A Saven1, L D Piro. 1. Scripps Clinic and Research Foundation, La Jolla, California.
Abstract
OBJECTIVE: To determine whether clinical cross-resistance and intolerance exists between the nucleosides 2'-deoxycoformycin (DCF) and 2-chlorodeoxyadenosine (2-CdA) in the treatment of patients with hairy cell leukemia despite similar structures and mechanisms of action. DESIGN: Phase II clinical study. SETTING: Referral cancer center. PARTICIPANTS: Five patients with hairy cell leukemia who had been previously treated with DCF. INTERVENTION: Single course of 2-CdA at 0.1 mg/kg body weight per day for 7 days by continuous intravenous infusion. RESULTS: Of five patients, three were resistant to and two were intolerant of (having had life-threatening toxic reactions) DCF therapy. Four patients obtained a complete response with a median follow-up period of more than 11 months. The other patient in whom splenectomy, interferon, and DCF treatments were unsuccessful had a partial response lasting 2 months and subsequently died of Streptococcus pneumoniae bacteremia. Three of the four patients with complete responses remain in unmaintained remission, whereas the fourth has progressive splenic enlargement with stable hematologic parameters. The median leukocyte count increased from 2.0 x 10(9)/L to 3.8 x 10(9)/L, the median absolute neutrophil count increased from 0.56 x 10(9)/L to 2.73 x 10(9)/L, the median hemoglobin level increased from 112 g/L to 140 g/L, and the median platelet count increased from 55 x 10(9)/L to 123 x 10(9)/L. Two patients had culture-negative neutropenic fever associated with treatment. CONCLUSIONS: 2-Chlorodeoxyadenosine induced complete responses in patients with hairy cell leukemia resistant to DCF, suggesting a lack of cross-resistance. Also, 2-CdA is not prohibitively toxic in patients intolerant of DCF.
OBJECTIVE: To determine whether clinical cross-resistance and intolerance exists between the nucleosides 2'-deoxycoformycin (DCF) and 2-chlorodeoxyadenosine (2-CdA) in the treatment of patients with hairy cell leukemia despite similar structures and mechanisms of action. DESIGN: Phase II clinical study. SETTING: Referral cancer center. PARTICIPANTS: Five patients with hairy cell leukemia who had been previously treated with DCF. INTERVENTION: Single course of 2-CdA at 0.1 mg/kg body weight per day for 7 days by continuous intravenous infusion. RESULTS: Of five patients, three were resistant to and two were intolerant of (having had life-threatening toxic reactions) DCF therapy. Four patients obtained a complete response with a median follow-up period of more than 11 months. The other patient in whom splenectomy, interferon, and DCF treatments were unsuccessful had a partial response lasting 2 months and subsequently died of Streptococcus pneumoniae bacteremia. Three of the four patients with complete responses remain in unmaintained remission, whereas the fourth has progressive splenic enlargement with stable hematologic parameters. The median leukocyte count increased from 2.0 x 10(9)/L to 3.8 x 10(9)/L, the median absolute neutrophil count increased from 0.56 x 10(9)/L to 2.73 x 10(9)/L, the median hemoglobin level increased from 112 g/L to 140 g/L, and the median platelet count increased from 55 x 10(9)/L to 123 x 10(9)/L. Two patients had culture-negative neutropenic fever associated with treatment. CONCLUSIONS:2-Chlorodeoxyadenosine induced complete responses in patients with hairy cell leukemia resistant to DCF, suggesting a lack of cross-resistance. Also, 2-CdA is not prohibitively toxic in patients intolerant of DCF.
Authors: G R Weiss; J G Kuhn; J Rizzo; L S Smith; G I Rodriguez; J R Eckardt; H A Burris; S Fields; K VanDenBerg; D D von Hoff Journal: Cancer Chemother Pharmacol Date: 1995 Impact factor: 3.333