Carboplatin and hypomagnesemia: Is it really a problem?

BACKGROUND: Carboplatin has largely replaced cisplatin in ovarian/peritoneal/tubal cancer (OC) due to comparable activity and reduced toxicity, particularly nephrotoxicity and hypomagnesemia. Anecdotally hypomagnesemia occurs commonly with carboplatin, however there are limited data available regarding frequency or severity. AIMS: To quantify incidence and severity of hypomagnesemia in patients receiving carboplatin-based chemotherapy for OC; to explore a dose-response relationship with carboplatin and assess potential confounding variables. METHODS: A retrospective single-center review of all OC patients receiving carboplatin-based chemotherapy as first/subsequent line between 2012 and 2018 was performed. Data on patient/disease characteristics, potential confounders (gastrointestinal/renal impairment, premorbid hypomagnesemia and concomitant medications), dose, electrolytes, and magnesium replacement were collected. RESULTS: One hundred four of 144 (72%) patients had at least one hypomagnesemia event, 11 of 104 (11%) grade 2, and 11 of 104 (11%) grade 3/4 in severity. Multivariate analysis showed a significant association between hypomagnesemia and treatment duration (P < .001). Premorbid hypomagnesemia was associated with a significantly longer duration and higher grade of hypomagnesemia (P = .021 and P < .001, respectively). Vomiting, diarrhea, and confounding medications were associated with hypomagnesemia (P = .019 and P = .028, respectively). Fourteen percent of hypomagnesemia events never resolved suggesting a significant cohort post-carboplatin are at risk of long-term renal toxicity. The effect of magnesium replacement could not be accurately assessed due to limited documentation of replacement. CONCLUSION: Hypomagnesemia is common in patients receiving carboplatin-based chemotherapy for OC, and although generally mild, a significant minority were severe. Several high-risk groups were identified including patients with premorbid hypomagnesemia, vomiting, diarrhea, or taking certain medications. Further research is warranted to understand when hypomagnesemia is clinically relevant and determine the impact of interventions.

Vedolizumab in combined immune checkpoint therapy-induced infliximab-refractory colitis in a patient with metastatic melanoma: A case report.

BACKGROUND: Dual checkpoint inhibition improves response rates in treatment naïve patients with metastatic melanoma compared to monotherapy. However, it confers a higher rate of toxicity, including immune-related colitis. Steroids may not resolve symptoms in all cases. The use of vedolizumab, a humanized monoclonal antibody against α4ß7 integrin has proven effective in cases refractory to standard treatment. CASE SUMMARY: We report the case of a 27-year-old female with Stage IVd metastatic melanoma treated with ipilimumab and nivolumab. She developed severe colitis refractory to methylprednisolone, infliximab and mycophenolate mofetil but responded to vedolizumab. CONCLUSION: This case report supports vedolizumab use in severe immune related colitis refractory to standard immunosuppression.

Young adults diagnosed with high grade gliomas: Patterns of care, outcomes, and impact on employment.

There is limited information on the patterns of care and outcomes of high grade gliomas (HGGs) in young adults, in particular, the impact it has on a person's employment. We retrospectively identified young adult patients (age ≤ 40 years old) with newly diagnosed high grade gliomas treated between January 2013 and June 2018 across four major neuro-oncology centres in Australia. Patient demographics, tumour characteristics and treatment parameters were collected and outcomes determined. A total of 113 patients were identified with a median follow up of 27.0 months (range 1.0-70.2 months). The median age was 31 years, majority were male (65%) and employed (71.6%). IDH mutations were detected in 66 (62%) cases. The median progression-free survival (PFS) was 38.0 months (95% CI 23.3-52.7 months) and median overall survival (OS) was not reached. Patients with IDH wild type anaplastic astrocytoma and glioblastoma had a significantly shorter median PFS (19.3 months vs. NR, p = 0.001) and median OS (43.5 months vs NR, p = 0.007) than those with IDH mutated grade III anaplastic astrocytoma and oligodendroglioma. There was no significant difference in median OS or PFS between patients who underwent gross or subtotal tumour resection. Significantly, after diagnosis only 36 (32%) patients reported being employed. Young patients with IDH wild type astrocytomas and glioblastoma had better outcomes than reported historical controls. Most patients did not continue in employment post diagnosis.

Combined immune therapy grade IV dermatitis in metastatic melanoma.

Checkpoint inhibition is the mainstay of treatment in metastatic melanoma. More recently combined cytotoxic T-lymphocyte antigen-4 and programmed-death-1 blockade has resulted in improved response rates and overall survival in treatment naïve patients compared to monotherapy albeit with increased rates of adverse events. Dermatologic toxicities are an emerging consequence of the use of checkpoint inhibitors and have reportedly been more prevalent with the use of combined therapy. However, grade 3 and 4 adverse event rates are still less than 5%. Here, we report a case of a 63-year-old Caucasian male with metastatic melanoma treated with first line combined ipilimumab and nivolumab who then developed a steroid refractory, biopsy confirmed pityriasis lichenoides-like, drug related rash that resolved with cyclosporine. Time of onset was 24 days and presenting symptoms demonstrated a maculopapular rash presenting over the back and chest with pruritus. Unfortunately, the patient subsequently had multi-organ failure with acute kidney injury requiring dialysis, hypotension requiring vasopressor support, hepatic dysfunction, and bilateral lung infiltrates resulting in a fatal outcome. This case report highlights the effective use of cyclosporine as an immunomodulatory agent in the management of severe dermatological toxicity due to combination immunotherapy.