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Original Article
Retrospective analysis on the clinical efficacy of bevacizumab combined with FOLFOX4 in the first line treatment of metastatic colorectal cancer
Eun Mi Lee, Lee Chun Park, Ho Sup Lee, Seong Hoon Shin, Yang Soo Kim
Kosin Medical Journal 2017;32(2):170-178.
DOI: https://doi.org/10.7180/kmj.2017.32.2.170
Published online: January 19, 2017

Department of Internal Medicine, College of Medicine, Kosin University, Busan, Korea

Corresponding Author: Yang Soo Kim, Department of Internal Medicine, College of Medicine, Kosin University, 262, Gamcheon-ro, Seo-gu, Busan 49267, Korea Tel: +82-51-990-5820 Fax: +82-51-990-5820 E-mail: yas@kosinmed.or.kr
• Received: April 8, 2015   • Accepted: September 9, 2015

Copyright © 2017 Kosin University School of Medicine Proceedings

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • Objectives
    The addition of bevacizumab to standard chemotherapy has been improved survival outcomes in patients with metastatic colorectal cancer. However, the combination of bevacizumab with oxaliplatin-based chemotherapy as first-line treatment showed limited survival benefit. The purpose of this study was to investigate the clinical efficacy and toxicity of the combination of bevacizumab to oxaliplatin and leucovorin (FOLFOX4) in the first-line treatment of patient with metastatic colorectal cancer.
  • Methods
    Between December 2004 and September 2009, medical records of patients who were diagnosed with metastatic colorectal cancer and received the first line chemotherapy with bevacizumab and FOLFOX4, were retrospectively reviewed.
  • Results
    A total of forty patients were analyzed. The median age of the patients was 55 years (range, 33-80), and 55% was male. The patients received a total of 206 cycles of therapy (median 4 cycles per patient; range 1 – 15 cycles). Of these 40 patients, none achieved complete response (CR) and 15 achieved a partial response (PR), for the overall response rate (ORR) 37.5% (95% CI, 22.5-52.5). Median progression free survival (PFS) was 6.9 months (95% CI, 3.4-10.5) and median overall survival (OS) was 22.6 months (95% CI, 17.3-27.8The most common grade 3 or 4 hematologic toxicity and non-hematologic toxicity were neutropenia (10.0%) and diarrhea (10.0%), respectively. Two patients experienced gastrointestinal perforation.
  • Conclusions
    In this study, the combination bevacizumab with FOLFOX4 was associated with favorable OS, but did not showed favorable PFS and ORR.
  • Keywords: Bevacizumab; Colorectal cancer; FOLFOX
Fig. 1.
Survival curves by the Kaplan–Meier method.
kmj-32-170f1.jpg
Table 1.
Patient characteristics (n = 40)
Characteristic Data
Age, years [median (range)] 55 (33-80)
≤ 60 years 28 (70.0)
> 60 years 12 (30.0)
Gender [n (%)]
Male 22 (55.0)
Female 18 (45.0)
Site of primary tumor [n (%)]
Colon 21 (52.5)
Rectum 19 (47.5)
ECOG PS [n(%)]
0-1 31 (77.5)
≥ 2 9 (22.5)
Number of metastatic site [n (%)]
1 site 21 (52.5)
≥ 2 sites 19 (47.5)
Site of metastasis [n (%)]
Liver 27 (67.5)
Lung 13 (32.5)
Peritoneum 3 (7.5)
Lymph nodes 7 (17.5)
Bone 12 (30.0)
Prior resection of primary tumor [n (%)] 25 (62.5)
Prior adjuvant treatment [n (%)] 18 (45.0)
Initial CEA level(ng/mL) [median(range)] 29.5 (0.8-2359.0)
< 3.5 ng/mL 4 (10.0)
≥ 3.5 ng/mL 36 (90.0)

ECOG: Eastern Cooperative Oncology Group

PS: performance status

CEA: carcinoembryonic antigen

Table 2.
Toxicity profile (According to NCI-CTCAE1)version3.0)
Grade III or IV [n(%)]
Hematologic
Anemia 0
Neutropenia 4(10.0)
Thrombocytopenia 0
Febrile neutropenia 0
Non-hematologic
Nausea 0
Anorexia 1(2.5)
Diarrhea 4(10.0)
Peripheral neuropathy 0
GI bleeding 0
GI perforation 2(5.0)
Hypertension 0
Proteinuria 1(2.5)

NCI-CTCAE: National Cancer Institute Common Terminology Criteria for Adverse Events

GI: gastrointestinal

Table 3.
Tumor responses and results of treatment
Responses [n %)] 95% CI
Complete response 0 (0) -
Partial response 15 (37.5) 22.5-52.5
Stable disease 18 (45.5) 30.0-62.5
Progressive disease 7 (17.5) 7.5-30.0
Overall response rate 15 (37.5) 22.5-52.5
Disease control rate 33 (82.5) 70.0-92.5

CI: confidence interval

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        Retrospective analysis on the clinical efficacy of bevacizumab combined with FOLFOX4 in the first line treatment of metastatic colorectal cancer
        Kosin Med J. 2017;32(2):170-178.   Published online January 19, 2017
        DOI: https://doi.org/10.7180/kmj.2017.32.2.170
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      Figure
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      Retrospective analysis on the clinical efficacy of bevacizumab combined with FOLFOX4 in the first line treatment of metastatic colorectal cancer
      Image
      Fig. 1. Survival curves by the Kaplan–Meier method.

      Fig. 1.

      Retrospective analysis on the clinical efficacy of bevacizumab combined with FOLFOX4 in the first line treatment of metastatic colorectal cancer

      Patient characteristics (n = 40)

      Characteristic Data
      Age, years [median (range)] 55 (33-80)
      ≤ 60 years 28 (70.0)
      > 60 years 12 (30.0)
      Gender [n (%)]
      Male 22 (55.0)
      Female 18 (45.0)
      Site of primary tumor [n (%)]
      Colon 21 (52.5)
      Rectum 19 (47.5)
      ECOG PS [n(%)]
      0-1 31 (77.5)
      ≥ 2 9 (22.5)
      Number of metastatic site [n (%)]
      1 site 21 (52.5)
      ≥ 2 sites 19 (47.5)
      Site of metastasis [n (%)]
      Liver 27 (67.5)
      Lung 13 (32.5)
      Peritoneum 3 (7.5)
      Lymph nodes 7 (17.5)
      Bone 12 (30.0)
      Prior resection of primary tumor [n (%)] 25 (62.5)
      Prior adjuvant treatment [n (%)] 18 (45.0)
      Initial CEA level(ng/mL) [median(range)] 29.5 (0.8-2359.0)
      < 3.5 ng/mL 4 (10.0)
      ≥ 3.5 ng/mL 36 (90.0)

      Toxicity profile (According to NCI-CTCAE1)version3.0)

      Grade III or IV [n(%)]
      Hematologic
      Anemia 0
      Neutropenia 4(10.0)
      Thrombocytopenia 0
      Febrile neutropenia 0
      Non-hematologic
      Nausea 0
      Anorexia 1(2.5)
      Diarrhea 4(10.0)
      Peripheral neuropathy 0
      GI bleeding 0
      GI perforation 2(5.0)
      Hypertension 0
      Proteinuria 1(2.5)

      Tumor responses and results of treatment

      Responses [n %)] 95% CI
      Complete response 0 (0) -
      Partial response 15 (37.5) 22.5-52.5
      Stable disease 18 (45.5) 30.0-62.5
      Progressive disease 7 (17.5) 7.5-30.0
      Overall response rate 15 (37.5) 22.5-52.5
      Disease control rate 33 (82.5) 70.0-92.5
      Table 1. Patient characteristics (n = 40)

      ECOG: Eastern Cooperative Oncology Group

      PS: performance status

      CEA: carcinoembryonic antigen

      Table 2. Toxicity profile (According to NCI-CTCAE1)version3.0)

      NCI-CTCAE: National Cancer Institute Common Terminology Criteria for Adverse Events

      GI: gastrointestinal

      Table 3. Tumor responses and results of treatment

      CI: confidence interval

      Table 1.

      Table 2.

      Table 3.

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