Hypocalcemia in a Patient With Metastatic Prostate Cancer From Denosumab Treatment.

Denosumab is a humanized monoclonal antibody that binds RANKL to inhibit osteoclast activity. It is indicated for the prevention of skeletal-related events (SRE) in patients with solid tumors who have bone metastasis and in patients with multiple myeloma. Hypocalcemia is one of the known side effects of denosumab, which can be prevented with calcium supplementation. We present a case of a 72-year-old male with diagnosed metastatic prostate cancer who had received one dose of denosumab 10 days prior to presentation with fatigue, insomnia, and somnolence. His labs showed severe (Grade 4) hypocalcemia, which improved with intravenous calcium supplementation. This case highlights a known but life-threatening side effect of denosumab and the potential need for prolonged calcium monitoring in patients placed on the drug.

Metastatic Rectal Small Cell Carcinoma: A Case Report.

We report a case of metastatic small cell carcinoma presenting as a rectal mass in an 80-year-old male with a history of change in bowel movement and rectal pain for six months. A computed tomography (CT) scan of the abdomen and pelvis was done, which showed a large rectal mass with many liver metastases. He had a diagnostic colonoscopy, which showed a large obstructing rectal mass, and the biopsy result came back as small cell carcinoma. He underwent palliative diverting colostomy without complications. Initially, there was a plan to treat the patient with systemic chemotherapy with etoposide and carboplatin, but given the acute kidney injury, there was a delay in treatment. After the first cycle of chemotherapy, the patient had severe nausea and vomiting. After a discussion with the patient and his family, he decided on hospice care and passed away in a few weeks.

Incidence and Risk of Thyroid Dysfunction in Advanced or Metastatic Non-small Cell Lung Cancer Patients Treated with Pembrolizumab: A Meta-analysis.

Thyroid dysfunction is one of the major side effects associated with Pembrolizumab in the treatment of advanced or metastatic non-small cell lung cancer (NSCLC). We performed a systematic review and meta-analysis of randomized clinical trials to determine its overall incidence. A literature search was conducted using the electronic database engines PubMed and Google Scholar from inception to March 2019. Eligible studies were prospective randomized clinical trials with advanced or metastatic NSCLC. The pooled incidence, risk ratio (RR), and 95% confidence interval (CI) of thyroid dysfunction were calculated using the random-effect model. Given the possibility of a between-study variance, we used the random-effect model rather than the fixed-effect model. A total of four studies, including 1603 patients, were selected for analysis. Among patients receiving Pembrolizumab, the overall incidence of all-grade thyroid dysfunction was 19.8% (95% CI: 16.6-23.3%). Pembrolizumab was associated with a significantly increased risk of thyroid dysfunction of all grades, with a relative risk of 3.9 (95% CI: 2.08-7.42%, p= 0.084) in comparison with the controls. Therefore, there is a significant increase in developing thyroid dysfunction in advanced or metastatic NSCLC patients treated with Pembrolizumab.

Rash associated with rivaroxaban use.

PURPOSE: A case of a patient who developed a hypersensitivity reaction to rivaroxaban in the form of a diffuse, exanthematous rash is reported. SUMMARY: After starting rivaroxaban for treatment of cancer-associated deep vein thrombosis (DVT) with pulmonary embolism (PE), a 69-year-old Caucasian woman arrived at an oncology clinic with a diffuse, exanthematous (morbilliform) rash on her neck and torso, spreading to her upper and lower extremities. She reported that the symptoms started to develop about 48 hours after transitioning from subcutaneous enoxaparin to oral rivaroxaban. The patient's symptoms did not subside with diphenhydramine 25-50 mg orally every 6-8 hours. The patient was switched back to enoxaparin therapy for continued anticoagulation therapy. On day 5, rivaroxaban and diphenhydramine were discontinued. Oral dexamethasone 4 mg twice daily was initiated, and the patient transitioned from rivaroxaban to enoxaparin 1 mg/kg every 12 hours subcutaneously. On day 8, the rash had diminished considerably and was present only on her thighs. Analysis of the case using the adverse drug reaction probability scale of Naranjo et al. indicated that rivaroxaban was the probable cause of the hypersensitivity reaction. Four prior case reports of rivaroxaban hypersensitivity manifesting as a rash have been previously reported, with this being the first in a female and the first in a patient undergoing treatment of DVT and PE in the setting of active cancer. CONCLUSION: A 69-year-old Caucasian woman developed a diffuse, exanthematous rash on day 3 of rivaroxaban treatment. Symptoms abated after rivaroxaban discontinuation and treatment with dexamethasone.

Thrombotic thrombocytopenic purpura: the masquerader.

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder with a mortality rate of up to 90% if left untreated, and is characterized by microvascular thrombi, mainly in small arteries and capillaries, thrombocytopenia, hemolysis, and neurological abnormalities. Malignant hypertension (HTN) is a clinical syndrome characterized by severe hypertension associated with end-organ damage; including encephalopathy, renal dysfunction, and retinal hemorrhage due to platelet aggregation in the microcirculation leading to thrombotic microangiopathy (TMA). These are similar to TTP. Malignant hypertension can cause endothelial injury and fibrinoid necrosis in the vessel wall which results in its clinical manifestations. Therefore, it is difficult to differentiate malignant hypertension from TTP. However, it is critical to differentiate these two entities, as early initiation of plasmapheresis in TTP can be life saving. TTP is considered a masquerader as it can present with few clinical features and, if the index of suspicion is not very high, lead to mortality.

Cyclophosphamide therapy in granulomatous hepatitis: cure or culprit?

Three months after diagnosis of Wegener granulomatosis, an 84-year-old woman who was treated with cyclophosphamide (CPY) and prednisone developed deranged liver function tests (LFTs). Treatment with CPY was held, which led to normalization of LFTs, but after reinitiating of CPY, LFTs started increasing. Liver biopsy showed noncaseating epithelioid granulomas within liver lobules consistent with granulomatous hepatitis. Patient died within 2 months secondary to liver failure. This elevation of transaminases was considered to be secondary to CPY-induced hepatotoxicity. Involvement of liver in patients with Wegener granulomatosis is seen but it presents with necrotizing granulomatous vasculitis. CPY-induced hepatitis is an extremely rare phenomenon with only 1 case reported in literature. Clinicians and hepatologists should be aware of this potentially serious complication when CPY therapy is initiated. Baseline LFTs and periodic assessment are recommended before and during treatment with CPY.

Targeted therapies in the management of colorectal carcinoma: role of bevacizumab.

Colorectal cancer continues to be an important public health concern, despite improvements in screening and better systemic chemotherapy. The integration of targeted therapies in the treatment of colon cancer has resulted in significant improvements in efficacy outcomes. Angiogenesis is important for tumor growth and metastasis and is an important target for new biological agents. Bevacizumab is a humanized recombinant antibody that prevents vascular endothelial growth factor (VEGF) receptor binding, and inhibits angiogenesis and tumor growth. The addition of bevacizumab to fluoropyrimidine-based chemotherapy, with or without irinotecan or oxaliplatin, in both the first- and second-line treatment of metastatic colorectal cancer, significantly increased median progression-free survival and overall survival in select randomized phase III studies. Ongoing studies are evaluating the role of bevacizumab in the adjuvant treatment of colon cancer. Common toxicities associated with bevacizumab include hypertension, bleeding episodes, and thrombotic events. This review will focus on the integration of bevacizumab in the treatment paradigm of colon cancer and the management of its side effects.

Neoadjuvant chemoradiation for rectal cancer: is more better?

Neoadjuvant chemoradiation is now considered the clear preferable adjuvant standard of care in the management of stage II/III rectal cancer. Neoadjuvant fluorouracil (5-FU) plus radiation results in a decrease in local relapse rates and a favorable toxicity profile in comparison with postoperative adjuvant 5-FU plus radiation therapy. Recent nonrandomized comparative studies have shown that capecitabine (Xeloda) plus radiation result in downstaging and pathologic complete responses equivalent to those of 5-FU plus radiation, making this combination an acceptable alternative neoadjuvant treatment. The addition of oxaliplatin (Eloxatin) or irinotecan (Camptosar) to 5-FU or capecitabine concurrently with radiation therapy appears to result in more favorable pathologic responses in phase I/II trials. These combinations should be investigated further in larger phase III studies before they are endorsed in the routine neoadjuvant treatment of rectal cancer. This article will review the progress of chemoradiation over the past 2 decades, current standards of care, and investigational treatments in the neoadjuvant treatment of rectal cancer.