Clinical Practice Patterns in Chemotherapeutic Treatment Regimens for Metastatic Colorectal Cancer

McLean, James; Rho, Young Soo; Kuruba, Gayathri; Mamo, Aline; Gilabert, Marine; Kavan, Tomas; Panasci, Lawrence; Melnychuk, David; Batist, Gerald; Kavan, Petr

doi:10.1016/j.clcc.2015.10.003

Cited by 31 publications

(26 citation statements)

References 13 publications

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“…In contrast, in the US, the most common third line treatment regimens are EGFR-containing therapies, such as combination of cetuximab and irinotecan, panitumumab or cetuximab monotherapy [15]. In other countries, such as Canada, although oxaliplatin and irinotecan were also the most common chemotherapy backbones for firstand second-line, chemotherapy was usually not used alone [17,18]. This may imply poor treatment outcomes of targeted therapy in late lines, and a lack of consensus on both the timing and options for third-line treatment during the study period (2011)(2012)(2013)(2014)(2015)(2016).…”

Section: Discussionmentioning

confidence: 99%

“…As multiple chemotherapeutic and targeted biologic agents emerged, treatment patterns and sequences for mCRC patients have significantly evolved over the past decade [12]. Several studies have reported the complex and changing treatment pattern among mCRC patients in the United States [13][14][15][16], Canada [17], and some European countries [18,19]. However, there is a lack of key real-world evidence on the clinical characteristics and treatment patterns of CRC/mCRC patients in China.…”

Section: Introductionmentioning

confidence: 99%

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Disease characteristics and treatment patterns of Chinese patients with metastatic colorectal cancer: a retrospective study using medical records from China

Wang

Zhu

et al. 2020

BMC Cancer

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Background: Colorectal cancer (CRC) is the third most prevalent cancer in China but few large-scale studies were conducted to understand CRC patients. The current study is aimed to gain a real-world perspectives of CRC patients in China.Methods: Using electronic medical records of sampled patients between 2011 and 2016 from 12 hospitals in China, a retrospective cohort study was conducted to describe demographics and disease prognosis of CRC patients, and examine treatment sequences among metastatic CRC (mCRC) patients. Descriptive, comparative and survival analyses were conducted. Results: Among mCRC patients (3878/8136, 48%), the fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and other oxaliplatin-based regimens were the most widely-used first-line treatment (42%). Fluorouracil, leucovorin, irinotecan (FOLFIRI) and other irinotecan-based regimens dominated the second-line (40%). There was no a dominated regimen for the third-line. The proportion of patients receiving chemotherapy with targeted biologics increased from less than 20% for the first-and second-lines to 34% for the third-line (p < 0.001). The most common sequence from first-to second-line was from FOLFOX and other oxaliplatin-based regimens to FOLFIRI and other irinotecan-based regimens (286/1200, 24%). Conclusions:Our findings reflected a lack of consensus on the choice of third-line therapy and limited available options in China. It is evident o continue promoting early CRC diagnosis and to increase the accessibility of treatment options for mCRC patients. As the only nationwide large-scale study among CRC and mCRC patients before more biologics became available in China, our results can also be used as the baseline to assess treatment pattern changes before and after more third-line treatment were approved and covered into the National Health Insurance Plan in China between 2017 and 2018.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Disease characteristics and treatment patterns of Chinese patients with metastatic colorectal cancer: a retrospective study using medical records from China

Wang

Zhu

et al. 2020

BMC Cancer

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“…Fluorouracil (5-FU)-based chemotherapy is generally considered as the first-line treatment for advanced CRC [35]. Response rates to 5-FU treatment are between 10–20% in the advanced CRC [36], and a better response rate has been reported using combined chemotherapy regimens of 5-FU and oxaliplatin which is 40–50% [37].…”

Section: Discussionmentioning

confidence: 99%

Reduced NOV expression correlates with disease progression in colorectal cancer and is associated with survival, invasion and chemoresistance of cancer cells

Park

et al. 2017

Oncotarget

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Aberrant expression of nephroblastoma overexpressed (NOV) has been evident in certain malignancies. In the current study, we aim to investigate the role played by NOV in colorectal cancer (CRC). NOV expression was determined in a cohort of 359 CRC tissues and 174 normal colorectal tissues. Its impact on CRC cells was investigated using in vitro NOV knockdown and overexpression models. NOV transcripts were reduced in the CRC tumours compared with the paired adjacent normal colorectal tissues (p < 0.01) and was associated with distant metastases. NOV knockdown resulted in increased cell proliferation and invasion of RKO cells, whilst an opposite effect was seen in the HT115 NOV over expressing cells. A positive association between Caspase-3/-8 and NOV was seen in NOV knockdown and overexpression cell lines which contributed to the survival of serum deprived CRC cells. Further investigation showed that NOV regulated proliferation, survival and invasion through the JNK pathway. NOV knockdown in RKO cells reduced the responsiveness to 5-Fluorouracil treatment, whilst overexpression in HT115 cells exhibited a contrasting effect. Taken together, NOV is reduced in CRC tumours and this is associated with disease progression. NOV inhibits the proliferation and invasion of CRC cells in vitro. Inhibition of proliferation is mediated by a regulation of Caspase-3/-8, via the JNK pathway, which has potential for predicting and preventing chemoresistance.

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“…While surgical resection at early stages may lead to complete eradication of tumors, CRC at advanced stages requires systemic chemotherapy and/or irradiation . In addition to cytotoxic reagents, some molecularly targeted drugs such as angiogenesis inhibitors (bevacizumab and ramucirumab), anti‐EGFR antibodies (cetuximab and panitumumab) and multi‐kinase inhibitors (regorafenib) are currently used for CRC treatments …”

Section: Introductionmentioning

confidence: 99%

Genomic profiles of colorectal carcinoma with liver metastases and newly identified fusion genes

et al. 2019

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Every year, approximately 1.2 million cases of colorectal carcinoma (CRC) are newly diagnosed worldwide. Although metastases to distant organs are often fatal complications of CRC, little information is known as to how such metastatic lesions are formed. To reveal the genetic profiles for CRC metastasis, we conducted whole‐exome RNA sequencing on CRC tumors with liver metastasis (LM) (group A, n = 12) and clinical stage‐matched larger tumors without LM (group B, n = 16). While the somatic mutation profiles were similar among the primary tumors and LM lesions in group A and the tumors in group B, the A‐to‐C nucleotide change in the context of “AAG” was only enriched in the LM regions in group A, suggesting the presence of a DNA damage process specific to metastasis. Genes already known to be associated with CRC were mutated in all groups at a similar frequency, but we detected somatic nonsynonymous mutations in a total of 707 genes in the LM regions, but not in the tumors without LM. Signaling pathways linked to such “LM‐associated” genes were overrepresented for extracellular matrix‐receptor interaction or focal adhesion. Further, fusions of the ADAP1 (ArfGAP with dual PH domain 1) were newly identified in our cohort (3 out of 28 patients), which activated ARF6, an ADAP1‐substrate. Infrequently, mutated genes may play an important role in metastasis formation of CRC. Additionally, recurrent ADAP1 fusion genes were unexpectedly discovered. As these fusions activate small GTPase, further experiments are warranted to examine their contribution to CRC carcinogenesis.

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Clinical Practice Patterns in Chemotherapeutic Treatment Regimens for Metastatic Colorectal Cancer

Cited by 31 publications

References 13 publications

Disease characteristics and treatment patterns of Chinese patients with metastatic colorectal cancer: a retrospective study using medical records from China

Disease characteristics and treatment patterns of Chinese patients with metastatic colorectal cancer: a retrospective study using medical records from China

Reduced NOV expression correlates with disease progression in colorectal cancer and is associated with survival, invasion and chemoresistance of cancer cells

Genomic profiles of colorectal carcinoma with liver metastases and newly identified fusion genes

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