Prevention of Anemia in Patients with Solid Tumors Receiving Platinum-Based Chemotherapy by Recombinant Human Erythropoietin (rHuEpo): A Prospective, Open Label, Randomized Trial by the Hellenic Cooperative Oncology GroupBamias A.a · Aravantinos G.d · Kalofonos C.b · Timotheadou N.c · Siafaka V.e · Vlahou I.f · Janinis D.d · Pectasides D.g · Pavlidis N.a · Fountzilas G.c
Oncology Departments,aIoannina University Hospital, Ioannina, bRio University Hospital, Patras, and cAHEPA University Hospital, Thessaloniki, dThird Internal Medicine Department, Agii Anargyri Hospital, Athens, ePsycho-Oncology Unit and fBiochemistry Department, Ioannina University Hospital, Ioannina, and gFirst Internal Medicine Department, Metaxa Hospital, Athens, Greece
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
Objectives: Platinum compounds are commonly associated with significant anemia. Erythropoietin administration has been found effective in correcting anemia in patients with solid tumors receiving chemotherapy. We conducted a randomized, open label study to assess the efficacy of erythropoietin in preventing transfusions and significant anemia (hemoglobin <10 g/dl) in patients with solid tumors receiving platinum-based chemotherapy. Methods: One hundred forty-four patients with hemoglobin <13 g/dl were included in this study (72 in each arm). Patients in the treatment arm received 10,000 U of recombinant human erythropoietin (rHuEPO) thrice weekly s.c. during platinum-based chemotherapy, while patients in the control arm received no treatment. Results: All patients were evaluable for efficacy. Transfusions were reduced by the administration of rHuEPO (15.3 vs. 33.3%, p = 0.019), and fewer patients developed significant anemia (16.6 vs. 45.8%, p < 0.0001). Subgroup analysis showed that patients with observed to predicted (O/P) serum erythropoietin levels ≤0.9 and responders to chemotherapy benefited from erythropoietin administration in contrast to patients with O/P >0.9 or non-responders. Conclusions: rHuEPO at a dose of 10,000 U thrice weekly prevents transfusions and development of significant anemia in patients with solid tumors receiving platinum-based chemotherapy.
© 2003 S. Karger AG, Basel
Johnson R, Roodman G: Hematological manifestations of malignancy. Dis Mon 1989;35:726–768.
Doweiko JP, Goldberg MA: Erythropoietin therapy in cancer patients. Oncology 1991;5:31–37.
- Miller CB, Jones RJ, Piantadosi S, Abeloff MD, Spivak JL: Decreased erythropoietin response in patients with the anemia of cancer. N Engl J Med 1990;322:1689–1692.
- Kaye SB, Lewis CR, Paul J, Duncan ID, Gordon HK, Kitchener HC, Cruickshank DJ, Atkinson RJ, Soukop M, Rankin EM: Randomized study of two doses of cisplatin with cyclophosphamide in epithelial ovarian cancer. Lancet 1992;340:329–333.
- Martoni A, Panetta A, Angelelli B, Melotti B, Pannuti F: A phase II study of carboplatin and cyclophosphamide in advanced ovarian carcinoma. J Chemother 1993;5:47–51.
- Oberhoff C, Neri B, Amadori D, Petry KU, Gamucci T, Rebmann U, Nowrousian MR, Voigtmann R, Monfardini S, Armand JP, Herrmann R, Netter-Pinon J, Tubiana-Mathieu N, Zwierzina H: Recombinant human erythropoietin in the treatment of chemotherapy-induced anemia and prevention of transfusion requirement associated with solid tumors. A randomized, controlled study. Ann Oncol 1998;9:255–260.
- Rothmann SA, Paul P, Weick JK, McIntyre WR, Fantelli F: Effect of cis-diamiminedichloroplatinum on erythropoietin production and hemopoietic progenitor cells. Int J Cell Cloning 1985;3:415–423.
Cella D: The Functional Assessment of Cancer Therapy-Anemia (FACT-An) scale: A new tool for the assessment of outcomes in cancer anemia and fatigue. Semin Hematol 1997;34(suppl 2):13–19.
Ludwig H, Sundal E, Pesherstorfer M, Leitgeb C, Bauernhofer T, Beinhauer A, Samonigg H, Kappleper AW, Fritz E: Recombinant human erythropoietin for the correction of cancer-associated anemia with and without concomitant cytotoxic chemotherapy. Cancer 1995;73:2535–2542.
- Surgenor DM, Wallace EL, Hao SHS, Chapman RH: Collection and transfusion of blood in the United States 1982–1988. N Engl J Med 1990;322:1646–1651.
- Pincus T, Olsen W, Russell I, Wolfe F, Harris ER, Schnitzer TJ, Boccagno JA, Krantz SB: Multicenter study of recombinant human erythropoietin in correction of anemia in rheumatoid arthritis. Am J Med 1990;89:161–168.
- Eschbach JW, Egrie JC, Downing MR, Browne JK, Adamson JW: Correction of the anemia of end-stage renal disease with recombinant human erythropoietin. Results of a combined phase I and phase II clinical trial. N Engl J Med 1987;316:73–78.
Abels RI, Larholt KM, Krantz KD, Bryant EC: Recombinant human erythropoietin (r-HuEPO) for the treatment of the anemia of cancer. Acta Haematol 1992;87:4–11.
- Case DC, Bukowski M, Carey RW, Fishkin EH, Henry DH, Jacobson RJ, Jones SE, Keller AM, Kugler JW, Nichols CR, Salmon SE, Silver RT, Storniolo AM, Wampler GL, Dooley KM, Nelson RA, Abels RI: Recombinant human erythropoietin therapy for anemic cancer patients on combination chemotherapy. J Natl Cancer Inst 1993;85:801–806.
- Demetri GD, Kris M, Wade J, Degos L, Cella D: Quality-of-life benefit in chemotherapy patients treated with epoetin α is independent of disease response or tumor type: Results from a prospective community oncology study. Procrit Study Group. J Clin Oncol 1998;16:3412–3425.
- Dunphy FR, Dunleavy TL, Harrison BR, Boyd JS, Varvares MA, Dunphy CH, Rodriguez JJ, McDonough EM, Minster JR, McGrady MD: Erythropoietin reduces anemia and transfusions after chemotherapy with paclitaxel and carboplatin. Cancer 1997;79:1623–1628.
- Del Mastro L, Venturini M, Lionetto R, Garrone O, Melioli G, Pasquetti W, Sertoli MR, Bertelli G, Cavanese G, Constantini M, Rosso R: Randomized phase III trial evaluating the role of erythropoietin in the prevention of chemotherapy-induced anemia. J Clin Oncol 1997;15:2715–2721.
James RD, Wilkinson PM, Belli F, Welch R, Cowan R: Recombinant human erythropoietin in patients with ovarian carcinoma and anemia secondary to cisplatin and carboplatin chemotherapy: Preliminary results. Acta Haematol 1992;87(suppl 1):12–15.
- Glaspy J, Bukowski R, Steinberg D, Taylor C, Tchekmedyian S, Vadhan-Raj S: Impact of therapy with epoetin α on clinical outcomes in patients with nonmyeloid malignancies during cancer chemotherapy in community oncology practice. Procrit Study Group. J Clin Oncol 1997;15:1218–1234.
- Ludwig H, Fritz E, Leitbeg C, Pecherstofer M, Samonigg H, Schuster J: Prediction of response to erythropoietin treatment in chronic anemia of cancer. Blood 1994;84:1056–1063.
- Benguin Y, Yerna M, Loo M, Weber M, Fillet G: Erythropoiesis in mutliple myeloma: Defective red cell production due to inappropriate erythropoietin production. Br J Haematol 1992;82:648–653.
- Coates A, Gebski V, Bishop JF, Jeal PN, Woods RL, Snyder R, Tattersall MH, Byrne M, Harvey V, Gill G: Improving the quality of life during chemotherapy for advanced breast cancer: A comparison of intermittent and continuous treatment strategies. N Engl J Med 1987;317:1490–1495.
Cella DF, Bonomi AE: Measuring quality of life: 1995 Update. Oncology 1995;9(suppl 11):47–60.
World Health Organization: WHO Handbook for Reporting Results of Cancer Treatment. WHO Offset Publication No 48. Geneva, WHO, 1979.
Looney W, Stanley B: Exploratory repeated measures analysis for two or more groups. Am Stat 1977;43:220–225.
Fisher L, Belle G: Biostatistics: A Methodology for the Health Sciences. New York, Wiley, 1993.
Fisher RA: The logit of inductive inference. J R Stat Soc 1935;98:39–82.
- Mehta CR, Patel NR, Tsiatis AA: Exact significance testing to establish treatment equivalence with ordered categorical data. Biometrics 1984;40:819–825.
- Koch G, Landis J, Freeman J, Freeman JH Jr, Lehnen RC: A general methodology for the analysis of experiments with repeated measurement of categorical data. Biometrics 1977;33:133–158.
Koch G, Amara A, Stokes E, Gillings B: Some views on parametric and non-parametric analysis for repeated measurements. Int Stat Rev 1980;48:249–265.
Hosmer DW, Lemeshow S: Applied Logistic Regression. New York, Wiley, 1989.
Mantel N, Byar D: Marginal homogeneity, symmetry and independence. Commun Stat 1978;A7:953–976.
- Breslow N, Day N: Indirect standardization and multivariate models for rates, with reference to the age adjustment of cancer incidence and relative frequency data. J Chronic Dis 1975;28:289–303.
- Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC: The European Organization for Research and Treatment of Cancer QLQ-C30: A quality-of-life instrument for use in clinical trials in oncology. J Natl Cancer Inst 1993;85:365–376.
- Platanias LC, Miller GB, Mick R, Hart RD, Ozer H, McEvilly JM, Jones RJ, Ratain MJ: Treatment of chemotherapy-induced anemia with recombinant human erythropoietin in cancer patients. J Clin Oncol 1991;9:2021–2026.
- Glimelius B, Linné T, Hoffman K, Larsson L, Svensson JH, Nasman P, Svensson B, Helmers C: Epoetin beta in the treatment of anemia in patients with advanced gastrointestinal cancer. J Clin Oncol 1998;16:434–440.
- Groopman JE, Itri LM: Chemotherapy-induced anemia in adults: Incidence and treatment. J Natl Cancer Inst 1999;91:1616–1634.
- Skillings JR, Sridhar FG, Wong C, Paddock L: The frequency of red cell transfusion for anemia in patients receiving chemotherapy. Am J Clin Oncol 1993;16:22–25.
Canetta R, Rozencweig M, Carter SK: Carboplatin: The clinical spectrum to date. Cancer Treat Rep 1985;12(suppl A):125–136.
- Von Hoff DD, Schilsky R, Reichert CM, Reddick RL, Rozencweig M, Young RC, Muggia FM: Toxic effects of cisdichlorodiammineplatinum (II) in man. Cancer Treat Rep 1979;63:1527–1531.
- Piroso E, Erslev A, Caro J: Inappropriate increase in erythropoietin titers during chemotherapy. Am J Hematol 1989;32:248–254.
Cazzola M, Messinger D, Battistel V, Bron D, Cimino R, Enller-Ziegler L, Essers U, Greil R, Grossi A, Jager G, LeMevel A, Najman A, Silingardi V, Spriano M, van Hoof A, Ehmer B: Recombinant human erythropoietin in the anemia associated with multiple myeloma or non-Hodgkin’s lymphoma: Dose finding and identification of predictors of response. Blood 1995;86:4466–4453.
Huinik WW: Controlled multicenter study of the influence of two different dosages of subcutaneous rHuEPO on the development of anemia and transfusion dependency in patients with ovarian carcinoma treated with platinum-based combination chemotherapy; in Smyth JF, Boogaerts MA, Ehmer BRM (eds): rhErythropoietin in Cancer Supportive Treatment. New York, Dekker, 1996, pp 99–112.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.