A dose-escalation study of oxaliplatin/capecitabine/irinotecan (XELOXIRI) and bevacizumab as a first-line therapy for patients with metastatic colorectal cancer.

Abstract

PURPOSE:

The aim of this study was to determine the recommended dose (RD) of a triweekly capecitabine, oxaliplatin, irinotecan, and bevacizumab (XELOXIRI/bevacizumab) regimen that was easier to administer than FOLFOXIRI/bevacizumab, using capecitabine instead of 5-fuorouracil (5-FU), in patients with metastatic colorectal cancer (mCRC).

METHODS:

Patients received oxaliplatin (100 mg/m(2), day 1), capecitabine (1,700 mg/m(2) per day from day 2 to 15), irinotecan (100, 120, 150 mg/m(2) for dose levels 1, 2, 3, day 1), and bevacizumab (7.5 mg/kg, day 1), repeated every 3 weeks. Dose-limiting toxicities (DLTs) were assessed in the first two cycles to determine the maximum tolerated dose (MTD).

RESULTS:

Twelve patients received a median of 6.5 cycles of therapy (range 2-12). The DLT was grade 4 neutropenia, observed in one of six patients at dose level 2. The MTD was not reached at dose level 3. Therefore, the RD of irinotecan was defined as 150 mg/m(2). The most common grade ≥3 toxicities were neutropenia (41 %), anemia (17 %), diarrhea (8 %), and febrile neutropenia (8 %). The response rate and median progression-free survival were 83 % and 15 months, respectively.

CONCLUSIONS:

XELOXIRI/bevacizumab is a feasible regimen for patients with mCRC, neutropenia was the DLT, and the RD of irinotecan is 150 mg/m(2). The response rate observed is very promising and warrants further investigation.

• Authors: Yasushi Sato, Hiroyuki Ohnuma, Masahiro Hirakawa, Minoru Takahashi, Takahiro Osuga, Yutaka Okagawa, Kazuyuki Murase, Kohichi Takada, Yutaka Kawano, Satoshi Iyama, Tsuyoshi Hayashi, Tsutomu Sato, Koji Miyanishi, Rishu Takimoto, Masayoshi Kobune, Kenji Okita, Toru Mizuguchi, Tomohisa Furuhata, Koichi Hirata, Junji Kato
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 75 Issue 3 Pg. 587-94 (Mar 2015) ISSN: 1432-0843 [Electronic] Germany
• PMID: 25577134 (Publication Type: Controlled Clinical Trial, Journal Article)

Chemical References

• Antibodies, Monoclonal, Humanized
• Organoplatinum Compounds
• Oxaliplatin
• Deoxycytidine
• Bevacizumab
• Capecitabine
• Irinotecan
• Fluorouracil
• Camptothecin

Topics

• Aged
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
• Bevacizumab
• Camptothecin (administration & dosage, analogs & derivatives)
• Capecitabine
• Colorectal Neoplasms (drug therapy, pathology)
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Disease-Free Survival
• Dose-Response Relationship, Drug
• Feasibility Studies
• Fluorouracil (administration & dosage, analogs & derivatives)
• Humans
• Irinotecan
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasm Metastasis
• Organoplatinum Compounds (administration & dosage)
• Oxaliplatin
• Treatment Outcome