Hypomethylating Agents for Treatment of Elderly Patients with Refractory Acute Myeloid Leukemia - A Case Report with a Focused Review of Literature.

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.

Phase II trial of sorafenib in patients with advanced anaplastic carcinoma of the thyroid.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Cognitive dysfunction in postmenopausal breast cancer patients on aromatase inhibitors.

As mortality in breast cancer patients has improved, morbidity of treatment has become increasingly important. Cognitive dysfunction has been considered as a morbid condition that may possibly result from aromatase inhibitor therapy, the standard treatment in postmenopausal, estrogen/progesterone receptor-positive breast cancer patients. Chemotherapy has been associated with cognitive dysfunction through neuropsychological testing and neurological functional imaging, but the relationship between estrogen and cognition remains largely unexplained. In focusing on aromatase inhibitor therapy, most of the studies yielding mixed results have been limited by confounders and small numbers of populations studied. This article briefly summarizes the major studies evaluating aromatase inhibitor therapy and cognitive dysfunction while considering new directions in future study design.

Anaplastic thyroid cancer: a review of epidemiology, pathogenesis, and treatment.

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.

Cerebrospinal fluid leak during treatment with bevacizumab and irinotecan after carmustine-impregnated wafers placement in patients with grade 2 oligodendroglioma and glioblastoma multiforme: report of two cases and review of literature.

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.

Combretastatin A4 phosphate: a novel vascular disrupting agent.

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.

Ocular surface squamous neoplasia in patients with HIV infection in sub-Saharan Africa.

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.

Circulating tumor cells in the management of breast cancer.

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.

Role of obesity and exercise in breast cancer survivors.

Over 60% of the American population meets the criteria for obesity, and obesity is very common in patients with breast cancer. Many studies have shown that obese patients with breast cancer have a worse prognosis compared to normal weight individuals. Tumor characteristics and other factors contribute to this. Exercise could reverse some of the pathophysiologic factors that contribute to this increased risk, and has been shown in some studies to improve survival in patients with breast cancer. In addition to administering anticancer therapy, cancer clinicians should make concerted attempts to get patients to enroll in weight management and exercise programs, which could improve survival in patients with breast cancer.

A phase II trial of fosbretabulin in advanced anaplastic thyroid carcinoma and correlation of baseline serum-soluble intracellular adhesion molecule-1 with outcome.

BACKGROUND: 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). METHODS: 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. RESULTS: 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 (p < 0.009). CONCLUSIONS: 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.

Changing healthcare practice for older adults with late-stage non-small cell lung cancer: practical considerations of targeted therapy in primary care and oncology.

Healthcare practice for cancer care is rapidly evolving because of advances in technology, scientific discovery, drug development, and aging demographics in America. Among the substantive changes in science and drug development is targeted therapy. Targeted agents are changing the scope of practice in treating lung cancer-the leading cause of cancer death in older adults. Given the growing use of these agents in cancer management, shared awareness of practical management considerations between specialists and primary care providers is important. This article reviews targeted therapy in late-stage non-small cell lung cancer (NSCLC) and shared care concerns in continuity of care of older Americans with this disease. Important practice points for providers caring for older patients with late-stage lung cancer treated with targeted therapy are presented through an educational guide addressing potential management concerns.