FTORAFUR IN COMBINATION WITH OXALIPLATIN AND IRINOTECAN IN PATIENTS WITH DISSEMINATED COLORECTAL CANCER: PRELIMINARY RESULTS

Objective: to develop an effective, well-tolerated, convenient for outpatient care (without installing a subclavian catheter) three-component treatment regimen that includes ftorafur – an original oral fluoropyrimidine drug.

Materials and methods. The study included 25 patients with disseminated colorectal cancer that have never received specific pharmacotherapy. We evaluated the efficacy and safety of a new first-line three-component treatment regimen with oxaliplatin + irinotecan + ftorafur. Patients in group 1 (n = 6) received this regimen for 3 weeks, whereas patients in group 2 (n = 19) received it for 2 weeks.

Results. Only preliminary results of the study are currently available. Median time to progression and overall survival are not yet estimated. Three (50 %) patients from group 1 achieved partial regression of metastases; 3 patients from this group had long-term (≥6 months) disease stabilization. Therapeutic effect (partial remission + long-term stabilization) was observed in all patients. Time without progression varied between 6 and 20 months. In group 2, therapeutic effect was estimated in 18 patients that received at least 2 courses of chemotherapy. Eight out of these 18 patients had partial response (2 of them underwent radical surgery); 8 patients had disease stabilization. Thus, 88.8 % of patients from group 2 responded to treatment. In the whole study population (both groups), response to treatment was achieved in 91 % of patients.

Conclusion. Our preliminary results suggest that the combination of oxaliplatin, irinotecan and ftorafur is safe and has an acceptable toxicity profile; therefore, it can be used in weakened patients.

1. Jemal А., Bray F., Center М.М. et al. Global cancer statistics. Cancer J Clin 2011; 61(2):69–90. PMID: 21296855. DOI: 10.3322/caac.20107.

2. Grundmann R.T., Hermanek P., Merkel S. Diagnosis and treatment of colorectal liver metastases. Zentralbl Chir 2008;133(3):267–84. PMID: 18563694. DOI: 10.1055/s-2008-1076796.

3. Hopt U.T., Drognitz O., Neeff H. Timing of resection in patients with colorectal carcinoma and synchronous liver metastases. Zentralbl Chir 2009;134(5):425–9. PMID: 19757342. DOI: 10.1055/s-0029-1224612.

4. Kanas G.P., Taylor A., Primrose J.N. et al. Survival after liver resection in metastatic colorectal cancer: review and metaanalysis of prognostic factors. Clin Epidemiol 2012;4:283–301. PMID: 23152705. DOI: 10.2147/CLEP.S34285.

5. Pawlik T.M., Choti M.A. Surgical therapy for colorectal metastases to the liver. J Gastrointest Surg 2007;11(8):1057–77. PMID: 17530336. DOI: 10.1007/s11605-006-0061-3.

6. Masi G., Loupakis F., Pollina L. et al. Long-term outcome of initially unresectable metastatic colorectal cancer patients treated with 5-fluorouracil/leucovorin, oxaliplatin and irinotecan (FOLFOXIRI) followed by radical surgery of metastases. Ann Surg 2009;249(3):420–5. PMID: 19247029. DOI: 10.1097/SLA.0b013e31819a0486.

7. Vasile E., Masi G., Fornaro L. et al. A multicenter phase II study of the combination of oxaliplatin, irinotecan and capecitabine in the first-line treatment of metastatic colorectal cancer. Br J Cancer 2009;100(11):1720–4. PMID: 19436300. DOI: 10.1038/sj.bjc.6605075.

8. Ychou M., Viret F., Kramar A. et al. Tritherapy with 5-fluorouracil/leucovorin, irinotecan and oxaliplatin (FOLFIRINOX): a phase II study in colorectal cancer patients with non-resectable liver metastases. Cancer Chemother Pharmacol 2008;62(2):195–201. PMID: 17901955. DOI: 10.1007/s00280-007-0588-3.

9. NCCN Clinical Practice Guidelines in Oncology. Available at: https://www.nccn.org/professionals/physician_gls/default.aspx.

10. Grothey A., Sargent D., Goldberg R.M., Schmoll H.J. Survival of patients with advanced colorectal cancer improves with the availability of 5-fluorouracil/leucovorin, irinotecan and oxaliplatin in the course of treatment. J Clin Oncol 2004;22(7):1209–14. PMID: 15051767. DOI: 10.1200/JCO.2004.11.037.

11. Falcone A., Ricci S., Brunetti I. et al. Phase III trial of infusional 5-fluorouracil, leucovorin, oxaliplatin and irinotecan (FOLFOXIRI) compared to infusional 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol 2007;25(13):1670–6. PMID: 17470860. DOI: 10.1200/JCO.2006.09.0928.

12. Van Cutsem E., Lang I., Folprecht G. et al. Cetuximab plus FOLFIRI in the treatment of metastatic colorectal cancer (mCRC): the influence of KRAS and BRAF biomarkers on outcome: updated data from the CRYSTAL trial. J Clin Oncol 2010;281:4000.

13. Bokemeyer C., Bondarenko I., Makhson A. et al. Fluorouracil, leucovorin and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol 2009;27(5):663–71. PMID: 19114683. DOI: 10.1200/JCO.2008.20.8397.

14. Douillard J.Y., Siena S., Cassidy J. et al. Randomized phase III trial of panitumumab with infusional 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol 2010;28(31):4697–705. PMID: 20921465. DOI: 10.1200/JCO.2009.27.4860.

15. Tyagi P., Grothey A. Commentary on a phase III trial of bevacizumab plus XELOX or FOLFOX4 for first-line treatment of metastatic colorectal cancer: the NO16966 trial. Clin Colorectal Cancer 2006;6(4):261–4. PMID: 17241510. DOI: 10.3816/CCC.2006.n.044.