Irinotecan plus raltitrexed as second‐line chemotherapy for metastatic colorectal cancer: A retrospective study
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SUBMITTER: Lian J
PROVIDER: S-EPMC11234808 | biostudies-literature | 2024 Jun
REPOSITORIES: biostudies-literature
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Project description:ObjectivesClinical studies have shown that bevacizumab plus chemotherapy significantly improves efficacy in metastatic colorectal cancer (mCRC). This prospective study aims to investigate the efficacy and safety of changing second-line treatment to raltitrexed-based chemotherapy regimens plus bevacizumab in mCRC patients who have failed the first-line fluorouracil-based chemotherapy regimen with or without bevacizumab/cetuximab.MethodsThis is a prospective, open-label, multicenter, phase II clinical study. A total of 100 patients with mCRC after failure of the first-line fluorouracil-based chemotherapy regimen with or without bevacizumab/cetuximab were enrolled from November 2016 to October 2021, and received second-line raltitrexed-based chemotherapy regimen plus bevacizumab. Patients were treated for 6 cycles, and efficacy evaluation over stable disease were followed by maintenance treatment of bevacizumab and raltitrexed until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), safety, and toxicity.ResultsNinety-four patients were treated with SALIRI (raltitrexed + irinotecan) plus bevacizumab, and six patients with SALOX (raltitrexed + oxaliplatin) plus bevacizumab. Median PFS was 8.4 (95% CI: 6.2-11.0) months, including 8.2 (95% CI 6.2, 11.0) months in the SALIRI group and 11.6 (95% CI 3.1, NA) months in the SALOX group. Median OS was 17.6 (95% CI 15.2, 22.0) months in the SALIRI group and 17.1 (95% CI 4.1, NA) months in the SALOX group. ORR and DCR were 25.5% and 87.2% in the SALIRI group, and 33.3% and 83.3% in the SALOX group, respectively. A low incidence of grade 3-4 adverse events was observed.ConclusionsRaltitrexed-based chemotherapy regimens plus bevacizumab improved survival duration in mCRC patients with failed first-line therapy. Therefore, treatment with raltitrexed-based chemotherapy regimens plus bevacizumab could be a superior therapeutic option for second-line chemotherapy in mCRC (ClinicalTrials.gov registration number: NCT03126071).
| S-EPMC11423381 | biostudies-literature
Project description: Not available
| S-EPMC11337918 | biostudies-literature
Project description:BackgroundThere is no clear consensus on the recommended second-line treatment for patients with metastatic pancreatic cancer who have disease progression following gemcitabine-based therapy. We retrospectively evaluated the clinical outcomes of liposomal irinotecan (nal-IRI) plus fluorouracil/leucovorin (FL) and FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin) in patients who had failed on the first-line gemcitabine-based therapy.Patients and methodsFrom January 2015 to August 2019, 378 patients with MPC who had received nal-IRI/FL (n = 104) or FOLFIRINOX (n = 274) as second-line treatment across 11 institutions were included in this retrospective study.ResultsThere were no significant differences in baseline characteristics between groups, except age and first-line regimens. With a median follow-up of 6 months, the median progression-free survival (PFS) was 3.7 months with nal-IRI/FL versus 4.6 months with FOLFIRINOX (P = 0.44). Median overall survival (OS) was 7.7 months with nal-IRI/FL versus 9.7 months with FOLFRINOX (P = 0.13). There was no significant difference in PFS and OS between the two regimens in the univariate and multivariate analyses. The subgroup analysis revealed that younger age (<70 years) was associated with better OS with FOLFIRINOX. In contrast, older age (≥70 years) was associated with better survival outcomes with nal-IRI/FL. Adverse events were manageable with both regimens; however, the incidence of grade 3 or higher neutropenia and peripheral neuropathy was higher in patients treated with FOLFIRINOX than with nal-IRI/FL.ConclusionsSecond-line nal-IRI/FL and FOLFIRINOX showed similar effectiveness outcomes after progression following first-line gemcitabine-based therapy. Age could be the determining factor for choosing the appropriate second-line therapy.
| S-EPMC7878976 | biostudies-literature
Project description:BackgroundBiologicals, in combination with chemotherapy, are recommended as first-line treatment of metastatic colorectal cancer (mCRC); however, evidence guiding the appropriate management of older patients with mCRC is limited.ObjectiveThis study was undertaken to compare the efficacy and safety outcomes in older versus younger patients with mCRC who received first-line biological therapy.MethodsThis retrospective analysis used pooled data from five trials undertaken by the Spanish Cooperative Group for the Treatment of Digestive Tumours. All were studies of adults with advanced CRC who received first-line treatment with chemotherapy plus bevacizumab, cetuximab or panitumumab, stratified by age (≥ 65 vs. < 65 years). Endpoints included progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and safety.ResultsIn total, 999 patients from five studies were included in the analysis: 480 (48%) were aged ≥ 65 years, and 519 (52%) were aged < 65 years. Median PFS did not differ significantly between patients aged ≥ 65 and < 65 years (9.9 vs. 9.4 months; hazard ratio [HR] 1.01; 95% confidence interval [CI] 0.88-1.17). Median OS was significantly shorter in older than in younger patients (21.3 vs. 25.0 months; HR 1.21; 95% CI 1.04-1.41). There was no significant difference between older and younger patients in ORR (59 vs. 62%). Patients aged ≥ 65 years experienced significantly more treatment-related grade 3 or higher adverse events (61.67%) than did patients aged < 65 years (45.86%).ConclusionsBiologicals plus chemotherapy is an effective first-line treatment option for selected patients aged ≥ 65 years with mCRC and has a manageable safety profile and efficacy comparable to that observed in younger patients.
| S-EPMC7914239 | biostudies-literature
Project description:PurposeEtirinotecan pegol (EP) is a long-acting topoisomerase-I inhibitor designed to provide sustained exposure to SN-38 (active metabolite of irinotecan). This phase II study compared EP versus irinotecan as second-line treatment for KRAS-mutant, irinotecan-naïve, metastatic colorectal cancer (mCRC).MethodsPatients were randomized to EP 145 mg/m2 or irinotecan 350 mg/m2 Q21d until disease progression/unacceptable toxicity. The primary endpoint was progression-free survival (PFS) with response determined by central radiologic review (RECIST version 1.1).ResultsThe study was terminated before completing accrual due to evolving standards of care. Eighty-three patients were randomized. Median PFS was longer with EP versus irinotecan (4.0 versus 2.8 months, respectively; HR 0.65; 95% CI 0.40-1.04; P = 0.07). Six-month PFS rates were 32.8 and 15.4%, respectively. Median OS was 9.6 and 8.4 months in EP and irinotecan arms, respectively (HR 0.91; 95% CI 0.56-1.49). ORRs were 10 and 5%, respectively (P = 0.676); median DOR was significantly longer in EP arm (7.9 versus 1.4 months; P = 0.018). The most common grade-3/4 adverse events for EP and irinotecan were diarrhea (21 vs 20%), neutropenia (10 vs 22%), abdominal pain (14 vs 5%), nausea (14 vs 2%), and vomiting (12 vs 7%), respectively.ConclusionEP is active and safe for second-line treatment of KRAS-mutant, irinotecan-naïve mCRC.
| S-EPMC6863159 | biostudies-literature
Project description:No standard second-line regimen exists for the treatment of advanced esophageal squamous cell carcinoma (ESCC). The aim of this study was to evaluate the efficacy and safety of irinotecan and fluorouracil-based chemotherapy as a second or third-line regimen for advanced ESCC patients.We retrospectively reviewed a cohort of 27 consecutive patients with advanced ESCC in one institute, treated with a combination of irinotecan plus fluorouracil-based regimens after the failure of first-line platinum-based therapy. Nine patients were treated with 150-160 mg/m(2) irinotecan and 400 mg/m(2) fluorouracil (5-FU) on day 1, followed by 2000 mg/m(2) 5-FU during a 48-hour infusion every two weeks. Eighteen patients received 150-160 mg/m(2) irinotecan on day 1 and 80-120 mg/day S-1 on days 1-10 every two weeks. The S-1 dose was based on the patients' body surface area.Twenty-four of the 27 patients were assessable for response. One (3.7%) patient achieved complete response, seven (25.9%) achieved partial response, eight (29.6%) had stable disease, and eight (29.6%) had progressive disease. The median progression-free and overall survival were 4.8 (95% confidence interval [CI]: 1.2-8.4) and 10.5 months (95% CI: 8.4-12.7), respectively. Grade 3 neutropenia and diarrhea were detected in four (15%) and one (4%) patient, respectively. No grade 4 toxicity was noted.Our study indicates that an irinotecan plus 5-FU-based regimen is effective and well-tolerated as a second or third-line chemotherapy for patients with advanced ESCC.
| S-EPMC4773301 | biostudies-other
Project description:BackgroundExposing patients with metastatic colorectal cancer (mcrc) to all three active chemotherapeutic agents (oxaliplatin, irinotecan, fluorouracil) has improved survival. The benefit of second-line chemotherapy after a first-line triplet is not clearly defined. We evaluated the efficacy of second-line chemotherapy in patients who had received first-line triplet therapy.MethodsThe medical records of patients treated on a prospective trial of first-line triplet therapy were reviewed for second-line treatment. Univariate and multivariate analyses were performed to establish factors of prognostic significance.ResultsOf the 53 patients who received first-line triplet therapy, 28 (53%) received second-line chemotherapy [13 men; 8 with a colon primary; mutant KRAS in 10, wild-type in 15, and unknown status in 3; Eastern Cooperative Oncology Group performance status (ps) of 1 in 16 patients, ps 2 in 3, ps 3 in 2, and unknown in 7; involved organs: liver in 17 patients, lung in 16, and peritoneum in 8]. Second-line chemotherapy consisted of xelox or folfox in 13 patients, xeliri or folfiri in 12, and single-agent irinotecan in 3. Concurrent bevacizumab was given in 16 patients (57%), and cetuximab, in 2 (7%). Median survival was 28.0 months [95% confidence interval (ci): 22.8 months to 33.2 months] for patients receiving second-line therapy and 23.0 months (95% ci: 13.2 months to 32.8 months) for those not receiving it. Best response was partial in 6 patients (21%), stable disease in 11 (39%), and progressive disease in 11 (39%). Median progression-free survival was 4.8 months (95% ci: 2.4 months to 9.6 months), and overall survival was 15 months (95% ci: 9.6 months to 20.4 months).ConclusionsSecond-line chemotherapy after first-line triplet therapy in mcrc is feasible and suggests efficacy comparable to that reported for second-line therapy after a doublet, regardless of the agent used.
| S-EPMC6380651 | biostudies-literature
Project description:BackgroundThe ML18174 study, which showed benefits of bevacizumab (BEV) continuation beyond progression (BBP) for metastatic colorectal cancer (mCRC), excluded patients with first-line progression-free survival (PFS) shorter than 3 months. The present study was conducted to evaluate the efficacy of second-line chemotherapy after early disease progression during first-line chemotherapy containing bevacizumab.MethodsThe subjects of this study were mCRC patients who experienced disease progression < 100 days from commencement of first-line chemotherapy containing BEV initiated between Apr 2007 and Dec 2016. Second-line chemotherapy regimens were classified into two groups with and without BEV/other anti-angiogenic agents (BBP and non-BBP) and efficacy and safety were compared using univariate and multivariate analysis.ResultsSixty-one patients were identified as subjects of this study. Baseline characteristics were numerically different between BBP (n = 37) and non-BBP (n = 25) groups, such as performance status (0-1/> 2/unknown: 89/8/3 and 56/40/4%), RAS status (wild/mutant/unknown: 32/54/16 and 76/16/8%). Response rate was 8.6% in BBP group and 9.1% in non-BBP group (p = 1.00). Median PFS was 3.9 months in BBP group and 2.8 months in non-BBP group (HR [95%CI]: 0.79 [0.46-1.34], p = 0.373, adjusted HR: 0.87 [0.41-1.82], p = 0.707). Median overall survival was 8.5 months in BBP group and 5.4 months in non-BBP group (HR 0.66 [0.38-1.12], p = 0.125, adjusted HR 0.53 [0.27-1.07], p = 0.078).ConclusionIn mCRC patients who experienced early progression in first-line chemotherapy, second-line chemotherapy showed poor clinical outcomes regardless use of anti-angiogenic agents.
| S-EPMC8555183 | biostudies-literature
Project description:BackgroundCapecitabine is used mainly with oxaliplatin to treat metastatic colorectal cancer (mCRC). Results from capecitabine plus irinotecan (XELIRI) with or without bevacizumab (BV) have been reported in Europe but not in Japan. Consequently, the safety and efficacy of XELIRI plus BV in Japanese patients with mCRC were assessed in a single-arm phase II study.MethodsEligible patients had had prior chemotherapy containing BV for mCRC and wild-type or heterozygous UGT1A1. Therapy in each 21-day treatment cycle consisted of capecitabine (800 mg/m(2) twice daily on days 1-15), irinotecan (200 mg/m(2) on day 1), and BV (7.5 mg/kg on day 1). The primary endpoint was dose-limiting toxicity in phase I and progression-free survival (PFS) in phase II.ResultsA total of 34 patients (6 in phase I, 28 in phase II) were enrolled from May 2010 to June 2011. Baseline characteristics included a median age of 60 years (range: 22-74 years) for 24 men and 10 women. No dose-limiting toxicities appeared in phase I. Median PFS was 240 days (95% confidence interval: 179-311 days). Overall response rate was 18.1%, and the disease-control rate was 90.9%. The incidence of adverse events frequently associated with irinotecan and capecitabine were neutropenia (any grade, 55.9%; grade 3 or 4, 11.8%), diarrhea (any grade, 50%; grade 3 or 4, 5.9%), and hand-foot syndrome (any grade, 61.8%; grade 3 or 4, 5.9%).ConclusionOur results suggest that XELIRI plus BV is well tolerated and effective as a second-line treatment for mCRC in Japanese patients. This regimen could be especially appropriate for patients resistant to oxaliplatin-based regimens.
| S-EPMC4221367 | biostudies-literature
Project description:BackgroundThe multicenter, open-label, randomized, phase III EPIC study (EMR 062202-025) investigated cetuximab plus irinotecan versus irinotecan in patients with epidermal growth factor receptor-detectable metastatic colorectal cancer (mCRC) that progressed on first-line fluoropyrimidine- and oxaliplatin-based chemotherapy; we report the outcomes of patients with RAS-wild-type (wt) disease.Materials and methodsAvailable DNA samples from RAS-unselected patients (n = 1,164 of 1,298 [89.7%]) were reanalyzed for RAS mutations using beads, emulsion, amplification, and magnetics. Baseline characteristics, efficacy, safety, and poststudy therapy were assessed. RAS-wt status was defined as a mutated RAS allele frequency of ≤5%, with all relevant alleles being analyzable.ResultsBaseline characteristics were comparable between the groups (n = 452 patients with RAS-wt mCRC; cetuximab plus irinotecan n = 231, irinotecan n = 221) and between the RAS-wt and RAS-unselected populations. In the cetuximab plus irinotecan versus irinotecan arms, median overall survival was 12.3 versus 12.0 months, median progression-free survival (PFS) was 5.4 versus 2.6 months, and objective response rate (ORR) was 29.4% versus 5.0%, respectively. Quality of life (QoL) was improved in the cetuximab plus irinotecan arm. Serious adverse events occurred in 45.4% (cetuximab plus irinotecan) and 42.4% (irinotecan) of patients. In total, 47.1% of patients in the irinotecan arm received subsequent cetuximab therapy.ConclusionPFS, ORR, and QoL were improved with cetuximab plus irinotecan as a second-line treatment in patients with RAS-wt mCRC, confirming that cetuximab-based therapy is suitable in this population. Almost half of patients in the irinotecan arm received poststudy cetuximab, masking a potential overall survival benefit of cetuximab addition.Implications for practiceCetuximab is approved for the treatment of RAS-wild-type metastatic colorectal cancer (mCRC). In this retrospective analysis of the phase III EPIC study (cetuximab plus irinotecan vs. irinotecan alone as second-line treatment in patients with RAS-unselected mCRC), the subgroup of patients with RAS-wild-type mCRC who received cetuximab plus irinotecan had improved progression-free survival, objective response rate, and quality of life compared with the RAS-unselected population. These findings suggest that cetuximab-based therapy is a suitable second-line treatment for patients with RAS-wild-type mCRC.
| S-EPMC7873334 | biostudies-literature