Optimalno trajanje terapije u prvoj liniji tretmana kod metastatskog kolorektalnog karcinoma
Sažetak
Uvod/Cilj. Standardne opcije u prvoj liniji lečenja metastatskog karcinoma debelog creva (mCRC) su 5-fluorouracil, folinska kiselina i oksaliplatin (FOLFOX4)/kapecitabin, oksaliplatin (CapOx) uz dodatak bevacizumaba (bev) i 5-fluorouracil, folinska kiselina i irinotekan (FOLFIRI) uz dodatak bev. Cilj rada bio je da se uporedi ukupni odgovor (overall response rate – ORR), period do progresije bolesti (progression-free survival – PFS) i ukupno preživljavanje (overall survival – OS) u grupama bolesnika sa mCRC koji su u prvoj liniji primali FOLFIRI/bev vs. FOLFOX4/bev. Takodje, cilj je bio i da se uporedi sigurnosni profil u ovim grupama bolesnika, kao i da se ispita optimalna dužina lečenja i karakteristike bolesnika koji su imali najbolje ishode lečenja. Metode. Retrospektivno-prospektivnim ispitivanjem obuhvaćeni su
bolesnici sa mCRC, lečeni primenom hemioterapijskog protokola za prvu liniju terapije, u kombinaciji sa bev (FOLFOX4/bev, odnosno, FOLFIRI/bev). Efikasnost lečenja procenjena je na osnovu ORR, PFS i OS, a bezbednost lečenja praćenjem neželjenih reakcija. Rezultati. Parametar ORR bio je 70% u FOLFIRI/bev grupi i 50% u FOLFOX4/bev grupi. Medijana PFS za FOLFIRI/bev grupu (n = 30) iznosila je 15,6 meseci, odnosno 12,1 meseci za FOLFOX4/bev grupu (n = 30) [hazard ratio (HR) 0,85; 95% interval poverenja (IP) 0,47–1,53; p = 0,5591]. Medijana OS iznosila je 24,7 meseci u FOLFIRI/bev grupi i 19,9 meseci u FOLFOX4/bev grupi (HR 0,67; 95% IP 0,37–1,23; p = 0,1552). U obe grupe bolesnika bolji terapijski odgovor imali su bolesnici koji su primili više od 9 ciklusa indukcione terapije u poređenju sa bolesnicima koji su primili manje od 9 ciklusa. U FOLFOX4/bev grupi, PFS je iznosio 16,9 meseci, a OS 22, 1 mesec za bolesnike koji su primili više od 9 ciklusa, u odnosu na 9,7 meseci (PFS) i 17,6 meseci (OS) za bolesnike koji su primili manje od devet ciklusa terapije. U FOLFIRI/bev grupi, PFS je iznosio 9 meseci za bolesnike koji su primili manje od devet ciklusa terapije u odnosu na 18,8 meseci za bolesnike koji su primili više od 9 ciklusa, dok je OS iznosio 18,0 meseci u odnosu na 27,7 meseci u tim grupama bolesnika. Neželjenih dejstava gradusa 3 i 4 imalo je 7% bolesnika u FOLFIRI/bev grupi, a u FOLFOX4/bev grupi 27%. Zaključak. Bolesnici koji su primili FOLFIRI/bev protocol, u odnosu na one lečene FOLFOX4/bev protokolom, imali su bolji ORR (70% vs. 50%), PFS (15,6 meseci vs. 12,1 meseci) i OS (24,7 meseci vs. 19,9 meseci). U obe grupe bolesnika bolji ishod imali su bolesnici koji su primali indukcionu terapiju 4–6 meseci (9 do 12 ciklusa).
Reference
World Health Organization. The Global Health Observatory. Explore a world of health data. Available from: https://www.
who.int/gho/DATABASE/en/
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016; 66(1): 7–30.
Quasar Collaborative Group. Gray R, Barnwell J, McConkey C, Hills RK, Williams NS, Kerr DJ. Adjuvant chemotherapy ver-sus observation in patients with colorectal cancer: a random-ised study. Lancet 2007; 370(9604): 2020–9.
Saltz LB, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 2008; 26(13): 2013–9.
Kabbinavar F, Hurwitz HI, Fehrenbacher L, Meropol NJ, Novotny WF, Lieberman G, et al. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 2003; 21(1): 60–5.
Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004; 350(23): 2335–42.
Kabbinavar FF, Schulz J, McCleod M, Patel T, Hamm JT, Hecht JR, et al. Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial. J Clin Oncol 2005; 23(16): 3697–705.
Guan ZZ, Xu JM, Luo RC, Feng FY, Wang LW, Shen L, et al. Efficacy and safety of bevacizumab plus chemotherapy in Chinese patients with metastatic colorectal cancer: a random-ized phase III ARTIST trial. Chin J Cancer 2011; 30(10): 682–9.
Tebbutt NC, Wilson K, Gebski VJ, Cummins MM, Zannino D, van Hazel GA, et al. Capecitabine, bevacizumab, and mitomy-cin in first-line treatment of metastatic colorectal cancer: re-sults of the Australasian Gastrointestinal Trials Group Ran-domized Phase III MAX Study. J Clin Oncol 2010; 28(19): 3191–8.
Cunningham D, Lang I, Marcuello E, Lorusso V, Ocvirk J, Shin DB, et al. AVEX study investigators. Bevacizumab plus cape-citabine versus capecitabine alone in elderly patients with pre-viously untreatedmetastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol 2013; 14(11): 1077–85.
Welch S, Spithoff K, Rumble R, Maroun J. Group GCDS. Bevaci-zumab combined with chemotherapy for patients with ad-vanced colorectal cancer: a systematic review. Ann Oncol 2009; 21(6): 1152‒62.
Botrel TEA, Clark LGO, Paladini L, Clark OAC. Efficacy and safety of bevacizumab plus chemotherapy compared to chem-otherapy alone in previously untreated advanced or metastatic colorectal cancer: a systematic review and meta-analysis. BMC Cancer 2016; 16: 677.
Kozloff M, Ulcickas Yood M, Berlin J, Flynn PJ, Kabbinavar FF, Purdie DM, et al. Clinical outcomes associated with bevacizumab-containing treatment of metastatic colorectal cancer: the BRiTE observational cohort study. Oncologist 2009;14(9):862-70.
Jordan F, Grundmann N, Schenkirsch G, Maerkl B, Messmann H, Anthuber M, et al. Impact of Primary Tumor Localization on the Efficacy of Bevacizumab in Metastatic Colorectal Cancer. Anticancer Res 2018; 38(9): 5539‒46.
You XH, Wen C, Xia ZJ, Sun F, Li Y, Wang W, et al. Primary Tumor Sidedness Predicts Bevacizumab Benefit in Metastatic Colorectal Cancer Patients. Front Oncol 2019; 9: 723.
Baraniskin A, Buchberger B, Pox C, Graeven U, Holch JW, Schmie-gel W, et al. Efficacy of bevacizumab in first-line treatment of metastatic colorectal cancer: A systematic review and meta-analysis. Eur J Cancer 2019; 106: 37‒44.
Gruenberger T, Bridgewater J, Chau I, García Alfonso P, Rivoire M, Mudan S, et al. Bevacizumab plus mFOLFOX-6 or FOL-FOXIRI in patients with initially unresectable liver metastases from colorectal cancer: the OLIVIA multinational randomised phase II trial. Ann Oncol 2015; 26(4): 702‒8.
Cremolini C, Loupakis F, Antoniotti C, Lupi C, Sensi E, Lonardi S, et al. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular sub-group analyses of the open-label, phase 3 TRIBE study. Lan-cet Oncol 2015; 16(13): 1306‒15.
Yamazaki K, Nagase M, Tamagawa H, Ueda S, Tamura T, Mura-ta K, et al . Randomized phase III study of bevacizumab plus FOLFIRI and bevacizumab plus mFOLFOX6 as first-line treatment for patients with metastatic colorectal cancer (WJOG4407G). Ann Oncol 2016; 27(8): 1539‒46.
Van Cutsem E, Rivera F, Berry S, Kretzschmar A, Michael M, DiBartolomeo M, et al. First BEAT investigators. Safety and ef-ficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal can-cer: the BEAT study. Ann Oncol 2009; 20(11): 1842‒7.
Lund CM, Vistisen KK, Dehlendorff C, Rønholt F, Johansen JS, Nielsen DL. Age-dependent differences in first-line chemo-therapy in patients with metastatic colorectal cancer: the DISCO study. Acta Oncol 2018; 57(11): 1445‒54.