title: Phase I/II study incorporating intravenous hydroxyurea into high-dose chemotherapy for patients with primary refractory or relapsed and refractory intermediate-grade and high-grade malignant lymphoma.
abstract: OBJECTIVE
  A phase I/II study was performed to evaluate the incorporation of hydroxyurea (HU) into high-dose chemotherapy of non-Hodgkin's lymphoma (NHL).
  
  
  METHODS
  Thirty-eight patients with primary refractory and refractory relapsed NHL were treated with carmustine (BCNU) (300 mg/m2 on day -8), cyclophosphamide (Cy) (2.5 g/m2/d on days -8 and -7), etoposide (E) (150 mg/m2 every 12 hours on days -6, -5, and -4), and HU (BCHE) with autologous hematopoietic stem-cell rescue. Twenty-one patients received HU in a dose escalation of 2 to 12 g/m2 intravenously (IV) by 72-hour continuous infusion. When the IV formulation was not available, 17 patients were given 18 g/m2 of HU orally in divided doses every 6 hours over the same 72-hour period.
  
  
  RESULTS
  The dose-limiting toxicity of 72-hour continuous infusion HU in this regimen was mucositis. Endotracheal intubation was necessary to protect the airway in two thirds of patients treated at 12 g/m2. Six patients (oral BCHE, five of 17; IV BCHE, one of 21) died with nonresponding or progressive disease and, at least in part, from the complications of the high-dose chemotherapy. Seventeen patients (45%) achieved complete remission (CR). More patients treated with IV BCHE achieved CR than patients treated with oral BCHE (12 of 21 v five of 17; P < .1, chi 2 test). Nine patients (two of 17 oral BCHE and seven of 21 IV BCHE) remain disease-free as of January 31, 1994, with a minimum follow-up time of 3 years. The lower mortality and higher response rate with IV BCHE translated into a significantly superior probability of progression-free survival (PFS) (33% at 4 year v 12% for oral BCHE; P = .048, log-rank test).
  
  
  CONCLUSIONS
  High-dose BCHE is effective treatment for primary refractory and refractory relapsed NHL. Continuous IV HU appears to be less toxic and more effective than intermittent oral HU in this regimen.
authors.affiliation: Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, USA.
authors.forename: W P
authors.initials: WP
authors.lastname: Vaughan
authors.forename: E
authors.initials: E
authors.lastname: Kris
authors.forename: J
authors.initials: J
authors.lastname: Vose
authors.forename: P J
authors.initials: PJ
authors.lastname: Bierman
authors.forename: P
authors.initials: P
authors.lastname: Gwilt
authors.forename: J O
authors.initials: JO
authors.lastname: Armitage
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D002330:Carmustine / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000009:adverse effects; D007262:Infusions, Intravenous; D008228:Lymphoma, Non-Hodgkin / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000187:drug effects; D012008:Recurrence; D012074:Remission Induction; D012307:Risk Factors; D013280:Stomatitis / Q000139:chemically induced; D016019:Survival Analysis
chemical_list: D005047:Etoposide; D003520:Cyclophosphamide; D002330:Carmustine; D006918:Hydroxyurea