Albumin-bound paclitaxel in solid tumors: clinical development and future directions

Madappa N Kundranda,1 Jiaxin Niu21Medical Oncology, Banner MD Anderson Cancer Center, Gilbert, 2Department of Medical Oncology, Cancer Treatment Centers of America, Goodyear, Arizona, USA Abstract: Albumin-bound paclitaxel (nab-paclitaxel) is a solvent-free formulation of paclitaxel that was initially developed more than a decade ago to overcome toxicities associated with the solvents used in the formulation of standard paclitaxel and to potentially improve efficacy. Nab-paclitaxel has demonstrated an advantage over solvent-based paclitaxel by being able to deliver a higher dose of paclitaxel to tumors and decrease the incidence of serious toxicities, including severe allergic reactions. To date, nab-paclitaxel has been indicated for the treatment of three solid tumors in the USA. It was first approved for the treatment of metastatic breast cancer in 2005, followed by locally advanced or metastatic non-small-cell lung cancer in 2012, and most recently for metastatic pancreatic cancer in 2013. Nab-paclitaxel is also under investigation for the treatment of a number of other solid tumors. This review highlights key clinical efficacy and safety outcomes of nab-paclitaxel in the solid tumors for which it is currently indicated, discusses ongoing trials that may provide new data for the expansion of nab-paclitaxel’s indications into other solid tumors, and provides a clinical perspective on the use of nab-paclitaxel in practice.Keywords: nab-paclitaxel, breast, lung, pancreas, ovarian, melanom

Novel Diagnostic and Predictive Biomarkers in Pancreatic Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease for a multitude of reasons including very late diagnosis. This in part is due to the lack of understanding of the biological behavior of PDAC and the ineffective screening for this disease. Significant efforts have been dedicated to finding the appropriate serum and imaging biomarkers to help early detection and predict response to treatment of PDAC. Carbohydrate antigen 19-9 (CA 19-9) has been the most validated serum marker and has the highest positive predictive value as a stand-alone marker. When combined with carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA 125), CA 19-9 can help predict the outcome of patients to surgery and chemotherapy. A slew of novel serum markers including multimarker panels as well as genetic and epigenetic materials have potential for early detection of pancreatic cancer, although these remain to be validated in larger trials. Imaging studies may not correlate with elevated serum markers. Critical features for determining PDAC include the presence of a mass, dilated pancreatic duct, and a duct cut-off sign. Features that are indicative of early metastasis includes neurovascular bundle involvement, duodenal invasion, and greater post contrast enhancement. 18-F-fluorodeoxyglucose (18-FDG) radiotracer uptake and changes following treatment may predict patient overall survival following treatment. Similarly, pretreatment apparent diffusion coefficient (ADC) values may predict prognosis with lower ADC lesions having worse outcome. Although these markers have provided significant improvement in the care of pancreatic cancer patients, further advancements can be made with perhaps better combination of markers or discovery of unique marker(s) to pancreatic cancer

When the Tumor Lyses: A Case Report on Spontaneous Tumor Lysis Syndrome

Tumor lysis syndrome (TLS) is an oncological emergency characterized by severe electrolyte disturbance that typically occurs when hematologic cancer patients have been started on systemic chemotherapy. We present an uncommon case of spontaneous TLS (STLS) occurring in a patient with cholangiocarcinoma. The patient was a 59-year-old male with newly diagnosed differentiated carcinoma of unknown origin who presented with weakness, fatigue, and lightheadedness. Initial imaging revealed cholangiocarcinoma with innumerable pulmonary and hepatic metastases. The laboratory values showed leukocytosis, hypercalcemia, and lactic acidosis. He was diagnosed and treated for sepsis of pulmonary origin. Over the next 3 days, the patient's clinical condition steadily worsened despite aggressive treatment, with new-onset hypoxic respiratory failure, acute kidney injury, and septic shock. Chemotherapy was administered, with new laboratory values showing hyperuricemia and hyperkalemia, consistent with STLS. The patient was transferred to the ICU and emergently started on dialysis but expired a day later from multi-organ failure. To our knowledge, this is the second case of STLS in cholangiocarcinoma. Our patient was unique in that he presented with hypercalcemia and normal phosphorus levels, instead of the typical hyperphosphatemia and secondary consumptive hypocalcemia. While the exact pathophysiology of STLS is still elusive, we believe that the patient's initial sepsis-induced hypotension, aggressively enlarging tumor, and extent of metastasis all contributed to his rapid decline. Given the high mortality rate with TLS and its vague presentation, particularly in a chemotherapy-naive solid tumor, a high level of clinical suspicion is needed to improve patients' outcome.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Metastatic Breast Cancer with Extensive Osseous Metastasis Presenting with Symptomatic Immune Thrombocytopenic Purpura and Anemia: A Case Report and Review of the Literature

Background: Immune thrombocytopenic purpura (ITP) is a rare acquired bleeding disorder with an estimated incidence of 1 in 10,000 people in the general population. The association of ITP with breast cancer is an even rarer entity with very limited reports in the English literature. Case Presentation: We report a case of a 51-year-old female with no significant past medical history who presented with sudden onset of malaise, syncope, gingival bleed and epistaxis. She was found to have severe thrombocytopenia (platelet count 6,000/μl) and anemia (hemoglobin 7.2 g/dl). Her workup led to the diagnosis of metastatic ductal breast cancer with extensive bone metastasis. Bone marrow biopsy demonstrated myelophthisis which was initially thought to be consistent with her presentation of thrombocytopenia and anemia. Therefore, the patient was started on hormonal therapy for the treatment of her metastatic breast cancer. After 3 months of therapy, she did not improve and developed severe mucosal bleeding. Her clinical presentation was suspicious for ITP and immune-mediated anemia, and hence she was started on steroids and intravenous immunoglobulin. The patient had a dramatic response to therapy with normalization of her platelet count and hemoglobin within 2 weeks. Conclusion: To our knowledge, this is the first reported case of metastatic breast cancer presenting with symptomatic ITP and anemia, and both symptoms are postulated to be immune-mediated