Cladribine in hairy cell leukemia 13
Figure 1. Mechanism of action of cladribine.
days. Eleven patients achieved a complete remission
Table I. Initial response to cladribine in HCL.
after a single infusion of cladribine, characterized by
Responses (%)
normalization of peripheral blood and bone marrow,
and disappearance of lymphadenopathy. The median
No. of Minor/
duration of response was 15.5 months and no serious
Investigator patients Complete Partial None
toxic reactions were observed [6]. Table I details the Saven et al. [7] 349 319 22 8
response rates in clinical trials where patients
Estey et al. [8] 46 36 5 5
received cladribine as initial therapy. The most
Juliusson and 16 12 0 4
extensive single institution experience is at Scripps
Liliemark [9]
Hoffman et al. [10] 49 37 12 0
Clinic in La Jolla, California, where long-term
Tallman et al. [11] 50 40 9 1
follow-up of 349 patients have been reported [7]. Dearden et al. [12] 45 38 7 0
The standard dose is 0.1 mg/kg per day by contin-
Total 555 482 (87%) 55 (10%) 18 (3%)
uous intravenous infusion over seven days. The
HCL, hairy cell leukemia.
initial dose of 0.085 mg/kg per day found on the
package insert results from the standardization of
the drug using the extinction coefficient of chlor- responders compared with partial responders was
oadenine, which was slightly lower than that of statistically significant, p50.0005, (Figure 2).
2-chlorodeoxyadenosine. At that time, the drug was Although a direct comparison between cladribine
synthesized in the laboratory of Dr. Ernest Beutler, and pentostatin is lacking, cladribine has emerged as
The Scripps Research Institute. the preferred initial therapy because of the brevity of
In 1998, Saven et al. published data on 349 treatment, higher CR rates, and safe toxicity profile.
patients treated at Scripps Clinic. Ninety-one percent
of patients achieved a complete response (CR) with a
Alternate dosing schedules of cladribine
52 month median duration of response. Ninety
patients (26%) relapsed at a median of 29 months. Although the standard dose of cladribine is 0.1 mg/
The time to treatment failure rate was 19% at 48 kg per day by continuous intravenous infusion over
months. The overall survival rate was 96% at 48 seven days, several authors have published alternate
months [7]. In 2003, Goodman et al. published the dosing schedules. The goal of these schemas was to
results of 207 of these patients with at least seven reduce the prolonged myelosuppression, facilitate
years of follow-up. Ninety-five percent achieved a treatment, and reduce toxicities that can be seen with
CR, with an overall response rate of 100%. The continuous seven-day intravenous infusions. Julius-
median duration of initial response was 98 months. son et al. treated 73 patients with cladribine at a dose
The overall survival rate was 97% at 108 months of 3.4 mg/m
2
per day by subcutaneous injection daily
[13]. The time to treatment failure of complete for seven days. Fifty-nine patients (81%) achieved
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