Triple-Regimen of Vemurafenib, Irinotecan, and Cetuximab for the Treatment of BRAFV600E-Mutant CRC: A Case Report and Review

Mutation of the BRAF proto-oncogene is found in approximately 10% of colorectal cancers (CRC), with much of the mutation conferred by a V600E mutation. Unlike other CRC subtypes, BRAF-mutant CRC have had relatively limited response to conventional therapies and overall poor survival. We present the case of a 75-year-old man with severe nonischemic cardiomyopathy on a LifeVest who was found to have a transverse colonic mass with widespread hepatic metastatic disease and was subsequently found to have BRAFV600E-mutant CRC (MSI High/dMMR). After a failed therapy with FOLFOX and pembrolizumab, the patient was started on a regimen of vemurafenib, irinotecan, and cetuximab (VIC) based on the SWOG 1406 trial which had shown improved progression-free survival and response rate for the treatment of BRAFV600E-mutant metastatic CRC. After 40 cycles of VIC, the patient attained complete response and is in remission off chemotherapy with significant improvement. This case highlights the effectiveness of the triple-regimen of vemurafenib, irinotecan, and cetuximab as a treatment option for BRAFV600E-mutant CRC, which is a treatment regimen based on the SWOG 1406 trial, and also demonstrates the synergistic role of BRAFV600E inhibitors and EGFR inhibitors in the treatment of BRAFV600E-mutant CRC.

Damage to the musculoskeletal system during eradication therapy of Helicobacter pylori with levofloxacin

Eradication therapy is the mainstay of treatment for H. pylori-associated diseases. A case of the development of tendinitis of the left patellar ligament proper during eradication therapy using a triple regimen with levofoloxacin for 14 days for exacerbation of duodenal ulcer is presented.

Treatment of Interstitial Lung Disease In Anti-MDA5-Positive Dermatomyositis: A Retrospective Study of 87 Patients

Objectives: The prognosis of anti-melanoma differentiation-associated gene (MDA5) antibody-positive dermatomyositis (DM)-interstitial lung disease (ILD) (anti-MDA5 -positive DM-ILD) is often poor, especially in rapidly progressive interstitial lung disease (RPILD). So far there is no established therapy. This study evaluated the efficacy and safety of pharmacological treatments for anti-MDA5-positive DM-ILD. Methods: This retrospective study comprised 87 anti-MDA5-positive DM-ILD patients. We reviewed the clinical characteristics, laboratory findings, lung function treatments, and outcomes of the 87 patients. Cox regression analysis was used to identify predictors of 6-month survival. The association between different combined immunosuppressive regimen and 6-month survival were evaluated.Results: High level of CYFRA21-1 and low PaO2/FiO2 ratio were associated with poor prognosis. Corticosteroid (CS) alone treatment group with higher CYFRA21-1 and lower PaO2/FiO2 ratio showed worse 6-month survival than the combination of CS with immunosuppressants group (p<0.01). In addition, tacrolimus/cyclosporine-treated anti-MDA5-positive DM Non-RPILD exhibited a better survival, comparing with tacrolimus/cyclosporine combined intravenous cyclophosphamide (IVCY)-treated patients (p<0.05). Conclusion: Addition of immunosuppressants to CS, were associated with better 6-month survival in anti-MDA5-positive DM-ILD. The triple regimen (CS, tacrolimus/cyclosporine and IVCY) was not superior to duple one (CS, tacrolimus/cyclosporine) in anti-MDA5-positive DM Non-RPILD.

A 24-Year-Old Female Transplant Recipient with Type 2 Membranoproliferative Glomerulonephritis and Disseminated Shingles: A Cautionary Tale of Deferring to Primary Care

In this report, the case of a 24-year-old Caucasian female with type 2 membranoproliferative glomerulonephritis status post-living donor kidney transplant managed on triple regimen immunosuppressive therapy who developed shingles is discussed. With its onset, she promptly reached out to her nephrologist who deferred her to primary care. Prior to seeing her primary provider, she developed disseminated herpes zoster. She consulted emergency services where she was given inadequate care and again deferred to primary care. One day later, the dissemination included her entire torso, face, oral cavity, and all extremities. Fortunately, the patient had the insight to again reach out to her nephrologist who arranged for her to be admitted for appropriate care 6 days after her initial inquiry that carried 6 days of zoster progression. This case demonstrates how it is pertinent that specialists recognize potentially lethal complications associated with the conditions they follow. Although convenient to defer to primary care, if specialists were to take on the responsibility of providing a broader scope of care for their unique subsets of patients, it would likely result in a reduction in the 80% of serious medical errors that occur as a result of miscommunication, or lack thereof, between care providers.

Palonosetron for Patients Undergoing High or Moderate Emetogenic Chemotherapy

This report identified high to moderate quality evidence from clinical studies and economic evaluations, as well as high-quality guidelines regarding the use of palonosetron in the prevention of chemotherapy-induced nausea and vomiting in adult and pediatric patients receiving different emetogenic chemotherapies. Interpretations of the findings should be taken with caution because of the presence of some identified limitations in both clinical and economic evidence. In adult patients receiving high emetogenic chemotherapy, a fixed antiemetic combination of netupitant and palonosetron (NEPA) plus dexamethasone demonstrated noninferiority relative to a triple regimen of granisetron-aprepitant-dexamethasone. Similarly, palonosetron had similar efficacy compared to granisetron with the co-administration of neurokinin 1 receptor antagonist (e.g., aprepitant or fosaprepitant) and dexamethasone. However, in the absence of aprepitant, a 2-drug combination of palonosetron-dexamethasone appeared to be significantly more effective than granisetron-dexamethasone for the prevention of both acute and delayed emesis. In adult patients receiving moderate emetogenic chemotherapy, palonosetron plus dexamethasone was found to be noninferior compared with ondansetron plus dexamethasone. Similar efficacy was also observed between palonosetron plus dexamethasone and transdermal granisetron plus dexamethasone. In a mixed population of adult patients receiving high or moderate emetogenic chemotherapy, a palonosetron regimen appeared to have greater efficacy than ondansetron for delayed emesis. The efficacy of triple regimen of palonosetron-aprepitant-dexamethasone and granisetron-aprepitant-dexamethasone was comparable at all phases. In pediatric patients receiving high emetogenic chemotherapy, palonosetron plus dexamethasone had similar efficacy compared with ondansetron plus dexamethasone in the acute phase, but was more effective in delayed and overall phases of chemotherapy-induced nausea and vomiting. In a mixed population of pediatric patients receiving high or moderate emetogenic chemotherapy, palonosetron plus dexamethasone was noninferior to ondansetron plus dexamethasone. There were no significant differences between palonosetron and ondansetron or between palonosetron and granisetron treatment regimens in adverse events or quality of life. A cost-utility analysis revealed that NEPA plus dexamethasone was dominant (i.e., cost less, more effective) relative to granisetron-aprepitant-dexamethasone and ondansetron-aprepitant or fosaprepitant-dexamethasone in adult patients receiving high emetogenic chemotherapy. In contrast, double or triple regimens of palonosetron was not cost-effective compared to granisetron regimens, mainly due to large difference in price and small quality-adjusted life-years gained. These economic evaluations may not be applicable to the Canadian context. The identified high-quality guidelines have recommendations on the use of specific antiemetic regimens for adult and pediatric patients receiving high emetogenic chemotherapy or moderate emetogenic chemotherapy and suggest that palonosetron may be offered as an alternative to other 5-hydroxytryptamine-3 receptor antagonists and that 1 5-hydroxytryptamine-3 receptor antagonist is not preferred over another based on the available evidence.

Combinatorial Treatment of Tinzaparin and Chemotherapy Can Induce a Significant Antitumor Effect in Pancreatic Cancer

Pancreatic Cancer (PC) is recognized as a highly thrombogenic tumor; thus, low-molecular-weight heparin (LMWH) such as tinzaparin is routinely used for PC patients. On the basis of combinatorial therapy approaches to treat highly malignant and refractory cancers such as PC, we hypothesized that tinzaparin can augment the effectiveness of traditional chemotherapeutic drugs and induce efficient antitumor activity. PANC-1 and MIAPaCa-2 were incubated alone or in combination with tinzaparin, nab-paclitaxel and gemcitabine. In vivo evaluation of these compounds was performed in a NOD/SCID mouse using a model injected with PANC-1. Tinzaparin enhances the anti-tumor effects of nab-paclitaxel and gemcitabine in mtKRAS PC cell lines via apoptosis in in vitro experiments. The triple combination power acts through the induction of apoptosis, reduction of the proliferative potential and angiogenesis; hence, contributing to a decrease in tumor volume observed in vivo. The triple regimen provided an extra 24.3% tumor reduction compared to the double combination (gemcitabine plus nab-paclitaxel). Combinatorial strategies can create novel therapeutic approaches for the treatment of patients with PC, achieving a better clinical outcome and prolonged survival. Further prospective randomized research is needed and the investigation of various concentrations of tinzaparin above 150 UI/Kg, would potentially provide a valuable synergistic effect to the conventional therapeutic compounds.

Tenofovir disoproxil fumarate and emtricitabine maintenance strategy in virologically controlled adults with low HIV-1 DNA: 48 week results from a randomized, open-label, non-inferiority trial

Objectives Low HIV reservoirs may be associated with viral suppression under a lower number of antiretroviral drugs. We investigated tenofovir disoproxil fumarate/emtricitabine as a maintenance strategy in people living with HIV (PLHIV) with low HIV-DNA. Methods TRULIGHT (NCT02302547) was a multicentre, open-label, randomized trial comparing a simplification to tenofovir disoproxil fumarate/emtricitabine versus a triple regimen continuation (tenofovir disoproxil fumarate/emtricitabine with a third agent, control arm) in virologically suppressed adults with HIV-DNA &lt;2.7 log10 copies/106 PBMCs and no prior virological failure (VF). The primary endpoint (non-inferiority margin 12%) was the percentage of participants with a plasma viral load (pVL) &lt;50 copies/mL in ITT (Snapshot approach) and PP analyses at Week 48 (W48). Results Of the 326 participants screened, 223 (68%) were randomized to the tenofovir disoproxil fumarate/emtricitabine arm (n = 113) or control arm (n = 110). At W48, the tenofovir disoproxil fumarate/emtricitabine and control arms maintained a pVL &lt; 50 copies/mL in 100/113 (88.5%) and 100/110 (90.9%) participants, respectively (ITT difference 2.4%, 95% CI –5.9 to 10.7; PP difference 3.4%, 95% CI –4.2 to 11.0). Six VFs occurred in the tenofovir disoproxil fumarate/emtricitabine arm (two with emerging mutations M184V and K65R) versus two in the control arm (ITT difference 3.5%, 95% CI –1.9 to 9.4). All VFs were resuppressed after treatment modification. Conclusions Although non-inferiority was shown, simplification to tenofovir disoproxil fumarate/emtricitabine should not be used for most PLHIV because of a low risk of VF with resistance.

Adherence and Associated Factors of Treatment Regimen in Drug-Susceptible Tuberculosis Patients

Background: Adherence to tuberculosis (TB) drugs is one of the key aspects of global TB control, yet there is a lack of epidemiological evidence on the factors influencing adherence to TB drugs. Thus, this study aimed to explore the adherence and factors associated with adherence among TB patients in South Korea.Methods: We conducted a cohort study using a sampled national healthcare database from 2017 to 2018. Our study population included incident TB patients initiating quadruple or triple regimen who were available for follow-up for 180-days. Adherence was evaluated using the proportion of days covered (PDC): 1) adherent group: patients with PDC ≥80%; 2) non-adherent group: patients with PDC &lt;80%. Kaplan-Meier analysis was conducted to calculate the median time-to-discontinuation in the study population. We calculated the adjusted odds ratios (aOR) with 95% confidence intervals (CI) to assess factors associated with adherence to TB drugs using logistic regression.Results: Of 987 patients, 558 (56.5%) were adherent and 429 (43.5%) were non-adherent, with the overall mean PDC of 68.87% (standard deviation, 33.37%). The median time-to-discontinuation was 113 days (interquartile range 96–136) in the study population. Patients initiating quadruple regimen were more likely to adhere in comparison to the triple regimen (aOR 4.14; 95% CI 2.78–6.17), while those aged ≥65 years (aOR 0.53; 95% CI 0.35–0.81), with a history of dementia (aOR 0.53; 95% CI 0.34–0.85), and with history of diabetes mellitus (aOR 0.70; 95% CI 0.52–0.96) were less likely to adhere to the drug.Conclusion: Approximately 45% of TB patients were non-adherent to the drug, which is a major concern for the treatment outcome. We call for intensified attention from the authorities and healthcare providers to reinforce patients’ adherence to the prescribed TB drugs.