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

Purpose: a phase I/II study was performed to evaluate the incorporation of hydroxyurea (HU) into high-dose chemotherapy of non-Hodgkin's lymphoma (NHL). Patients and Methods: Thirty-eight patients with primary refractory and refractory relapsed NHL were treated with carmustine (BCNU) (300 mg/m(2) on day -8), cyclophosphamide (cy) (2.5 g/m(2)/d on days -8 and -7), etoposide (E) (150 mg/m(2) 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/m(2) intravenously (IV) by 72-hour continuous infusion. When the IV formulation was not available, 17 patients were given 18 g/m(2) 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/m(2). 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). Conclusion: 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 the regimen.