SALIRI-based (raltitrexed plus irinotecan) therapy as a second-line treatment for patients with metastatic colorectal cancer (SALLY): A prospective, multicenter, non-interventional, registry study.
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SUBMITTER: Qin S
PROVIDER: S-EPMC11337918 | biostudies-literature | 2024 Jul
REPOSITORIES: biostudies-literature
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SALIRI-based (raltitrexed plus irinotecan) therapy as a second-line treatment for patients with metastatic colorectal cancer (SALLY): A prospective, multicenter, non-interventional, registry study.
Qin Shuqui S Li Jin J Zhou Aiping A Zhang Yanqiao Y Yuan Xianglin X Zhu Liangjun L Qin Baoli B Zeng Shan S Shen Lin L Yuan Ying Y Wang Weibo W Liang Jun J Zhang Xianwen X Ye Feng F Chen Ping P Wang Huaizhang H Yu Zhenyan Z Yue Lu L Fang Yong Y Xiong Jianping J Yang Jianwei J Wan Yiye Y Yin Xianli X Wang Wenling W Xu Nong N Wang Xiaohong X Xiao Zemin Z Su Huafang H Wang Ying Y Gu Kangsheng K Tu Shuiping S Wang Zishu Z Liu Bo B Hu Xiaohua X Liu Weixian W Li Xiaofeng X
Cancer communications (London, England) 20240708 8
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Project description:The present study evaluated the efficiency, prognostic factors for and the safety of irinotecan combined with raltitrexed (TOMIRI) in patients with metastatic colorectal cancer (CRC). Outcome data of patients who received TOMIRI as first-, second- and third- or later-line treatment regimens were assessed to compare the efficacy of this regimen. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and disease control rate (DCR) were evaluated for each group. Kaplan-Meier curves and univariate and multivariate analyses were performed to evaluate efficacy. From January 2017 to December 2019, TOMIRI was administered as a first-line treatment in 23 patients, second-line treatment in 164 patients and third- or later-line treatment in 18 patients. Irinotecan and 5-fluorouracil (FOLFIRI) was administered to another 50 patients, who served as the control group. The median PFS was 9, 7 and 6 months and the median OS was 37, 21 and 17 months for first-, second- and third- or later-line treatments, respectively. The ORRs of the included patients were 21.7, 13.4 and 11.1%, respectively, and the DCRs were 91.3, 81.7 and 66.7%, respectively. Compared with FOLFIRI, TOMIRI as a second-line chemotherapy treatment was associated with longer survival of the patients with CRC. Further analysis demonstrated that pathologic tumor-node-metastasis category, carcinoembryonic antigen, carbohydrate antigen 19-9, treatment cycles, targeted therapy, treatment of local metastases and first-line PFS were prognostic factors for second-line treatment. Among these, the number of treatment cycles was of vital importance. Hepatic dysfunction was the most commonly reported grade 1-2 (55.1%) and grade 3-4 (7.3%) adverse event. Neutropenia (12.2%), thrombocytopenia (10.2%), anemia (27.3%), proteinuria (38.1%) and hematuria (21.0%) were also common grade 1-2 adverse events. In conclusion, TOMIRI may be recommended as an effective and safe second-line treatment for metastatic CRC in the clinic.
| S-EPMC11234808 | biostudies-literature
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:ImportanceThere is therapeutic uncertainty regarding use of combination or single-agent chemotherapy in the treatment of patients with gallbladder cancer who experience disease progression after first-line chemotherapy.ObjectiveTo compare the efficacy of capecitabine plus irinotecan (CAPIRI) vs irinotecan (IRI) alone in patients with advanced gallbladder cancer (GBC) who have disease progression after gemcitabine-based first-line treatment.Design, setting, and participantsThe GB-SELECT trial was a multicenter, open-label, phase 2, randomized clinical trial of CAPIRI vs IRI alone for treatment of gallbladder cancer in patients who had disease progression after prior gemcitabine-based chemotherapy.The study was carried out in 2 tertiary care institutions in India. Patients aged between 18 and 70 years with histopathologic diagnosis of adenocarcinoma gallbladder, advanced or metastatic disease, previous treatment with gemcitabine-based chemotherapy, adequate hematologic, liver, and renal functions, and ECOG performance status of 1 or less were included in the study between August 2018 and January 2020. The data were analyzed for this report with cutoff on May 19, 2020.InterventionsPatients were randomized 1:1 to receive capecitabine, 1700 mg/m2 per day, on days 1 to 14 plus intravenous irinotecan, 200 mg/m2, on day 1 or intravenous irinotecan, 240 mg/m2, on day 1, in 21-day cycles until disease progression or unacceptable toxic effects.Main outcomes and measuresThe primary end point was overall survival (OS) at 6 months. The secondary end points were progression-free survival and quality of life.ResultsA total of 98 patients were randomized, 49 in each arm, with median (range) age of 51 (29-70) years, with 60 (61%) being women. In the CAPIRI vs IRI arms, the number of deaths at 6 months, 6-month OS, and median OS were 35, 34, 38.4% (95% CI, 24.2%-52.6%) and 5.16 (95% CI, 4.26-6.06) months vs 34, 29, 54.2% (95% CI, 39.4%-69.0%) and 6.28 (95% CI, 4.25-8.30) months, respectively, with a hazard ratio of 1.02 (95% CI, 0.64-1.49, P = .93). There were no chemotherapy-related deaths but more patients required dose modification in CAPIRI compared with the IRI arm (13 [27%] vs 4 [9%], respectively, P = .03).Conclusions and relevanceThere was no significant difference in OS between treatment with capecitabine plus irinotecan or irinotecan alone among previously treated patients with gallbladder cancer. Single-agent irinotecan should be the preferred treatment option for such patients.Trial registrationCTRI/2017/10/010112.
| S-EPMC7716253 | 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: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:BackgroundLimited second-line therapeutic options are available for metastasis pancreatic cancer (mPC). We aimed to explore the efficacy and safety of oxaliplatin plus irinotecan (IROX) in mPC patients.MethodsThis is an open-label, Phase 2, randomized study of mPC patients (aged 18-75 years) who failed when using gemcitabine plus S-1 as first-line therapy. Block randomization with a block size of four was used to randomly assign patients (1:1) between October 2015 and December 2017 to receive either IROX (oxaliplatin 85 mg/m2 and irinotecan 160 mg/m2) or irinotecan monotherapy (irinotecan 180 mg/m2) until disease progression, unacceptable adverse events, or consent withdrawal. The primary end point was overall survival, and the secondary end points were progression-free survival, overall response rate, and adverse event rate.ResultsA total of 74 patients were enrolled in this study, including 44 males and 30 females, with an average age of 61 years. The median overall survival was 10.2 and 6.7 months (adjusted hazard ratio [HR], 0.7; 95% confidence interval [CI], 0.4-1.2; P = 0.20) and the median progression-free survival was 5.1 and 2.3 months (adjusted HR, 0.4; 95% CI, 0.2-0.6; P < 0.01) in the IROX group and irinotecan group, respectively. The overall response rates were 18.4% (7/38) in the IROX group and 5.5% (2/36) in the irinotecan group (P = 0.06). Grade 3-4 adverse events occurred in 34% (13/38) of patients in the IROX group and 19% (7/36) of patients in the irinotecan group (P = 0.15).ConclusionsIROX had no significant survival benefit over irinotecan monotherapy in our study. However, IROX reduced the risk of disease progression by 60%, with acceptable toxicity.
| S-EPMC9897170 | biostudies-literature
Project description:ObjectiveApatinib and irinotecan are used as systematic therapies for advanced gastric adenocarcinoma (GAC) and gastroesophageal junction adenocarcinoma (GEJA), while the evidence for their combination as second-line therapy in these patients is limited. This study aimed to evaluate the efficacy and safety of second-line apatinib plus irinotecan for the treatment of GAC and GEJA.MethodsIn this prospective, multicenter phase II clinical study, 28 patients with advanced GAC or GEJA who received second-line apatinib plus irinotecan were recruited.ResultsIn total, 1 (3.6%) patient achieved complete response, 7 (25.0%) patients achieved partial response, 13 (46.4%) patients had stable disease, and 4 (14.3%) patients showed progressive disease, while clinical response was not evaluable or not assessed in 3 (10.7%) patients. The objective response rate and disease control rate were 28.6% and 75.0%, respectively. Meanwhile, the median (95% confidence interval (CI)) progression-free survival (PFS) was 4.5 (3.9-5.1) months, and the median (95% CI) overall survival (OS) was 11.3 (7.4-15.1) months. By multivariate Cox regression analysis, male sex, liver metastasis, and peritoneal metastasis were independently associated with worse PFS or OS, while treatment duration ≥5 months was independently associated with better OS. In terms of the safety profile, 89.3% of patients experienced treatment-emergent adverse events of any grade, among which 82.1% of patients had grade 1-2 adverse events and 64.3% of patients had grade 3-4 adverse events.ConclusionApatinib plus irinotecan as second-line therapy achieves a good treatment response and satisfactory survival with tolerable safety in patients with advanced GAC or GEJA.
| S-EPMC10166633 | 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:LESSON LEARNED:Panitumumab plus irinotecan is not active for the treatment of esophageal adenocarcinoma. BACKGROUND:Esophageal adenocarcinoma (EAC) is a lethal cancer with increasing incidence. Panitumumab (Pa) is a fully humanized IgG2 monoclonal antibody against human EGFR. Cetuximab (Cx) combined with irinotecan (Ir) is active for second-line treatment of colorectal cancer. This phase II study was designed to evaluate Pa plus Ir as second-line therapy for advanced EAC. METHODS:The primary endpoint was response rate (RR). Patients with one prior treatment were given Pa 9 mg/m2 on day 1 and Ir 125 mg/m2 on days 1 and 8 of each 21-day cycle. Inclusion criteria were confirmed EAC, measurable disease, no prior Ir or Pa, performance status <2, and normal organ function. RESULTS:Twenty-four patients were enrolled; 18 were eligible and evaluable. These patients were all white, with a median age of 62.5 years (range, 33-79 years), and included 15 men and 3 women. The median number of cycles was 3.5. The most common grade 1-2 adverse events were fatigue, diarrhea, anemia, leukopenia, and hypoalbuminemia. Grade 3-4 adverse events included hematologic, gastrointestinal, electrolyte, rash, fatigue, and weight loss. The median follow-up was 7.2 months (range, 2.3-14 months). There were no complete remissions. The partial response rate was 6% (1/18; 95% confidence interval [CI], 0.01-0.26). The clinical benefit (partial response [PR] plus stable disease [SD]) rate was 50%. The median overall survival was 7.2 months (95% CI, 4.1-8.9) with an 11.1% 1-year survival rate. The median progression-free survival was 2.9 months (95% CI, 1.6-5.3). CONCLUSION:Irinotecan and panitumumab as second-line treatment for advanced EAC are not active.
| S-EPMC6192615 | 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