Platinum-based chemotherapy is not standard of care for unselected or genetically selected metastatic castration-resistant prostate cancer (mCRPC) patients. A retrospective assessment of 71 patients was performed on platinum use in the Netherlands. Genetically unselected patients yielded low response rates. For a predefined subanalysis of all patients with comprehensive next-generation sequencing, 30 patients were grouped based on the presence of pathogenic aberrations in genes associated with DNA damage repair (DDR) or aggressive variant prostate cancer (AVPC). Fourteen patients (47%) were DDR deficient (DDRd), of which seven with inactivated BRCA2 (BRCA2mut). Six patients classified as AVPC. DDRd patients showed beneficial biochemical response to carboplatin, largely driven by all BRCA2mut patients having >50% prostate-specific antigen (PSA) decline and objective radiographic response. In the wild-type BRCA2 subgroup, 35% had a >50% PSA decline (P = .006) and 16% radiographic response (P < .001). Median overall survival was 21 months for BRCA2mut patients vs 7 months (P = .041) for those with functional BRCA2. AVPC patients demonstrated comparable responses to non-AVPC, including a similar overall survival, despite the poor prognosis for this subgroup. In the scope of the registration of poly-(ADP)-ribose polymerase inhibitors (PARPi) for mCRPC, we provide initial insights on cross-resistance between PARPi and platinum compounds. By combining the literature and our study, we identified 18 patients who received both agents. In this cohort, only BRCA2mut patients treated with
Intravenous flucloxacillin is one of the most frequently used high-dose penicillin therapies in hospitalized patients, forming the cornerstone treatment of invasive Staphylococcus aureus infection. Being a nonreabsorbable anion, flucloxacillin has been suggested to cause hypokalaemia, although the frequency and magnitude of this unwanted effect is unknown. In a retrospective cohort, we investigated the incidence and extent of hypokalaemia after initiation of intravenous flucloxacillin or ceftriaxone therapy. In total, 77 patients receiving flucloxacillin (62% male, mean age 70.5 years) and 84 patients receiving ceftriaxone (46% male, mean age 70.8 years) were included.Hypokalaemia occurred significantly more often in patients receiving flucloxacillin than ceftriaxone (42% vs 14%, p < 10 −4 ). Moreover, follow-up potassium levels were significantly lower during flucloxacillin therapy. In general, women were more prone to develop hypokalaemia than men. In conclusion, intravenous flucloxacillin use is associated with a striking incidence of hypokalaemia. Therefore, standardized potassium measurements are necessary.
Background: Cemiplimab is a programmed cell death receptor-1 inhibitor with antitumour activity for cutaneous squamous cell carcinoma (CSCC) and acceptable safety proved in its pivotal trial. We provide the first data on cemiplimab safety in daily practice from the named patient programme (NPP) for advanced CSCC in Spain.Methods: This cemiplimab NPP was performed from March 2019 to March 2020. It included patients aged 18 years with advanced CSCC and ineligible for surgery, radiation therapy or clinical trials. The cemiplimab safety was assessed according to treatment-emergent adverse events (TEAEs) reported until March 2021.Results: 140 patients were included (median age [interquartile range, IQR] 77.0 [65.0-84.0] years; age 80 38%; men 71.7%; 1 comorbidity 83%; ECOG 0-1 86.3%; locally advanced CSCC 60.7%; cemiplimab as first-line therapy 67.7%). Cemiplimab was received for a median (IQR) of 8.0 (3.0-14.0) cycles. Fifty-eight (41.4%) patients showed 1 of the 163 TEAEs reported, which most frequently included diarrhoea n¼7, asthenia n¼6, constipation n¼4 and abdominal pain n¼4. Fourteen (8.6%) were immune-mediated, mainly bronchitis n¼2, pneumonitis n¼2 and hepatitis n¼2. Seventy-eight (47.9%) TEAEs were grade 3, most frequently pneumonia n¼3, COVID-19 n¼3, general physical health deterioration n¼2, pyrexia n¼2, renal transplant failure n¼2, sepsis n¼2, acute kidney injury n¼2 and respiratory failure n¼2. Twenty-one (12.9%) were treatment-related (TREAEs): 11 (6.7%) were grade 1-2 (diarrhoea n¼3 and asthenia, hepatotoxicity, malnutrition, odynophagia, polymyalgia rheumatica, pneumonitis, pruritus, and skin toxicity), 9 (5.5%) grade 3 (acute kidney injury, adrenal insufficiency, abdominal pain, blood creatinine increased, dysphagia, haematuria, immune-mediated enterocolitis, panniculitis, surgical wound infection) and 1 (0.6%) unknown grade. Cemiplimab was withdrawn due to TREAEs in only 5 (3.6%) patients. The TEAE outcome was fatal in 29 (17.8%); none related to cemiplimab.Conclusions: This NPP supports the real-life safety of cemiplimab for CSCC, showing an acceptable safety profile consistent with previous reports.
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