haematologica vol. 87(8):august 2002 Cyclophosphamide, pegylated liposomal doxorubicin (Caelyx  ), vincristine and prednisone (CCOP) in elderly patients with diffuse large B-cell lymphoma: results from a prospective phase II study RODRIGO MARTINO,* GRANADA PEREA ,* MARÍA DOLORES CABALLERO,° MARÍA V. MATEOS,* J OSEP M. RIBERA , # J AIME PÉREZ DE O TEYZA , @ REYES A RRANZ, ^ MARÍA J OSÉ T EROL , § J ORGE SIERRA ,* J ESÚS F. SAN MIGUEL ° Malignant Lymphomas research paper haematologica 2002; 87:822-827 http://www.haematologica.ws/2002_08/822.htm Background and Objectives. Anthracycline-based com- bination chemotherapy regimens are the standard ther- apy for patients with diffuse large B-cell lymphoma (DLB- CL), but such regimens may be poorly tolerated in elder- ly patients. Design and Methods. In a prospective phase II study we analyzed the feasibility of a regimen (CCOP) that includes pegylated liposomal doxorubicin (Caelyx  ) plus vin- cristine, cyclophosphamide and prednisone in patients with DLBCL above the age of 60 years. Results. Thirty-three patients, with a median age of 74 years, were enrolled in the study. The overall response rate was 64% (49% complete remissions and 15% par- tial remissions). The estimated one-year overall and event-free survivals were 55% (95% CI, 38-72) and 45% (95%CI, 28-62), respectively. The only relevant toxicity was neutropenia, which reached grades 3-4 in 21 cases (64%). Interpretation and Conclusions. These results suggest that CCOP appears to be an acceptable alternative for elderly patients with DLBCL, and randomized trials against a conventional doxorubicin-containing regimen are justified. © 2002, Ferrata Storti Foundation Key words: liposomal doxorubicin, Caelyx  , non-Hodgkin’s lymphoma, elderly. A nthracycline-based combination chemother- apy regimens are the standard therapy for patients with diffuse large B-cell lymphoma (DLBCL), which is the most frequent of the so-called aggressive non-Hodgkin’s lymphomas. 1 The optimal standard management of patients with advanced chronological age is, however, controversial, since these patients tolerate much more poorly the tox- icity of standard chemotherapy. Age is in fact the most important prognostic factor in patients with DLBCL, 2 and the response rate to and tolerance of cyclophosphamide, conventional doxorubicin (or adriamycin), vincristine and prednisone (CHOP) were much worse in patients over 65 years of age in several studies. 3-6 More recent reports on CHOP and other anthracycline- based regimens suggest that the outcome in selected elderly patients is sim- ilar to that in younger patients, but the treatment- related mortality is still between 10 to 15%, most deaths being caused by infections. 7-14 Among the non-hematologic toxicities of adriamycin, grade 3- 4 cardiotoxicity occurred in 3- 8% of patients in these studies. Pegylated liposomal doxorubicin (Caelyx®, Schering Plough S.A., Spain) has been shown to reduce the cardiac toxicity of conventional dox- orubicin while having at least similar efficacy in patients with Kaposi´s sarcoma and several solid tumors, especially breast cancer. 15,16 However, to our knowledge there have been no published stud- ies in patients with lymphoma. We report here the first study of a CHOP-like regimen with the adri- amycin substituted by Caelyx® in patients with DLBCL above 60 years of age. Design and Methods This prospective phase II study was carried out in six centers in Spain between December 1998 and December 2000. The study was approved by the Spanish Drug Agency (Protocol CCOP-LNH98) and each hospital’s ethical committee, and patients Correspondence: Dr. Rodrigo Martino, MD, Servei d'Hematologia Clínica, Hospital de la Santa Creu i Sant Pau, Av. Sant Antoni Mª Claret 167, 08025 Barcelona, Spain. Phone: international +34.9.32919396. Fax: international +34.9. 32919466. E-mail: rmartino@hsp.santpau.es Divisions of Clinical Hematology of *Hospital de la Santa Creu i Sant Pau, Barcelona; ° Hospital Clínico Universitario de Salamanca; # Hospital Germans Trias i Pujol, Badalona; @ Hospital Ramón YCajal, Madrid; ^Hospital de la Princesa, Madrid; § Hospital Clínico de Valencia, Spain ©Ferrata Storti Foundation