First-Line Treatment with Irinotecan and Raltitrexed in Metastatic Colorectal Cancer

Aparicio, Jorge; Vicent, J. M.; Maestu, Inmaculada; Bosch, C.; Galán, Antonio; Busquier, Isabel; Llorca, Cristina; Garcera, S.; Campos, Juan; López-Tendero, Pedro; Balcells, Miquel

doi:10.1159/000084821

Cited by 13 publications

(9 citation statements)

References 41 publications

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“…On the basis of the predefined eligibility criteria, we selected 12 studies [3][4][5][7][8][9][10][11][12][13][14][15] that fulfilled the qualitative and quantitative requirements of the systematic analysis. A total of 735 patients were enrolled across the selected trials (range, 37-94).…”

Section: Resultsmentioning

confidence: 99%

“…Aparicio et al [7] Carnaghi et al [4] Cascinu et al [3] Chiara et al [8] Feliu et al [10] Feliu et al [9] TOMIRI Feliu et al [9] TOMOX Gravalos et al [5] Martoni et al [11] Neri et al [12] Santini et al [13] Seitz et al [15] Scheithauer et al [14] 0 required, unlike fluoropyrimidines [1]. In addition, results reported at the American Society of Clinical Oncology meeting in 2000 suggest that the prophylactic use of the 5-HT3 antagonist ondansetron reduces the severity of nausea and diarrhea, preventing dehydration, and the use of dexamethasone reduces the incidence of fever and fatigue [23].…”

Section: Lower Limitmentioning

confidence: 99%

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A systematic review of raltitrexed-based first-line chemotherapy in advanced colorectal cancer

et al. 2014

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Raltitrexed is a thymidylate synthase inhibitor belonging to the antimetabolite class of cytotoxic drugs. It is also effective in colorectal cancer (CRC) both as a single agent and in combination with other drugs, in particular in those patients with cardiologic risk factors or previous cardiotoxicity. The efficacy of first-line raltitrexed-based chemotherapy containing oxaliplatin (TOMOX) and irinotecan (TOMIRI) was investigated in this systematic review. Studies that enrolled advanced CRC patients for first-line therapy with TOMOX/TOMIRI combinations were identified using electronic databases (Pubmed, SCOPUS, Web of Science, EMBASE, and the Cochrane Library). A systematic analysis was carried out using Comprehensive Meta Analysis (version 2.2.064) software to calculate the pooled response rate and 95% confidence limits. The median pooled overall survival and progression-free survival were also calculated. Results for TOMOX and TOMIRI studies were compared using the two-sided Student's t-test. We tested for significant heterogeneity using Cochran's χ-test and I index. Twelve studies published between 2001 and 2012 were eligible for this analysis and a total of 735 patients were enrolled in these studies. The overall response rate was 40% (95% confidence interval 34-46%): 43.9% for TOMOX and 34.1% for TOMIRI arms. The weighted median overall survival and progression-free survival times were 14.6 and 6.7 months, respectively. Neutropenia and liver toxicity were more frequent with TOMOX, whereas neutropenia and diarrhea were more frequent with TOMIRI. However, compared with historical FOLFOX and FOLFIRI trials, raltitrexed-based doublets are associated with less neutropenia and gastrointestinal toxicity and uncommon cardiotoxicity. TOMOX and TOMIRI doublets are active as first-line chemotherapy for advanced CRC and seem useful in particular when the use of 5-fluorouracil is contraindicated for cardiac comorbidity.

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Section: Resultsmentioning

confidence: 99%

Section: Lower Limitmentioning

confidence: 99%

A systematic review of raltitrexed-based first-line chemotherapy in advanced colorectal cancer

et al. 2014

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“…RIR as an active regimen in gastrointestinal malignancies has been demonstrated in a phase I clinical and pharmacogenetic trial [11]. Other published single-arm studies also considered RIR as a suboptimal e cient schedule at the expense of moderate toxicity for patients with metastatic CRC in rst-or secondline treatment [12][13][14]. Moreover, a randomized phase II study compared RIR with raltitrexed alone as second-line treatment in patients with gemcitabine-pretreated advanced pancreatic adenocarcinoma and also indicated that the combination therapy with superior survival [15].…”

Section: Discussionmentioning

confidence: 99%

Biweekly Raltitrexed in Combination with Irinotecan (RIR) as Second-Line Therapy for Patients with Metastatic Colorectal Cancer: A Non-Randomized, Open-Label Phase II Trial.

Cheng

Zhou

Chen

et al. 2020

Preprint

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Background Irinotecan-based doublet chemotherapy strategy was standard second-line backbone treatment for patients with oxaliplatin‑refractory metastatic colorectal cancer(mCRC). The aim of this study was to evaluate tolerability and efficacy of raltitrexed combined with irinotecan biweekly administered as the second-line therapy for mCRC patients.Methods The study was a single-center, non-randomized, open-label phase II trial. Patients with mCRC after failure with first-line treatment of oxaliplatin and fluoropyrimidine or its derivatives were enrolled. Irinotecan (180 mg/m2) and raltitrexed (2.5 mg/m2) were given intravenously on day 1. Cycles were repeated every 2 weeks. The primary endpoint was progression-free survival, and the secondary endpoints included overall response rate, disease control rate, overall survival and treatment related adverse events. Results Between December 2012 and October 2016, 35 patients were enrolled. 33 and 35 patients were assessed for response and safety, respectively. The overall response rate (ORR) was 8.6 %, and the disease control rate (DCR) was 71.4%. The median progression-free survival (PFS) was 4.5 months (95% CI 3.8–5.2). The median overall survival was 12.0 months (95% CI 8.5–15.5). Four patients received conversion therapy to no evidence of disease (NED), and 2 patients were still alive with beyond 24 months survival. The most common grade 3/4 hematological adverse events were leukopenia (8.6%), neutropenia (5.7%). The most common grade 3/4 nonhematological adverse events were anorexia (14.3%), vomiting (14.3%), nausea (11.4%) and fatigue (8.6%). Two patients discontinued the protocol treatment because of treatment-related gastrointestinal adverse events. No one died from treatment-related events. The incidence and severity of toxicity was irrelevant to UGT1A1 status.Conclusions The combination of irinotecan with raltitrexed is an active, convenient and acceptable toxic regimen for second-line treatment for mCRC patients, which needs further study as a chemotherapy backbone to be combined with targeted agents in mCRC.Trial registration No. ChiCTR-ONC-12002767. The study was registered with the Chinese Clinical Trial Registry at 29 Octorber 2012, http://www.chictr.org.cn/index.aspx.

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“…Grade 3/4 leukopenia occurred in 5 (13.15%) patients. According to previous reports, most studies used 300-350 mg/m 2 irinotecan in the treatment of colorectal cancer [28,29]. A lower dose of irinotecan (200mg/m 2 ) combined with raltitrexed was administered to treat patients with advanced pancreatic adenocarcinoma from a randomized multicenter phase II study [19].…”

Section: Discussionmentioning

confidence: 99%

Clinical efficacy of irinotecan plus raltitrexed chemotherapy in refractory esophageal squamous cell cancer: a retrospective study

Liu

Jia

Xiao-lin

et al. 2019

Preprint

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Background: The optimal chemotherapy regimen for refractory esophageal squamous cell cancer patients is uncertain. Our retrospective study assessed the efficacy and safety of irinotecan plus raltitrexed in esophageal squamous cell cancer patients who were previously treated with multiple systemic therapies. Methods: Between January 2016 and December 2018, records of 38 esophageal squamous cell cancer patients who underwent irinotecan plus raltitrexed chemotherapy after at least one line of chemotherapy were reviewed. Efficacy assessment was performed every two cycles according to the RECIST version 1.1. Results: A total of 95 cycles of chemotherapy were administered, and the median course was 3 (range 2–6). There was no treatment-related death. Nine patients had partial response, 21 had stable disease and 8 had progressive disease. The overall objective response rate was 23.68% (9/38) and the disease control rate was78.94% (30/38). After a median follow-up of 18.5 months, the median progression-free survival and overall survival were 105 days and 221 days respectively. There were 5 patients (13.15%) with grade 3/4 leukopenia, 3 patients (7.89%) with grade 3/4 neutropenia and 1 patient (2.63%) with grade 3/4 diarrhea. Conclusions: The combination of irinotecan plus raltitrexed was effective for pretreated esophageal squamous cell cancer patients. Further studies are needed to determine the optimal dose of the two drugs.

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First-Line Treatment with Irinotecan and Raltitrexed in Metastatic Colorectal Cancer

Cited by 13 publications

References 41 publications

A systematic review of raltitrexed-based first-line chemotherapy in advanced colorectal cancer

A systematic review of raltitrexed-based first-line chemotherapy in advanced colorectal cancer

Biweekly Raltitrexed in Combination with Irinotecan (RIR) as Second-Line Therapy for Patients with Metastatic Colorectal Cancer: A Non-Randomized, Open-Label Phase II Trial.

Clinical efficacy of irinotecan plus raltitrexed chemotherapy in refractory esophageal squamous cell cancer: a retrospective study

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