title: Phase I/II trial of nonpegylated liposomal doxorubicin, cyclophosphamide, vincristine, and prednisone in the treatment of newly diagnosed aggressive non-Hodgkin's lymphoma.
abstract: BACKGROUND
  The toxicity and efficacy of nonpegylated liposomal doxorubicin (TLC D-99) when substituted for conventional doxorubicin in the CHOP (doxorubicin/cyclophosphamide/vincristine/prednisone) regimen were evaluated in the treatment of newly diagnosed patients with aggressive non-Hodgkin's lymphoma. Liposomal doxorubicin at doses of 40 mg/m2, 50 mg/m2, 60 mg/m2, and 80 mg/m2 was given with fixed doses of cyclophosphamide, vincristine, and prednisone. Chemotherapy cycles were repeated every 21 days.
  
  
  METHODS
  Forty-seven patients with a median age of 55 years (range, 25-83 years) were studied.
  
  
  RESULTS
  No dose-limiting toxicities were observed at any level. Reversible grade 3/4 neutropenia was the most common toxicity (95.8%). Most nonhematologic side effects were grade 1/2 in severity. Complete remissions were documented in 31 of 46 evaluable patients (67.4%) and partial remissions in 7 (15.2%), for an overall major response rate of 82.6%. The median duration of complete remission is > or = 27.7 months (range, 2.4 months to > or = 59.8 months). An exploratory objective was to correlate multidrug resistance-1 (MDR-1) expression with outcome. Immunohistochemistry for MDR-1-related p-glycoprotein was assessed in lymphoma tissues from 27 patients. Of the 27 lymphoma tissues studied, 8 (30%) were MDR-1 positive at diagnosis. The complete response rate was 63% in MDR-1-positive lymphomas and 74% in the MDR-1-negative cases (P = 0.66).
  
  
  CONCLUSIONS
  Nonpegylated liposomal doxorubicin in combination with cyclophosphamide, vincristine, and prednisone is an active regimen for patients with newly diagnosed, aggressive non-Hodgkin's lymphoma. The regimen is relatively well tolerated, with hematologic suppression as the major toxicity. Liposomal encapsulation might evade resistance caused by MDR-1 expression.
authors.affiliation: Division of Hematology, Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA. tulpule@usc.edu
authors.forename: Anil
authors.initials: A
authors.lastname: Tulpule
authors.forename: Byron M
authors.initials: BM
authors.lastname: Espina
authors.forename: Nancy
authors.initials: N
authors.lastname: Berman
authors.forename: Laura H
authors.initials: LH
authors.lastname: Buchanan
authors.forename: D Lynne
authors.initials: DL
authors.lastname: Smith
authors.forename: Andy
authors.initials: A
authors.lastname: Sherrod
authors.forename: Dharshika
authors.initials: D
authors.lastname: Dharmapala
authors.forename: Conway
authors.initials: C
authors.lastname: Gee
authors.forename: William D
authors.initials: WD
authors.lastname: Boswell
authors.forename: Bharat N
authors.initials: BN
authors.lastname: Nathwani
authors.forename: Lauri
authors.initials: L
authors.lastname: Welles
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Levine
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage*; D012074:Remission Induction; D013997:Time Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage*
chemical_list: D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone