title: Paclitaxel plus topotecan treatment for patients with relapsed or refractory aggressive non-Hodgkin's lymphoma.
abstract: BACKGROUND
  Used as single agents, paclitaxel and topotecan have demonstrated promising activity in treating patients with relapsed aggressive non-Hodgkin's lymphoma (NHL). We conducted a phase II clinical trial to investigate the activity and tolerability of the combination of both drugs.
  
  
  METHODS
  Patients with refractory or relapsed aggressive NHL who had previously been treated with a maximum of two prior chemotherapeutic regimens were given intravenous infusions of paclitaxel 200 mg/m2 over three hours on day one and topotecan 1 mg/m2 over 30 minutes daily from days one to five. All patients received daily subcutaneous injections of filgrastim (granulocyte colony-stimulating factor) 5 microg/kg starting 24 hours after the last dose of chemotherapy until neutrophil recovery. Treatments were repeated every three weeks for a maximum of six courses. Patients who achieved partial remission or complete remission (CR) after at least two courses were offered stem cell transplantation, if eligible.
  
  
  RESULTS
  Of the 71 patients eligible for this trial, 66 (93%) were evaluable for treatment response. The median age was 53 years (range 23 to 74 years). Thirty-six percent of the patients had previously been treated with ara-C/platinum-based regimens, and 48% failed to achieve CR after primary induction therapy. Sixty-seven percent of the patients had elevated lactate dehydrogenase levels at the time of treatment initiation. The overall response rate was 48% (95% confidence interval (95% CI): 36%-61%). Patients who had primary refractory disease had a response rate of 31%, compared with 65% for patients who did not. Similarly, the response rate of patients who failed to achieve CR after their most recent previous therapy was 37%, compared with a 65% response rate in patients who relapsed from a first or second CR. The median duration of response was six months. A total of 199 courses were given, with a median of three courses per patient. Neutropenia at levels < or = 500 leukocytes per microliter was observed after 32% of the courses, and thrombocytopenia at levels < or = 20,000 platelets per microliter was observed after 17% of the courses. Grade 3-4 neutropenic fever occurred after 6% of the courses. Non-hematologic toxic effects were predominantly grade 1-2.
  
  
  CONCLUSIONS
  The combination of paclitaxel and topotecan is an effective first or second line salvage therapy for patients with relapsed or refractory aggressive NHL who had prior anthracycline- or platinum-based chemotherapy.
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA. ayounes@mail.mdanderson.org
authors.forename: A
authors.initials: A
authors.lastname: Younes
authors.forename: H A
authors.initials: HA
authors.lastname: Preti
authors.forename: F B
authors.initials: FB
authors.lastname: Hagemeister
authors.forename: P
authors.initials: P
authors.lastname: McLaughlin
authors.forename: J E
authors.initials: JE
authors.lastname: Romaguera
authors.forename: M A
authors.initials: MA
authors.lastname: Rodriguez
authors.forename: B I
authors.initials: BI
authors.lastname: Samuels
authors.forename: J L
authors.initials: JL
authors.lastname: Palmer
authors.forename: F
authors.initials: F
authors.lastname: Cabanillas
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009504:Neutrophils / Q000187:drug effects; D017239:Paclitaxel / Q000008:administration & dosage; D019772:Topotecan / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D019772:Topotecan; D017239:Paclitaxel