High-dose XXXX in hypertonic saline: reduced @entity137 of a modified dose schedule and correlation with plasma pharmacokinetics. A Northern California Oncology Group Pilot Study in @entity1149 .

@entity1 @entity137 @entity1149 @entity900 @entity1897 @entity3 @entity902 @entity2359
Although increased efficacy has been described with a five-day schedule of high-dose @entity900 (CDDP) in hypertonic saline, severe myelosuppression and cumulative @entity2359 have limited the usefulness of this therapy. In order to evaluate a possible dose-response relationship in @entity1149 ( @entity1149 ), 17 @entity1 with @entity3 were treated with a modified dose schedule delivering the same total dose (200 mg/m2) in a divided day 1 and 8 schedule. During a pilot study, a total of 47 cycles of therapy were administered, with a median of three cycles per @entity1 and a median total cumulative dose of 600 mg/m2. Nine of 17 @entity1 received at least 600 mg/m2. While nephrotoxicity was similar to previous reports of the five-day schedule, the incidence and severity of myelosuppression and @entity1897 were markedly reduced. Using this modified schedule, severe myelosuppression did not occur. Clinically severe @entity1897 developed in only one @entity1 (6%). The overall response rate was 47% (eight of 17 @entity1 ). Plasma @entity902 pharmacokinetics during five cycles of the modified day 1 and 8 schedule were compared with pharmacokinetics of the five-day schedule. Accumulation of plasma ultrafiltrate @entity902 occurred in the five-day schedule, but not in the day 1 and 8 schedule. This difference in pharmacokinetics is one possible explanation for the reduced @entity137 of this modified schedule. Although the degree of activity seen in this pilot study is encouraging, the efficacy of high-dose CDDP in @entity1149 remains to be defined. In view of reduced myelosuppression and @entity2359 , further trials with this modified schedule are indicated.
