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NIPENT(pentostatin) injection, powder, lyophilized, for solu(二)
tatin half-life in patients with renal impairment (CrCl <50 mL/min, n=2) was 18 hours, which was much longer than that observed in patients with normal renal function (CrCl >60 mL/min, n=14), about 6 hours.
CLINICAL STUDIES
The following table provides efficacy results for 4 groups (columns) of patients with hairy cell leukemia: patients who initially received NIPENT, patients who initially received alpha-interferon (IFN), and 2 different groups of patients who received NIPENT after proving to be refractory to, or intolerant of IFN therapy. The first 2 groups represent treatment results from the SWOG 8691 study, a large multicenter study comparing NIPENT and IFN in untreated (frontline) patients with confirmed hairy cell leukemia. The third group represents eva luable patients from the SWOG study who crossed over to NIPENT after initially receiving IFN. The fourth group, labeled NCI Phase 2 studies, displays pooled results of 2 noncomparative studies (MD Anderson and CALGB), in which NIPENT was used to treat patients with confirmed IFN-refractory disease.
In the SWOG 8691 study, NIPENT was administered at a dose of 4 mg/m2 every 2 weeks. After 6 months of treatment, patients were eva luated for response. If a complete response was achieved, 2 additional doses of NIPENT were administered and then discontinued. If a partial response was achieved, NIPENT was continued for up to an additional 6 months. NIPENT was discontinued for stable disease after 6 months or progressive disease after 2 months of therapy. IFN was administered 3 million units subcutaneously 3 times per week. Patients who achieved a complete or partial response after 6 months of treatment continued on IFN for another 6 months. IFN was discontinued if patients did not achieve a complete or partial response after 6 months of initial treatment or progressed after 2 months. This study allowed crossover of patients intolerant of, or refractory to, initial treatment.
Interferon-refractory patients enrolled into the MD Anderson study received NIPENT at a dose of 4 mg/m2 every other week for 3 months and responding patients received 3 additional months. CALGB patients received 4 mg/m2 of NIPENT every other week for 3 months and responding patients were treated monthly for up to 9 additional months. Almost all patients had a PS of 0 to 2 in the Phase 2 and 3 studies.
For each study, a complete response (CR) required clearing of the peripheral blood and bone marrow of all hairy cells, normalization of organomegaly and lymphadenopathy by physical examination, and recovery of hemoglobin to at least 12 g/dL, platelet count to at least 100,000/mm3, and granulocyte count to at least 1500/mm3. A partial response (PR) required that the percentage of hairy cells in the blood and bone marrow decrease by more than 50%, enlarged organs and lymph nodes decrease by more than 50% by physical examination, and hematologic parameters had to meet the same criteria as for complete response. The table below reports the response rate for 2 groups of patients: (1) eva luable, ie, patients who could be eva luated for response and (2) Intent-to-Treat, ie, patients diagnosed with hairy cell leukemia.
FRONTLINE
IFN-REFRACTORYa
eva luable
eva luable
SWOG 8691b
NCI Phase 2
Parameter
NIPENT
IFN
Crossover
Studies
N = 138
N=130
N=79
N=44
Response Rates (%)
eva luable CR
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