A triplet combination with oxaliplatin/capecitabine/irinotecan (XELOXIRI) plus cetuximab (Cmab) as a first-line therapy in wild-type KRAS, metastatic colorectal cancer: a dose escalating study

Date

08 Oct 2016

Session

Poster Display

Presenters

Yasushi Sato

Citation

Annals of Oncology (2016) 27 (6): 149-206. 10.1093/annonc/mdw370

Authors

Y. Sato1, H. Ohnuma1, M. Hirakawa1, S. Kikuch1, M. Takahashi2, T. Okamoto3, Y. Tsuji4, K. Okita5, T. Furuhata5, I. Takemasa5, J. Kato1

Author affiliations

  • 1 Depertment Of Medical Oncology And Hematology, Sapporo Medical University School of Medicine, 060-8543 - Sapporo/JP
  • 2 Department Of Gastroenterology, Sapporo Kyoritsu Gorinbashi Hospital, Sapporo/JP
  • 3 Department Of Gastroenterology, Kiyota Hospital, Sapporo/JP
  • 4 Department Of Medical Oncology, Tonan Hospital, 060-0001 - Sapporo/JP
  • 5 Department Of Surgery, Surgical Oncology And Science, Sapporo Medical University School of Medicine, Sapporo/JP
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Background

We previously reported the promising activity of a triweekly oxaliplatin/capecitabine/irinotecan (XELOXIRI) plus bevacizumab regimen, which was easier to administer than FOLFOXIRI/ bevacizumab, using capecitabine, instead of 5-fuorouracil, in pts with metastatic colorectal cancer (mCRC)(Cancer Chemother Pharmacol 2015). In order to achieve more potent efficacy, we explored the dose limiting toxicity and feasibility of the combination XELOXIRI plus cetuximab (XELOXIRI/Cmab) in pts with KRAS wild type mCRC.

Methods

Pts were eligible if they had KRAS wild-type mCRC (liver and/or other metastases), ECOG PS 0-1, were either negative or heterozygous for UGT1A1*6 or UGT1A1*28 and were not pretreated for metastatic disease. Treatment consisted of oxaliplatin (100 mg/m2 day 1), capecitabine (1700 mg/m2/day from day 2 to 15), irinotecan (100,120,150 mg/m2 for dose levels 1, 2, or 3, day 1) repeated every 3 weeks and weekly cetuximab (400 mg/m2 and, thereafter, 250 mg/m2, day 1). The dose of irinotecan was escalated if dose limiting toxicities (DLT) were absent in the first three pts per cohort, or if

Results

From Oct. 2012 to Dec. 2014, 12 pts (F/M: 5/7, median age: 64.5 years, PS 0/1: 11/1) received a median of 6 cycles of therapy (range 2-10). The DLT was Grade 4 neutropenia, which was observed in 1 of 6 patients at dose level 2. MTD was not reached at dose level 3. Therefore, the RD of irinotecan was defined as 150 mg/m2. Most common grade ≥ 3 toxicities were neutropenia (49%), diarrhea (16.7%), and febrile neutropenia (8.3 %). The response rate was 83.3% (CR: 1 pt and PR: 9 pts), including 4 conversion cases. At a median follow-up of 18.7 months, median PFS was 14.5 months and median OS was not yet reached.

Conclusions

The combination of XELOXIRI and cetuximab is feasible and has an acceptable toxicity profile; neutropenia was the DLT; recommended dose of irinotecan is 150 mg/m2. The observed response rate of 83.3% is very promising and warrants further investigation.

Clinical trial identification

Trial protocol number (UMIN000009144) release date (2012/10/18)

Legal entity responsible for the study

Sapporo Medical University School of Medicine

Funding

Sapporo Medical University School of Medicine

Disclosure

All authors have declared no conflicts of interest.

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