@entity1311 and XXXX in combination in the treatment of advanced @entity1149 : a phase II @entity137 , response, and survival analysis.

@entity1 @entity137 @entity1261 @entity882 @entity417 @entity3003 @entity648 @entity1149 @entity1311 @entity221 @entity3028 @entity16 @entity925 @entity4841 @entity1011 @entity3483 @entity420
PURPOSE: To determine the activity and @entity137 of combination @entity1311 (24 hours) and @entity3003 in advanced @entity1149 ( @entity1149 ). @entity1 AND METHODS: Eligibility required measurable disease (stage IV or stage IIIB with @entity3483 ), Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, absolute neutrophil count > or = 2,000/microL, platelet count > or = 100,000/microL serum @entity1011 concentration < or = 1.5 mg/dL, and @entity648 level < or = 2 mg/dL. @entity1311 was initially administered at a dose of 135 mg/m2/d, followed by @entity3003 on day 2 at a targeted area under the concentration-time curve (AUC) of 7.5 using the Calvert formula. @entity1261 ( @entity1261 ) 5 micrograms/kg subcutaneously (SC) on days 3 to 17 was introduced during the second and subsequent cycles. In @entity1 who sustained less than grade 4 myelosuppression, the @entity1311 dose was sequentially escalated 40 mg/m2 per cycle to a maximum of 215 mg/m2. Treatment was repeated at 3-week intervals for six cycles. RESULTS: From June 1993 through February 1994, 54 @entity1 were enrolled; 53 are assessable for @entity137 and response. The median age was 62 years (range, 34 to 84). Sixty-nine percent were male, 65% had @entity420 , and 93% had stage IV disease. Two hundred sixty-eight cycles were administered; 32 @entity1 (59%) completed all six cycles. Twenty-five unanticipated hospitalizations occurred during treatment (9.3% of cycles) in 20 @entity1 (37%). Myelosuppression was the principal @entity137 ; grade 3 or 4 @entity3028 occurred in 57% of @entity1 after the first cycle, but decreased to 35% during the second cycle after introduction of @entity1261 and consistently remained < or = 22% during subsequent cycles. Seven episodes of @entity221 occurred, all during the first cycle. Grade 3 or 4 @entity882 and @entity417 occurred in 47% and 33% of @entity1 , respectively. Eight @entity1 (15%) required platelet transfusions and 16 (30%) required packed RBC support. @entity16 , @entity925 / @entity4841 , and @entity882 , although generally mild, were cumulative. The @entity1311 dose was boosted to 215 mg/m2 in > or = 70% of @entity1 who received three or more cycles. At an AUC of 7.5, the median first-cycle @entity3003 dose was 424 mg/m2 (range, 273 to 709 mg/m2). The objective response rate was 62%, with five (9%) complete responses and 28 (53%) partial responses. The median progression-free survival time was 28 weeks and the median survival time 53 weeks. The 1-year survival rate is 54%. CONCLUSION: The @entity1311 - @entity3003 combination is active in advanced @entity1149 and may enhance survival; it merits further investigation in phase III trials.
