title: Dose-escalated CHOP plus etoposide (MegaCHOEP) followed by repeated stem cell transplantation for primary treatment of aggressive high-risk non-Hodgkin lymphoma.
abstract: Feasibility, safety, and efficacy of a 4-course high-dose chemotherapy (HDT) protocol including autologous stem cell transplantation (SCT) after courses 2, 3, and 4 was investigated in 110 patients, aged 18 to 60 years, with primary diagnosis of aggressive NHL (aNHL), and lactic dehydrogenase (LDH) levels above normal. At dose level 1 (DL1), course 1 consisted of cyclophosphamide 1500 mg/m2, doxorubicin (Adriamycin) 70 mg/m2, vincristine 2 mg, etoposide 450 mg/m2, and prednisone 500 mg. With courses 2 and 3 cyclophosphamide and etoposide were escalated to 4500 mg/m2 and 600 mg/m2, respectively. With course 4 cyclophosphamide and etoposide were given at 6000 mg/m2 and 1000 mg/m2, respectively. At DL2 etoposide was further increased to 600, 960, 960, and 1480 mg/m2 with courses 1 to 4, respectively. Therapy as per protocol was completed by 81.8% of patients. Overall survival at 5 years was 67.2%, freedom from treatment failure (FFTF) was 62.1%, and treatment-related mortality was 4.5%. There was a trend to better FFTF at DL2 compared to DL1 (66.9% versus 54.2%). Repetitive HDT with escalated CHOP plus etoposide is feasible and effective treatment of patients with aNHL. DL2 of this therapy is being used in an ongoing phase 3 study.
authors.affiliation: Department of Hematology and Oncology, University Hospital of Göttingen, Robert-Koch-Strasse 40, D-37075 Göttingen, Germany. b.glass@med.uni-goettingen.de
authors.forename: Bertram
authors.initials: B
authors.lastname: Glass
authors.forename: Marita
authors.initials: M
authors.lastname: Kloess
authors.forename: Martin
authors.initials: M
authors.lastname: Bentz
authors.forename: Günter
authors.initials: G
authors.lastname: Schlimok
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.forename: Alfred
authors.initials: A
authors.lastname: Feller
authors.forename: Lorenz
authors.initials: L
authors.lastname: Trümper
authors.forename: Markus
authors.initials: M
authors.lastname: Loeffler
authors.forename: Michael
authors.initials: M
authors.lastname: Pfreundschuh
authors.forename: Norbert
authors.initials: N
authors.lastname: Schmitz
mesh_terms: D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000401:mortality / Q000628:therapy*; D016399:Lymphoma, T-Cell / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D012189:Retrospective Studies; D012307:Risk Factors; D033581:Stem Cell Transplantation / Q000401:mortality; D014182:Transplantation, Autologous; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone