Cancer outcomes in patients requiring immunosuppression in addition to corticosteroids for immune-related adverse events after immune checkpoint inhibitor therapy.

AIM: To examine the cancer-specific outcomes for patients who experience immune-related adverse events requiring immunosuppression beyond corticosteroids. METHODS: We performed a retrospective case series of patients between January 1, 2009 and April 1, 2018, across three metropolitan hospitals in Adelaide, South Australia. Eligible patients were identified from pharmacy records. Patients with a solid organ malignancy had discontinued checkpoint inhibitor therapy due to toxicity, and required immunosuppression in addition to corticosteroids to treat any immune-related adverse event. RESULTS: From 3860 patient dispensation records of immunosuppressive medications, 19 eligible patients were identified. Eight received a CTLA-4 inhibitor, four a PD-1 inhibitor, five combination immunotherapy, and two remained blinded. Sixteen patients had melanoma and three had non-small cell lung cancer. Median time to treatment failure was 8.7 months, and median overall survival was 9.4 months. Of those evaluable, the objective response rate was 35%, while 53% had progressive disease. Four patients died due to complications of their irAE, while six died from progressive disease. CONCLUSION: Patients who received immunosuppression for checkpoint inhibitor therapy toxicity had variable outcomes. This in part reflects a heterogeneous population, and the evolution of irAE management over time. Several patients continued to derive a benefit after cessation of therapy despite the use of immunosuppressive medications; conversely, four died as a direct consequence of their irAE. Physicians should promptly introduce immunosuppressive therapy in patients not responding to corticosteroids to mitigate the risk of life-threatening adverse events, given that current evidence does not clearly demonstrate a detriment to cancer-specific outcomes.

Potential role of cannabidiol for seizure control in a patient with recurrent glioma.

Glioma-related epilepsy significantly impact on patients' quality of life, and can often be difficult to treat. Seizures cause significant morbidity for example neurocognitive deterioration, which may result from seizures themselves or due to adverse effects from antiepileptic drugs. Management of tumour with surgery, radiotherapy and chemotherapy may contribute to seizure control, but tumour related epilepsy is often refractory despite adequate treatment with standard anti-epileptic medications. Given the increasing interest in medicinal cannabis (or cannabidiol or CBD) as an anti-epileptic drug, CBD may help with seizure control in glioma patients with treatment-refractory seizures. Here we present a case of a young lady with recurrent glioma who had refractory seizures despite multiple anti-epileptic agents, who had significant benefit with CBD.

Relaxin for preventing preterm birth.

BACKGROUND: Preterm birth is a leading cause of perinatal morbidity and mortality. Early animal and clinical studies have provided some evidence to support an inhibitory effect of relaxin on preterm birth for women in preterm labour. OBJECTIVES: To assess the effects of relaxin for women in preterm labour on preterm birth and associated maternal and neonatal/infant health outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2013), and the reference lists of relevant papers. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials assessing the effects of relaxin compared with no treatment, a placebo, or an alternative tocolytic, for preventing preterm birth for women in preterm labour. Primary review outcomes included birth within 28 hours of treatment, birth within seven days of treatment, perinatal mortality, and a serious neonatal adverse outcome composite. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of included studies. MAIN RESULTS: We included three quasi-randomised controlled trials, with a total of 149 women and their babies. All three trials were at a high risk of bias. When comparing women receiving relaxin with those who did not receive relaxin, there was a significant reduction in birth within seven days of treatment in one trial of 30 women (risk ratio (RR) 0.50, 95% confidence interval (CI) 0.29 to 0.87), yet no significant difference was seen for perinatal mortality in this trial (RR 0.83, 95% CI 0.32 to 2.15). The second and third included trials did not report on any of the primary outcomes pre-specified in the review, including birth within 48 hours of treatment, birth within seven days of treatment, perinatal mortality, and serious neonatal adverse outcomes.One trial found a significant increase in pregnancy prolongation for women receiving relaxin (RR 8.00, 95% CI 1.14 to 56.33; 30 women). None of the three included trials found significant differences in the outcomes of fetal death, neonatal death, birthweight or preterm birth, and no trial reported on longer-term outcomes for the babies. AUTHORS' CONCLUSIONS: There is limited randomised controlled trial evidence available on the effect of relaxin during pregnancy for preventing preterm birth for women in preterm labour. Evidence from one quasi-randomised trial suggested a reduction in birth within seven days of treatment for women receiving relaxin, compared with women in a control group, however this trial was at a high risk of bias and included only 30 women. There is thus insufficient evidence to support or refute the use of relaxin in women in preterm labour for preventing preterm birth.