Clinical Implication of Anti-Angiogenic Effect of Regorafenib in Metastatic Colorectal Cancer.

Abstract

BACKGROUND:

Regorafenib induces distinct radiological changes that represent its anti-angiogenic effect. However, clinical implication of the changes is unclear.

METHODS:

Tumor attenuation as measured by Hounsfield units (HU) in contrast-enhanced computed tomography (CT) and cavitary changes of lung metastases were analyzed in association with treatment outcome of metastatic colorectal cancer patients (N = 80) treated with regorafenib in a prospective study.

RESULTS:

141 lesions in 72 patients were analyzed with HU. After 2 cycles of regorafenib, 87.5% of patients showed decrease of HU (Median change -23.9%, range -61.5%-20.7%). Lesional attenuation change was modestly associated with metabolic changes of 18-fluoro-deoxyglucose positron emission tomography-CT (Pearson's r = 0.37, p = 0.002). Among 53 patients with lung metastases, 17 (32.1%) developed cavitary changes. There were no differences in disease control rate, progression-free survival, or overall survival according to the radiological changes. At the time of progressive disease (PD) according to RECIST 1.1, HU was lower than baseline in 86.0% (43/50) and cavitary change of lung metastasis persisted without refilling in 84.6% (11/13).

CONCLUSION:

Regorafenib showed prominent anti-angiogenic effect in colorectal cancer, but the changes were not associated with treatment outcome. However, the anti-angiogenic effects persisted at the time of PD, which suggests that we may need to develop new treatment strategies.

• Authors: Yoojoo Lim, Sae-Won Han, Jeong Hee Yoon, Jeong Min Lee, Jung Min Lee, Jin Chul Paeng, Jae-Kyung Won, Gyeong Hoon Kang, Seung-Yong Jeong, Kyu Joo Park, Kyung-Hun Lee, Jee Hyun Kim, Tae-You Kim
• Journal: PloS one (PLoS One) Vol. 10 Issue 12 Pg. e0145004 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26671465 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Phenylurea Compounds
• Pyridines
• regorafenib

Topics

• Adult
• Aged
• Angiogenesis Inhibitors (therapeutic use)
• Colorectal Neoplasms (blood supply, drug therapy, pathology)
• Disease-Free Survival
• Female
• Humans
• Male
• Middle Aged
• Neoplasm Metastasis
• Neovascularization, Pathologic (drug therapy)
• Phenylurea Compounds
• Pyridines
• Treatment Outcome
• Tumor Burden