Oxaliplatin-associated shock in stage III colorectal cancer patients: real-world evidence in Taiwan.

Background: Oxaliplatin-associated shock (referred to as shock) is a rare but life-threatening adverse event. Objectives: This pioneering cohort study aimed to quantitatively investigate the association between oxaliplatin use and shock in patients with stage III colorectal cancer (CRC), identify potential independent risk factors for shock, and assess the cycle-to-shock during oxaliplatin treatment. Design: The study utilized a nested case-control (NCC) design to assess the association between oxaliplatin and shock and employed a case-crossover approach to address unmeasured confounders. Methods: All newly diagnosed stage III CRC patients were identified from the CRC Health Database (2012-2016). Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CIs) for oxaliplatin's link to shock incidence. Results: Among 6932 oxaliplatin recipients, 331 suffered shock. In all, 3309 controls were selected via risk-set sampling for the shock cases. Oxaliplatin use is associated with a doubled risk of shock (adjusted OR: 2.08, 95% CI: 1.23-3.52). Two independent risk factors were male sex (adjusted OR: 1.33, 95% CI: 1.05-1.69) and heart diseases (adjusted OR: 1.65, 95% CI: 1.17-2.32). The case-crossover analysis revealed a more than fourfold risk (OR: 4.4, 95% CI: 1.67-11.62). In total, 22 of 331 shock cases were exposed to oxaliplatin within 2 days of shock onset, with a median cycle-to-shock time at the seventh cycle. Conclusion: Oxaliplatin use significantly increased shock risk in stage III CRC patients. Male sex and heart disease are two independent risk factors.

This pioneering study identified potential independent risk factors and the cycle-to-shock of oxaliplatin-associated shock which is a rare but life-threatening adverse event Why was the study done? Oxaliplatin-induced anaphylactic shock (referred to as shock) is a rare but life-threatening adverse event which is a harmful and undesirable experience associated with medical care in a patient. What did the researchers do? This pioneering cohort study aimed to quantitatively investigate the association between oxaliplatin use and shock in patients with stage III colorectal cancer (CRC), identify potential independent risk factors for shock and assess the cycle-to-shock during oxaliplatin treatment. All newly diagnosed stage III CRC patients were identified from the CRC Health Database (2012­2016). The study utilized a nested case-control (NCC) design to assess the association between oxaliplatin and shock and employed a case-crossover approach to address unmeasured confounders. Conditional logistic regression was used to quantify the association between oxaliplatin and shock incidence. What did the researchers find? Among 6,932 oxaliplatin recipients, 331 suffered shock. 3,309 controls were selected via risk-set sampling for the shock cases. Oxaliplatin use is associated with a doubled risk of shock. Independent risk factors were male sex and heart diseases. The risk of shock was 33% higher for males and 65% higher for people with heart diseases compared to females and those without heart diseases. The case-crossover analysis revealed a more than four-fold risk of shock of oxaliplatin. Twenty-two of 331 shock cases were exposed to oxaliplatin within two days before the shock onset. The median cycle-to-shock time is at the seventh cycle. What do the findings mean? Oxaliplatin use significantly increased shock risk in stage III CRC patients. Male sex and having heart diseases are two independent risk factors.

Survival outcomes of beta-blocker usage in HER2-positive advanced breast cancer patients: a retrospective cohort study.

Background: Clinical trials investigating the effects of beta-blockers (BBs) on cancer are underway. Evidence from preclinical research suggests that BBs could serve as anticancer agents and immune boosters. There is conflicting evidence regarding the effect of BB use on clinical outcomes in patients with breast cancer. Objectives: The study aimed to determine whether BB use is associated with progression-free survival (PFS) and overall survival (OS) in patients receiving anti-human epidermal growth factor receptor 2 (HER2) treatment for advanced breast cancer. Design: Retrospective hospital-based study. Methods: The participants enrolled were breast cancer patients with advanced HER2-positive status who initiated trastuzumab monotherapy or concomitant therapy with trastuzumab and any dose of BB. The patients were enrolled between January 2012 and May 2021 and divided into three groups based on whether they received a BB or not in the therapeutic regimen: BB-/trastuzumab+, BB+ (non-selective)/trastuzumab+, and BB+ (selective)/trastuzumab+. PFS and OS were the primary and secondary endpoints, respectively. Results: The estimated median PFS in the BB-/trastuzumab+, BB+ (non-selective)/trastuzumab+, and BB+ (selective)/trastuzumab+ groups was 51.93, 21.50, and 20.77 months, respectively. The corresponding OS was 56.70, 29.10, and 27.17 months. The intergroup differences in these durations were significant. Both PFS [adjusted hazard ratio (HR): 2.21, 95% confidence interval (CI): 1.56-3.12; p < 0.001]) and OS (adjusted HR: 2.46, 95% CI: 1.69-3.57; p < 0.001) were worse when BBs were used. Conclusion: Our study provides important evidence that BB use potentially has a negative effect on patients with HER2-positive advanced breast cancer. Nevertheless, despite the study's results, cardiovascular disease (CVD) should be appropriately treated in patients with HER2-positive advanced breast cancer. Other types of drugs can be used to treat CVD, but BB use should be avoided. Large real-world database and prospective studies should be conducted to validate the results of this study.

Use of beta-blockers for cancer therapy Summary: Background • Evidence from preclinical research suggests that beta-blockers (BBs) could serve as anticancer agents and immune boosters. • Beta-blockers could therefore be a potential therapy for cancers. • Trastuzumab is a drug that affects the overall survival (OS) and progression-free survival (PFS) of patients with HER2-positive breast cancer by binding to the extracellular domain of HER2. • This study investigates the effect of BBs on trastuzumab therapy in patients with advanced breast cancer. Method • This retrospective study was conducted between January 2012 and May 2021. • Patients with HER2-positive advanced breast cancer who were treated using trastuzumab monotherapy or trastuzumab concomitantly with any dose of a BB were recruited and divided into three groups. • One group received only the trastuzumab (BB−/trastuzumab+), another group received both BB+ (non-selective) and trastuzumab [BB+ (non-selective)/trastuzumab+], and the third group received both BB+ (selective) and trastuzumab [BB+ (selective)/trastuzumab+]. • The PFS and OS were determined and compared between the treatment groups. Results • We enrolled 221 patients (mean age: 56.1 ± 11.1 years) in the study. • The estimated median PFS and OS were significantly lower in the BB+ (non-selective)/trastuzumab+ and BB+ (selective)/trastuzumab+ groups than in the BB−/trastuzumab+ group. • The use of BBs was associated with worse PFS and OS in patients with HER2-positive advanced breast cancer. Conclusion • Trastuzumab treatment was independently associated with poorer PFS and OS for patients who used BB prior to initiating trastuzumab therapy for advanced HER2-positive breast cancer. • BB use potentially has a negative effect on patients with HER2-positive advanced breast cancer. • Future studies with larger sample sizes are needed to validate our findings.

Survival Outcomes of Calcium Channel Blocker Therapy in Patients With Non-Small Cell Lung Cancer Treated With Epidermal Growth Factor Receptor Inhibitors: A Retrospective Study.

BACKGROUND: Non-cancer drugs are currently being repurposed for cancer treatment. Mounting evidence highlights the influence of calcium channels on tumorigenesis and progression. Hence, inhibition of calcium signaling may be a promising cancer treatment strategy. OBJECTIVE: In this study, we aimed to examine whether calcium channel blockers (CCBs) affect the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with non-small cell lung cancer (NSCLC). DESIGN: We conducted a retrospective analysis. METHODS: In this study, conducted between January 2009 and June 2021, patients with NSCLC treated with erlotinib, or gefitinib for at least 1 week were enrolled and divided into 2 groups: CCBs-/EGFR-TKIs+ and CCBs+/EGFR-TKIs+, depending on whether they received CCB therapy. Progression-free survival (PFS) and overall survival (OS) were determined as the primary and secondary endpoints, respectively. RESULT: : The estimated median PFS and OS for the CCBs-/EGFR-TKIs+group were 7.70 and 12.17 months, respectively, and they were significantly different from those of the CCBs+/EGFR-TKIs+ group (10.43 and 18.07 months, respectively). CCB use was associated with improved PFS (adjusted hazard ratios [HR] 0.77, 95% confidence interval [CI]: 0.61-0.98; P = .035) and OS (adjusted HR 0.66, 95% CI: 0.51-0.84; P < .001). CONCLUSION: Calcium channels have been implicated in cancer pathogenesis. Our findings revealed the potential additive anticancer effects of CCBs when used concomitantly with EGFR-TKIs. However, study limitations, including the retrospective nature and small number of patients, necessitate large-scale prospective studies on the therapeutic potential of CCB as an adjunctive therapy with EGFR-TKIs in patients with NSCLC.

Clinical impact of tetracyclines and/or proton pump inhibitors on the efficacy of epidermal growth factor receptor inhibitors in non-small cell lung cancer: a retrospective cohort study.

BACKGROUND: This retrospective cohort study examined the impact of tetracyclines (TCs) and proton pump inhibitors (PPIs) alone or in combination on the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with non-small cell lung cancer (NSCLC). METHODS: Patients with NSCLC treated with gefitinib or erlotinib for at least 1 week between January 2009 and October 2021 were enrolled and divided into four groups based on the presence/absence of TC and/or PPI in the therapeutic regimen: TC-/PPI-, TC + /PPI-, TC-/PPI + , TC + /PPI + . Progression-free survival (PFS) and overall survival (OS) were the primary and secondary endpoints, respectively. RESULTS: The estimated median PFS and OS of 347 included patients with NSCLC were 8.57 (95% confidence interval [CI]: 7.66-9.48) months and 13.10 (95% CI: 11.03-15.17) months, respectively. Co-administration of EGFR-TKIs with PPIs decreased the PFS and OS, while that with TCs improved the PFS and OS. However, the concomitant use of EGFR-TKIs, TCs, and PPIs yielded survival rates similar to that of EGFR-TKI therapy alone. CONCLUSIONS: The administration of EGFR-TKIs with other drugs poses a challenge in managing patients with NSCLC. Therefore, reassessing the indications and necessity of TC or PPI therapy is essential for patients receiving erlotinib or gefitinib. The benefits and risks of possible discontinuation due to the clinical relevance of this interaction should be considered.

Cost-effectiveness and clinical outcomes of intermittent/continuous proton pump inhibitors infusion in high bleeding risk of ulcers: A retrospective observational cohort study.

ABSTRACT: The purpose of this study was to evaluate the clinical outcomes, including patient prognosis and medication expense, of proton pump inhibitors administered by high-dose continuous infusion (HDC, 80 mg loading dose, then 8 mg/h for 72 hours) or non-high-dose intermittent infusion (NHDI, 40 mg qd or 40 mg q12 h, for 3 days) regimens in high-risk patients with bleeding peptic ulcers.In this retrospective cohort study, patients with peptic ulcers and endoscopic hemostasis between January, 2013 and December, 2015 were included. The primary endpoints were rebleeding and mortality rates within 7 days. The secondary endpoints were length of stay (LOS), transfusion units of packed red blood cells (PRBCs), and the number needed to treat.A total of 335 patients met the inclusion criteria during the 3-year follow-up period. The cumulative incidence of rebleeding within 7 days was 20.4% and 11.2% in the HDC and NHDI groups, respectively, with a significant difference (P = .021). The mortality rate was 12.1% and 7.3% in the HDC and NHDI groups, respectively, with no significant difference (P = .136). Univariate Cox proportional hazards model analysis showed that the risk of rebleeding within 7 days in the HDC group was higher than that in the NHDI group. The hazard ratio for HDC vs. NHDI was 1.93 (P = .021). There were significant differences in LOS (P = .034) and PRBC units (P = .005) for risk of rebleeding within 7 days, as well as in transfusion units of PRBCs for mortality rate analysis (p < 0.001), between the HDC and NHDI groups. The results showed that the NHDI regimen could reduce the risk of rebleeding within 7 days in 1 of 11 patients (number needed to treat = 11) and could reduce medication cost by US$ 400 to 800.The NHDI regimen showed a lower risk of rebleeding within 7 days, shorter LOS, and fewer PRBC units than that of the HDC regimen. Receiving NHDI has better cost-effective outcomes than that of HDC for patients with high-risk bleeding peptic ulcers.

Real-world prevalence of hepatitis B virus reactivation in cancer patients in Taiwan.

BACKGROUND: Hepatitis B virus carriers who receive systemic cancer chemotherapy have been found to be at a higher risk of hepatitis B virus reactivation. However, lack of standard prophylaxis protocol resulted in life-threatening adverse events. OBJECTIVE: This retrospective study is to investigate prevalence and chemotherapy drug-induced hepatitis B virus reactivation in all types of cancer patients and establish an institutional clinical practice protocol.Methodology: This retrospective cohort study evaluated the incidence of hepatitis B virus infection, the pre-chemotherapy screening rate of hepatitis B surface antigen (HBsAg), and the severity of hepatitis B virus reactivation of cancer patients receiving intravenous chemotherapy between 2013 and 2014. Patients receiving local chemotherapy with intra-cavity instillation, drug- or alcohol-related hepatitis, or chemotherapy for immune diseases were excluded. RESULTS: In total 784 patients, 404 patients (51.53%) underwent hepatitis B virus serum antigen (HBsAg) testing before chemotherapy, and 61 patients (7.78%) tested positive. Only 32 patients (4.08%) received prophylactic hepatitis B virus antiviral therapy. Patients receiving prophylactic antiviral drugs were significantly lower risk of hepatitis B virus reactivation than nonprophylaxis (relative risk, RR: 0.53, number needed to treat, NNT: 12). Moreover, our study found specific single or combined chemotherapy that may cause hepatitis B virus reactivation different from those of other studies conducted in Western countries. The differences may refer to enzymes, proteins and immune response of patients. CONCLUSIONS: Our findings indicate that cancer patients receiving prophylactic antiviral drugs remain at risk of hepatitis B virus reactivation during chemotherapy. Therefore, the hepatitis B virus screen and chemotherapy control system was established in 2017 to reduce the risk of hepatitis B virus reactivation and improve patient safety.

Ganoderma tsugae Induces S Phase Arrest and Apoptosis in Doxorubicin-Resistant Lung Adenocarcinoma H23/0.3 Cells via Modulation of the PI3K/Akt Signaling Pathway.

Ganoderma tsugae (GT) is a traditional Chinese medicine that exhibits significant antitumor activities against many types of cancer. This study investigated the molecular mechanism by which GT suppresses the growth of doxorubicin-resistant lung adenocarcinoma H23/0.3 cells. Our results reveal that GT inhibits the viability of H23/0.3 cells in vitro and in vivo and sensitizes the growth suppression effect of doxorubicin on H23/0.3 cells. The data also show that GT induces S phase arrest by interfering with the protein expression of cyclin A, cyclin E, CDK2, and CDC25A. Furthermore, GT induces cellular apoptosis via induction of a mitochondria/caspase pathway. In addition, we also demonstrate that the suppression of cell proliferation by GT is through down-regulation of the PI3K/Akt signaling pathway. In conclusion, this study suggests that GT may be a useful adjuvant therapeutic agent in the treatment of lung cancer.