Efficacy and safety of irinotecan monotherapy as third-line treatment for advanced gastric cancer
Although irinotecan monotherapy is often used in third-line treatment after the failure of taxanes in Japanese clinical practice, its survival benefit is still unclear. The aim of this study is to investigate the efficacy and safety of irinotecan monotherapy as third-line treatment.
Clinical data from consecutive patients in whom irinotecan had been initiated as third-line treatment between December 2003 and July 2015 in Shizuoka Cancer Center were retrospectively analyzed. Patients who were refractory or intolerant to fluoropyrimidine with or without platinum in first-line treatment and subsequent therapy with taxanes were included in this study. Irinotecan was administered at 150 mg/m2 every 2 weeks.
The data of 50 patients who met the inclusion criteria were analyzed. The overall response rate was 18.4 % (7/38) among the patients with measurable disease. The median progression-free survival time was 66 days, and the median survival time was 180 days from the initiation of irinotecan therapy. The major grade 3 or 4 adverse events including neutropenia, fatigue, and anorexia were observed in 12 (24 %), 8 (16 %), and 7 (14 %), respectively. No treatment-related deaths occurred. Thirteen patients (26 %) required a dose reduction to 120 mg/m2 or less from the initiation of irinotecan.
This study suggests that irinotecan as third-line treatment has an anti-tumor effect and is feasible with optimal dose modification for advanced gastric cancer.
KeywordsAdvanced gastric cancer Irinotecan Third-line treatment Salvage line
The authors thank the patients and their families for their participation in this study.
Compliance with ethical standards
Conflict of interest
The authors have no potential conflicts of interest.
- 1.Ferlay J SI, Ervik M, et al. GLOBOCAN 2012 v1.0, Cancer incidence and mortality worldwide: IARC CancerBase No. 11. Lyon, France: International agency for research on Cancer; 2013. http://globocan.iarc.fr (accessed Oct 7, 2015)
- 2.Statistics and Information Department MoH, Labour and Welfare. Vital statistics in 2014 (in Japanese). http://www.mhlwgojp/Accessed 1 Nov 2015
- 5.Thuss-Patience PC, Kretzschmar A, Bichev D et al (2011) Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer–a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer 47:2306–2314. doi: 10.1016/j.ejca.2011.06.002 CrossRefPubMedGoogle Scholar
- 8.Fuchs CS, Tomasek J, Yong CJ et al (2014) Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 383:31–39. doi: 10.1016/s0140-6736(13)61719-5 CrossRefPubMedGoogle Scholar
- 9.Hironaka S, Ueda S, Yasui H et al (2013) Randomized, open-label, phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 trial. J Clin Oncol 31:4438–4444. doi: 10.1200/jco.2012.48.5805 CrossRefPubMedGoogle Scholar
- 10.Wilke H, Muro K, Van Cutsem E et al (2014) Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol 15:1224–1235. doi: 10.1016/s1470-2045(14)70420-6 CrossRefPubMedGoogle Scholar
- 11.NCCN Clinical Practice Guidelines in Oncology Gastric Cancer v.3 2015, accessed Nov 9, 2015, at http://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf
- 15.Li J, Qin S, Xu J et al (2016) Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Apatinib in Patients With Chemotherapy-Refractory Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction. J Clin Oncol 34:1448–1454. doi: 10.1200/jco.2015.63.5995 CrossRefPubMedGoogle Scholar
- 16.Kang EJ, Im SA, Oh DY et al (2013) Irinotecan combined with 5-fluorouracil and leucovorin third-line chemotherapy after failure of fluoropyrimidine, platinum, and taxane in gastric cancer: treatment outcomes and a prognostic model to predict survival. Gastric Cancer 16:581–589. doi: 10.1007/s10120-012-0227-5 CrossRefPubMedGoogle Scholar
- 17.Higuchi K, Tanabe S, Shimada K et al (2014) Biweekly irinotecan plus cisplatin versus irinotecan alone as second-line treatment for advanced gastric cancer: a randomised phase III trial (TCOG GI-0801/BIRIP trial). Eur J Cancer 50:1437–1445. doi: 10.1016/j.ejca.2014.01.020 CrossRefPubMedGoogle Scholar
- 18.Nishikawa K, Fujitani K, Inagaki H et al (2015) Randomised phase III trial of second-line irinotecan plus cisplatin versus irinotecan alone in patients with advanced gastric cancer refractory to S-1 monotherapy: TRICS trial. Eur J Cancer 51:808–816. doi: 10.1016/j.ejca.2015.02.009 CrossRefPubMedGoogle Scholar