of Response to Leucovorin, 5-Fluorouracil, and Oxaliplatin Therapy in Patients with Metastatic Colorectal Cancer

The aimofthisstudy was to evaluate 39-deoxy-39- 18 F-fluorothymidine ( 18 F-FLT) PET for early prediction of the standard anatomic response and survival outcomes in patients with metastatic colorectal cancer (mCRC) receiving leucovorin, 5-fluorouracil (5-FU), and oxaliplatin (FOLFOX). Methods: The main eligibility criteria included histologically confirmed mCRC, $1 extrahepatic measurable lesions, and no prior chemotherapy in a metastatic setting. Chemotherapy consisted of leucovorin on day 1, followed by the continuous infusion of 5-FU on days 1 and 2, and oxaliplatin on day 3. In the second and subsequent cycles of chemotherapy, oxaliplatin was administered simultaneously with leucovorin on day 1. 18 F-FLT PET scans were obtained 3 times during the first cycle of chemotherapy: before chemotherapy, 24 h after infusion of 5-FU (day 2), and 48 h after completion of chemotherapy (day 5). The maximum standardized uptake value (SUVMAX )o f18F-FLT was measured. Treatment responses were assessed by CT after 3 cycles of FOLFOX. Results: Eighteen patients were included in the study. The response rate after 3 cycles of FOLFOX was 27.8% (5/ 18). The SUVMAX was increased in responders (P 5 0.043) and nonresponders (P , 0.001) on day 2 and was decreased, compared with baseline values, on day 5 in responders only (P 5 0.043). Receiver-operating-characteristic curve analysis indicated that the use of a threshold of an SUVMAX increase on day 2 of #45.8% resulted in a sensitivity of 100%, specificity of 69.2%, and relative risk of 2.250 (P 5 0.029) for the diagnosis of responders. Use of a threshold of an SUVMAX decrease on day 5 of $10.6% resulted in a sensitivity of 100%, specificity of 76.9%, and relative risk of 2.667 (P 5 0.007). Patients with low 18 F-FLT flare tended to have longer survivals than patients with high flare (2-y overall survival rate, 77.8% vs. 44.4%; P 5 0.051). Conclusion: The 18 F-FLT flare observed during 5-FU infusion was associated with poor treatment response in patients with mCRC. The degree of 18 F-FLT flare might be used to predict the outcome of patients who receive infusional 5-FU–based chemotherapy.