Pharmacokinetically-guided preoperative FOLFOX chemotherapy for locally advanced colon cancer patients
| Autor: | Jorge Baixauli, Mariano Ponz-Sarvise, Azucena Aldaz, Jose Luis Hernandez-Lizoain, Lucia Granero, Lucia Ceniceros, Patricia Martinez, Javier Rodríguez, Carlos Pastor, Ana Chopitea, Jorge Arredondo, Fernando Lapuente |
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| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Journal of Clinical Oncology. 38:4104-4104 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | 4104 Background: Preliminary results from ongoing randomised trials suggest that neoadjuvant chemotherapy (NAC) may be an alternative approach to conventional adjuvant therapy. We assessed the feasibility and activity of incorporating a pharmacokinetically (PK) guided dose adjustment of 5-FU within preoperative Folfox. Methods: Radiologically staged LACC pts, T4 or T3 with extramural depth >5mm beyond the muscularis propia, were planned to receive 4-6 biweekly cycles of Oxalipatin (85mg/m²), Leucovorin (400 mg/m²), bolus 5-FU (400 mg/m2) and infusional 5-FU (initial dose of 2400mg/m² in 46h and subsequent cycles tailored according to PK monitoring in order to reach a target 5-FU area under the curve (AUC) between 20-30 mg∙h∙L-1). Dihidrouracil deshidrogenase was determined before the first cycle in order to detect pts with 5-Fu intolerance. Three serum samples were obtained during the 5-Fu infusion in the first two cycles. Pathological tumor regression was graded according to the MSKCC classification and toxicity to the NCI-CTCAE 4.0. Results: From June 2012 to August 2017, 45 pts (M/F: 35/10; median age 63) with LACC (T3: 66.7%; T4: 31.1%; T2: 2.2%; N+:66.6%) were evaluated. Median dose of 5-FU was 4500 mg. 48.9% of the pts required a 5-FU dose increase to reach the target AUC. Side effects profile included G3 neutropenia (3 pts), G2 diarrhea (2 pts) and G2 asthenia (9 pts). NAC was discontinued in 3 pts due to small bowell obstruction requiring surgery (no progressive disease during NAC). R0 resection rate was 100% (93.3% laparoscopy-assited). MSKCC score included grades 4, 3+ and 3 in 11.1%, 26.7% and 28.9% of pts, respectively. A complete pathological response was found in 5 pts (11.1%). Median number of harvested nodes was 16 (7-51), 80% ypN0. Those pts with AUC 25-30 had a 3-fold higher likelihood of achieving a MSKCC 3, 3+ and 4 responses. Median time to hospital discharge was 7 days (range 4-22). After a median follow-up of 60 months (44-66), 5-year actuarial PFS is 88.8%. Conclusions: Preoperative PK-adjusted FOLFOX in LACC pts is safe and well tolerated, achieving remarkable rates of major pathological responses and R0 resections. |
| Databáze: | OpenAIRE |
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