Efficacy and Safety of FOLFIRI after Failure of FOLFOX-4 in Advanced Gastric Cancer

Hye Jung Kwon; Moo In Park; Seun Ja Park; Won Moon; Sung Eun Kim; Hae Won Lee; Youn Jung Choi; Jae Hyun Kim

doi:10.4166/kjg.2015.66.1.10

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

Original Article

Korean J Gastroenterol 2015;66(1):10-16.

Published online: 4 October 2015

DOI: https://doi.org/10.4166/kjg.2015.66.1.10

Efficacy and Safety of FOLFIRI after Failure of FOLFOX-4 in Advanced Gastric Cancer

Hye Jung Kwon, Moo In Park, Seun Ja Park, Won Moon, Sung Eun Kim, Hae Won Lee, Youn Jung Choi, Jae Hyun Kim

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

Correspondence to: Moo In Park, Department of Internal Medicine, Kosin University College of Medicine, 262 Gamcheon-ro, Seo-gu, Busan 602-702, Korea. Tel: +82-51-990-5061, Fax: +82-51-990-5055, E-mail: mipark@ns.kosinmed.or.kr

Received 10 April 2015 Revised 12 May 2015 Accepted 15 May 2015

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Keywords: FOLFIRI protocol, Advanced gastric carcinoma, Second line chemotherapy, FOLFOX-4 protocol

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).

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
Variable	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
Variable	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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