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The prognosis of elderly patients with acute myeloid leukemia (AML) is poor. Intensive chemotherapy with the combination of cytarabine and anthracyclines is typically used as the first-line treatment in the elderly with newly diagnosed AML who are able to tolerate this regimen. Unfortunately, many patients are refractory to this treatment approach. The role of hypomethylating agents in the treatment of elderly patients with refractory AML has not been clearly defined. Therefore, we conducted a focused literature review to assess the role of hypomethylating agents in elderly patients with refractory AML. In addition, we present a case report of a patient with refractory AML, who was subsequently treated with azacytidine and showed an immediate response after one treatment cycle. He then proceeded to undergo nine more cycles. Ten months after the start of treatment with azacytidine, he remains in complete remission with incomplete hematologic recovery. Given the positive results noted in multiple retrospective studies and in the presented case report, large-scale, prospective studies are needed to further define the role of hypomethylating agents in the treatment of elderly patients with refractory AML.

Anaplastic thyroid cancer (ATC) is a rare but highly aggressive malignancy with a median survival of 3-5 months. The BRAF oncogene is mutated to its active form in up to 24% of ATC cases. Sorafenib is a tyrosine kinase inhibitor that acts on the RAF-1 serine/threonine kinase. In preclinical mouse models, sorafenib inhibits the growth of ATC xenografts and improves survival. No study of sorafenib in ATC has been conducted. We conducted a multi-institutional phase II trial of sorafenib in patients with ATC who had failed up to two previous therapies.The primary endpoint of the trial was the Response Evaluation Criteria In Solid Tumors (RECIST)-defined imaging response rate. Twenty patients with ATC were treated with sorafenib 400 mg twice daily.Two of the 20 patients had a partial response (10%) and an additional 5 of 20 (25%) had stable disease. The duration of response in the two responders was 10 and 27 months, respectively. For the patients with stable disease, the median duration was 4 months (range 3-11 months). The overall median progression-free survival was 1.9 months with a median and a 1-year survival of 3.9 months and 20%, respectively. Toxicity was manageable and as previously described for sorafenib, including hypertension and skin rash.Sorafenib has activity in ATC, but at a low frequency and similar to our previous experience with fosbretabulin. One patient with a response had previously progressed on fosbretabulin. Toxicities were both predictable and manageable.

SUMMARY The majority of patients with breast cancer are estrogen- and progesterone-receptor positive, and have benefited from the development of anti-estrogen therapies, such as tamoxifen and aromatase inhibitors. Unfortunately, metastatic patients will eventually develop resistance to these agents. Inhibitors of the mTOR, particularly everolimus, show promising activity in this group of patients. mTOR inhibition appears to reverse resistance to anti-estrogen therapy in the estrogen-receptor-/progesterone-receptor-positive subset. Additionally, they may have a similar effect by reversing anti-HER2 resistance in patients who overexpress HER2. This article reviews the mechanism of action of mTOR inhibitors and summarizes the available clinical data of their use in breast cancer.

Anaplastic thyroid cancer (ATC) is an uncommon malignancy of the thyroid. Only 1-2% of thyroid cancers are anaplastic, but the disease contributes to 14–50% of the mortality with a median survival of 3 to 5 months. Most patients diagnosed with this disease are 65 years of age or older. The incidence of anaplastic thyroid cancer is decreasing worldwide. Most patients present with a rapidly growing neck mass, dysphagia, or voice change. We performed a comprehensive literature search using PubMed focusing on the treatment of anaplastic thyroid cancer including historical review of treatment and outcomes and investigations of new agents and approaches. A total of sixteen chart review and retrospective studies and eleven prospective studies and/or clinical trials were reviewed. The current standard therapeutic approach is to consider the disease as systemic at time of diagnosis and pursue combined modality therapy incorporating cytoreductive surgical resection where feasible and/or chemoradiation either concurrently or sequentially. Doxorubicin is the most commonly used agent, with a response rate of 22%. Several new agents are currently under investigation. Referral of patients for participation in clinical trials is needed.

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.