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Combretastatin A4 phosphate (CA4P) is the lead compound of a relatively new class of agents termed vascular disrupting agents that target existing tumor blood vessels. Rapid tumor blood flow shutdown has been demonstrated in preclinical models and patients by various techniques such as dynamic contrast-enhanced MRI, perfusion computed tomography and PET scans following CA4P infusion. CA4P typically induces rapid tumor necrosis in the center of the tumor and leaves a rim of viable cells in the periphery. In oncology, CA4P does not appear to be that active by itself, but may be more efficacious when combined with chemotherapy, antiangiogenic therapy and radiation therapy. Studies are currently underway, which combine CA4P with antiangiogenic agents. Side effects have included hypertension, tumor pain and occasional cardiovascular toxicity, without any significant myelosuppression or disabling systemic symptoms. The utility of CA4P for conditions other than cancer, which involves neovascularization such as macular degeneration, is also being explored.

Most deaths from breast cancer are from metastatic disease. Tests that predict an individual's risk of developing metastatic disease could be useful. There is growing evidence that circulating tumor cells (CTC) could help predict recurrence and effectiveness of therapy. However, there are unresolved issues with CTC detection methods and their implementation in the community. The utility of CTC testing in the management of breast cancer is unclear based on current studies. This article reviews the role of CTC testing in the management of early and metastatic breast cancer.

Placement of carmustine-impregnated wafers has become a common practice after surgical resection of malignant gliomas. Bevacizumab is used as a second-line agent for the treatment of malignant gliomas and is sometimes used in patients who have had recent wafer implantation. We describe two cases of fatal cerebrospinal fluid (CSF) leak in patients treated with bevacizumab and irinotecan after 4 weeks of carmustine wafer implantation. Possible mechanisms for the CSF leak in these patients are discussed. We recommend waiting for a longer period of time before starting bevacizumab in patients who had implantation of carmustine wafers.

Ocular surface squamous neoplasia (OSSN) in sub-Saharan countries is an aggressive tumor that affects younger patients and appears to be increasing in incidence. There are data to suggest the association of this disease with solar radiation exposure, HIV, and human papilloma virus (HPV). This trend possibly reflects the association of the high incidence of HIV, concomitant high incidence of exposure to HPV, and the solar radiation exposure that people in this region of the world receive. We undertook a PubMed search with the terms 'ocular surface squamous neoplasia', 'conjunctival carcinoma', 'HIV' and 'HPV', and 'sub-Saharan/Africa' to ascertain the scope of the problem and to review the available data, with an emphasis on publications of 2009 and the first quarter of 2010.There is increasing evidence of a significant association between HIV seropositivity and OSSN. The role of HPV as contributing to the cause of OSSN is being investigated.Patients with conjunctival cancer in sub-Saharan Africa are typically younger and more than 50% have underlying HIV infection. Initial presentation can be asymptomatic; however, many of these patients have advanced disease before they seek medical help and OSSN appears to have a more aggressive clinical course in sub-Saharan Africa. Treatment in Africa is primarily surgical. Chemotherapy and antiviral agents have been used. A diagnosis of OSSN in younger patients in sub-Saharan Africa should prompt HIV serotesting.

Fosbretabulin is a novel vascular-disrupting agent that has antitumor activity against anaplastic thyroid cancer (ATC) cell lines, xenografts, and demonstrable efficacy in a phase I trial. This phase II study determined the efficacy and safety of fosbretabulin in patients with advanced ATC and whether fosbretabulin altered the natural history of ATC by virtue of doubling the median survival. A secondary aim evaluated the prognostic value of serum soluble intracellular adhesion molecule-1 (sICAM).Twenty-six patients received fosbretabulin 45 mg/m(2) as a 10-minute intravenous infusion on days 1, 8, and 15 of a 28-day cycle. sICAM levels were obtained at baseline, over the first two cycles, and end of therapy. Treatment was continued until disease progression.Fosbretabulin was well tolerated; grade 3 toxicity was observed in nine patients (35%), and grade 4 toxicity in one (4%). QTc prolongation delayed treatment in four causing one to stop treatment. Median survival was 4.7 months with 34% and 23% alive at 6 and 12 months, respectively. Median duration of stable disease in seven patients was 12.3 months (range, 4.4-37.9 months). Baseline serum sICAM levels were measured in 24 patients with a median 253.5 ng/mL. There was a significant difference in event-free survival among tertiles of baseline sICAM levels (p0.009).There were no objective responses seen with single-agent fosbretabulin as administered in this trial, and we did not observe a doubling of survival as our primary endpoint. This is among the largest prospective trials ever conducted for ATC. Fosbretabulin has an acceptable safety profile in patients with advanced ATC, and one-third survived more than 6 months. Despite a small sample size, low baseline sICAM levels were predictive of event-free survival. Further prospective validation of sICAM as a therapeutic biomarker and exploring combination regimens with fosbretabulin are warranted.

e17037 Background: Acneform rash is associated with cetuximab, can be treatment limiting and has been shown to correlate with tumor response. The rash is thought to have an inflammatory component t...

5588 Background: ATC is a rare, undifferentiated solid tumor with dismal outcome. Contemporary systemic analyses of the epidemiology, outcome and survival of ATC are lacking. We examined the natura...

6058 Background: Sorafenib (bay 43–9006) is an oral, small molecule tyrosine kinase inhibitor of the raf-1 protein kinase receptor, VEGFR2 and PDGFR-β with antiangiogenic properties. We are conducting an open label, phase II study of sorafenib in patients with biopsy-proven ATC to evaluate if its objective response rate is >20% and to further characterize its safety profile. Methods: Patients with progressive ATC, after cytotoxic chemotherapy with or without radiation were given sorafenib, on a fixed dosing schedule of 400 mg PO bid on 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or patient refusal. Response was evaluated every 8 weeks with body scans using RECIST criteria. We employed a 2-stage study design: if none of the first 18 patients respond the study is terminated, otherwise accrual is continued to a total of 36 patients at which point if ≤3 of the patients respond, the treatment option is rejected. Results: To date 16 patients (10 male) have enrolled in the study. Median age is 55 years; with (range 28–79). Median time on study is 2 months. Median number of cycles given is 2 (range 1–27). Two of 15 evaluable patients (13%) have partial response (PR) and 4 patients (27%) have stable disease (SD). Median duration of PR/SD is 5.1 months (range 1–24.7months). Median time to progression is 1.5 months. Median duration of survival is 3.5 months (range 1–26 months). All patients at time of reporting are deceased. Most common toxicities are lymphopenia (81%) and fatigue (62%). Grade 3 toxicities include lymphopenia (25%), rash with desquamation, weight loss, and chest pain (all 12%). Grade 4 toxicities include dyspnea (6%) and lymphopenia (6%). There has been no significant cardiovascular toxicity. One patient died on study with rapidly progressive disease. Conclusions: Sorafenib demonstrates objective tumor response in the first 15 evaluable and pretreated patients with advanced ATC. This trial is ongoing and supported in part by NIH grant nos. CA62502. [Table: see text]