FOLFOXIRI and bevacizumab in metastatic colorectal cancer

Rahman, Ahmadur

doi:10.1016/s1470-2045(14)71112-x

Cited by 5 publications

(6 citation statements)

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“…Since the optimal sequence and interval for SBRT and systemic therapy are still unclear, targeted therapy combined with chemotherapy has proven to be effective in the treatment of metastatic CRC. [28][29][30][31][32] In our study, the patients who received chemotherapy combined with bevacizumab before SBRT had a longer PFS and N-PFS. Moreover, we found that two of the three patients not receiving any systemic therapy after SBRT showed poor status, which indicated that selecting suitable patients for SBRT was important for the overall treatment.…”

Section: Discussionmentioning

confidence: 49%

“…Patients in the OP group were more likely to relapse at distant sites (defined as new progress in our study), which was similar to our result. Since the optimal sequence and interval for SBRT and systemic therapy are still unclear, targeted therapy combined with chemotherapy has proven to be effective in the treatment of metastatic CRC 28–32 . In our study, the patients who received chemotherapy combined with bevacizumab before SBRT had a longer PFS and N‐PFS.…”

Section: Discussionmentioning

confidence: 61%

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Stereotactic body radiotherapy prolongs the progression‐free survival and delays the change of systemic therapy regimen in patients with lung oligoprogressive metastatic colorectal cancer

Dong

Geng

et al. 2021

Asia-Pac J Clncl Oncology

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Purpose:To analyze the effect of stereotactic body radiotherapy (SBRT) on colorectal cancer (CRC) patients with lung oligoprogression (OP).Method: Patients with lung OP from CRC treated by SBRT at our center were included in this retrospective analysis. The progression-free survival (PFS), change of systemic therapy (CST), local control (LC), and overall survival (OS) were analyzed. Cumulative incidence was used to report CST, and the Kaplan-Meier method was used to evaluate PFS and LC.Results: A total of 17 patients with 38 lung OP lesions treated by SBRT from October 2012 to December 2018 were involved. All patients had undergone radical resection for primary CRC and administered with standard systemic therapy regimens (seven for the first line and 10 for the second line). Among them, nine (52.9%) had received targeted therapy before SBRT, 14 (82.4%) patients underwent chemotherapy, and 12 received targeted therapy after SBRT. Six patients (35.3%) underwent CST after a median time of 5.2 months (range: 1.7-27.5 months). The median follow-up was 9.9 months, and the 1-year OS rate for all patients was 73.5%. Progression was observed in of 14 of 17 patients (82.4%), and the 6-month PFS for all patients was 25.9%. Univariate analysis indicated that only targeted therapy before SBRT was a beneficial prognostic indicator for 6-month PFS (P = .026) and N-PFS (P = .013). The 1-year LC for all 38 lesions was 77.8%, and during and after SBRT, no grade 3 or higher toxicities were observed. Conclusion:SBRT combined with systemic therapy made partial CRC patients with lung OP avoid the progress within 6 months and delayed the need for CST to 5.2 months, and targeted therapy before SBRT was a positive indicator of PFS.

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Section: Discussionmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 61%

Stereotactic body radiotherapy prolongs the progression‐free survival and delays the change of systemic therapy regimen in patients with lung oligoprogressive metastatic colorectal cancer

Dong

Geng

et al. 2021

Asia-Pac J Clncl Oncology

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“… 2 , 3 Their median survival time is highly variable, ranging from 6 to 18 months, with a large range within each study subgroup. 4 – 6 Furthermore, optimal treatment strategies are highly controversial, aiming to balance a favorable effect on progression-free survival (PFS) and overall survival (OS) versus adverse events (AEs) in these patients. 6 …”

Section: Introductionmentioning

confidence: 99%

“…2,3 Their median survival time is highly variable, ranging from 6 to 18 months, with a large range within each study subgroup. [4][5][6] Furthermore, optimal treatment strategies are highly controversial, aiming to balance a favorable effect on progression-free survival (PFS) and overall survival (OS) versus adverse events (AEs) in these patients. 6 Combination treatment schedules with a modified 5-fluorouracil, folinate, oxaliplatin, and irinotecan (FOLFOXIRI) regimen plus a molecularly targeted drug (cetuximab [CE] or bevacizumab [BE]) in the first-line setting have been acknowledged as the standard processing scheme on the basis of published clinical efficacy and safety profiles.…”

Section: Introductionmentioning

confidence: 99%

Cetuximab versus bevacizumab maintenance following prior 8-cycle modified FOLFOXIRI plus cetuximab in Asian postmenopausal women with treatment-naive KRAS and BRAF wild-type metastatic colorectal cancer

Chen

Zheng

et al. 2020

J Int Med Res

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Objective To assess the efficacy and safety of cetuximab (CE) versus bevacizumab (BE) maintenance treatment after prior 8-cycle modified 5-fluorouracil, folinate, oxaliplatin, and irinotecan (FOLFOXIRI) plus CE induction therapy in treatment-naive KRAS and BRAF wild-type (wt) metastatic colorectal cancer (mCRC). Methods From 2012 to 2017, prospectively maintained databases were reviewed to assess Asian postmenopausal women with treatment-naive KRAS and BRAF wt mCRC who underwent modified FOLFOXIRI plus CE induction therapy, followed by CE or BE maintenance until disease progression or death. Co-primary clinical endpoints were progression-free survival (PFS) and overall survival (OS). Results A total of 222 women were included (CE n = 110 and BE n = 112). At a median follow-up of 27.0 months (interquartile range, 6.5–38.6 months), median PFS was 21.9 months (95% confidence interval [CI] 16.4–24.4) and 17.7 months (95% CI 11.3–19.0) for CE and BE groups, respectively (hazard ratio [HR] 0.31, 95% CI 0.15–0.46); median OS was 26.0 months (95% CI 23.4–28.7) and 22.7 months (95% CI 21.2–24.3) for CE and BE groups, respectively (HR 0.22, 95% CI 0.11–0.37). Conclusions CE maintenance treatment is more poorly tolerated but has a slightly more modest survival benefit compared with BE maintenance treatment in mCRC.

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“…The first line treatment for early-stage colon cancer is surgical resection, which may be preceded (neoadjuvant) or followed by (adjuvant) chemotherapy for later stage disease (Braun et al, 2011;Werner et al, 2016). Chemotherapeutic options usually involve combinations of oxaliplatin (OX), 5-fluorouracil (5-FU), leucovorin/folinic acid (FA), and irinotecan (IR) -these combinations are offered as FOLFOX (OX, 5-FU and FA), FOLFIRI (IR,, or FOLFOXIRI (all four) (Braun et al, 2011;Goldberg et al, 2004;A. Rahman, 2014).…”

Section: Colorectal Cancer Incidence Treatment and Mortalitymentioning

confidence: 99%

Characterisation of cancer stem cells and the renin-angiotensin system in colon adenocarcinoma

Munro¹

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Colorectal cancer (CRC) is the third most common cancer and the second highest cause of cancer deaths globally. More than 70% of CRC-related deaths are due to metastasis to the liver. The cancer stem cell (CSC) concept hypothesises that CSCs drive tumour growth, chemoresistance, recurrence and metastasis. Markers such as CD133, LGR5 and EpCAM, have been used to identify and isolate CSCs in CRC. However, these markers are often expressed by cells with no stem cell properties and are not expressed by all tumour-initiating cells. An improved range of markers to define CSCs is needed. In 2007, adult mouse and human fibroblasts were reprogrammed into a stem cell state and defined as induced pluripotent stem cells (iPSCs) using transcription factors OCT4, SOX2, NANOG, KLF4 and c-MYC. These genes have well-documented roles in embryonic development and the maintenance of pluripotency, and their expression has been investigated in a range of cancers. <br><br>The renin-angiotensin system (RAS) physiologically maintains blood pressure and volume and is also acknowledged to play a role in cancer. Over-expression of (pro)renin receptor (PRR), angiotensin II type 1 receptor (AT1R) and type 2 receptor (AT2R), and angiotensin-converting enzyme (ACE) have been reported in cancer. Epidemiological studies investigating the effect of RAS inhibitors on cancer outcomes have shown contradictory results.<br><br>This thesis investigates the expression of iPSC markers and RAS components in colon adenocarcinoma (CA) with three specific aims: (1) to compare CA-derived primary cell lines to their original CA tissues; (2) to investigate the expression profiles of iPSC markers in CA; and (3) to investigate expression of RAS components by CA CSCs and to determine whether CSCs can be targeted by RAS modulators. <br><br>DNA sequencing was carried out to compare the mutational profiles of formalin-fixed paraffin-embedded (FFPE) CA tissues and CA-derived cell lines to confirm whether the cell lines were a suitable in vitro model for the parent tumours.<br><br><div>Proteomics was performed to determine proteomic differences between CA tissues and patient-matched normal colon (NC) tissues, CA-derived cell lines and NC-derived cells, and between low grade CA (LGCA) tissues and cell lines and high grade CA (HGCA) tissues and cell lines. Biological processes which may link the RAS and CA were investigated, revealing enrichment of various signalling pathways that may play roles in CA onset and progression directly or via the RAS.</div><div><br></div>Western blotting and immunohistochemical staining showed elevated protein levels of OCT4, SOX2, NANOG, c-MYC, AT2R, PRR and cathepsin D in CA tissues relative to their patient-matched NC tissues, with SOX2, ACE and cathepsin B at similar levels and KLF4 less abundant in CA compared with NC tissues. Co-expression analysis by immunofluorescence staining showed a small number of epithelial cells co-expressed NANOG, SOX2, KLF4, c-MYC and CD133, as well as PRR, ACE2 and AT2R, while a small number of stromal cells co-expressed OCT4 and AT2R. This indicates the presence of at least one CSC subpopulation in CA, which expresses RAS components. HGCA tissue-derived cell lines expressed higher levels of OCT4 and SOX2 than LGCA-derived cell lines. The primary cell lines were sorted based on EpCAM expression. These EpCAM High and EpCAM Low cell subpopulations could undergo directed differentiation down the three embryonic lineages. A small number of CA-derived cells, particularly within the HGCA-derived cells, formed tumourspheres. Treatment of HGCA-derived cell lines with RAS modulators revealed that β-blockers and AT2R antagonists consistently reduced their metabolism, tumoursphere formation and iPSC marker expression. <br><br>The findings of this thesis suggest that CA-derived cell lines expressing iPSC markers have stem cell function and express RAS components. Furthermore, RAS modulators may directly influence CSCs in CA by reducing iPSC marker gene expression. This indicates a potential role for RAS modulators in regulating CSCs, which merits further investigation.

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FOLFOXIRI and bevacizumab in metastatic colorectal cancer

Cited by 5 publications

References 0 publications

Stereotactic body radiotherapy prolongs the progression‐free survival and delays the change of systemic therapy regimen in patients with lung oligoprogressive metastatic colorectal cancer

Stereotactic body radiotherapy prolongs the progression‐free survival and delays the change of systemic therapy regimen in patients with lung oligoprogressive metastatic colorectal cancer

Cetuximab versus bevacizumab maintenance following prior 8-cycle modified FOLFOXIRI plus cetuximab in Asian postmenopausal women with treatment-naive KRAS and BRAF wild-type metastatic colorectal cancer

Characterisation of cancer stem cells and the renin-angiotensin system in colon adenocarcinoma

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