Abstract
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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.
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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.
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Conclusions
- In this study, the combination bevacizumab with FOLFOX4 was associated with favorable OS, but did not showed favorable PFS and ORR.
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Keywords: Bevacizumab; Colorectal cancer; FOLFOX
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) |
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) |
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 |
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