Efficacy of apatinib combined with FOLFIRI in the first-line treatment of patients with metastatic colorectal cancer

SummaryObjective. To evaluate the efficacy and safety of apatinib combined with FOLFIRI in the first-line treatment of advanced metastatic colorectal cancer (mCRC) and explore potential factors of efficacy. Methods. Twenty mCRC patients treated at Affiliated Cancer Hospital of Shanxi Medical University from March 2017 to March 2019 were included according to the enrolment criteria. They provided informed consent and were treated with apatinib combined with FOLFIRI according to the scheduled regimen until disease progression or unacceptable toxicity occurred. The primary endpoint was OS. The secondary endpoints included PFS, ORR, DCRand safety. OS and PFS were calculated using Kaplan–Meier curves. Univariate and multivariate Cox regression analyses were used to evaluate independent prognostic factors of OS and PFS. R was used to determine cut-off values for biochemical indicators. Forest maps were drawn for Cox univariate results and the relationships between NLR and ECOG, which were significant in univariate analysis, and OS were represented by Kaplan–Meier curves. Results. The median OS and PFS were 16.135 months (95% CI: 9.211–22.929) and 6 months (95% CI: 5.425–6.525). Multivariate Cox analysis showed that NLR and CEA were independent prognostic factors. The most common grade 3–4 adverse events were hypertension, diarrhoea, increased alkaline phosphatase, decreased leukocytes and decreased neutrophils. Conclusion. Apatinib combined with FOLFIRI for the first-line treatment of advanced unresectable mCRC showed good efficacy and safety. The baseline NLR was predictive of efficacy, and a low baseline NLR (HR: 0.2895, P = 0.0084) was associated with improved OS.Clinical Research Registration Number: ChiCTR1800015308.

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Efficacy of Apatinib Combined with FOLFIRI in the First-Line Treatment of Patients with Metastatic Colorectal Cancer

10.21203/rs.3.rs-833709/v1 ◽

2021 ◽

Author(s):

Xuetong Rong ◽

Haiyi Liu ◽

Hongmei Yu ◽

Jian Zhao ◽

Jie Wang ◽

...

Keyword(s):

Colorectal Cancer ◽

Prognostic Factors ◽

Metastatic Colorectal Cancer ◽

Cox Regression ◽

Univariate Analysis ◽

Line Treatment ◽

Efficacy And Safety ◽

First Line ◽

Kaplan Meier ◽

First Line Treatment

Abstract Objective: To evaluate the efficacy and safety of apatinib combined with FOLFIRI in the first-line treatment of advanced metastatic colorectal cancer (mCRC) and explore potential factors of efficacy. Methods: Twenty mCRC patients treated at Affiliated Cancer Hospital of Shanxi Medical University from March 2017 to March 2019 were included according to the enrolment criteria. They provided informed consent and were treated with apatinib combined with FOLFIRI according to the scheduled regimen until disease progression or unacceptable toxicity occurred. The primary endpoint was OS. The secondary endpoints included PFS, ORR, DCRand safety. OS and PFS were calculated using Kaplan-Meier curves. Univariate and multivariate Cox regression analyses were used to evaluate independent prognostic factors of OS and PFS. R was used to determine cut-off values for biochemical indicators. Forest maps were drawn for Cox univariate results and the relationships between NLR and ECOG, which were significant in univariate analysis, and OS were represented by Kaplan-Meier curves. Results: The median OS and PFS were 16.135 months (95% CI: 9.211–22.929) and 6 months (95% CI: 5.425–6.525). Multivariate Cox analysis showed that NLR and CEA were independent prognostic factors. The most common grade 3–4 adverse events were hypertension, diarrhoea, increased alkaline phosphatase, decreased leukocytes and decreased neutrophils. Conclusion: Apatinib combined with FOLFIRI for the first-line treatment of advanced unresectable mCRC showed good efficacy and safety. The baseline NLR was predictive of efficacy, and a low baseline NLR (HR: 0.2895, P=0.0084) was associated with improved OS.

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The efficacy and safety of XELOX plus bevacizumab with oxaliplatin stop-and-go strategy in first-line treatment for metastatic colorectal cancer: Final report of CCOG-0902 study.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e14552 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e14552-e14552

Author(s):

Naomi Hayashi ◽

Goro Nakayama ◽

Kiyoshi Ishigure ◽

Hiroyuki Yokoyama ◽

Toyohisa Yaguchi ◽

...

Keyword(s):

Colorectal Cancer ◽

Maintenance Therapy ◽

Disease Control ◽

Metastatic Colorectal Cancer ◽

Final Report ◽

Line Treatment ◽

Efficacy And Safety ◽

First Line ◽

Stop And Go ◽

First Line Treatment

e14552 Background: XELOX plus bevacizumab (BEV) is an established first line therapy for metastatic colorectal cancer (mCRC). However, the cumulative neurotoxicity of oxaliplatin often requires therapy to be discontinued while the patient is still responding. The aim of this study was to evaluate efficacy and safety of XELOX plus BEV with oxaliplatin stop and go strategy. Methods: Fifty four patients with unresectable mCRC were enrolled as first line treatment. They were treated with four cycles of XELOX plus BEV, followed by maintenance therapy with capecitabine (Cape) plus BEV. Reintroduction of oxaliplatin was scheduled after eight cycles of Cape plus BEV or upon tumor progression. The primary endpoint was progression free survival (PFS). Results: Forty nine patients (90%) achieved to the maintenance therapy and thirty two patients (59%) were reintroduced oxaliplatin. After a median follow-up time of 24.2 months, median PFS was 13.4 months (95%CI: 11.7-15.1), median duration of disease control was 13.8 months (95%CI: 11.6-16.0) and median overall survival was 29.0 months (95%CI: 23.1-34.9). The response rate and disease control rate were 57.4% and 96.3% in the initial XELOX plus BEV therapy, 6.1% and 73.5% in Cape plus BEV maintenance therapy, and 0% and 72.4% in reintroduced XELOX plus BEV therapy. The incidence of neuropathy was 38% in initial therapy, 33% in maintenance therapy and 43% in reintroduced therapy. Conclusions: XELOX plus bevacizumab therapy with oxaliplatin stop-and-go strategy was feasible to maintain long disease control without increasing severe neurotoxicity in first-line treatment for mCRC. Clinical trial information: UMIN000006478.

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Comparison between the three oxaliplatin-based regimens with bevacizumab in patients with metastatic colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.687 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 687-687

Author(s):

Yoshihito Ohhara ◽

Mitsukuni Suenaga ◽

Satoshi Matsusaka ◽

Eiji Shinozaki ◽

Nobuyuki Mizunuma ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Progression Free Survival ◽

Line Treatment ◽

First Line ◽

Kaplan Meier ◽

Hand Foot Syndrome ◽

Chemotherapeutic Treatment ◽

Grade 3 ◽

First Line Treatment

687 Background: XELOX (capecitabine/L-OHP) therapy that includes orally administered ﬂuoropyrimidine instead of infusional fluorouracil (5-FU) was approved for metastatic colorectal cancer (mCRC) in Sep 2009 in Japan. A pivotal trial (NO16966 study) demonstrated the non-inferiority of XELOX to FOLFOX (5-FU/L-OHP/LV) and the superiority of those L-OHP-based regimens plus bevacizumab (BV) to those without in the first-line treatment of mCRC. We evaluated the safety and efficacy of XELO+BV compared with FOLFOX4 or mFOLFOX6 plus BV in the first-line treatment for mCRC patients at a single institute. Methods: Between Jun 2007 and Nov 2008, 85 patients received FOLFOX4+BV (FF4 arm), between Dec 2008 and Sep 2009, 40 patients received mFOLFOX6+BV (FF6 arm), and between Oct 2009 and Sep 2010, 60 patients received XELOX+BV (XELOX arm). The best overall responses were evaluated using RECIST 1.0 during chemotherapeutic treatment, and adverse events were graded according to CTCAE ver.3.0. Progression-free survival (PFS) was estimated by Kaplan-Meier methods. Results: Characteristics of patients of FF4 arm, FF6 arm, and XELOX arm were below: median age, 60 yr vs. 62 yr vs. 60.5 yr; gender (male), 48.2 % vs. 62.5 % vs. 58.3%. The overall response rates (CR+PR) were 61.1 %, 72.5 %, and 75 % (95% CI; 50.6-71.8%, 58.0-87.0%, and 63.7-86.3%). Median PFS were 17.0 months, 15.5 months, and 14.4 months, respectively (cut-off: Aug 31, 2011). There were no statistical significances not only between FF4 arm and FF6 arm (log-rank; p=0.641), but also between XELOX arm and FF4+FF6 (FOLFOX) arm (log-rank; p=0.138). FOLFOX arm was associated with higher incidence of grade 3/4 neutropenia than XELOX arm. Grade3 diarrhea and hand-foot syndrome (HFS) were more frequent in XELOX arm. Conclusions: This study suggests that XELOX arm was equal to FOLFOX arm, regardless of regimen, in tumor response and PFS. Further follow-up is necessary to confirm the benefit on survival.

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469P Efficacy and safety of anlotinib combined with CAPEOX in first-line treatment of patients with RAS and BRAF wild-type unresectable metastatic colorectal cancer - A single-arm, multi-center, phase II study (ALTER-C-002 trial)

Annals of Oncology ◽

10.1016/j.annonc.2020.08.580 ◽

2020 ◽

Vol 31 ◽

pp. S440

Author(s):

K. Ding ◽

Y. Liu ◽

J. Chen ◽

J. Ying ◽

Q. Xu ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Phase Ii ◽

Phase Ii Study ◽

Line Treatment ◽

Efficacy And Safety ◽

Wild Type ◽

First Line ◽

First Line Treatment ◽

Unresectable Metastatic Colorectal Cancer

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A Phase 2b, Double-Blind, Randomized Study Evaluating the Efficacy and Safety of Sorafenib (SOR) Compared With Placebo (PBO) When Administered in Combination With Chemotherapy (Modified FOLFOX6) for First-line Treatment (tx) of Patients (Pts) With Metastatic Colorectal Cancer (mCRC). The RESPECT Trial

European Journal of Cancer ◽

10.1016/s0959-8049(11)70118-6 ◽

2011 ◽

Vol 47 ◽

pp. 11 ◽

Cited By ~ 5

Author(s):

J. Tabernero ◽

R. Garcia-Carbonero ◽

C.H. Könne ◽

P.J. O'Dwyer ◽

A. Sobrero ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Randomized Study ◽

Line Treatment ◽

Efficacy And Safety ◽

First Line ◽

Double Blind ◽

Modified Folfox6 ◽

First Line Treatment

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Efficacy and safety of XELIRI plus cetuximab versus XELOX plus cetuximab in first-line treatment of metastatic colorectal cancer (mCRC).

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.e14122 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. e14122-e14122

Author(s):

J. Ocvirk ◽

M. Boc ◽

M. Rebersek ◽

T. Mesti ◽

M. Ebert

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Line Treatment ◽

Efficacy And Safety ◽

First Line ◽

First Line Treatment

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The efficacy and safety of XELOX plus bevacizumab with oxaliplatin stop-and-go strategy in first-line treatment for metastatic colorectal cancer: CCOG 0902 study.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.564 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 564-564

Author(s):

Takuya Watanabe ◽

Goro Nakayama ◽

Kiyoshi Ishigure ◽

Naomi Hayashi ◽

Toyohisa Yaguchi ◽

...

Keyword(s):

Colorectal Cancer ◽

Maintenance Therapy ◽

Disease Control ◽

Metastatic Colorectal Cancer ◽

Progression Free Survival ◽

Line Treatment ◽

Efficacy And Safety ◽

First Line ◽

Stop And Go ◽

First Line Treatment

564 Background: XELOX plus bevacizumab (BEV) is an established first-line therapy for metastatic colorectal cancer (mCRC). However, the cumulative neurotoxicity of oxaliplatin often requires therapy to be discontinued while the patient is still responding. The aim of this study was to evaluate efficacy and safety of XELOX plus BEV with oxaliplatin stop and go strategy. Methods: Fifty four patients with unresectable mCRC were enrolled as first-line treatment. They were treated with four cycles of XELOX plus BEV, followed by maintenance therapy with capecitabine (Cape) plus BEV. Reintroduction of oxaliplatin was scheduled after eight cycles of Cape plus BEV or upon tumor progression. The primary endpoint was progression free survival (PFS). Results: Forty nine patients (90%) achieved to the maintenance therapy and thirty one patients (59%) were reintroducted oxaliplatin. The response rates and disease control rates were 57% and 96% in the initial XELOX plus BEV, 6.1% and 73% in Cape plus BEV maintenance therapy. Median PFS in initial XELOX plus BEV was 11.0 months (95%CI: 7.8-14.1). One year survival rate was 86%. Conclusions: XELOX plus BEV was feasible as a first line treatment with mCRC. The most cases achieved disease control during Cape plus BEV maintenance therapy. Clinical trial information: UMIN000006478.

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A meta-analysis of efficacy and safety of S-1 monotherapy or combination therapy as first-line treatment in metastatic colorectal cancer

International Journal of Colorectal Disease ◽

10.1007/s00384-020-03606-x ◽

2020 ◽

Vol 35 (8) ◽

pp. 1567-1574

Author(s):

Zhan Wang ◽

Miao-Miao Wang ◽

Wen-Li Zhou ◽

Chen-Yang Ye ◽

Wei-Ping Dai ◽

...

Keyword(s):

Colorectal Cancer ◽

Combination Therapy ◽

Metastatic Colorectal Cancer ◽

Meta Analysis ◽

Line Treatment ◽

Efficacy And Safety ◽

First Line ◽

First Line Treatment

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EGFR-targeted treatments in patients with metastatic colorectal cancer: Experience of panitumumab.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15028 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15028-e15028

Author(s):

Mahmut Gumus ◽

Caglayan Geredeli ◽

Mahmut Ucar ◽

Serap Kaya ◽

Hacer Demir ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Metastatic Colorectal Cancer ◽

Skin Rash ◽

Univariate Analysis ◽

Hematologic Toxicity ◽

Line Treatment ◽

First Line ◽

Targeted Treatments ◽

First Line Treatment

e15028 Background: Overall survival times have been exceeded three years by the targeted treatments in metastatic colorectal cancer (MCC) . The sequence of these agents and the possible side effects constitute our discussions. We aimed to investigate the efficacy and tolerability of panitumumab use in this study. Methods: In this study 168 MCC patients from 15 different centers that were treated with panitumumab in first or second line settings were evaluated respectively. Progression free survival (PFS) and overall survival(OS) time were calculated in case of the patients treated with targeted treatments in first line setting. Results: The median follow-up time was 12(3-82) months. The median age was 60 (24-86) years and 36 % of the patients were female. Panitumumab as a component of first line treatment was used in 66 % of the patients. Median 6 (1-18) cycles treatment were given to the patients as first line chemotherapy. The median PFS was 11 (SE:2; 95% CI: 7-15) months in patients treated with panitumumab while 12 (SE:1; 95% CI: 10-14) months in patients treated with bevacizumab containing regimens as first line treatment (p:0.836). The median OS was 32 (SE:12; 95% CI: 7-56) months in patients treated with panitumumab containing regimen and the median OS has not been reached in bevacizumab group (p: NS). In univariate analysis, female gender and left-sided colon tumors have favorable PFS (p:0.030 and p:0.023 respectively). No difference between bevacizumab or panitumumab containing regimen in right- sided tumors have observed (p:0.812). But in left-sided tumors, the panitumumab containing regimens have favorable PFS (8 vs 13 months. p:0.023). Grade 2 or higher skin rash was observed in 49% . Diarrhea in 38%, neuropathy in 30%, different hematologic toxicity in 14% and infusion reaction in 2.2% of the patients were detected. The skin rash was associated to panitumumab containing regimen (p:0.000). Other toxicity frequencies were not statistically significant in both groups. Conclusions: Compilation of current life data in MCC treatment will reveal the efficacy and tolerability in our daily practice beyond as data in clinical trials. These data together with more experience will guide the optimization of the treatments.

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