Journal List > Korean J Gastroenterol > v.66(1) > 1007405

Kwon, Park, Park, Moon, Kim, Lee, Choi, and Kim: Efficacy and Safety of FOLFIRI after Failure of FOLFOX-4 in Advanced Gastric Cancer

Abstract

Background/Aims

The purpose of this study was to investigate the efficacy and safety of irinotecan based FOLFIRI chemotherapy as a second-line treatment after failure of FOLFOX-4 chemotherapy in patients with advanced gastric cancer.

Methods

Fifty-two patients who were pathologically diagnosed with unresectable gastric cancer and received FOLFIRI chemotherapy after failure of FOLFOX-4 chemotherapy between September 2005 and February 2012 were enrolled in this study. Data were collected by retrospectively reviewing the medical records. The response to chemotherapy was assessed every 3 cycles by World Health Organization criteria and long term survival was analyzed. The toxicities were evaluated for every course of chemotherapy according to National Cancer Institution (NCI) toxicity criteria version 3.0.

Results

Median age of the patients was 57 years. Median overall survival (OS) and time to progression (TTP) were 7.8 and 5 months, respectively. The number of patients showing complete remission, partial remission, stable disease, and progressive disease were 0 (0.0%), 9 (17.3%), 30 (57.7%), and 13 (25.0%), respectively. The overall response rate was 17.3%. During a total of 345 cycles, anemia worse than NCI toxicity grade 3 occurred in 2.9%, leukopenia in 20.3%, neutropenia in 12.2%, and thrombocytopenia in 1.5%. Patients with less organ involvement by metastasis, less than 34 U/mL of CA 19–9 and good responsiveness to third cycle of second line chemotherapy were associated with longer OS and TTP.

Conclusions

FOLFIRI chemotherapy has a modest efficacy with acceptable toxicities in patients with advanced gastric cancer as a second-line treatment. Further well-controlled studies are needed to elucidate the efficacy of FOLFIRI chemotherapy as second-line treatment in patients with advanced stomach cancer.

References

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Fig. 1.
Overall survival and progression free survival of patients after FOLFIRI combination therapy. (A) The median overall survival was 7.8 months (95% CI, 6.6–9.0). (B) The median time to progression was 5 months (95% CI, 2.3–7.7).
kjg-66-10f1.tif
Table 1.
Baseline Characteristics
Characteristic Patient
Sex (male:female) 35 (67.3):17 (32.7)
Age (yr) 57 (26–78)
ECOG
 0–1 22 (42.3)
 2 30 (57.7)
Metastatic number at beginning of 2nd line chemotherapy
 1 16 (30.8)
 ≥2 36 (69.2)
Metastatic lesion at beginning of 2nd line chemotherapy
 Lymph node only 16
 Liver 16
 Peritoneum 13
 Bone 6
 Lung 4
Differentiation
 Well-moderate 16 (30.8)
 Poor or signet ring cell 25 (48.1)
 Undifferentiated 11 (21.1)
Hemoglobin (g/dL)
 ≥12 13 (25.0)
 <12 39 (75.0)
CEA level
 Elevated 29 (55.8)
 Normal range 23 (44.2)
CA 19–9 level
 Elevated 20 (38.5)
 Normal range 32 (61.5)
Albumin level
 Normal range 39 (75.0)
 Decreased 13 (25.0)
TTP under 1st line chemotherapy
 < Median value (7.9 mo) 18 (34.6)
 ≥ Median value (7.9 mo) 34 (65.4)

Values are presented as n (%), median (range), or n only.

Table 2.
Treatment Response to FORFIRI Chemotherapy
Response a Patient
Complete remission 0 (0)
Partial remission 9 (17.3)
Stable disease 30 (57.7)
Progressive disease 13 (25.0)
Response rate 17.3
Disease control rate 75.0

Values are presented as n (%) or percent only.

a World Health Organization criteria.

Table 3.
Prognostic Factor according to Univariate Analysis
Variable Overall survival
Time to progression
Duration (mo) p-value Duration (mo) p-value
Number of metastasis   0.018   0.039
 1 13.0   8.1  
 ≥2 7.2   4.4  
CA 19–9   0.001   ≤0.001
 ≤34 U/mL 11.7   9.5  
 >34 U/mL 4.9   3.1  
Diseases progression   0.001   ≤0.001
 CR/PR/SD 11.0   8.2  
 PD 3.9   1.7  

CR, complete remission; PR, partial remission; SD, stable disease; PD, progression disease.

Table 4.
Prognostic factor according to Cox Multivariate Analysis
Variable Overall survival
Time to progression
Hazard ratio (95% CI) p-value Hazard ratio (95% CI) p-value
No. of metastasis (≥2 vs. 1) 4.677 (1.170–12.793) 0.003 2.792 (1.004–7.763) 0.049
CA 19–9 (≤34 vs. >34) 2.145 (1.039–4.430) 0.039 2.784 (1.211–6.403) 0.016
Disease progression (PD vs. CR/PR/SD) 5.791 (2.356–14.238) ≤0.001 42.445 (11.023–163.442) ≤0.001

PD, progression disease; CR, complete remission; PR, partial remission; SD, stable disease.

Table 5.
Toxicity Profiles of FOLFIRI (per Patient)
Hematologic toxicities Grade 1 Grade 2 Grade 3 Grade 4
Leukopenia 121 (35.1) 42 (12.2) 33 (9.6) 37 (10.7)
Neutropenia 104 (30.1) 55 (15.9) 34 (9.9) 8 (2.3)
Anemia 207 (60.0) 102 (29.6) 9 (2.6) 1 (0.3)
Thrombocytopenia 117 (33.9) 14 (4.1) 4 (1.2) 1 (0.3)

Valuese are presented as n (%).

Table 6.
Comparison with Other Studies Using Irinotecan-based Chemotherapy in Korea
Variable Kim et al.17 Seo et al.19 Jeon et al.18 Our study
Irinotecan, LV and 5-FU regimens (mg/m2) 150, 100, 1,000 a 180, 200, 400 b+600 a 150, 200, 400 b+600 a 160 or 180, 200, 400 b+600 a
Patient (n) 64 51 32 52
Median age (yr) 55 55 59 57
Response rate (%) 21 18 9.4 17.3
Median overall survival (mo) 7.6 9.1 5.8 7.8
Median time to progression (mo) 2.5 3.2 2 5
Grade 1–2 neutropenia (%)   11 37.5 47.0
Grade 3–4 neutropenia (%) 11 17 21.9 12.2
Grade 3–4 anemia (%)   4 6.2 2.9
Grade 3–4 thrombocytopenia (%) 3 2 3.1 1.5

LV, lymph node; 5-FU, 5-fluorouracil.

a Continuous infusion for 22 hours

b bolus infusion for 2 hours.

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