P-0265 Msi+ Stage II/III Colon Cancer Patients Benefit from Capecitabine Adjuvant Monotherapy

Autor: Biljana Angelovska, Nikola Mitrevski, Aleksandra Kapedanovska Nestorovska, Nadica Matevska, Aleksandar Dimovski, Djingis Jashar, Natalija Angelovska Petrusevska, Toni Josifovski, Aleksandar Eftimov
Rok vydání: 2012
Předmět:
Zdroj: Annals of Oncology. 23:iv106
ISSN: 0923-7534
DOI: 10.1016/s0923-7534(20)30195-2
Popis: Introduction There is a significant variation in survival among patients with colon cancer treated with 5-FU-based therapies. Microsatellite instability (MSI) and 18q loss of heterozygosity (18qLOH) are most frequently associated with lack of benefit from fluoropyrimidine based therapies but the clinical validity of the use of these markers in unselected patients is still controversial. The aim of this study was to evaluate the predictive and prognostic value of MSI, 18q LOH, and MTHFR C677T and TS promoter polymorphisms on efficacy (defined as relapse-free survival, RFS) and toxicity (adverse events and laboratory tests, graded according to the NCI-CTCAE v3.0) in colon cancer patients treated with capecitabine adjuvant monotherapy. Methods A total of 188 patients with resected colon cancer (122 in the treatment and 66 in the control group) were included in the analysis. Inclusion criteria for the treatment group were stage III (53 patients) or high-risk stage II (69 patients) colon cancer and capecitabine monotherapy in adjuvant setting (1250mg/m2 bid 12 hours apart for 14 days, repeated every 3 weeks for a total of 8 cycles). The control group consisted of 66 patients (40 stage II and 26 stage III) treated with surgery only. The follow-up data on relapse-free survival were available for a median of 44 months for both groups. Paired DNA samples from tumors and peripheral blood were genotyped for TS promoter and MTHFR C677T variants, mismatch repair and 18q LOH status of tumors using QF-PCR and/or PCR-RFLP. Results The treatment with capecitabine was generally well tolerated; 114 (93.4%) patients completed the treatment protocol. A 25% dose reduction was necessary in 30 (24.5%) patients mainly due to mild to moderate hand-foot syndrome, diarrhea and/or nausea. None of the evaluated markers was predictive for toxicity. Disease relapse was diagnosed in 38 patients (33.3%) in the treatment group and in 28 patients (42.4%) in the control group (HR 0.71, 95%CI 0.43 to 1.18, p=0.17). MSI+ genotype was a positive predictive factor for RFS compared to MSI- genotype in the treatment group (HR 0.27, 95%CI 0.11-0.64, p=0.05). A statistically significant difference was obtained in RFS between MSI+ patients treated with capecitabine and control MSI+ patients that did not receive any adjuvant treatment (HR 0.19, 95%CI 0.05-0.71, p=0.02) indicating that MSI+ colon cancer patients can benefit from capecitabine adjuvant monotherapy. Similar trend was observed for the presence of 18q LOH, but the data did not reach statistical significance (HR 0.54, 95%CI 0.20 – 1.46, p=0.17). MTHFR C677T and TS promoter variants, tumor stage or localization and age and gender of the patients were not predictive of RFS of the adjuvant treatment. Conclusion Microsatellite instability (MSI+) can be used as a predictive marker for relapse-free survival of colon cancer patients treated with capecitabine adjuvant monotherapy.
Databáze: OpenAIRE
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