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

Article information

Kosin Med J. 2017;32(2):170-178

Publication date (electronic) : 2017 January 19

doi : https://doi.org/10.7180/kmj.2017.32.2.170

Eun Mi Lee , Lee Chun Park , Ho Sup Lee , Seong Hoon Shin , Yang Soo Kim

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 2015 April 08; 2015 April 28; Accepted 2015 September 09.

Abstract

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.

Table 1.

Patient characteristics (n = 40)

Table 2.

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

Table 3.

Tumor responses and results of treatment

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Fig. 1.

Survival curves by the Kaplan–Meier method.

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