An International Phase 2 Study of Pazopanib in Progressive and Metastatic Thyroglobulin Antibody Negative Radioactive Iodine Refractory Differentiated Thyroid Cancer.

Multikinase inhibitors have clinical activity in radioactive iodine refractory (RAIR) differentiated thyroid cancers (DTCs) but are not curative; optimal management and salvage therapies remain unclear. This study assessed clinical effects of pazopanib therapy in RAIR-DTC patients with progressive disease, examining in parallel biomarker that might forecast/precede therapeutic response. Assessment of responses and toxicities and of any association between thyroglobulin (Tg) changes cycle 1 and RECIST (response evaluation criteria in solid tumors) response to pazopanib therapy were prospectively undertaken in Tg antibody negative RAIR-DTC patients.

A phase II study of the orally administered negative enantiomer of gossypol (AT-101), a BH3 mimetic, in patients with advanced adrenal cortical carcinoma.

Background Adrenal cortical carcinoma (ACC) is a rare cancer with treatment options of limited efficacy, and poor prognosis if metastatic. AT-101 is a more potent inhibitor of B cell lymphoma 2 family apoptosis-related proteins than its racemic form, gossypol, which showed preliminary clinical activity in ACC. We thus evaluated the efficacy of AT-101 in patients with advanced ACC.

Phase I trial of vandetanib in combination with gemcitabine and capecitabine in patients with advanced solid tumors with an expanded cohort in pancreatic and biliary cancers.

Background: Vandetanib is a multitargeted tyrosine kinase inhibitor that affects vascular endothelial growth factor receptor (VEGF), epidermal growth factor (EGF), and rearranged during transfection (RET) mediated receptors which are important for growth and invasion of biliary and pancreatic cancers. This phase I study evaluated the safety profile of vandetanib in combination with standard doses of gemcitabine and capecitabine in order to determine the maximum tolerated dose (MTD).

Methods: In this single center phase I trial, patients received gemcitabine intravenously (i.

Treatment of advanced thyroid cancer with axitinib: Phase 2 study with pharmacokinetic/pharmacodynamic and quality-of-life assessments.

Background: In a previous phase 2 trial, axitinib was active and well tolerated in patients with advanced thyroid cancer. In this second phase 2 trial, the efficacy and safety of axitinib were evaluated further in this population, and pharmacokinetic/pharmacodynamic relationships and patient-reported outcomes were assessed.

Methods: Patients (N = 52) with metastatic or unresectable, locally advanced medullary or differentiated thyroid cancer that was refractory or not amenable to iodine-131 received a starting dose of axitinib 5 mg twice daily.

Approach to the thyroid cancer patient with extracervical metastases.

Patients with distant, or extracervical, metastases from differentiated thyroid cancer require multimodality diagnostic, therapeutic, and monitoring approaches. Whereas cure is the initial goal, especially in those with small, radioiodine-avid pulmonary metastases, improved survival and management of symptoms become the primary objective in many patients with persistent disease, especially those with bone metastases. Levothyroxine therapy with suppression of serum TSH is a primary therapy in all patients with advanced differentiated thyroid cancer, and this therapy has been shown to improve overall survival and slow disease progression.

Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study.

Purpose: Patients with advanced, incurable thyroid cancer not amenable to surgery or radioactive iodine ((131)I) therapy have few satisfactory therapeutic options. This multi-institutional study assessed the activity and safety of axitinib, an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 in patients with advanced thyroid cancer.

Patients And Methods: Patients with thyroid cancer of any histology that was resistant or not appropriate for (131)I were enrolled onto a single-arm phase II trial to receive axitinib orally (starting dose, 5 mg twice daily).

A Phase II multi-institutional trial of chemoradiation using weekly docetaxel and erythropoietin for high-risk postoperative head and neck cancer patients.

Purpose: To determine efficacy and toxicities of postoperative concurrent chemoradiation using docetaxel in high-risk head and neck cancer.

Methods And Materials: High-risk patients were enrolled 2-8 weeks after surgery. Treatment included 60 Gy for 6 weeks with weekly docetaxel 25 mg/m(2) and erythropoietin alpha 40,000 U for hemoglobin < or =12 g/dL.

Chemoprevention of squamous cell carcinoma of the oral cavity.

Squamous cell carcinoma of the oral cavity has long been seen as an attractive candidate for chemoprevention strategies. Because of the poor out-comes associated with the disease, the presence of identifiable premalignant lesions, and the failure of local preventive therapies, such as surgery, many investigators have hoped to find an effective chemopreventive compound. Initial enthusiasm surrounding high-dose retinoids gave way to concerns regarding toxicity and short duration of response.

Phase II trial of gefitinib 250 mg daily in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck.

Purpose: An objective response rate of 11% was reported in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) treated with 500 mg daily gefitinib although the recommended dose in lung cancer is 250 mg. This study evaluated the efficacy and toxicity of 250 mg daily gefitinib in patients with recurrent and/or metastatic SCCHN.

Experimental Design: Phase II trial with objective response rate as the primary end point.

The role of folates in squamous cell carcinoma of the head and neck.

The primary objective of this review is to explore the hypothesis that folate insufficiency may be important in the pathogenesis of squamous cell carcinomas of the head and neck (SCCHN) and that folate repletion may be an effective component of chemoprevention. The main results are that folate insufficiency disrupts DNA global and specific gene methylation patterns such that the activity of certain tumor suppressor genes such as p16 and possibly p53 may be lost. Folate pool imbalance and impaired repair mechanisms may contribute to DNA instability and strand breaks.

Immune reconstitution inflammatory syndrome associated with Kaposi sarcoma during potent antiretroviral therapy.

Rapidly progressive Kaposi sarcoma (KS) lesions with lymphadenopathy and tissue swelling occurred in a patient during antiretroviral treatment, despite an increased CD4(+) lymphocyte count and decreased HIV-1 level and KS-associated herpesvirus replication, suggesting immune reconstitution inflammatory syndrome. Inflammation resolved coincident with decreases in the CD4(+) lymphocyte count during paclitaxel treatment, whereas KS cleared only after prolonged antiretroviral therapy and chemotherapy.

Dexamethasone regulation of gastrin-releasing peptide receptor in human lung cells.

We investigated the effects of the glucocorticoid, dexamethasone (Dex), on expression of the gastrin-releasing peptide (GRP) receptor by human small cell lung carcinoma (SCLC) SHP77 cells. After 12h of 10nM Dex exposure, a six-fold increase in the peak of GRP receptor mRNA compared with untreated controls (10.5+/-4 versus 1.

Transfusion-related acute lung injury (TRALI) following platelet transfusion in a patient receiving high-dose interleukin-2 for treatment of metastatic renal cell carcinoma.

Transfusion-related acute lung injury (TRALI) is an uncommon life-threatening complication of hemotherapy. It is hypothesized to be the result of two independent insults: the first related to the clinical status of the patient and the second to the infusion of biologic response modifiers within blood components. We present a case of TRALI in a patient who received high-dose Interleukin-2 (IL-2) as treatment for metastatic renal cell carcinoma, where IL-2 is speculated to have been the first insult and transfusion of platelet concentrate the second.

Inhibition of proliferation of human small cell lung cancer cells expressing an autocrine system for gastrin releasing peptide by antisense oligodeoxynucleotides to gastrin releasing peptide receptor.

The objectives of this study were to investigate the effect of antisense (AS) oligodeoxynucleotides (ODNs) directed against gastrin releasing peptide (GRP) receptor mRNA on proliferation of human small cell lung cancer (SCLC) NCI-H345 cells which express the autocrine system for GRP. The methods used were to expose human SCLC cell lines to antisense ODNs or sense ODNs and to measure their proliferation by spectrophotometric assay or viable cell counts. Our results demonstrated that the single or combined AS ODNs against GRP receptor inhibited proliferation of human SCLC NCI-H345 cells significantly by 37% (P<0.