Hype and hope of hepatic arterial infusion for colorectal cancer.
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ABSTRACT:
SUBMITTER: Ghiringhelli F
PROVIDER: S-EPMC8050592 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundHepatic arterial infusion (HAI) of chemotherapy is an option for the treatment of patients with liver metastases from colorectal cancer (LMCRC). Though HAI with oxaliplatin (HAI-Ox) is generally used, intravenous (IV) 5-fluoro-uracil (5FU)-oxaliplatin-irinotecan HAI (HAI-Folfirinox) is feasible and leads to curative-intent surgery in 30% of pretreated patients. We compared the efficacy and safety of HAI-Ox and HAI-Folfirinox.MethodsPatients who underwent HAI chemotherapy for LMCRC were retrospectively included from 2008 to 2019 from six French expert centers.ResultsData were collected from 273 previously treated patients with LMCRC. Patients received HAI-Folfirinox (n = 52) or HAI-Ox (n = 221) combined with IV chemotherapy. The objective response rate (ORR) was 43.2% in patients with HAI-Folfirinox and 45.9% (ns) in patients with HAI-Ox. Median overall survival (OS) was 17 months (95% CI: 15-32.3) with HAI-Folfirinox and 26.2 months (95% CI: 19.4-34.4; p = 0.1) with HAI-Ox. Median progression-free survival (PFS) was 7.9 months (95% CI: 4.9-10.3) with HAI-Folfirinox and 6.4 months (95% CI: 6.0-7.7; p = 0.6) with HAI-Ox. The secondary liver resection rate was 35.6% with HAI-Folfirinox and 16.7% with HAI-Ox (p = 0.007). Grade 2 and above toxicities were significantly more frequent with HAI-Folfirinox. In the global population, only 2 factors were prognostic for OS in multivariable analyses: liver-only disease [hazard ratio (HR): 0.4; 95% CI 0.20-0.83; p = 0.013] and local complications of the catheter (HR: 3.8; 95% CI 1.6-9.0; p = 0.002).ConclusionHepatic arterial infusion results in high response rates, secondary resections, and long survival in pretreated patients with LMCRC.
| S-EPMC9243466 | biostudies-literature
Project description:BackgroundHepatic arterial infusion chemotherapy delivers the drug directly to the liver. We aim to explore the benefits and tolerability of Hepatic arterial infusion chemotherapy plus regorafenib in advanced colorectal liver metastasis refractory to standard systemic chemotherapy.MethodsThis study analyzed 47 patients treated with hepatic arterial infusion chemotherapy plus regorafenib after standard systemic oxaliplatin and/or irinotecan in combination with bevacizumab or cetuximab between Jan 2017 and Jun 2020. Regorafenib was given for only 3 weeks in a 4-week cycle.ResultsAmong 47 patients, 32 (68%) were males. The median age was 61 (29-75). With a median follow-up of 22.2 months (3.7-50.7 months). Before Hepatic arterial infusion chemotherapy administration in combination with regorafenib, 34 (72.3%) patients previously received ≥ 2 prior lines of systemic therapy and 37 (78.7%)patients previously received targeted biological treatment (anti-VEGF or anti-EGFR, or both). The initial doses of regorafenib were 40 mg/d (n = 1, 2.13%), 80 mg/d (n = 11, 23.43%), 120 mg/d (n = 2, 4.26%), and 160 mg/d (n = 23, 48.94%), while for 24.6% (n = 14) dose was unknown. Median Overall Survival was 22.2 months. Median Progression-Free Survival was 10.8 (95% CI: 9.0-13.7) months. Common Adverse Events were hand-foot skin reaction (12.77%), fatigue (6.38%), vomiting (6.38%), and decreased appetite (6.38%). Only 2 patients discontinued regorafenib due to Adverse Events.ConclusionsRegorafenib combined with Hepatic arterial infusion was effective and tolerable in patients with liver predominant metastasis of colorectal cancer. Hence, this therapy can be considered as an alternative for second- or subsequent lines of therapy in patients refractory to standard systemic chemotherapy.
| S-EPMC9251591 | biostudies-literature
Project description:Probiotic bacteria have been associated with various health benefits and included in overwhelming number of foods. Today, probiotic supplements are consumed with increasing regularity and record a rapidly growing economic value. With billions of heterogeneous populations of probiotics per serving, probiotic supplements contain the largest quantity of probiotics across all functional foods. They often carry antibiotic-resistant determinants that can be transferred to and accumulate in resident bacteria of the gastrointestinal tract and risk their acquisitions by opportunistic pathogens. While the health benefits of probiotics have been widely publicized, this health risk, however, is underrepresented in both scientific studies and public awareness. On the other hand, the human gut presents conditions that are unfavorable for bacteria, including probiotics. It remains uncertain if probiotics from supplements can tolerate acids and bile salts that may undermine their effectiveness in conferring health benefits. Here, we put into perspective the perceived health benefits and the long-term safety of consuming probiotic supplements, specifically bringing intolerance to acids and bile salts, and the long-standing issue of antibiotic-resistant gene transfer into sharp focus. We report that probiotics from supplements examined in this study have poor tolerance to acids and bile salts while also displaying resistance to multiple antibiotics. They could also adapt and gain resistance to streptomycin in vitro. In an environment where consuming supplements is considered a norm, our results and that of others will put in perspective the persisting concerns surrounding probiotic supplements so that the current hype does not overpower the hope.
| S-EPMC7058552 | biostudies-literature
Project description:The antibody molecule is modular and separate domains can be extracted through biochemical or genetic means. It is clear from review of the literature that a wave of novel, antigen-specific molecular forms may soon enter clinical evaluation. This report examines the developmental histories of therapeutics derived from antigen-specific fragments of antibodies produced by recombinant processes. Three general types of fragments were observed, antigen-binding fragments (Fab), single chain variable fragments (scFv) and "third generation" (3G), each representing a successive wave of antibody fragment technology. In parallel, drug developers have explored multi-specificity and conjugation with exogenous functional moieties in all three fragment types. Despite high hopes and an active pipeline, enthusiasm for differentiating performance of fragments should, perhaps, be tempered as there are yet few data that suggest these molecules have distinct clinical properties due only to their size.
| S-EPMC2828581 | biostudies-literature
Project description:The identification of numerous breast cancer antigens has generated increasing enthusiasm for the application of immune-based therapies in breast malignancies. Although the use of monoclonal antibodies has revolutionized the "targeted therapy" of breast cancer, and the immunomodulatory effects of bisphosphonates continue to be evaluated, few studies to date have demonstrated widespread utility for other forms of immunotherapy. The present review assesses modern research and explores whether the hopes for immunotherapy can overcome the hype.
| S-EPMC3031364 | biostudies-literature
Project description:The primary goal to achieve cure in oncology is to reduce recurrence, maximize disease-free survival, maintain function, and optimize quality of life. Surgery remains the mainstay treatment modality in rectal cancer. The current trend is to perform least invasive method of doing complex surgeries while not compromising in the oncological of functional outcomes of patients. Total mesorectal excision (TME) for rectal cancer surgery entails removal of the rectum with its fascia as an intact unit while preserving surrounding vital structures. The procedure is technically challenging because of the narrow and deep pelvic cavity housing the rectum encased by fatty lymph vascular tissue within the perirectal fascia, distally the anal sphincter complex, and an intimate surrounded by vital structures like ureter, vessels, and nerves. Robotic technology enables overcoming these difficulties caused by complex pelvic anatomy. This system can facilitate better preservation of the pelvic autonomic nerve and thereby achieve favorable postoperative sexual and voiding functions after rectal cancer surgery. The nerve-preserving TME technique includes identification and preservation of the superior hypogastric plexus nerve, bilateral hypogastric nerves, pelvic plexus, and neurovascular bundles.
| S-EPMC7714808 | biostudies-literature
Project description:BACKGROUND:Hepatic arterial infusion chemotherapy (HAIC) is frequently used to treat advanced hepatocellular carcinoma (HCC) in Asian countries. However, there is a lack of evidence supporting the use of HAIC. SUMMARY:Many studies report high response rates in patients with advanced HCC receiving HAIC, and clinical responses translate to survival benefits. Therefore, prediction of an antitumor response is important in selecting appropriate treatments. There are no proven post-sorafenib therapeutic measures or procedures for HCC patients with poor liver function, and HAIC is one of the few options for patients in these situations. Despite studies showing its effectiveness, the use of HAIC for treatment of advanced HCC is unclear because convincing data from large-scale randomized clinical trials are lacking. For HAIC to become a standard treatment for HCC, such trials must establish its efficacy compared with other HCC therapies; prediction of antitumor response in HAIC may aid trial design, and a multi-center, open-labelled, randomized clinical trial of HAIC in advanced HCC is currently in progress. Optimization of HCC treatment protocols and regimens is also required. KEY MESSAGE:We think that both HAIC and sorafenib are effective treatments for advanced HCC, and this review presents evidence supporting this contention.
| S-EPMC4608627 | biostudies-literature
Project description: Not available
| S-EPMC557997 | biostudies-literature
Project description:Stem cell-based therapies are emerging as a promising strategy to tackle cancer. Multiple stem cell types have been shown to exhibit inherent tropism towards tumours. Moreover, when engineered to express therapeutic agents, these pathotropic delivery vehicles can effectively target sites of malignancy. This perspective considers the current status of stem cell-based treatments for cancer and provides a rationale for translating the most promising preclinical studies into the clinic.
| S-EPMC4234304 | biostudies-literature
Project description:BackgroundAlthough 80% of patients with metastatic colorectal cancer (CRC) experience liver metastases, only 10-25% undergo resection at the time of diagnosis. Even in initially unresectable conditions, if appropriate treatment is provided, such as surgical conversion through a combination of hepatic arterial infusion (HAI) chemotherapy and systemic chemotherapy (sys-CT), better overall survival can be expected. Therefore, this study aims to evaluate the efficacy of HAI oxaliplatin in combination with sys-CT plus targeted therapy in patients with unresectable CRC with liver-only metastasis.MethodsThis is a single-center, randomized, open-label phase II trial (NCT05103020). Patients with untreated CRC, who have liver-only metastases and for whom liver resection is potentially possible but deemed infeasible at the time of initial diagnosis by a multidisciplinary team, will be eligible. Patients will be randomly assigned in a 1:1 ratio to either the combined HAI oxaliplatin and modified systemic 5-fluorouracil, folinic acid, and irinotecan (FOLFIRI) plus targeted therapy group or the systemic FOLFIRI plus targeted therapy group. Both regimens will be repeated every 2 weeks for a total of 12 cycles. The primary objective of this study is to compare the rate of conversion to liver resection. The surgical conversion rate is expected to increase by 25% with HAI oxaliplatin in combination with sys-CT plus targeted therapy (40% in the experimental arm versus 15% in the control arm) (power, 80%; two-sided alpha-risk, 5%). The secondary objectives include overall survival, progression-free survival, and objective response rate.DiscussionThis is the first randomized controlled trial to investigate the efficacy of HAI oxaliplatin in combination with sys-CT plus targeted therapy as first-line treatment from the initial diagnosis in patients with unresectable CRC with liver-only metastasis, aiming to significantly increase the surgical conversion rate.Trial registrationClinicalTrials.gov, (NCT05103020). Trial registration date: November 2, 2021.
| S-EPMC10363309 | biostudies-literature