Pergamon EuropranJoumaIofConVol. 31A,Nos 1304,~~. 2157-2163,1995 Copyright 0 1995 ElsevierScience Ltd Printed in Great Britain. AU rights reserved 0959-8049195 $9.50+0.00 Original Paper A Single-blind, Randomised, Vehicle-controlled Dose-finding Study of Recombinant Human Granulocyte Colony-stimulating Factor (Lenograstim) in Patients Undergoing Chemotherapy for Solid Cancers and Lymphoma A.-M. Seymour,’ E. de Carnpo~,~ N. Thatcher,2 J. De Greve,3 D. Cunningham,4 A. Howell,’ E. Tueni,5 D.G. Bran,’ zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA WI?. Steward,6 W.E. Berdel,7 A. Knuth,8 J. Lorenz,’ A.R. Timothy, lo A. Yver” and M.A. Richards1 Clinical Oncology Unit, Guy’s Hospital, St Thomas Street, London SE1 9RT; 2CRC Department of Medical Oncology, The Christie Hospital and Holt Radium Institute, Wilmslow Road, Manchester M20 9BX, U.K.; 3Department of Medical Oncology and Haematology, Academic Hospital - V.U.B., Laarbeeklan 101, 1090 Brussels, Belgium; 4Department of Oncology, Royal Marsden Hospital, Downs Road, Sutton SM2 5PT, U.K.; 51nstitut J. Bordet, 1 rue Heger Bordet, 1000 Brussels, Belgium; 6Beatson Oncology Centre, The Western Infirmary, Glasgow Gil 6NT, U.K.; 7Klinikum Steglitz, Freie Universitat Berlin, Hindenburgdamm 30, D-12200 Berlin; *Department of Haematology and Oncology, Krankynhaus Nordwest, Steinbacker Hohl2-26,60488 Frankfurt-on-Main; 9Department of Pneumology, Universitatsklinikum Mainz, Langenbeckstr. 1, D55131 Mainz, Germany; lODepartment of Rad.iotherapy and Oncology, St Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, U.K.; and “Chugai-Rhone Poulenc, 20 Avenue Raymond Aron, 92165 Antony Cedex, France This study evaluated the effect of glycosylated recombinant human granulocyte colony-stimulating factor (tHuG- CSF; lenograstim) on neutrophil granulocyte counts and on cells of other haematopoietic lineages in 66 patients with solid cancer or lymphoma who received myelosuppressive chemotherapy. Beginning 1 day after completion of chemotherapy, patients received lenograstim (at dosages of 0.5, 2, 5 or 10 pgkg) or vehicle subcutaneously once daily for 14 consecutive days. Compared with vehicle, lenograstim significantly accelerated neutrophil recovery after chemotherapy in a dose-dependent manner. Mean neutrophil counts recovered to >l.Q x lo9 cells/l by day 13 in the vehicle group compared with days 11, 10,8 and 7 in the 0.5,2,5 and 10 @kg lenograstim groups, respectively. Doses of 0.5 and 2 t&kg of lenograstim had a significant effect on the duration of neutropenia (cl.0 x lo9 cells/l), the area under the absolute neutrophil count (ANC) curve and the time to ANC nadir. The dose of 5 pgkg additionally decreased the total area of neutropenia and gave the narrowest range of values for all neutrophil parameters, while the 10 pgkg dose brought no added benefit. A dose-response effect of lenograstim on time to neutrophil recovery was observed both for patients who received chemotherapy on a single day (n = 35) and for those who received chemotherapy over several days (II = 29). Based on these lklings, a dose of 5 &kg/day was chosen for further trials. Key words: rHuG-CSF, lenograstim, granulocyte colony-stimulating factor, neutropenia, chemotherapy, solid cancer EurJ Cancer, Vol. 31A, Nos 13/14, pp. 2157-2163,1995 Correspondence to M.A. Richards. Revised 26 Sep. 1994; accepted 9 Dec. 1994. 2157