BACKGROUND.Sunitinib and sorafenib are small molecules that inhibit the vascular endothelial growth factor and related receptors with substantial clinical activity reported in metastatic renal cell carcinoma (RCC). Cytopenia and macrocytosis have been described in patients treated with these agents.METHODS.A retrospective review of all patients with metastatic RCC who were treated with sunitinib or sorafenib for at least 3 months at the Cleveland Clinic Taussig Cancer Institute was undertaken. Complete blood count (CBC) data including red blood cell indices were recorded at baseline, after 3 months of therapy, and at the end of treatment.RESULTS.A total of 61 patients were treated with sunitinib and 37 patients were treated with sorafenib with available CBC data. In patients treated with sunitinib, the median corpuscular volume (MCV) increased significantly at 3 months compared with baseline (median increase of 5.1 femtoliters [fL]; P < .001) and continued to increase throughout treatment. Patients who developed hypothyroidism had a larger MCV increase at 3 months than patients who remained euthyroid (P = .06), although macrocytosis was observed in patients without hypothyroidism. Ten patients discontinued sunitinib therapy, and the MCV decreased in all patients within 2 to 4 months, without further intervention. Bone marrow analysis of 4 patients revealed a hypocellular bone marrow with trilineage hematopoiesis and no evidence of metastasis. There was no evidence of folate or vitamin B12 deficiency. In contrast to sunitinib, there was no change in the MCV for patients treated with sorafenib.CONCLUSIONS.Macrocytosis was a common occurrence after treatment with sunitinib but not sorafenib in patients with metastatic RCC. Sunitinib‐induced macrocytosis is reversible with drug discontinuation. Cancer 2008. © 2008 American Cancer Society.

No abstract

No abstract

TRAIL/Apo-2 L, a member of the Tumor Necrosis Factor cytokine family, induces apoptosis specifically in malignant cells. A combination of TRAIL and radiation is highly synergistic in in vitro experiments. In addition to this additive effect, we observed that TRAIL is induced by irradiation of certain cell lines. The induction begins approximately 2 hours after irradiation. This might even enhance the antineoplastic effect of ionizing radiation and partially explain the abscopal effect observed in hematopoietic malignancies. TRAIL levels were evaluated in 17 patients treated with radiation for Hodgkin's and non-Hodgkin's lymphoma. We did not observe a specific TRAIL expression pattern that could be correlated with histology, disease status, volume of disease, radiation dose, and other antineoplastic therapies, but a definite pattern observed in a single patient remained constant over time. TRAIL and interferons display a common pattern of gene expression at certain nodal points of interaction between the two physiologic pathways. Our hypothesis is that the radiation-induced changes in TRAIL expression observed in patients undergoing therapeutic radiation may be emblematic of the various physiologic pathways induced or inhibited by ionizing radiation and may even be partially responsible for the "bystander effect" observed in unirradiated cells in close proximity to irradiated cells.

5048 Background: Sorafenib is an orally bioavailable VEGF receptor inhibitor with anti-tumor activity in metastatic RCC. Sunitinib, another VEGF receptor inhibitor, induces biochemical hypothyroidism in 85% of metastatic RCC pts, the majority of whom have signs or symptoms of hypothyroidism (Rini BI et al. JNCI 2007 99(1):81–83). Thus, the incidence of TFT abnormalities in pts with metastatic RCC receiving sorafenib was investigated. Methods: The medical records of pts with metastatic RCC receiving sorafenib in one of five clinical trials at the Cleveland Clinic Taussig Cancer Center were reviewed. TFTs (TSH, T4, FTI and T3), patient demographics and clinical outcomes were recorded. Results: Between February 2004 and November 2006, 71 pts (49 males, 22 females) were treated with sorafenib. Baseline pt characteristics included a median age of 62 years (range, 35–87), 87% of pts had clear cell histology and 97% had prior nephrectomy. Forty-two pts had TFTs measured while receiving sorafenib and 19/42 pts (45%; 95% CI: 30–61%) had abnormal TFTs. The TFT abnormalities were consistent with hypothyroidism (13 pts), euthyroid sick syndrome (2 pts) or hyperthyroidism (4 pts). The median values in pts with abnormal TFTs were: TSH-7 μU/ml, T3–79 ng/dl, T4–12.7 μg/dl, FTI- 5.4; these values are just outside the normal laboratory ranges. The majority of pts did not have clinical signs or symptoms that could be attributed solely to thyroid dysfunction; only one pt (2%) received thyroid hormone replacement. The estimated progression free survival for pts with normal TFTs is 7.5 months vs. 6.1 months for pts with abnormal TFTs (p=0.79). Conclusion: Mild biochemical TFTs abnormalities are common in pts with metastatic RCC treated with sorafenib. However, severe TFT abnormalities and/or clinical signs/symptoms of thyroid dysfunction are not seen, and thyroid replacement therapy is not often indicated. In contrast to sunitinib, where the high incidence and clinical relevance of thyroid dysfunction requires routine monitoring, pts with metastatic RCC receiving sorafenib should have TFTs monitored only if clinically indicated. [Table: see text]