FOLFIRI as Second-line Chemotherapy after Failure of FOLFOX4 in Advanced Colorectal Cancer: A Korean Single-center Experience

Jae Hyun Kim; Seun Ja Park; Moo In Park; Won Moon; Sung Eun Kim; Ki Hwan Ku; Sung Eun Song; Je Hun Kim

doi:10.4166/kjg.2014.63.1.18

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Kim, Park, Park, Moon, Kim, Ku, Song, and Kim: FOLFIRI as Second-line Chemotherapy after Failure of FOLFOX4 in Advanced Colorectal Cancer: A Korean Single-center Experience

Original Article

Korean J Gastroenterol 2014;63(1):18-24.

Published online: 4 October 2014

DOI: https://doi.org/10.4166/kjg.2014.63.1.18

FOLFIRI as Second-line Chemotherapy after Failure of FOLFOX4 in Advanced Colorectal Cancer: A Korean Single-center Experience

Jae Hyun Kim, Seun Ja Park, Moo In Park, Won Moon, Sung Eun Kim, Ki Hwan Ku, Sung Eun Song, Je Hun Kim

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

Correspondence to: Seun Ja Park, Division of Gastroenterology, 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: parksj6406@yahoo.co.kr

Received 24 October 2013 Revised 17 November 2013 Accepted 2 December 2013

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.

Abstract

Background/Aims

The incidence of colorectal cancer has been increasing every year in Korea. Irinotecan- or oxaliplatin-based regimens including biologic agents are known to be effective in patients with advanced colorectal cancer. But in practice, FOLFOX (combination of oxaliplatin, 5-fluorouracil, and leucovorin) or FOLFIRI (combination of irinotecan, 5-fluorouracil, and leucovorin) regimens without biologic agents are more commonly used in Korea due to of the high costs of biologic agents. The aim of this study was to evaluate the efficacy and toxicity of FOLFIRI following FOLFOX4 in patients with advanced colorectal cancer.

Methods

A total of 54 patients with advanced colorectal cancer who were treated between May 2005 and May 2013 with FOLFOX4 as first-line chemotherapy and with FOLFIRI as second-line chemotherapy at Kosin University Gospel Hospital (Busan, Korea) were reviewed retrospectively.

Results

A total of 54 patients received second-line FOLFIRI chemotherapy. Five patients (9.3%) had a partial response, 29 patients (53.7%) had a stable disease. The median overall survival was 8.90 months and the median time to progression was 4.33 months. Toxicities were tolerable.

Conclusions

In a Korean population, FOLFIRI as second-line chemotherapy is effective and well tolerated in patients with advanced colorectal cancer after failure of FOLFOX4. Although the efficacy of FOLFIRI in this study was lower than that of second-line FOLFIRI with biologic agents, these results can help in the formulation of a treatment strategy for financially troubled patients.

Keywords: Colorectal cancer, Chemotherapy, IFL protocol, FOLFOX 4 protocol

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Fig. 1.

Overall survival (OS) curve of patients with advanced colorectal cancer who treated with FOLFIRI after failed FOLFOX4. FOLFIRI, combination of irinotecan, 5-fluorouracil, and leucovorin; FOLFOX, combination of oxaliplatin, 5-fluorouracil, and leucovorin.

Fig. 2.

Time to progression (TTP) curve of patients with advanced colorectal cancer who treated with FOLFIRI after failed FOLFOX4. FOLFIRI, combination of irinotecan, 5-fluorouracil, and leucovorin; FOLFOX, combination of oxaliplatin, 5-fluorouracil, and leucovorin.

Table 1.

Patient Characteristics

Characteristic	Data
Gender
Male	38 (70.4)
Female	16 (29.6)
Age (yr)	65 (46–82)
ECOG performance status
0	8 (14.8)
1	33 (61.1)
2	13 (24.1)
Previous operation
Yes	17 (31.5)
Low anterior resection	8 (14.8)
Segmentectomy	4 (7.4)
Miles operation	3 (5.5)
Right hemicolectomy	1 (1.9)
Left hemicolectomy	1 (1.9)
No	37 (68.5)
Location of primary tumor
Ascending colon	8 (14.8)
Transverse colon	3 (5.5)
Descending colon	0 (0)
Sigmoid colon	19 (35.2)
Rectum	24 (44.5)
Site of metastasis
Lungs	9 (16.6)
Liver	27 (50.0)
Lungs and liver	10 (18.5)
Lymph nodes only	6 (11.1)
Brain	1 (1.9)
Bone	1 (1.9)
Differentiation
Well	11 (20.4)
Moderate	32 (59.2)
Poorly	0 (0)
Unknown	11 (20.4)
Complete blood count
Hemoglobin (g/dL)	11.7 (9.0–14.5)
White blood cell (×10⁹/L)	7.050 (3.0–16.7)
Platelet (×10⁹/L)	192 (83–457)
First-line FOLFOX4 cycles	11 (3–27)
Second-line FOLFIRI cycles	8 (2–46)

Values are presented as n (%) or median (range). ECOG, Eastern Clinical Oncology Group; FOLFOX, combination of oxaliplatin, 5-fluorouracil, and leucovorin; FOLFIRI, combination of irinotecan, 5-fluorouracil, and leucovorin.

Table 2.

Treatment Efficacy of FOLFIRI as Second-line Chemotherapy after Failure of FOLFOX4 in Advanced Colorectal Cancer

Response	Patient
Complete response	0 (0)
Partial response	5 (9.2)
Stable disease	29 (53.7)
Progressive disease Not assessable	13 (24.1) 7 (13.0)

Values are presented as n (%).

FOLFIRI, combination of irinotecan, 5-fluorouracil, and leucovorin; FOLFOX, combination of oxaliplatin, 5-fluorouracil, and leucovorin.

Table 3.

Toxicity Profiles of FOLFIRI as Second-line Chemotherapy after Failure of FOLFOX4 in Advanced Colorectal Cancer (per Patient)

Toxicity	NCI-CTCAE grade
Toxicity	Grade 1	Grade 2	Grade 3	Grade 4
Hematologic toxicities
Leukopenia	21 (38.9)	26 (48.1)	15 (27.8)	8 (14.8)
Neutropenia	28 (51.9)	30 (55.6)	28 (51.9)	23 (42.6)
Anemia	52 (96.3)	36 (66.6)	7 (12.9)	3 (5.6)
Thrombocytopenia	14 (25.9)	8 (14.8)	5 (9.3)	2 (3.7)
Non-hematologic toxicities
Nausea	13 (24.1)	2 (3.7)	0	0
Vomiting	2 (3.7)	2 (3.7)	0	0
Diarrhea	10 (18.5)	2 (3.7)	0	0

Values are presented as n (%).

NCI-CTCAE, National Cancer Institute-Common Terminology Criteria for Adverse Events (ver. 4.02); FOLFIRI, combination of irinotecan, 5-fluorouracil, and leucovorin; FOLFOX, combination of oxaliplatin, 5-fluorouracil, and leucovorin.

Table 4.

Comparison with Other Studies Using Second-line FOLFIRI Chemotherapy

Reference	Patients (n)	Regimen of chemotherapy	RR (%)	OS (median, mo)	TTP (median, mo)	Grade 3–4 netropenia (%)
André et al.²¹	33	I 180 (D1) for 2 hrs, 5-FU bolus 400 (D1)+infusion 2,400–3,000 (D1-D2) for 46 hrs, LV 400 (D1) for 2 hrs	5.5	9.8	4.1	15
Tournigand et al.⁴	69	I 180 (D1) for 2 hrs, 5-FU bolus 400 (D1)+infusion 2,400–3,000 (D1-D2) for 46 hrs, LV 200 (D1) for 2 hrs	4	20.6^a	2.3	21
Mabro et al.²³	65	I 100 (D1-D2) for 1 hr, 5-FU infusion 2,000 (D1-D2) for 46 hrs, LV 200 (D1) for 2 hrs	23	10.5	4.7	37
Zhang et al.²⁴	80	I 180 (D1) for 2 hrs, 5-FU bolus 400 (D1)+infusion 2,400 (D1-D2) for 46 hrs, LV 200 (D1) for 2 hrs	12.5	NR	3.2	24.1
Bao et al.²²	57	I 180 (D1) for 2 hrs, 5-FU bolus 400 (D1)+infusion 2,400 (D1-D2) for 46 hrs, LV 200 (D1) for 2 hrs	7.5	7.8	4.8	12.9
This study	54	I 180 (D1) for 2 hrs, 5-FU bolus 400 (D1)+infusion 600 (D1-D2) for 22 hrs, LV 100 (D1) for 2 hrs	9.3	8.9	4.33	27.2

FOLFIRI, combination of irinotecan, 5-fluorouracil, and leucovorin; RR, response rate; OS, overall survival; TTP, time to progression; I, irinotecan; 5-FU, 5-fluorouracil; LV, leucovorin; NR, not reported.

^a From the first day of first line chemotherapy to death.

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