Abstract
3624 Background: Treatment of ACRC with 5FU/LV has a response rate (RR) < 25%. In a retrospective study both low TS and low DPD gene expression levels in metastases of ACRC were positive predictive factors of a response to 5FU (Salonga et al: CCR 2000). In contrast, the efficacy of oxaliplatin and irinotecan is supposedly independent of TS and DPD. Methods: Gene expression levels of TS and DPD using a quantitative RT-PCR assay were determined in pretreatment needle biopsies of metastatic tissue in previously untreated pts with ACRC. The cut-off values for TS and DPD relative to B-actin were 5 x 10 –3 and 45 x 10 -3, respectively. Chemotherapy consisted in arm A (low TS and low DPD) of weekly bolus 5FU/LV 500mg/m2 and in arm B (high TS and/or DPD) of 3-weekly oxaliplatin 85 mg/m2 and irinotecan 200 mg/m2. After progression, cross-over to the other regimen was allowed. Toxicity and response were evaluated every 3 and 9 weeks, respectively. Statistics using X2 test (one-sided, p<.05, 80 % power) required 20 evaluable pts in arm A to detect a significant increase of RR > 50%. Results: 47 out of 54 pts with a biopsy were treated in arm A (n=26) or arm B (n=21). 7 pts were not allocated to arm A or B due to deteriorating condition (3), other chemotherapy (2) and metastectomy (2). All pts in arm A were evaluable for response, and partial response (PR) was observed in 11 (RR 42 %) and stable disease (SD) in 9 pts. All but 1 pt in arm B were evaluable, with a PR in 5 (RR 25%) and SD in 9 pts. No responses were observed in 11 pts with a high TS/DPD after crossover to 5FU/LV, while crossover to the other regimen (n=10) resulted in 1 PR and 4 SD. No neutropenic fever or toxic deaths occurred. Conclusions: This study shows a higher efficacy of monotherapy with 5FU/LV in pts with a low level of TS and DPD than expected in unselected pts. As the need for fresh metastatic tumor tissue hampers this approach, investigation of alternative methods for TS and DPD assessment and other predictive markers is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis
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