Efficacy and safety of bevacizumab in combination with irinotecan and capecitabine in first-line treatment of metastatic colorectal cancer

Saša M Jungić; Biljana Tubić; Radoslav Gajanin; Zdenka Gojković; Ivanka Rakita

doi:10.2298/VSP150513173J

Saša M Jungić Clinic of Oncology University Clinical Center Banjaluka, Banjaluka, Bosnia and Herzegovina
Biljana Tubić Agency for Medicines and Medical Devices of Bosnia and Herzegovina, Banjaluka, Bosnia and Herzegovina
Radoslav Gajanin Department of Pathology, University Clinical Center Banjaluka, Banjaluka, Bosnia and Herzegovina
Zdenka Gojković Clinic of Oncology, University Clinical Center Banjaluka, Banjaluka, Bosnia and Herzegovina
Ivanka Rakita Clinic of Oncology, University Clinical Center Banjaluka, Banjaluka, Bosnia and Herzegovina

DOI: https://doi.org/10.2298/VSP150513173J

Keywords: colorectal neoplasms, neoplasm metastasis, antineoplastic combined chemotherapy protocols, drug toxicity,

Abstract

Background/Aim. The efficacy and safety of bevacizumab (BEV) in combination with capecitabin and irinotecan in first-line therapy for patients with metastatic colorectal cancer (mCRC) were studied. In order to improve safety and efficacy of chemotherapy, as well as to reduce adverse reactions to a minimum, doses of active agents applied were changed in relation to previously employed schedules. Methods. Patients with histologically documented mCRC with no previously received chemotherapy or with received adjuvant or neoadjuvant chemotherapy, which ended 6 months before capecitabin treatment (1000 mg/m² per os from the 2nd to 8th day of each cycle), irinotecan (175 mg/m² iv every 2 weeks), plus bevacizumab (5 mg/kg iv every 2 weeks) were observed. Results. This prospective study included 35 patients of both sexes. The overall response rate (ORR) of 28.6%, partial response (PR) of 28.6%, progressive disease (PD) of 28.6% and stable disease (SD) of 42.8% were found. The progression-free survival (PFS) of the analyzed patients was 11.3 (95% CL: 9.1–12.9) months while overall survival (OS) of the included patients was 25.2 (95% CL: 17.4–28.4) months and 117 adverse effects were recorded in 24 patients. Alopecia, nausea and vomiting, hemorrhage, hand-foot syndrome, diarrhea, abdominal pain, proteinuria, and hypertension (51.4%, 37.1%, 37.1%, 25.7%, 22.8%, 20.0%, 20.0% and 17.1%, respectively) were most frequently observed adverse effects. Conclusion. The results of this clinical trial support and recommend the use of bevacizumab plus capecitabin and irinotecan in the doses and schedule applied throughout this study as the first-line treatment of mCRC patients.

References

García-Alfonso P, Muñoz-Martin AJ, Alvarez-Suarez S, Jerez-Gilarranz Y, Riesco-Martinez M, Khosravi P, et al. Bevacizumab in combination with biweekly capecitabine and irinotecan, as first-line treatment for patients with metastatic colorectal cancer. Br J Cancer 2010; 103(10): 1524−8.

Fuchs CS, Marshall J, Barrueco J. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: Updated results from the BICC-C study. J Clin Oncol 2008; 26(4): 689−90.

Fuchs CS, Marshall J, Mitchell E, Wierzbicki R, Ganju V, Jeffery M, et al. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: Results from the BICC-C Study. J Clin Oncol 2007; 25(30): 4779−86.

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.

Hoff PM, Ansari R, Batist G, Cox J, Kocha W, Kuperminc M, et al. Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: Results of a randomized phase III study. J Clin Oncol 2001; 19(8): 2282−92.

Van Cutsem E, Hoff PM, Harper P, Bukowski RM, Cunningham D, Dufour P, et al. Oral capecitabine vs intravenous 5-fluorouracil and leucovorin: Integrated efficacy data and novel analyses from two large, randomised, phase III trials. Br J Cancer 2004; 90(6): 1190−7.

Scheithauer W, Kornek GV, Raderer M, Schüll B, Schmid K, Kovats E, et al. Randomized multicenter phase II trial of two different schedules of capecitabine plus oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 2003; 21(7): 1307−12.

Tewes M, Schleucher N, Achterrath W, Wilke HJ, Frings S, Seeber S, et al. Capecitabine and irinotecan as first-line chemotherapy in patients with metastatic colorectal cancer: Results of an extended phase I study. Ann Oncol 2003; 14(9): 1442−8.

Bajetta E, Di Bartolomeo M, Mariani L, Cassata A, Artale S, Frustaci S, et al. Randomized multicenter phase II trial of two different schedules of irinotecan combined to capecitabine as first line treatment in metastatic colorectal cancer. Cancer 2004; 100(2): 279−87.

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). EJC 2009; 45(2): 228−47.

Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457−81.

Welch S, Spithoff K, Rumble RB, Maroun J. Gastrointestinal Cancer Disease Site Group. Bevacizumab combined with chemotherapy for patients with advanced colorectal cancer: A systematic review. Ann Oncol 2010; 21(6): 1152−62.

Giantonio BJ, Catalano PJ, Meropol NJ, O'dwyer PJ, Mitchell EP, Alberts SR, et al. Bevacizumab in Combination With Oxaliplatin, Fluorouracil, and Leucovorin (FOLFOX4) for Previously Treated Metastatic Colorectal Cancer: Results From the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 2007; 25(12): 1539−44.

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 can-cer: A randomized phase III study. J Clin Oncol 2008; 26(12): 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.

Kabbinavar FF, Schulz J, McCleod M, Patel T, Hamm JT, Hecht RJ, 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.

van Cutsem E, Rivera F, Berry S, Kretzschmar A, Michael M, Dibartolomeo M, et al. Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLIRI and fluoropyrimidines in metastatic colorectal cancer: The BEAT study. Ann Oncol 2009; 20(11): 1842−7.

Saif MW, Elfiky A, Salem RR. Gastrointestinal perforation due to bevacizumab in colorectal cancer. Ann Surg Oncol 2007; 14(6): 1860−9.

Amit L, Ben-Aharon I, Vidal L, Leibovici L, Stemmer S. The impact of Bevacizumab (Avastin) on survival in metastatic solid tumors: A meta-analysis and systematic review. PLoS ONE 2013; 8(1): e51780.

Wagner AD, Arnold D, Grothey AA, Haerting J, Unverzagt S. Anti-angiogenic therapies for metastatic colorectal cancer. Cochrane Database Syst Rev 2009; 8(3): CD005392.

Golfinopoulos V, Salanti G, Pavlidis N, Ioannidis JP. Survival and disease-progression benefits with treatment regimens for advanced colorectal cancer: A meta-analysis. Lancet Oncol 2007; 8(10): 898−911.

Loupakis F, Bria E, Vaccaro V, Cuppone F, Milella M, Carlini P, et al. Magnitude of benefit of the addition of bevacizumab to first-line chemotherapy for metastatic colorectal cancer: Meta-analysis of randomized clinical trials. J Exp Clin Cancer Res 2010; 29(1): 58.

Ocaña A, Amir E, Vera F, Eisenhauer EA, Tannock IF. Addition of Bevacizumab to Chemotherapy for Treatment of Solid Tumors: Similar Results but Different Conclusions. JCO 2011; 29(3): 254−6.

Köhne CH, De Greve J, Hartmann JT, Lang I, Vergauwe P, Becker K, et al. Irinotecan combined with infusional 5-fluorouracil/folinic acid or capecitabine plus celecoxib or placebo in the first-line treatment of patients with metastatic colorectal cancer. EORTC study 40015. Ann Oncol 2008; 19(5): 920−6.