Systemic chemotherapy plus cetuximab after complete surgery in the treatment of isolated colorectal peritoneal carcinoma: COCHISE phase II clinical trial

Serge Evrard, Grégoire Desolneux, Carine Bellera, Thomas Esnaud, Yves Bécouarn, Denis Collet, Najim Chafai, Francois Marchal, Laurent Cany, Emilie Lermite, Michel Rivoire, Simone Mathoulin-Pélissier, Serge Evrard, Grégoire Desolneux, Carine Bellera, Thomas Esnaud, Yves Bécouarn, Denis Collet, Najim Chafai, Francois Marchal, Laurent Cany, Emilie Lermite, Michel Rivoire, Simone Mathoulin-Pélissier

Abstract

Objective: The primary objective of this non-randomised phase II study was to evaluate the combination of systemic chemotherapy plus cetuximab after complete cytoreductive surgery (CCS) for treatment of isolated colorectal peritoneal carcinoma (CRPC). This multicentre, prospective phase II clinical trial was conducted in seven national cancer referral centres, however research published during study recruitment indicated cetuximab treatment as ineffective in patients with mutated KRAS genes, leading to an additional exclusion criterion to the current protocol, excluding patients with mutated KRAS genes. This significantly impacted recruitment and the study did not achieve the necessary recruitment of 46 patients.

Results: Fourteen patients underwent CCS and were included in the study, however one did not provide informed consent and another received only one cycle of chemotherapy leading to 12 patients in the per protocol population for analysis. Adjuvant Folfox Cetuximab was administered when CCS was achieved for patients > 18 years with histologically proven CRPC and no other metastatic disease (liver, lungs, lymphadenopathy, etc.). CRPC median index was 5.00 (range: 1-17). Median PFS was 12.3 months [95% CI (3.7-28.2)] with 8.3% [95% CI (0.5-31.1)] and 0% PFS at 3 and 5 years respectively. Median OS was 43.4 months [95% CI (16.8-60)]. Trial registration Clinical Trials NCT00766142, October 3, 2008. Retrospectively registered.

Keywords: Colorectal cancer; Cytoreductive surgery; Hyperthermic intraperitoneal chemotherapy; KRAS gene; Peritoneal carcinomatosis.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Per protocol population 3-year progression-free survival

References

    1. Jayne DG, Fook S, Loi C, Seow-Choen F. Peritoneal carcinomatosis from colorectal cancer. Br J Surg. 2002;89(12):1545–1550. doi: 10.1046/j.1365-2168.2002.02274.x.
    1. Esquivel J, Elias D, Baratti D, Kusamura S, Deraco M. Consensus statement on the loco regional treatment of colorectal cancer with peritoneal dissemination. J Surg Oncol. 2008;98(4):263–267. doi: 10.1002/jso.21053.
    1. Sugarbaker PH, Ryan DP. Cytoreductive surgery plus hyperthermic perioperative chemotherapy to treat peritoneal metastases from colorectal cancer: standard of care or an experimental approach? Lancet Oncol. 2012;13(8):e362–e369. doi: 10.1016/S1470-2045(12)70210-3.
    1. Evrard S, Mazière C, Désolneux G. HIPEC: standard of care or an experimental approach? Lancet Oncol. 2012;13(11):e462–e463. doi: 10.1016/S1470-2045(12)70448-5.
    1. Verwaal VJ, van Ruth S, de Bree E, van Slooten GW, van Tinteren H, Boot H, et al. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol. 2003;21(20):3737–3743. doi: 10.1200/JCO.2003.04.187.
    1. Díaz Rubio E, Tabernero J, Van Cutsem E, Cervantes A, André T, Humblet Y, et al. Cetuximab in combination with oxaliplatin/5-fluorouracil (5-FU)/folinic acid (FA) (FOLFOX-4) in the first-line treatment of patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer: an international phase II study. J Clin Oncol. 2005;23(16_suppl):3535. doi: 10.1200/jco.2005.23.16_suppl.3535.
    1. Neuman HB, Greenberg CC. Comparative effectiveness research: opportunities in surgical oncology. Semin Radiat Oncol. 2014;24(1):43–48. doi: 10.1016/j.semradonc.2013.09.003.
    1. Gillern SM, Chua TC, Stojadinovic A, Esquivel J. KRAS status in patients with colorectal cancer peritoneal carcinomatosis and its impact on outcome. Am J Clin Oncol. 2010;33(5):456–460. doi: 10.1097/COC.0b013e3181b4b160.
    1. Kusamura S, Gonzalez-Moreno S, Nizri E, Baratti D, Guadagni S, Guaglio M, et al. Learning curve, training program, and monitorization of surgical performance of peritoneal surface malignancies centers. Surg Oncol Clin N Am. 2018;27(3):507–517. doi: 10.1016/j.soc.2018.02.009.
    1. Sugarbaker PH. Surgical management of carcinomatosis from colorectal cancer. Clin Colon Rectal Surg. 2005;18(3):190–203. doi: 10.1055/s-2005-916280.
    1. Glockzin G, Zeman F, Croner RS, Konigsrainer A, Pelz J, Strohlein MA, et al. Perioperative systemic chemotherapy, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy in patients with colorectal peritoneal metastasis: results of the prospective multicenter phase 2 COMBATAC Trial. Clin Colorectal Cancer. 2018;17(4):285–296. doi: 10.1016/j.clcc.2018.07.011.
    1. Lievre A, Bachet JB, Boige V, Cayre A, Le CD, Buc E, et al. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol. 2008;26(3):374–379. doi: 10.1200/JCO.2007.12.5906.
    1. Desolneux G, Maziere C, Vara J, Brouste V, Fonck M, Bechade D, et al. Cytoreductive surgery of colorectal peritoneal metastases: outcomes after complete cytoreductive surgery and systemic chemotherapy only. PLoS ONE. 2015;10(3):e0122816. doi: 10.1371/journal.pone.0122816.
    1. Mahteme H, Hansson J, Berglund A, Pahlman L, Glimelius B, Nygren P, et al. Improved survival in patients with peritoneal metastases from colorectal cancer: a preliminary study. Br J Cancer. 2004;90(2):403–407. doi: 10.1038/sj.bjc.6601586.
    1. Elias D, Raynard B, Farkhondeh F, Goere D, Rouquie D, Ciuchendea R, et al. Peritoneal carcinomatosis of colorectal origin. Gastroenterol Clin Biol. 2006;30(10):1200–1204. doi: 10.1016/S0399-8320(06)73512-6.
    1. Kusamura S, Dominique E, Baratti D, Younan R, Deraco M. Drugs, carrier solutions and temperature in hyperthermic intraperitoneal chemotherapy. J Surg Oncol. 2008;98(4):247–252. doi: 10.1002/jso.21051.
    1. Stevenson MG, Seinen JM, Pras E, Brouwers AH, van Ginkel RJ, van Leeuwen BL, et al. Hyperthermic isolated limb perfusion, preoperative radiotherapy, and surgery (PRS) a new limb saving treatment strategy for locally advanced sarcomas. J Surg Oncol. 2018;117(7):1447–1454. doi: 10.1002/jso.25008.

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit