Efficacy and Safety of New Product of Recombinant Erythropoietin to Treat Cisplatin-Containing Regimens-Induced Moderate Anemia in Cancer Patients

Background: Exogenous erythropoietin (EPO) is used widespread to treat patients with chemotherapy-induced anemia. Most of EPO products available in market are quite expensive causing limitation of their use, especially in developing countries. Recently, a new and more economic product of rHu-EPO has been produced in China by recombinant genetic engineering using E.coli. A multi center (in Indonesia), pre- and post-study, open lable without control, has been performed to evaluate the efficacy and safety of this alternative product of rHu-EPO to treat cisplatin-induced anemia in Indonesian population.

Methods: Thirty-seven patients with solid tumors and non-myeloid blood malignancies, receiving standard cisplatin-containing chemotherapy regimens were enrolled into this study. After chemotherapy, hemoglobin level of the patients were monitored since the first cycle of chemotherapy regimen.When moderate anemia (Hb 8 – 10 g/dl) was developed after chemotherapy (in any cycle of chemotherapy), the patient was enrolled into the study based on the inclusion and exclusion criteria. If the Hb level was < 8 g/dl, the patient would receive blood transfusion until 8 g/dl. rHu –EPO was given three times a week, 150 IU/body weight (SC) during the subsequent two cycles of chemotherapy regimens until the Hb level > 10 g/dl.The efficacy was assessed by the increasing of Hb level and hematocrit (Ht) from the base line until > 10 g/dl or Ht > 30 %. The safety was assessed by clinical signs and symptoms of adverse events.

Results: Of 37 patients, only 14 patients could be assessed. The remaining patients were excluded from the study due to some reasons; in 13 patients due to the Hb levels have been kept > 10 g%, 5 patients due to the positive stool Benzidine tests, 1 patient due to the positive Coombs test, and others. Of the analyzed 14 patients, 10 patients with solid tumor cancers and 4 patients with non myeloid hematological cancers, 10 males and 4 females, age ranged 17 – 72 years old, 10 patients received Cisplatin-5 FU regimens, 4 patients received Cisplatin plus other chemotherapies. Pre-EPO laboratory tests revealed the Hb levels ranged 8.83 – 9.45 g/dl, Ht 26.34 – 28.50 %, reticulocyte 1.48 – 2.42 %, MCV 81.92 – 91.48 fl,MCH 27.27 – 30.65 pg, ureum 21.75 – 30.33 mg/dl, creatinine 0.80 – 1.07 mg/dl, erythropoietin level 26.49 – 128.44 U/L, with negative Coombs tests and Benzidine tests. The dosage of rHu-EPO varied between 5,700 – 10,000 IU. The number of rHu-EPO given varied between 2 – 11 cycles. 2 patients received blood transfusions (each 2 units) prior to rHu-EPO. The efficacy of rHu-EPO was shown by statistical evaluation (paired t-test) comparing pre- and post-rHu-EPO, in which the Hb levels were significantly increased (p=0.000) as well as the Ht were significantly increased (p=0.014). The safety of the rHu- EPO was demonstrated by the minimum adverse events developed during the rHu-EPO administration which thought to be due to other drugs (e.g. chemotherapy) which were received concomitantly (fatigue 42.85 %, nausea & vomiting 35.71 %, anorexia 21.42 %, headache 14.28 %, stomatitis 14.28 %, fever 7.14 %, arthralgia 7.14 %, abdominal pain 7.14 %, cough 7.14 %, dysphagia 7.14 %).

Conclusion: The administration of the more affordable rHu-EPO has significantly increased the Hb levels as well as the Ht with minimum adverse events;the adverse events were mostly due to other drugs concomitantly received by the patients in Indonesian population.