An open label phase 1 study evaluation safety, tolerability, and maximum tolerated dose of oral administration of irinotecan in combination with capecitabine
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Oral administration of chemotherapy offers several advantages in comparison with intravenous administration. Previously, data on a new oral formulation of irinotecan have been published. The aim of the present study was to evaluate the safety, tolerability, and Maximum Tolerated Dose (MTD) of the new oral irinotecan formulation in combination with oral capecitabine.
The study was an open label, phase 1, single center, extension part in which oral irinotecan was investigated in combination with capecitabine. The MTD of irinotecan in combination with capecitabine was 17.5 mg/m2 once daily for 14 consecutive days in combination with capecitabine 800 mg/m2 twice daily. Eligible patients were adults with metastatic or unresectable solid tumors for which no standard curative or palliative therapies existed.
14 patients were included in the extension part. No grade 3 or 4 hematologic toxicities were observed. Non-hematological toxicities included grade 1 and 2 diarrhea, fatigue, cholinergic syndrome, vomiting, and weight loss. Totally, 3 grade 3 toxicities and no grade 4 event were reported. No objective responses were observed. Five patients had stable disease lasting median 14 weeks.
Capecitabine in combination with oral irinotecan could be a new treatment option offering a more convenient and patient friendly treatment strategy compared to intravenous irinotecan. The combination is fairly tolerated; however, further investigations are needed to assess the efficacy of this regimen.
KeywordsPhase 1 study Oral irinotecan Capecitabine Solid tumors
Funding was provided by Innovationsfonden (5184-00055B) and Kræftens Bekæmpelse (R110-A7013).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
- 2.Ducreux M, Cuhna AS, Caramella C, Hollebecque A, Burtin P, Goere D, Seufferlein T, Haustermans K, Van Laethem JL, Conroy T, Arnold D, Committee EG (2015) Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 26(Suppl 5):v56–68. https://doi.org/10.1093/annonc/mdv295 CrossRefGoogle Scholar
- 4.Berlin J, Benson AB, Rubin EH et al (2003) Phase I safety, pharmacokinetic and bioavailability study of a semi-solid matrix formulations of oral irinotecan i pateitns with advanced solid tumors. Proc Am Soc Clin Oncol 22:130 (abstract 521)Google Scholar
- 5.Dumez H, Awada A, Piccart M, Assadourian S, Semiond D, Guetens G, de Boeck G, Maes RA, de Bruijn EA, van Oosterom A (2006) A phase I dose-finding clinical pharmacokinetic study of an oral formulation of irinotecan (CPT-11) administered for 5 days every 3 weeks in patients with advanced solid tumours. Ann Oncol 17(7):1158–1165. https://doi.org/10.1093/annonc/mdl071 CrossRefGoogle Scholar
- 6.Kuppens IE, Dansin E, Boot H, Feger C, Assadourian S, Bonneterre ME, Beijnen JH, Schellens JH, Bonneterre J (2006) Dose-finding phase I clinical and pharmacokinetic study of orally administered irinotecan in patients with advanced solid tumors. Clin Cancer Res 12(12):3774–3781. https://doi.org/10.1158/1078-0432.CCR-05-2368 CrossRefGoogle Scholar
- 7.Schoemaker NE, Kuppens IE, Huinink WW, Lefebvre P, Beijnen JH, Assadourian S, Sanderink GJ, Schellens JH (2005) Phase I study of an oral formulation of irinotecan administered daily for 14 days every 3 weeks in patients with advanced solid tumours. Cancer Chemother Pharmacol 55(3):263–270. https://doi.org/10.1007/s00280-004-0874-2 CrossRefGoogle Scholar
- 8.Kumler I, Sorensen PG, Palshof J, Hogdall E, Skovrider-Ruminski W, Theile S, Fullerton A, Nielsen PG, Jensen BV, Nielsen DL (2018) Oral administration of irinotecan in patients with solid tumors: an open-label, phase I, dose escalating study evaluating safety, tolerability and pharmacokinetics. Cancer Chemother Pharmacol. https://doi.org/10.1007/s00280-018-3720-7 Google Scholar
- 12.Han JY, Nam BH, Kim HY, Yoon SJ, Kim HT, Lee JS (2012) A randomized phase II study of irinotecan plus cisplatin versus irinotecan plus capecitabine with or without isosorbide-5-mononitrate in advanced non-small-cell lung cancer. Ann Oncol 23(11):2925–2930. https://doi.org/10.1093/annonc/mds122 CrossRefGoogle Scholar
- 14.Park IH, Im SA, Jung KH, Sohn JH, Park YH, Lee KS, Sim SH, Park KH, Kim JH, Nam BH, Kim HJ, Kim TY, Lee KH, Kim SB, Ahn JH, Lee S, Ro J (2018) Randomized open label phase III trial of irinotecan plus capecitabine versus capecitabine monotherapy in patients with metastatic breast cancer previously treated with anthracycline and taxane: PROCEED Trial (KCSG BR 11 – 01). Cancer Res Treat. https://doi.org/10.4143/crt.2017.562 Google Scholar
- 15.Patt YZ, Lee FC, Liebmann JE, Diamandidis D, Eckhardt SG, Javle M, Justice GR, Keiser W, Salvatore JR, Bexon A, Lin E (2007) Capecitabine plus 3-weekly irinotecan (XELIRI regimen) as first-line chemotherapy for metastatic colorectal cancer: phase II trial results. Am J Clin Oncol 30(4):350–357. https://doi.org/10.1097/COC.0b013e31804b40bb CrossRefGoogle Scholar
- 17.Gennatas C, Michalaki V, Gennatas S, Papalambros E (2008) Irinotecan plus capecitabine as first-line chemotherapy in advanced colorectal cancer. Anticancer Res 28(3B):1923–1926Google Scholar
- 18.Xu RH, Muro K, Morita S, Iwasa S, Han SW, Wang W, Kotaka M, Nakamura M, Ahn JB, Deng YH, Kato T, Cho SH, Ba Y, Matsuoka H, Lee KW, Zhang T, Yamada Y, Sakamoto J, Park YS, Kim TW (2018) Modified XELIRI (capecitabine plus irinotecan) versus FOLFIRI (leucovorin, fluorouracil, and irinotecan), both either with or without bevacizumab, as second-line therapy for metastatic colorectal cancer (AXEPT): a multicentre, open-label, randomised, non-inferiority, phase 3 trial. Lancet Oncol 19(5):660–671. https://doi.org/10.1016/S1470-2045(18)30140-2 CrossRefGoogle Scholar