen blockade (MAB) were used extensively as the endocrine treatment and used as supplementary treatment before radical prostatectomy or pelvic radiotherapy in the past 10 years. Strum et al [2] described 142 patients receiving CAB. One hundred and thirty-three patients were studied for the assessment of continuously declining of hemoglobin levels. Hemoglobin level was declining to the nadir at a mean time of 5.6 months. Arango et al [5] documented that treatment with CAB (luteinizing hormone-releasing hormone agonists plus flutamide) for 3 months before radical prostatectomy markedly decreased the levels of hemoglobin and hematocrit and blood transfusion may be needed perioperatively. The anemia is a kind of normochromic normocytic anemia.

The degree of the anemia in the patients treated with CAB can be more serious than those only with the drug or only with castration and androgen receptor blockers (e.g. flutamide). The mechanism of CAB leading to anemia may include the reduction of erythropoiesis due to low androgen level, the elimination of androgens and blockade of androgen receptors and other anemia pathogenic factors [6].

The patients exhibiting serious anemia with angina, dyspnea or difficulty in respiration after androgen deprivation procedures can be treated with recombinant human erythropoietin (RHE). It is reported that stopping the CAB treatment may improve the anemia [2].

This program is supported by the Specific Grant of National Key Basic Research Program of China(2001CCA04900) and the Study on the assessment models and mechanisms of human disease induced by environmental pollutants.

References

[1] Ornstein DK, Beiser JA, Andriole GL. Anaemia in men receiving combined finasteride and flutamide therapy for advanced prostate cancer. BJU Int 1999; 83: 43-6.
[2] Strum SB, McDermed JE, Scholz MC, Johnson H, Tisman G. Anaemia associated with androgen deprivation in patients with prostate cancer receiving combined hormone blockade. Br J Urol 1997; 79: 933-41.
[3] Weber JP, Walsh PC, Peters CA, Spivak JL. Effect of revesible androgen deprivation on hemoglobin an serum immunoreactive erythropoietin in men. Am J Hematol 1991; 36: 190-4.
[4] Fonseca R, Rajkumar SV, White WL, Tefferi A, Hoagland HC.Anemia after orchiectomy. Am J Hematol 1998; 59: 230-3.
[5] Arango Toro O, Lorente Garin JA, Bielsa Gali O, Grino Garreta J, Gelabert Mas A. Anemia and neoadjuvant hormone therapy in radial surgery of localized cancer of the prostate. Actas Urol Esp 2001; 25: 105-9.

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Correspondence to: Dr. Li-Xin Qian, Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029,China.
Tel: +86-25-8371 8836 ext 6698, Fax: +86-25-8372 4440
Email: qianlx@jlonline.com
Received 2003-12-01 Accepted 2004-07-20