A phase 2, randomized trial evaluating the combination of dalantercept plus axitinib in patients with advanced clear cell renal cell carcinoma.

BACKGROUND: In a prior open-label study, the combination of dalantercept, a novel antiangiogenic targeting activin receptor-like kinase 1 (ALK1), plus axitinib was deemed safe and tolerable with a promising efficacy signal in patients with advanced renal cell carcinoma (RCC). METHODS: In the current phase 2, randomized, double-blind, placebo-controlled study, patients with clear cell RCC previously treated with 1 prior angiogenesis inhibitor were randomized 1:1 to receive axitinib plus dalantercept versus axitinib plus placebo. Randomization was stratified by the type of prior therapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were PFS in patients with ≥2 prior lines of anticancer therapy, overall survival, and the objective response rate. RESULTS: Between June 10, 2014, and February 23, 2017, a total of 124 patients were randomly assigned to receive axitinib plus dalantercept (59 patients) or placebo (65 patients). The median PFS was not found to be significantly different between the treatment groups (median, 6.8 months vs 5.6 months; hazard ratio, 1.11 [95% CI, 0.71-1.73; P = .670]). Neither group reached the median overall survival (hazard ratio, 1.39 [95% CI, 0.70-2.77; P = .349]). The objective response rate was 19.0% (11 of 58 patients; 95% CI, 9.9%-31.4%) in the dalantercept plus axitinib group and 24.6% (15 of 61 patients; 95% CI, 14.5%-37.3%) in the placebo plus axitinib group. At least 1 treatment-emergent adverse event of ≥grade 3 was observed in 59% of patients (34 of 58 patients) in the dalantercept group and 64% of patients (39 of 61 patients) in the placebo group. One treatment-related death occurred in the placebo plus axitinib group. CONCLUSIONS: Although well tolerated, the addition of dalantercept to axitinib did not appear to improve treatment-related outcomes in previously treated patients with advanced RCC.

Immunohistochemical determination of HER-2/neu, c-Kit (CD117), and vascular endothelial growth factor (VEGF) overexpression in malignant melanoma.

PURPOSE: To determine the prevalence and evaluate the possible prognostic value of the molecular targets in malignant melanoma, we studied the overexpression of HER-2/neu, c-Kit, and vascular endothelial growth factor (VEGF) in this patient population. MATERIALS AND METHODS: Overexpression of HER-2/neu, c-Kit, and VEGF was evaluated using immunohistochemical assays in 202 archival tissue specimens. RESULTS: Only two patients (0.9%) revealed HER-2/neu overexpression, whereas 46 (22.8%) revealed c-Kit and 42 (20.8%) specimens showed VEGF overexpression. Multivariate analysis performed did not show a significant difference in survival between c-Kit-positive and c-Kit-negative groups (P = 0.36) and VEGF-positive and VEGF-negative groups (P = 0.25). Interestingly, c-Kit was more likely to be overexpressed in the superficial spreading type and VEGF was overexpressed preferentially in the amelanotic melanoma type. CONCLUSIONS: HER-2/neu has no role in melanogenesis. Both c-Kit (expressed in superficial spreading disease) and VEGF (expressed in amelanotic melanoma) may have significant therapeutic implications as molecular targets, which warrants further investigation.

B-cell lymphoma mimicking multiple myeloma.

A 75-year-old white male presented with a one-month history of pain in the left shoulder. Early laboratory data revealed hypercalcemia. Extensive skeletal survey was remarkable for multiple lytic lesions in skull, right scapula, right humerus and left iliac crest. A bone marrow biopsy of the left iliac crest did not show evidence of plasma cell dyscrasia. A computed tomographic scan (CT) of the abdomen revealed a right renal mass and multiple lesions in the liver. A CT-guided biopsy of liver showed lymphoma cells strongly positive for CD19 and CD20 stains: findings consistent with B-cell lymphoma. Our case illustrates that B-cell lymphomas can clinically present in a fashion that mimics multiple myeloma in the form of hypercalcemia, renal failure and lytic bone lesions.

Immunohistochemical determination of vascular endothelial growth factor (VEGF) overexpression in malignant melanoma.

BACKGROUND: Molecular changes associated with the transition of melanoma cells from radial to vertical growth phase are not defined. To evaluate the role of VEGF in melanogenesis and determine its possible diagnostic and prognostic implications, we analyzed overexpression of VEGF in 202 cases of melanoma. MATERIALS AND METHODS: Overexpression of VEGF was evaluated in 202 archival paraffin-embedded tissue specimens using an avidin-biotin immunohistochemical (IHC) assay. RESULTS: Of the 202 melanoma specimens, 42 (20.8%) showed evidence of VEGF overexpression on IHC testing. Multivariate analysis performed using Cox proportional hazards method did not show a statistically significant survival difference between the VEGF-positive and negative groups (p = 0.25). CONCLUSION: Although of no significant prognostic value, VEGF may have critical therapeutic implications as a molecular target since it is expressed in about 20% of melanomas. The role of target-specific therapies against VEGF in malignant melanoma warrants further investigations.

Pancreatic metastasis and extrahepatic biliary obstruction in squamous cell lung carcinoma.

Primary lung cancer frequently metastasizes to distant organs. The pancreas is a relatively infrequent site of metastasis. As a result, extrahepatic bile duct obstruction (EHBDO) resulting from pancreatic metastasis from lung cancer is extremely rare and occurs mostly with small-cell lung cancer (SCLC). We report an unusual case in which a patient presented with jaundice and, after extensive workup, was diagnosed with squamous cell carcinoma of the lung with metastasis to the pancreas causing EHBDO. He underwent endoscopic retrograde cholangiopancreatography (ERCP) and the obstruction was relieved with a stent placement. The patient was treated with combination chemotherapy (carboplatin and paclitaxel) with a good clinical and radiographic response.

Predictive value of absent bone marrow iron stores in the clinical diagnosis of iron deficiency anemia.

The examination of Prussian-blue-stained bone marrow aspirates for the presence or absence of histiocytic iron granules has been considered the gold standard in evaluating iron-depeleted states. We performed this study to evaluate the predictive accuracy of absent stainable bone marrow iron for iron deficiency anemia (IDA). A retrospective study was performed on an unselected series of 53 consecutive bone marrow biopsy specimens. Only those patients who had totally depleted iron stores and who had iron studies done within 6 months of bone marrow biopsy were included in the study. Based on these criteria, 12 patients were found eligible. After complete evaluation to determine the cause of the patient's illness, the final diagnosis was IDA in only 6 patients (50%). There was no significant difference between the two groups as regards hemoglobin level, reticulocyte count, serum iron levels, total iron binding capacity, red blood cell mean corpuscular volume, ferritin and the transferrin saturation levels. The finding of absent bone marrow iron stores is not necessarily predictive of iron deficiency anemia. The finding of absent stores of iron in the bone marrow needs to be taken in conjunction with other laboratory findings and the clinical scenario while making a diagnosis of IDA, since certain other hematological diseases may co-exist.