FOLFIRI versus irinotecan monodrug as second-line treatment in metastatic colorectal cancer patients: An open, multicenter, prospective, randomized controlled phase III clinical study.
Weijian GuoXiaowei ZhangYusheng WangWen ZhangXin LiuWei ShenYifu HeXiaodong ZhuZhiyu ChenHongqiang WangMingzhu HuangZhe ZhangXiaoying ZhaoLi‐Xin QiuChenchen WangXuedan Sheng
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4038 Background: The most commonly used treatment methods for metastatic colorectal cancer (mCRC)are systemic chemotherapy, molecular targeted therapy and local treatment. The main chemotherapy drugs for mCRC include Irinotecan, Oxaliplatin and 5-Fu. V308 Research shows that FOLFOX and FOLFIRI can be standard first or second-line of each other in the treatment of metastatic colorectal cancer. However if the first-line treatment regimen containing 5-FU fails, whether it is necessary to re-challenge 5-FU when Irinotecan is applied in the second line is unknown. There is no head-to-head comparative study to answer whether the FOLFIRI regimen is better than the Irinotecan monodrug. Therefore, it is necessary to carry out a comparative study of FOLFIRI Versus Irinotecan monodrug to observe whether adding 5-Fu on the basis of Irinotecan can improve the therapeutic effect. Methods: This was a randomized phase III trial. Patients from 5 centers in China with metastatic colorectal adenocarcinoma, for whom first-line of chemotherapy including oxaliplatin combined with fluorouracil drugs (combined or not combined with targeted therapy) had failed, were enrolled. 172 patients with mCRC were randomly treated with FOLFIRI or Irinotecan monodrug were included in this study. FOLFIRI group: Irinotecan 180mg/m 2 ; Lecovorin 400mg/m 2 ; 5-Fu 400mg/m 2 ; 5-Fu 2400mg/m 2 CIV 46h. Irinotecan monodrug group 180mg/m 2 , The regimen was repeated every 2 weeks. The primary endpoint is PFS, and this clinical trail is a superiority trial. Results: ITT (Intention-To-Treat) analysis: Among 172 patients, 10 had PR, 93 had SD, and 63 had PD, 6 patients have not received efficacy evaluation yet. The ORR was 5.68% VS. 5.95%, and the DCR was 61.36% and 54.76% in FOLFIRI group and Irinotecan monodrug group, respectively. Adverse reactions included neutropenia, stomatitis, diarrhea, fatigue, abnormal liver enzymes, pyrexia, arrhythmia, nausea and most of these were grade 1-2. The dose reduction rate induced by drug tocixity of was 13.64% and 7.14% in FOLFIRI group and Irinotecan monodrug group, respectively. Conclusions: These data show that Irinotecan monodrug has the similar ORR and DCR with FOLFIRI regimen in second-line treatment of mCRC. Irinotecan monodrug has lower adverse effect. Clinical trial information: NCT02935764 .Keywords:
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The availability of irinotecan and oxaliplatin has dramatically altered both first- and second-line treatment of advanced colorectal cancer (CRC) compared with the era in which the sole treatment option in advanced disease was 5-fluorouracil (5-FU). Treatment options and strategies are becoming ever more enriched and complex with the recent availability of biologic agents such as bevacizumab and cetuximab. This article reviews randomized clinical trials assessing second-line treatment after failure of first-line single-agent 5-FU, irinotecan-based treatment, or oxaliplatin-based treatment. A number of conclusions can be drawn based on available data. (1) Second-line chemotherapy with active agents is superior to best supportive care alone. (2) Following 5-FU failure, active regimens include irinotecan, FOLFIRI, FOLFOX, and IROX, with IROX appearing to be superior to FOLFIRI. (3) Following irinotecanbased first-line treatment, FOLFOX is in general the best choice, and the combination of FOLFOX plus bevacizumab appears to be superior to FOLFOX alone. (4) Following first-line FOLFOX, irinotecan and FOLFIRI are currently the most appropriate options. Irinotecan plus cetuximab should emerge as an effective regimen. Further study is needed to define the best options in second-line therapy following the FOLFOXIRI triplet or the combination of bevacizumab plus chemotherapy. Studies are ongoing to determine optimal use of biologic agents, both in terms of when they should be used and in what combinations.
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In recent years there has been strong progress in the treatment of metastatic colorectal cancer (mCRC) patients. The gain of the median of the overall survival (mOS) rate was more than doubled due to the introduction in the clinical practice of new compounds, the work of a multidisciplinary team, the timely registration of the disease progress, prescription of combined chemotherapy in the second line. The article presents the immediate and long-term results of a comparative study carried out on the basis of Oncology Centers, 122 mCRC patients were included, most of these patients - 87(71,3%) had surgery firstly, after that all patients were treated with standard chemotherapy FOLFOX-4 in the first-line treatment and FOLFIRI in the second line treatment, two groups of patients in the first and second lines of treatment received a combination of chemotherapy and targeted agents (bevacizumab, cetuximab), depending on the biological properties of the tumor (RAS-gene mutation status). The following results: metastatic progression-free survival (mPFS) for FOLFOX-4 group accounted for 12.0(±1.2) months; FOLFOX-4 + Bevacizumab - 20.3(±1.2) months, FOLFOX-4 + cetuximab - 22.0(± 2.0) months; mPFS for second-line therapy for FOLFIRI + bevacizumab group amounted to 24.0(± 3.1) months, FOLFIRI + cetuximab 22.5(±2.5) months, FOLFIRI-1 8.0(±2.4) months, FOLFIRI-2 6.4(±2.6) months; mOS for FOLFOX-4 group was 49.5(±2.5) months; FOLFOX-4 + Bevacizumab - 45.8(±2.1) months; FOLFOX-4 + cetuximab - 37.4(± 2.0) months; mOS for second-line therapy for FOLFIRI + bevacizumab group was 37.8(± 2.1) months, FOLFIRI + cetuximab - 31.5(± 2.3) months, FOLFIRI-1 - 26.3(± 1.8) months, FOLFIRI-2 - 26.2(± 1.9) months. The adverse events during the treatment of patients are reported.
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目的：FOLFOX 是第三期大腸直腸癌術後標準輔助性化學治療。但是許多病人無法完成完整療程。本研究欲探討完成完整FOLFOX 療程的比率及其無法完成的原因。方法：由台北榮總大腸直腸外科資料庫收集2009 年一月至2015 年十二月第三期大腸直腸癌術後接受FOLFOX 治療之病人之基本資料、接受Oxaliplatin 之劑量及無法完成之原因做分析。結果：研究期間內內共866 個第三期大腸直腸癌病人接受手術。其中110 人沒有接受後續輔助性化學藥物治療，199 人接受其他療法，5 人於其他他醫院治療。最後收集572人分析。290 人 (50.6%) 完成完整療程，其Oxaliplatin 累計計劑量之中位數為984 mg/m^2(644~1210 mg/m^2)。無法完成完整療程的病人中，78 人 (27.7%) 是因為主治醫師預防性停藥，72 人 (25.5%) 因週邊神經病變，30 人 (10.6%) 因疾病進展更換療法，18 人 (6.4%)因對Oxaliplatin 過敏，19 人 (6.7%) 因為白血球過低過肝腎功能惡化，17 人 (6.0%) 因嚴重噁心嘔吐，12 人 (4.3%) 因為整體身體狀況變差，36 人 (12.8%) 自行要求停藥。因週邊神經病變而中斷治療的患者，其Oxaliplatin 的累積劑量中位數為746 mg/m^2，而因對Oxaliplatin 過敏中斷治療的患者，其累積劑量中位數為680.4 mg/m^2。結論：半數病人能完成完整療程，週邊神經病變及及醫師預防性停藥是無法完成完整療程之主因。研發預防或減緩週邊神經經病變副作用之化學治療方法應能增加完整療程達成率。
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e15048 Background: Efficacy results of Folfox or Folfiri chemotherapies (CT) are not different as 1 st line in mCRC patients, alone or with targeted therapies. No data reported on progression-free survival (PFS) of 1 st line Folfiri after Folfox-based adjuvant CT and of 2 nd line Folfiri-based CT after a Folfox-based 1 st line. The objective was to evaluate the efficacy of a Folfiri-based CT after adjuvant or 1 st line Folfox-based treatment. Methods: 210 of 568 pts from a mCRC database were retrospectively selected and divided in 2 cohorts: pts who received adjuvant Folfox then Folfiri as 1 st line treatment (n = 76, AdjF) and those treated with Folfox as 1 st line treatment then Folfiri 2 nd line (n = 134, FFox). PFS1 was the time from beginning of Folfox to 1 st progression and PFS2 the time from the Irinotecan-based CT to 2 nd progression. Results: Median age was 62 (22-80). 49.3% pts had synchronous liver (72%) metastases. Primary tumour was right and left colon in 22% and 70% patients. Primary tumour was resected in 91% pts (98.7% and 86.6% in the AdjF and FFox groups, p= 0.003). KRASand BRAF-mutated status were found in 21.8% and 4.7% pts. In the AdjF group, pts received Folfiri as 1 st line combined with Bevacizumab (Beva) or anti-EGFR therapy (Cetuximab or Panitumumab) in 70% and 13% cases. In the FFox group, 1 st line Folfox-based CT was associated with Beva and anti-EGFRs in 7 and 6% pts, and 2 nd line Folfiri-based CT with Beva or Aflibercept in 51 and 4% pts, and with anti-EGFRs in 7.5%. Median duration of a therapeutic line was 5 months (0-29.8). Grade 3-4 toxicities were for the AdjF and FFox groups respectively, diarrhea 13/15%, neutropenia (febrile) 16(7)/37%(1%) and neuropathy 24/18%. Response rates were 55.3% and 68.7% in the AdjF and FFox groups. Median PFS1 were 14 (95%CI:10-16) and 10 (95%CI:8-11) months in the AdjF and FFox groups, and PFS2 10 (95%CI:8-11) and 7 (95%CI:6-9) months, respectively. Median overall survival was 43 (95%CI:39-50) and 33 months (95%CI:26-36) respectively. Conclusions: Results in terms of survival are in favor of the AdjFFox group. It would be interesting to identify a subgroup of pts rapidly progressing after adjuvant Folfox, who might show the same profile than pts in the FFox group.
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A 73-year-old man had undergone right hemicolectomy for advanced colon cancer in May 2006, and he concurrently had multiple liver metastases. After the operation, the patient was given chemotherapy with FOLFIRI. A partial response was achieved for twelve months, and then the liver tumors enlarged. Second-line chemotherapy with FOLFOX was delivered. After several months the liver tumors further enlarged and a new pulmonary lesion appeared with an increased serum CEA level. Therefore, chemotherapy with S-1 (120 mg/day) was started, with 2 weeks' administration followed by a one-week drug-free period. Several months later, the liver tumors and tumor makers decreased. S-1 is expected to be an effective agent for the treatment of advanced colon cancer with liver metastases after FOLFIRI and FOLFOX.
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［背景］Oxaliplatinは，日本で合成された第3 世代の白金錯体系の抗悪性腫瘍剤であり，欧米ではOxaliplatin と持続投与5-FU/LV 併用（FOLFOX 療法）が進行再発大腸癌に対する標準的な化学療法としての地位を確立し広く施行されている。本邦では，2005 年4 月にOxaliplatinが承認され，当院でも切除不能進行・再発大腸癌に対するfirst-lineの化学療法としてFOLFOX 療法を積極的に施行している。［方法］2005 年6 月より2007 年8 月までに切除不能進行・再発大腸癌に対し，first-line としてFOLFOX4 およびmFOLFOX6 を施行した23 例を対象とし，その効果・安全性を検討した。FOLFOX4 は13 例に，mFOLFOX6は10 例に施行された。［結果］奏効率は50.0％であり，全生存期間は17.4 か月であった。投与回数の中央値は8.0，Oxaliplatinのrelative dose intensityは74.5％である。有害事象は，血液毒性ではGrade 3 以上の白血球減少を4 例，好中球減少を12 例に認め，非血液毒性ではGrade 3 の消化器毒性を1 例，Grade 3 の末梢神経障害を1例に認めたのみであった。［結語］FOLFOX 療法は，日本人においても進行再発大腸癌に対するfirst-lineの化学療法として比較的高い奏効性と安全性をもつ治療法であることが確認された。
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e15110 Background: The alteration of serum-iron level during chemotherapy is already reported (Follezou, NEOPLASMA 1985). However, the correlation to prognosis has not been evaluated. The aim of this study was to evaluate the correlation between prognosis and serum-iron level in advanced / metastatic colorectal cancer (aCRC / mCRC) patients treated by FOLFOX / FOLFIRI. Methods: Serum-iron levels, hemoglobin, AST and ALT serum levels in immediately pre and post chemotherapy were analyzed in 58 aCRC / mCRC patients received FOLFOX-4 / FOLFIRI therapy between April 2005 and September 2008. 26 patients received FOLFOX-4 / FOLFIRI therapy as the final chemotherapy died by the time of analysis. These patients were categorized into the high increase group and the low increase group using 200% increase as cut-off value and the prognosis was compared. Results: Mean serum-iron levels in immediately pre and post chemotherapy were 71.7±29.0μg/dl and 186.8±83.2μg/dl, respectively, and significant increase after chemotherapy was observed (p<0.001). This increase was transient and returns to pre chemotherapy level by the start of next course. This alteration was always observed on the chemotherapy. The median survival times from the initiation of FOLFOX-4 / FOLFIRI therapy for the high increase group (n: 5) and the low increase group (n: 21) were 487 and 182 days, respectively, and was significantly better in the high increase group (p=0.004). The alterations of hemoglobin, AST and ALT serum levels in immediately pre and post chemotherapy were not observed. Conclusions: It is suggested that serum-iron increase is a biological response not attributed to leakage from erythrocyte and hepatocyte. Significantly better prognosis in high serum-iron group may suggest the usefulness of serum-iron level to distinguish responder and non-responder in FOLFOX-4/FOLFIRI therapy. No significant financial relationships to disclose.
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Oxaliplatin with 5-fluorouracil plus leucovorin (FOLFOX) has become the standard treatment in patients with colorectal cancer. Among known toxicities induced by oxaliplatin, hematological, gastrointestinal and neurological toxicities are common. However, acute pulmonary toxicity associated with oxaliplatin is unusual. One case of interstitial lung disease associated with the FOLFOX protocol is reported here. (Korean J Gastroenterol 2010;55: 340-343)
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Colorectal cancer is a major global health concern, ranking third in prevalence and second in mortality. Developed countries have high incidence rates, while Pakistan is considered a low-risk region. Metastatic colorectal cancer requires targeted therapies like FOLFIRI and FOLFOX4, but their effectiveness in Pakistan is unknown. This study aims to provide insights, guide treatment decisions, and expand global understanding in the field. Objective: To compare therapeutic effects of FOLFOX4 and FOLFIRI for advanced colorectal cancer patients. Methods: The Medical Oncology Department of Jinnah Postgraduate and Medical Centre conducted a randomized controlled trial research from May 2022 to February 2023. Hundred patients of advanced colorectal cancer with a confirmed diagnosis of age 18 to 80 years, of either gender, were included. Randomly, 50 of these patients were in FOLFIRI group, and 50 in FOLFOX4 group. Both groups were compared for the treatment outcomes. Results: In the FOLFIRI group, the total response rate was 66%, whereas in the FOLFOX 4 group, it was 78%. In the FOLFIRI group, the median time to progression was 8 months, but in the FOLFOX 4 group, it was 9 months (p=0.06). In the FOLFIRI group, the total median survival time was 13 months, whereas in the FOLFOX 4 group, it was 14 months (p=0.280). Conclusions: The response rates between the two groups were similar, while FOLFOX 4 had a little higher rate of tumor control. FOLFIRI had a lower incidence of neutropenia, whereas FOLFOX 4 had a lower incidence of nausea and vomiting.
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