Extended survival with metastatic pancreatic cancer under fruquintinib treatment after failed chemotherapy: Two case reports
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PROVIDER: S-EPMC10955531 | biostudies-literature | 2024 Mar
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Project description:Hepatoid adenocarcinoma (HAC) is a rare and aggressive cancer subtype with a poor prognosis under metastatic conditions. Currently, there is no specific chemotherapy treatment protocol for advanced stages of the disease. This review evaluates two cases of HAC of gastric cardia with synchronous liver metastasis, which were successfully treated by chemotherapy with cisplatin (25 mg/m2 each day) (day 1 to day 3) and etoposide (100 mg/m2) (day 1 to day 3), every three weeks. A structured literary evaluation and reviewed pertinent articles are additionally presented to analyse the different approaches for the treatment of metastatic HAC (mHAC). The two described case reports demonstrated good partial responses to treatment and one of the two patients exhibited a good prognosis after a 9-year follow-up. A total of 20 case reports concerning the use of chemotherapy in mHAC were presented in the literature, 11 of which were regarding gastric HACs. The two aforementioned cases result in a total of 22 reports, 11 of which exhibited objective responses to chemotherapy, 8 patients demonstrated a partial response and 3 a complete response. The cisplatin-based regimen concerned 55% (12/22) patients and enabled 9 (75%) to exhibit a partial or complete response. A total of three patients exhibited a good prognosis in the long-term follow-up, all of them treated with a cisplatin-based regimen. It was demonstrated that the usual digestive regimens were not efficient in the treatment of HAC. In the absence of prospective trials, it may be hypothesized that cisplatin-based chemotherapy may be the most efficient first-line treatment in mHAC, with a 75% patient response, in accordance with the literature and follow-up cases.
| S-EPMC5769300 | biostudies-literature
Project description:Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. Median survival for metastatic patients is six to nine months and survivors beyond one year are exceptional. Pancreatic cancer is resistant to conventional chemotherapy and is often diagnosed at advanced stages. However, immunotherapy is a rapidly advancing new treatment modality, which shows promise in many solid tumor types. We present a patient with metastatic pancreatic cancer who underwent a synchronous resection of the primary tumour (pancreatoduodenectomy) and metastatic site (left hepatectomy) after multimodality neoadjuvant treatment with gemcitabine, nab-paclitaxel, and immunotherapy backbone with IMM-101 (an intradermally applied immunomodulator), as well as consolidation chemoradiation. Pathology of the specimens showed a complete response in both sites of the disease. The patient remains alive four years from the initial diagnosis and continues on maintenance immunotherapy. This exceptional response to initial chemo-immunotherapy was followed by a novel and off-protocol approach of low-dose capecitabine and IMM-101 as a maintenance strategy. The survival benefit and sustained performance status could set this as a new paradigm for the treatment of oligometastatic pancreatic cancer following response to systemic therapy and immunotherapy..
| S-EPMC4731256 | biostudies-literature
Project description:ObjectivesSurvival benefit of combination over single-agent chemotherapy for metastatic pancreatic ductal adenocarcinoma (PDAC) was demonstrated in younger patients in clinical trials. The authors aimed to evaluate whether this survival benefit of combination chemotherapy is present in elderly patients with metastatic PDAC.Materials and methodsThe authors identified elderly patients (age 65 y or older) with stage IV PDAC and extracted available clinical information from a prospectively maintained institutional pancreatic cancer registry from 2007 to 2016. The primary endpoint was overall survival. Cox proportional hazards regression was used for multivariable survival analyses. Survival outcomes for the entire cohort and by age group I (elderly, 65 to 75 y) and age group II (very elderly, older than 75 y) were assessed.ResultsA total of 606 patients were included with a median age of 73.8 years. Among them, 239 patients (39%) received combination chemotherapy and 152 patients (25.1%) received single-agent chemotherapy as first-line treatment. Combination chemotherapy was associated with significantly longer median overall survival compared with single-agent chemotherapy (10.9 vs. 7.5 mo, P<0.001) with hazard ratio 0.62 (95% confidence interval, 0.47-0.81; P=0.001) after adjusting for age, sex, comorbidity, Eastern Cooperative Oncology Group (ECOG) performance status, and carbohydrate antigen 19-9 level. Analyses by age groups indicated that very elderly patients (age group II) benefited from combination chemotherapy compared with single-agent chemotherapy with hazard ratio 0.56 (95% confidence interval, 0.31-1; P=0.049), comparable with the age group I (Page-treatment interaction=0.81).ConclusionElderly patients, even those older than 75 years, with metastatic PDAC benefited from combination chemotherapy.
| S-EPMC7395872 | biostudies-literature
Project description:ImportanceThe prognosis for patients with metastatic pancreatic ductal adenocarcinoma (PDAC) is dismal, due in part to chemoresistance. Bacteria-mediated mechanisms of chemoresistance suggest a potential role for antibiotics in modulating response to chemotherapy.ObjectiveTo evaluate whether use of peritreatment antibiotics is associated with survival among patients with metastatic PDAC treated with first-line gemcitabine or fluorouracil chemotherapy.Design, setting, and participantsUsing the population-based Surveillance, Epidemiology, and End Results-Medicare linked database, this retrospective cohort study analyzed data for patients diagnosed with PDAC between January 1, 2007, and December 31, 2017. Data analysis was conducted between September 1, 2021, and January 15, 2023. The population-based sample included 3850 patients with primary metastatic PDAC treated with first-line gemcitabine or fluorouracil chemotherapy. Patients who received antibiotics were matched based on propensity scores to patients who did not receive antibiotics.ExposuresReceipt of 5 or more days of oral antibiotics or 1 injectable antibiotic in the month before or after beginning first-line chemotherapy.Main outcomes and measuresOverall survival and cancer-specific survival. The end of follow-up was December 31, 2019, for overall survival and December 31, 2018, for cancer-specific survival.ResultsOf the 3850 patients treated with first-line gemcitabine (3150 [81.8%]) or fluorouracil (700 [18.2%]), 2178 (56.6%) received antibiotics. The mean (SD) age at diagnosis was 74.2 (5.8) years and patients were predominantly women (2102 [54.6%]), White (3396 [88.2%]), and from metropolitan areas (3393 [88.1%]) in the northeastern or western US (2952 [76.7%]). In total, 1672 propensity-matched pairs were analyzed. Antibiotic receipt was associated with an 11% improvement in overall survival (hazard ratio [HR], 0.89; 95% CI, 0.83-0.96; P = .003) and a 16% improvement in cancer-specific survival (HR, 0.84; 95% CI, 0.77-0.92; P < .001) among patients treated with gemcitabine. In contrast, there was no association between antibiotic receipt and overall survival (HR, 1.08; 95% CI, 0.90-1.29; P = .41) or cancer-specific survival (HR, 1.12; 95% CI, 0.90-1.36; P = .29) among patients treated with fluorouracil. In a subgroup of gemcitabine-treated patients who received antibiotics, nonpenicillin β-lactams were associated with an 11% survival benefit (HR, 0.89; 95% CI, 0.81-0.97; P = .01).Conclusions and relevanceIn this cohort study, receipt of perichemotherapy antibiotics was associated with improved survival among patients treated with gemcitabine, but not fluorouracil, suggesting that antibiotics may modulate bacteria-mediated gemcitabine resistance and have the potential to improve PDAC outcomes.
| S-EPMC10037151 | biostudies-literature
Project description: Not available
| S-EPMC11236459 | biostudies-literature
Project description:Fruquintinib, also called HMPL-013, was first discovered by Hutchison Whampoa Pharmaceuticals Co. Ltd., Shanghai, China, and it is an oral vascular endothelial growth factor receptor (VEGFR) inhibitor. In clinical trials, fruquintinib has demonstrated a survival benefit in metastatic colorectal cancer (mCRC) patients. The purpose of this study was to retrospectively evaluate the efficacy and toxicity of fruquintinib in real-world patients. We collected data from patients with mCRC treated with oral fruquintinib from 2018 to 2020 in six different institutions. Patients with mCRC initially received 5 mg of oral fruquintinib daily for 3 weeks. Progression-free survival (PFS) was evaluated using the KaplanMeier method. The efficacy and safety of fruquintinib were also assessed. Seventy-five patients were involved in our study, and 29.3% of patients achieved stable disease (SD). Median PFS was 5.4 months (95% CI: 4.8415.959). The treatment-emergent adverse events (TEAEs) with fruquintinib were acceptable with grade 3 TEAEs of 6%. The grade 3 TEAEs were handfoot skin reaction (HFSR), fatigue, and stomatitis. The ECOG performance status was associated with PFS. In this real-world study, the clinical activity of fruquintinib was consistent with what has been reported in previous clinical trials. The level of safety was acceptable, and the side effects were manageable.
| S-EPMC9110705 | biostudies-literature
Project description:BackgroundTreatment toxicity and disease-related symptoms of metastatic colorectal cancer (mCRC) can adversely affect quality of life (QoL). Maintaining QoL is an important treatment goal alongside improving survival outcomes. Quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) measures the quality of patients' survival by assessing the proportion of survival time that is free of symptoms/toxicity. The phase III FRESCO-2 study met its primary endpoint, demonstrating improved overall survival with fruquintinib plus best supportive care (BSC) versus placebo plus BSC [hazard ratio 0.66, 95% confidence interval (CI) 0.55-0.80, P < 0.001]. This post hoc Q-TWiST analysis compared the benefit-risk of fruquintinib versus placebo in all patients randomized in FRESCO-2.MethodsPatients with refractory mCRC in the USA, Europe, Japan, and Australia were randomized to receive fruquintinib (n = 461) or placebo (n = 230) plus BSC until disease progression or unacceptable toxicity. Patients' survival time was partitioned as follows: time from randomization with grade 3/4 treatment-emergent adverse events (TEAEs) before progression (TOX); time from randomization to progression without grade 3/4 TEAEs (TWiST); and time from progression to death/censoring (REL). Q-TWiST was calculated as the combined utility-weighted mean durations of each health state, assuming utility coefficients of 1 for TWiST and 0.5 for TOX and REL.ResultsQ-TWiST was improved when fruquintinib (versus placebo) was added to BSC, with a between-treatment difference of 2.0 months (95% CI 1.5-2.6 months, P < 0.05) and a relative improvement of 31.4%. This effect was primarily driven by the difference in the TWiST component [mean difference 2.1 months (95% CI 1.8-2.5 months), P < 0.05]. Q-TWiST improvements were consistent in all subgroups, including by age, sex, liver metastases, and primary tumor site. The subgroup and sensitivity analysis results confirmed the robustness of the primary analysis findings.ConclusionsFruquintinib provides a clinically meaningful quality-adjusted survival benefit versus placebo in refractory mCRC.
| S-EPMC11904580 | biostudies-literature
Project description:BackgroundPlatinum-based chemotherapy is the standard first-line treatment for recurrent/metastatic nasopharyngeal carcinoma (NPC); however, there is no standard regimen for those who failed first-line treatment. This study aimed to evaluate the efficacy and safety of apatinib in treating patients with recurrent/metastatic NPC who failed prior platinum-based chemotherapy.MethodsPatients aged 18-65 years with recurrent/metastatic NPC were treated with apatinib at an initial dose of 500 mg once daily and continued until disease progression, patient withdrawal, or unacceptable toxic effects. The primary endpoints were clinical benefit rate (CBR) and toxicity. Secondary endpoints included progression-free survival (PFS) and overall survival (OS).ResultsNineteen patients were enrolled in this study. At the final follow-up, the CBR was 52.6% (95% CI: 29.8-76.2%) in the intention-to-treat population. The median PFS and OS were 3.7 (95% CI: 0.6-6.8) months and 12.9 (95% CI: 9.3-16.5) months, respectively. The most common grade 3-4 adverse events (AEs) were hand-foot syndrome [3 (15.8%)], neutropenia [2 (10.5%)], proteinuria [2 (10.5%)], oral mucosal pain [2 (10.5%)], hypertension [1 (5.3%)], hyponatremia [1 (5.3%)], artery dissection [1 (5.3%)], and nasopharyngeal hemorrhage [1 (5.3%)]. A serious AEs was reported in one patient who died of nasopharyngeal hemorrhage. Treatment with apatinib did not significantly influence patient-reported quality-of-life, except for nausea/vomiting and pain (P<0.05).ConclusionsApatinib achieved modest disease control with acceptable toxicity in recurrent/metastatic NPC patients pretreated with platinum-based chemotherapy.
| S-EPMC8799112 | biostudies-literature
Project description:BackgroundFruquintinib has been approved by the Food and Drug Administration for refractory metastatic colorectal cancer (mCRC). In clinical practice, fruquintinib is sometimes used in combination with other drugs, but its efficacy and safety are still unknown. In this study, we present a comprehensive analysis of the real-world treatment modalities involving fruquintinib in late-line settings for mCRC across six centers in China.Patients and methodsPatients with refractory mCRC who received fruquintinib treatment in six centers in China between 1 January 2021 and 31 June 2022 were included in this study. Patients were categorized into two cohorts: the monotherapy group (treated solely with fruquintinib) and the combined group (received fruquintinib combined with chemotherapy and/or anti-programmed cell death protein 1 antibodies). Demographic, clinical, survival, and safety data were retrospectively analyzed. The study was registered at clinicaltrials.gov as NCT06202417.ResultsA total of 520 patients were included in this study. The median follow-up time was 9.7 months. The disease control rate was 64.8%. The median progression-free survival was 5.0 months and the median overall survival was 11.4 months. Of them, 387 (74.4%) were treated with fruquintinib alone, while 133 (25.6%) were administered fruquintinib plus chemotherapy and/or anti-programmed cell death protein 1 antibodies, respectively. Adverse events were reported by 91.3% (457/520) of patients. The rate of grade 3 or 4 toxicity was 42.4% (237/520). No treatment-related death occurred.ConclusionFruquintinib, either as a standalone treatment or in combination with other medications, demonstrates substantial efficacy and favorable tolerability in refractory mCRC patients.
| S-EPMC11693424 | biostudies-literature
Project description:ImportancePatients with metastatic colorectal cancer (CRC) have limited effective and tolerable treatment options.ObjectiveTo evaluate the efficacy and safety of oral fruquintinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, as third-line or later therapy in patients with metastatic CRC.Design, setting, and participantsFRESCO (Fruquintinib Efficacy and Safety in 3+ Line Colorectal Cancer Patients) was a randomized, double-blind, placebo-controlled, multicenter (28 hospitals in China), phase 3 clinical trial. From December 2014 to May 2016, screening took place among 519 patients aged 18 to 75 years who had metastatic CRC that progressed after at least 2 lines of chemotherapy but had not received VEGFR inhibitor therapy; 416 met the eligibility criteria and were stratified by prior anti-VEGF therapy and K-ras status. The final date of follow-up was January 17, 2017.InterventionsPatients were randomized in a 2:1 ratio to receive either fruquintinib, 5 mg (n = 278) or placebo (n = 138) orally, once daily for 21 days, followed by 7 days off in 28-day cycles, until disease progression, intolerable toxicity, or study withdrawal.Main outcomes and measuresThe primary end point was overall survival. Key secondary efficacy endpoints were progression-free survival (time from randomization to disease progression or death), objective response rate (confirmed complete or partial response), and disease control rate (complete or partial response, or stable disease recorded ≥8 weeks postrandomization). Duration of response was also assessed. Safety outcomes included treatment-emergent adverse events.ResultsOf the 416 randomized patients (mean age, 54.6 years; 161 [38.7%] women), 404 (97.1%) completed the trial. Median overall survival was significantly prolonged with fruquintinib compared with placebo (9.3 months [95% CI, 8.2-10.5] vs 6.6 months [95% CI, 5.9-8.1]); hazard ratio (HR) for death, 0.65 (95% CI, 0.51-0.83; P < .001). Median progression-free survival was also significantly increased with fruquintinib (3.7 months [95% CI, 3.7-4.6] vs 1.8 months [95% CI, 1.8-1.8] months); HR for progression or death, 0.26 (95% CI, 0.21 to 0.34; P < .001). Grades 3 and 4 treatment-emergent adverse events occurred in 61.2% (170) of patients who received fruquintinib and 19.7% (27) who received placebo. Serious adverse events were reported by 15.5% (43) of patients in the fruquintinib group and 5.8% (8) in the placebo group, with 14.4% (40) of fruquintinib-treated and 5.1% (7) of placebo-treated patients requiring hospitalization.Conclusions and relevanceAmong Chinese patients with metastatic CRC who had tumor progression following at least 2 prior chemotherapy regimens, oral fruquintinib compared with placebo resulted in a statistically significant increase in overall survival. Further research is needed to assess efficacy outside of China.Trial registrationClinicalTrials.gov Identifier: NCT02314819.
| S-EPMC6583690 | biostudies-literature