Journal List > Korean J Gastroenterol > v.63(1) > 1007207

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

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.

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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.
kjg-63-18f1.tif
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.
kjg-63-18f2.tif
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
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 20.6a 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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