A randomized phase III study of modified FOLFIRINOX (5-FU/LV, irinotecan, and oxaliplatin) versus S-1 alone chemotherapy as second-line chemotherapy for gemcitabine-failed metastatic pancreatic cancer
- Conditions
- Neoplasms
- Registration Number
- KCT0003534
- Lead Sponsor
- Gyeongsang National University Hospital
- Brief Summary
Background: The efficacy of modified FOLFIRINOX (mFOLFIRINOX), as a second-line chemotherapy treatment for metastatic pancreatic adenocarcinoma (mPAC), remains unconfirmed. This multicenter randomized phase-III trial aimed to elucidate the efficacy of mFOLFIRINOX as a second-line chemotherapy treatment for mPAC patients with a good performance status. Patients and Methods: Eighty mPAC patients (age, 19–75 years) who were refractory to first-line gemcitabine-based chemotherapy were randomly selected to receive mFOLFIRINOX or S-1. mFOLFIRINOX comprised oxaliplatin (65 mg/m2), irinotecan (135 mg/m2), and leucovorin (400 mg/m2) on day 1, and continuous 5-FU infusion (1,000 mg/m2) over 24 h on days 1–2 every 2 weeks. S-1 comprised body surface area-dependent oral S-1, divided into two doses per day on days 1–28 every 6 weeks. Results: Overall survival was the primary endpoint. The objective response and disease control rates were higher in the mFOLFIRINOX than in the S-1 group (15% vs. 2%; p=.04 and 67% vs. 37%; p=.007). The median progression-free survival rates were 5.2 and 2.2 months in the mFOLFIRINOX and S-1 groups, respectively (adjusted hazard ratio [HR]: .4; 95% confidence interval [CI]: .2-.6; p<.001). The median overall survival rates were 9.2 and 4.9 months in the mFOLFIRINOX and S-1 groups, respectively (adjusted HR: .4; 95% CI: .2-.7; p=.002). Grade 3-4 adverse events occurred in 56% and 17% of the patients in the mFOLFIRINOX and S-1 groups, respectively (p<.001). Conclusion: Administration of mFOLFIRINOX, as a second-line chemotherapy treatment for mPAC patients refractory to gemcitabine-based chemotherapy, resulted in increased survival rates than S-1 treatment alone.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 80
1) Adenocarcinoma of a pancreas that has been diagnosed histologically
2) Metastatic pancreatic cancer
3) In the case of a failure in the first-line chemotherapy, including gemcitabine, or a recurrence within six months after the adjuvant chemotherapy with gemcitabine
4) Age: Not more than 19 years old and not more than 70 years old
5) ECOG performance status of = 1
6) A person who has identified adequate bone marrow, liver, kidney and heart function
• Number of Absolute Neutrophiles (ANC) = 1.5 x 109 / L
• Number of thrombocytes = 100 x 109 / L
• Total bilirubin = 1.5 x upper limit of normal
( < 3.0 x ULN , in case of conducting of drainage procedure and expecting the normalization of the level )
• AST and/or ALT = 3 x upper limit of normal
• Creatinine = 1.5 mg dL or creatinine clearance = 50 ml / min
7) The person who signed the informed consent
1) Previously treated with irinotecan or oxaliplatin
2) Patients who receive fluoropyrimidine-based therapy including 5-FU within 6 months
3) Patients with central nervous system metastasis that are not controlled by steroids or radiation therapy
4) Allergic reaction for study drug
5) A person who has a history of malignancy except non-melanoma skin cancer, well-differentiated thyroid cancer, and cervical carcinoma in situ within five years
6) A person who cannot follow protocols such as non-cooperative or unable to follow-up
7) A person who is pregnant or breast-feeding
8) A person with grade 2 or more peripheral neuropathy with functional disability before registering to this study
9) Active infection or serious illness requiring systemic therapy
10) Contraindication to study drug
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Overall survival
- Secondary Outcome Measures
Name Time Method Treatment response rate;Safety and tolerability;Progression-free survival;Quality of life