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BMJ Case Reports Feb 2022Oxaliplatin is a chemotherapeutic agent used in a variety of malignancies such as colorectal cancer and pancreatic cancer. It is a platinum derivative that results in...
Oxaliplatin is a chemotherapeutic agent used in a variety of malignancies such as colorectal cancer and pancreatic cancer. It is a platinum derivative that results in direct cell cytotoxicity with resultant cell death. The most common side effects often noted are neurotoxicity, nausea, vomiting, diarrhoea, hepatotoxicity and myelosuppression. Oxaliplatin induced digital ischaemia and necrosis is a rare side effect that was observed in our patient. In general, digital ischaemia is a rare vascular disorder that is often associated with autoimmune disease. A patient with digital ischaemia due to oxaliplatin will be described in this case report.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Humans; Ischemia; Necrosis; Organoplatinum Compounds; Oxaliplatin
PubMed: 35131793
DOI: 10.1136/bcr-2021-247333 -
BMC Cancer Apr 2018Although acute oxaliplatin-induced neuropathy (OXIPN) is frequently regarded to be transient, recent studies have reported prolongation of infusion times, dose reduction... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although acute oxaliplatin-induced neuropathy (OXIPN) is frequently regarded to be transient, recent studies have reported prolongation of infusion times, dose reduction and treatment cessation following the first dose of oxaliplatin in quarter of patients. Acute OXIPN is also a well-established risk factor for chronic neuropathy. However, there is underreporting of these parameters during the acute phase (≤ 14 days). This paper systematically reviews the incidence of acute OXIPN and its impact on treatment in the first cycle.
METHODS
A systematic literature search was performed using PubMed and Medline. Published original articles were included if they described details about prevalence of oxaliplatin-induced acute neuropathy.
RESULTS
Fourteen studies, comprised of 6211 patients were evaluated. The majority of patients were treated with oxaliplatin in combination with leucovorin and fluorouracil (FOLFOX). Most studies used the National Cancer Institute Common Toxicity Criteria to assess acute neuropathy. Acute neuropathy (Grades 1-4) was the most common event with prevalence ranging from 4-98%, followed by haematological (1.4-81%) and gastrointestinal (1.2-67%) toxicities, respectively. Drug regimens, starting dose of oxaliplatin and neuropathy assessment tools varied across studies. In addition, moderate to severe toxicities were common in patients that received a large dose of oxaliplatin (> 85 mg/m) and/ or combined drugs. The majority of studies did not report the factors affecting acute neuropathy namely the range (minimal) doses required to evoke acute neuropathy, patient and clinical risk factors. In addition, there was no systematic reporting of the number of patients subjected to prolonged infusion, dose reduction, treatment delay and treatment cessation during the acute phase.
CONCLUSION
Despite the heterogeneity of studies regarding oxaliplatin starting dose, drug regimen, neuropathy assessment tools and study design, a large number of patients developed acute neuropathy. To develop a better preventive and therapeutic guideline for acute/chronic neuropathy, a prospective study should be conducted in a large cohort of patients in relation to drug regimen, starting/ranges (minimal) of doses producing acute neuropathy, treatment compliance, patient and clinical risk factors using a standardised neuropathy assessment tool.
Topics: Acute Disease; Antineoplastic Agents; Blood Physiological Phenomena; Gastrointestinal Tract; Humans; Incidence; Oxaliplatin; Peripheral Nervous System Diseases
PubMed: 29649985
DOI: 10.1186/s12885-018-4185-0 -
Frontiers in Immunology 2022Currently, there has been no direct comparison between programmed cell death protein 1 (PD-1) inhibitors plus different chemotherapy regimens in first-line treatments... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Currently, there has been no direct comparison between programmed cell death protein 1 (PD-1) inhibitors plus different chemotherapy regimens in first-line treatments for advanced gastric cancer (AGC). This study performed a network meta-analysis (NMA) to evaluate the efficacy and safety of PD-1 inhibitors plus oxaliplatin- or cisplatin-based chemotherapy.
METHODS
PubMed, Embase, and the Cochrane Central Register were used to seek a series of phase III randomized controlled trials (RCTs) studying on first-line PD-1 inhibitors plus chemotherapy and phase III RCTs comparing first-line oxaliplatin and cisplatin-based chemotherapy for AGC to perform NMA. The main outcome was overall survival (OS) and other outcomes included progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAEs).
RESULTS
Eight eligible RCTs involving 5723 patients were included. Compared with PD-1 inhibitors plus cisplatin-based chemotherapy, PD-1 inhibitors plus oxaliplatin-based chemotherapy could prolong the OS without statistical significance (hazard ratio [HR]: 0.82, 95% credible interval [CI]: 0.63-1.06). However, for patients with combined positive score (CPS) ≥ 1, PD-1 inhibitors plus oxaliplatin-based chemotherapy significantly prolonged the OS (HR: 0.75, 95% CI: 0.57-0.99). PFS in PD-1 inhibitors plus oxaliplatin-based chemotherapy was significantly longer than that in PD-1 inhibitors plus cisplatin-based chemotherapy (HR: 0.72, 95% CI: 0.53-0.99). Regarding safety, the incidence of ≥ 3 TRAEs was similar between PD-1 inhibitors plus oxaliplatin-based chemotherapy and PD-1 inhibitors plus cisplatin-based chemotherapy (RR: 0.86, 95% CI: 0.66-1.12). The surface under the cumulative ranking area curve (SUCRA) indicated that PD-1 inhibitors plus oxaliplatin-based chemotherapy ranked first for OS (97.7%), PFS (99.3%), and ORR (89.0%). For oxaliplatin-based regimens, there was no significant difference between nivolumab plus oxaliplatin-based chemotherapy and sintilimab plus oxaliplatin-based chemotherapy in terms of OS, PFS, ORR, and ≥3 TRAEs.
CONCLUSION
Compared with PD-1 inhibitors plus cisplatin-based chemotherapy, PD-1 inhibitors plus oxaliplatin-based chemotherapy significantly prolonged PFS. Considering both efficacy and safety, PD-1 inhibitors plus oxaliplatin-based chemotherapy might be a better option in the first-line treatment for AGC.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Humans; Immune Checkpoint Inhibitors; Network Meta-Analysis; Oxaliplatin; Stomach Neoplasms
PubMed: 36003374
DOI: 10.3389/fimmu.2022.905651 -
Cells Feb 2022Colorectal cancer is the second most common cancer in women, the third in men, and an important cause of cancer-related mortality. Recurrence and the development of...
Colorectal cancer is the second most common cancer in women, the third in men, and an important cause of cancer-related mortality. Recurrence and the development of chemotherapy resistance are major hindrances for patients' treatment. The presence of cancer stem cells with chemotherapy resistance able to generate proliferating tumor cells contributes to tumor recurrence and resistance. In addition, tumor cells can develop chemoresistance through adaptation mechanisms. In this article, cancer stem cells were isolated from HT29 and SW620 colorectal cancer cell lines. Oxaliplatin resistance was induced by a single drug treatment simulating the usual guidelines of patient treatment. A comparison of these two populations showed similarities since cancer stem cells presented increased oxaliplatin resistance, and resistant cells contained an increased number of cancer stem cells. Cancer stem cells isolated from resistant cells showed increased oxaliplatin resistance. Cell invasion capacity and epithelial-mesenchymal transition were increased both in cancer stem cells and oxaliplatin-resistant cells. mRNA expression analysis showed that both cell types shared a significant proportion of commonly regulated genes. In summary, the data presented indicate that colorectal cancer stem cells and oxaliplatin-resistant cells are highly related cell populations that might have interesting implications in the development of tumor recurrence and resistance to chemotherapy.
Topics: Colorectal Neoplasms; Drug Resistance, Neoplasm; Female; Humans; Male; Neoplasm Recurrence, Local; Neoplastic Stem Cells; Oxaliplatin
PubMed: 35159320
DOI: 10.3390/cells11030511 -
World Journal of Surgical Oncology Jun 2021The prognosis of pancreatic cancer (PC) is extremely poor, and most patients with metastatic PC still receive palliative care. Here, we report the efficacy and safety of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The prognosis of pancreatic cancer (PC) is extremely poor, and most patients with metastatic PC still receive palliative care. Here, we report the efficacy and safety of FOLFIRINOX (oxaliplatin, irinotecan, leucovorin, 5-fluorouracil) in the treatment of metastatic PC.
METHODS
We searched PubMed, Web of Science, EBSCO, and Cochrane library databases for articles that described efficacy and safety of FOLFIRINOX in patients with metastatic PC, from January 1996 to July 2020. The primary outcomes targeted included overall survival (OS) and progression-free survival (PFS).
RESULTS
We found that FOLFIRINOX could directly improve OS rate of patients with metastatic PC (HR 0.76, 95% Cl 0.67-0.86, p<0.001) but had no benefit on PFS. Results from subgroup analyses showed that FOLFIRINOX had superior benefits than monochemotherapy (HR 0.59, 95% Cl 0.52-0.67, p<0.001), followed by FOLFIRINOX versus combination chemotherapy (HR 0.76, 95% Cl 0.61-0.95, p<0.001). The result of FOLFIRINOX versus nab-paclitaxel + gemcitabine had no benefit (HR 0.91, 95% Cl 0.82-1.02, p>0.05). The main adverse events (AEs) targeted hematological toxicity and the gastrointestinal system, and included febrile neutropenia, a reduction in white blood cells and appetite, as well as diarrhea.
CONCLUSION
These findings indicated that FOLFIRINOX has potential benefits for the prognosis of patients with metastatic PC. Furthermore, there is no difference between the regimen of FOLFIRINOX and nab-paclitaxel + gemcitabine in this study. The application of FOLFIRINOX should be according to the actual situation of the patients and the experience of the doctors.
Topics: Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Irinotecan; Leucovorin; Oxaliplatin; Pancreatic Neoplasms; Prognosis
PubMed: 34154596
DOI: 10.1186/s12957-021-02291-6 -
International Journal of Clinical... Nov 2022Sinusoidal obstruction syndrome (SOS) refers to liver injury caused by hematopoietic stem cell transplantation (HSCT) and anticancer drugs including oxaliplatin.... (Observational Study)
Observational Study
BACKGROUND
Sinusoidal obstruction syndrome (SOS) refers to liver injury caused by hematopoietic stem cell transplantation (HSCT) and anticancer drugs including oxaliplatin. Increased splenic volume (SV) on computed tomography (CT) indicates oxaliplatin-induced SOS. Similarly, ultrasonography and liver stiffness measurement (LSM) by shear-wave elastography (SWE) can help diagnose SOS after HSCT; however, their usefulness for diagnosing oxaliplatin-induced SOS remains unclear. We investigated the usefulness of the Hokkaido ultrasonography-based scoring system with 10 ultrasonographic parameters (HokUS-10) and SWE in diagnosing oxaliplatin-induced SOS early.
METHODS
In this prospective observational study, ultrasonography and SWE were performed before and at 2, 4, and 6 months after oxaliplatin-based chemotherapy. HokUS-10 was used for assessment. CT volumetry of the SV was performed in clinical practice, and an SV increase ≥ 30% was considered the diagnostic indicator of oxaliplatin-induced SOS. We assessed whether HokUS-10 and SWE can lead to an early detection of oxaliplatin-induced SOS before an increased SV on CT.
RESULTS
Of the 30 enrolled patients with gastrointestinal cancers, 12 (40.0%) with an SV increase ≥ 30% on CT were diagnosed with SOS. The HokUS-10 score was not correlated with an SV increase ≥ 30% (r = 0.18). The change in rate of three HokUS-10 parameters were correlated with an SV increase ≥ 30% (r = 0.32-0.41). The change in rate of LSM by SWE was correlated with an SV increase ≥ 30% (r = 0.40).
CONCLUSIONS
The usefulness of HokUS-10 score was not demonstrated; however, some HokUS-10 parameters and SWE could be useful for the early diagnosis of oxaliplatin-induced SOS.
Topics: Humans; Hepatic Veno-Occlusive Disease; Oxaliplatin; Elasticity Imaging Techniques; Ultrasonography; Antineoplastic Agents
PubMed: 36042137
DOI: 10.1007/s10147-022-02235-4 -
Computational Intelligence and... 2022The aim of this study was to determine how gemcitabine, oxaliplatin combination, and apatinib affect immune function and SIL-2R and sicAM-1 levels in patients with... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The aim of this study was to determine how gemcitabine, oxaliplatin combination, and apatinib affect immune function and SIL-2R and sicAM-1 levels in patients with gallbladder cancer.
METHODS
Retrospective analysis of 116 patients with gallbladder cancer treated at our institution between February 2019 and February 2021. The patients were randomly divided into control and study groups, with 58 patients in each group. The study group received the combination of apatinib and the control group received gemcitabine and oxaliplatin. Immune function, serum tumor markers, short-term efficacy, survival measures, and incidence of adverse events were monitored and compared between the two groups.
RESULTS
CD3+, CD4+, CD4+/CD8+, and NK levels were significantly higher in both groups after treatment, while CD8+ levels were significantly lower; levels of sicAM-1, sicAM-1 (VEGF), and CEA were greatly reduced in both groups after treatment; there were significant differences between the study and control groups in terms of rr46.55% and DCR84.48%; at one year after treatment, the survival rate in the study group increased from 67.24% in the control group to 79.31%, with an increase in both PFs and 0S. Compared with the control group, the incidence of hypertension and myelosuppression, neutropenia, proteinuria, and hand-foot syndrome were lower in the study group ( < 0.05). All differences were statistically significant.
CONCLUSION
In the treatment of gallbladder cancer, the use of gemcitabine and oxaliplatin combined with apatinib can effectively control the progression of patients' disease.
Topics: Deoxycytidine; Gallbladder Neoplasms; Humans; Immunity; Oxaliplatin; Pyridines; Retrospective Studies; Gemcitabine
PubMed: 36059420
DOI: 10.1155/2022/4959840 -
Cell Death & Disease Jul 2022Chemoresistance remains the primary challenge of clinical treatment of gastric cancer (GC), making the biomarkers of chemoresistance crucial for treatment decision. Our...
Chemoresistance remains the primary challenge of clinical treatment of gastric cancer (GC), making the biomarkers of chemoresistance crucial for treatment decision. Our previous study has reported that p21-actived kinase 6 (PAK6) is a prognostic factor for selecting which patients with GC are resistant to 5-fluorouracil/oxaliplatin chemotherapy. However, the mechanistic role of PAK6 in chemosensitivity remains unknown. The present study identified PAK6 as an important modulator of the DNA damage response (DDR) and chemosensitivity in GC. Analysis of specimens from patients revealed significant associations between the expression of PAK6 and poorer stages, deeper invasion, more lymph node metastases, higher recurrence rates, and resistance to oxaliplatin. Cells exhibited chemosensitivity to oxaliplatin after knockdown of PAK6, but showed more resistant to oxaliplatin when overexpressing PAK6. Functionally, PAK6 mediates cancer chemoresistance by enhancing homologous recombination (HR) to facilitate the DNA double-strand break repair. Mechanistically, PAK6 moves into nucleus to promote the activation of ATR, thereby further activating downstream repair protein CHK1 and recruiting RAD51 from cytoplasm to the DNA damaged site to repair the broken DNA in GC. Activation of ATR is the necessary step for PAK6 mediated HR repair to protect GC cells from oxaliplatin-induced apoptosis, and ATR inhibitor (AZD6738) could block the PAK6-mediated HR repair, thereby reversing the resistance to oxaliplatin and even promoting the sensitivity to oxaliplatin regardless of high expression of PAK6. In conclusion, these findings indicate a novel regulatory mechanism of PAK6 in modulating the DDR and chemoresistance in GC and provide a reversal suggestion in clinical decision.
Topics: Ataxia Telangiectasia Mutated Proteins; Cell Line, Tumor; Drug Resistance, Neoplasm; Fluorouracil; Homologous Recombination; Humans; Oxaliplatin; Stomach Neoplasms; p21-Activated Kinases
PubMed: 35902562
DOI: 10.1038/s41419-022-05118-8 -
International Journal of Molecular... Feb 2022Next to breast cancer, advanced stage metastatic colon cancer represents a major cause for mortality in women. Germline or somatic mutations in tumor suppressor genes or... (Review)
Review
BACKGROUND
Next to breast cancer, advanced stage metastatic colon cancer represents a major cause for mortality in women. Germline or somatic mutations in tumor suppressor genes or in DNA mismatch repair genes represent risk factors for genetic predisposition of colon cancer that are also detectable in sporadic colon cancer. Conventional chemotherapy for colon cancer includes combination of 5-fluoro-uracil with oxaliplatin and irinotecan or targeted therapy with non-steroid anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors. Major limitations of these therapeutic interventions are associated with systemic toxicity, acquired tumor resistance and the emergence of drug resistant stem cells that favor initiation, progression and metastasis of therapy-resistant disease. These limitations emphasize an unmet need to identify tumor stem cell selective testable alternatives. Drug-resistant stem cell models facilitate the identification of new testable alternatives from natural phytochemicals and herbal formulations. The goal of this review is to provide an overview relevant to the current status of conventional/targeted therapy, the role of cancer stem cells and the status of testable alternatives for therapy-resistant colon cancer. Experimental models: Hyper-proliferative and tumorigenic cell lines from genetically predisposed colonic tissues of female mice represent experimental models. Chemotherapeutic agents select drug-resistant phenotypes that exhibit upregulated expressions of cellular and molecular stem cell markers. Mechanistically distinct natural phytochemicals effectively inhibit stem cell growth and downregulate the expressions of stem cell markers.
CONCLUSIONS
The present review discusses the status of colon cancer therapy and inherent limitations, cancer stem cell biology, potential lead compounds and their advantages over chemotherapy. The present experimental approaches will facilitate the identification of pharmacological and naturally-occurring agents as lead compounds for stem cell targeted therapy of colon cancer.
Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Colonic Neoplasms; Drug Resistance, Neoplasm; Female; Humans; Mice; Neoplastic Stem Cells; Oxaliplatin
PubMed: 35269660
DOI: 10.3390/ijms23052519 -
Cancer Science Dec 2023Dual-specificity tyrosine-regulated kinase 2 (DYRK2) is a protein kinase that phosphorylates p53-Ser46 and induces apoptosis in response to DNA damage. However, the...
Dual-specificity tyrosine-regulated kinase 2 (DYRK2) is a protein kinase that phosphorylates p53-Ser46 and induces apoptosis in response to DNA damage. However, the relationship between DYRK2 expression and chemosensitivity after DNA damage in colorectal cancer has not been well investigated. The aim of the present study was to examine whether DYRK2 could be a novel marker for predicting chemosensitivity after 5-fluorouracil- and oxaliplatin-induced DNA damage in colorectal cancer. Here we showed that DYRK2 knockout decreased the chemosensitivity to 5-fluorouracil and oxaliplatin in p53 wild-type colorectal cancer cells, whereas the chemosensitivity remained unchanged in p53-deficient/mutated colorectal cancer cells. In addition, no significant differences in chemosensitivity to 5-fluorouracil and oxaliplatin between scramble and siDYRK2 p53(-/-) colorectal cancer cells were observed. Conversely, the combination of adenovirus-mediated overexpression of DYRK2 with 5-fluorouracil or oxaliplatin enhanced apoptosis and chemosensitivity through p53-Ser46 phosphorylation in p53 wild-type colorectal cancer cells. Furthermore, DYRK2 knockout decreased chemosensitivity to 5-fluorouracil and oxaliplatin in p53 wild-type xenograft mouse models. Taken together, these findings demonstrated that DYRK2 expression was associated with chemosensitivity to 5-fluorouracil and oxaliplatin in p53 wild-type colorectal cancer, suggesting the importance of evaluating the p53 status and DYRK2 expression as a novel marker in therapeutic strategies for colorectal cancer.
Topics: Humans; Animals; Mice; Oxaliplatin; Tumor Suppressor Protein p53; Colorectal Neoplasms; Apoptosis; Fluorouracil; DNA Damage
PubMed: 37776195
DOI: 10.1111/cas.15973