title: Sequential doxorubicin and topotecan in relapsed/refractory aggressive non-Hodgkin's lymphoma: results of CALGB 59906.
abstract: Topoisomerase enzymes are critical components of genomic replication and function to minimize torsional stress on DNA. Sequential administration of a topoisomerase II inhibitor followed by a topoisomerase I inhibitor is potentially synergistic due to increased target enzyme levels. Patients with relapsed or refractory aggressive non-Hodgkin's lymphomas (NHL) were eligible for this phase II study of doxorubicin 25 mg/m2 intravenous (IV) on day 1 and topotecan 1.75 mg/m2/day IV on days 3 - 5, every 21 days. The trial objectives included the overall response rate, progression-free survival, and toxicity. Twenty-six patients were enrolled and 25 patients are assessable for toxicity and response. The median age was 58 (range 23 - 74) years. The patients had received a median of two (range one to five) prior regimens, including five patients with a prior stem cell transplant. Five patients (20%, 95% confidence interval 0.07, 0.42) responded with two (8%) complete remissions and three (12%) partial remissions; an additional four (16%) patients had stable disease. Both patients achieving a complete remission had Burkitt's lymphoma. There were no treatment-related deaths. In conclusion, the combination of doxorubicin and topotecan is well tolerated and has modest activity in relapsed/refractory NHL, with occasional patients having a prolonged remission. The activity in Burkitt's lymphoma should be investigated further.
authors.affiliation: University of Chicago, Chicago, IL 60637, USA. smsmith@medicine.bsd.uchicago.edu
authors.forename: Sonali M
authors.initials: SM
authors.lastname: Smith
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Johnson
authors.forename: Donna
authors.initials: D
authors.lastname: Niedzwiecki
authors.forename: J Paul
authors.initials: JP
authors.lastname: Eder
authors.forename: George
authors.initials: G
authors.lastname: Canellos
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Cheson
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Bartlett
mesh_terms: D000328:Adult; D000368:Aged; D002051:Burkitt Lymphoma / Q000188:drug therapy; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage* / Q000633:toxicity; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012074:Remission Induction; D016879:Salvage Therapy / Q000379:methods* / Q000401:mortality; D059004:Topoisomerase I Inhibitors; D019772:Topotecan / Q000008:administration & dosage* / Q000633:toxicity
chemical_list: D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D019772:Topotecan; D004317:Doxorubicin