As a multitargeted kinase inhibitor, sunitinib has carved its way into demonstrating itself as a most effective tyrosine kinase inhibitor in the treatment of metastatic renal cell carcinoma. Mechanistically, sunitinib inhibits multiple receptor tyrosine kinases, especially those involved in angiogenesis, that is, vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and proto-oncogene cKIT. Sunitinib has also been implicated in enhancing cancer invasiveness and metastasis. Mechanisms of resistance are poorly understood, but both intrinsic and acquired mechanisms are thought to be involved. While the side effects are manageable, sunitinib, like many other tyrosine kinase inhibitors, can be associated with serious toxicities that require careful management including frequent dose reductions. Although still in the early stage, emerging evidence points to an immunomodulatory role for sunitinib. It is also likely to contribute to the overall outcomes, especially those seen in metastatic renal cell carcinoma, and such effects are thought to be mediated by the proto-oncogene cKIT receptor. Combination with other modalities such as stereotactic body radiation therapy, therapeutic vaccines, and checkpoint inhibitors is being pursued for improved efficacy.

The human epidermal growth factor receptor 2 (HER2) is overexpressed in 25%–30% of breast cancer patients. Anti-HER2 therapies have changed the aggressive course of HER2+ breast cancer. In spite of the therapeutic benefits, their cardiotoxicities are major concerns, especially when used concurrently with anthracyclines.Here we present an elderly patient with relapsed HER2+ breast cancer. Her presentation for relapsed disease was unusual for the physical finding as well as the history of trastuzumab-induced severe cardiotoxicity while requiring additional anti-HER2 therapy. She received neoadjuvant anti-HER2 treatment for stage III breast caner. Due to severe reduction of cardiac ejection fraction (EF), she only received five doses of adjuvant transtuzumab. Unfortunately her disease relapsed one year later with chest wall lesions and a persistent low EF. We treated the patient with lapatinib combined with capecitabine which resulted rapid resolution of her chest wall lesion. More importantly, the patient had one year of disease control without deterioration in her ejection fraction. We discussed the management of recurrent HER2+ breast cancer with chest wall disease and the choice of anti-HER2 therapy in patients with a history of transtuzumab-induced cardiac dysfunction.

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6573 Background: Recent reports suggest that approximately 30% of patients with APL die during induction. This has been confirmed in large population-based studies in Sweden and the US. A recent analysis of SEER data from 13 population-based cancer registries with 1400 APL patients in the US showed that 17% of all patients and 24% of patients greater than 55 years of age die within one month of diagnosis. The most common causes of death are bleeding, infection, differentiation syndrome and multi-organ failure. Patients who survive induction have an excellent cure rate with few late relapses. Hence, decreasing early deaths is a high priority both at experienced as well as smaller centers with limited leukemia treatment experience in this highly curable disease. Methods: At Georgia Health Sciences University, between 7/2005 and 6/2009, 19 patients were diagnosed with APL. Seven patients (5 high-risk and 2 low-risk) died during induction resulting in an unusually high mortality rate of 37%. All patients who survived induction are still in remission at present. The high early death rate prompted us to develop a simple, 2 page treatment algorithm that focuses on quick diagnosis, prompt initiation of therapy, and proactive and aggressive management of all the major causes of death during induction. We also made our treatment protocol available to smaller treatment centers and helped the treating oncologists manage the patient during the first few days after diagnosis. Results: From 11/2010 to 12/2011, we treated 4 patients at GHSU and helped manage 4 patients at 2 outreach sites. The age range was 30 to 60; two patients were high-risk, 5 intermediate- and one low-risk. There were no deaths during induction and all eight patients proceeded to consolidation treatment. Conclusions: While we recognize that this is a small cohort, our own experience and a similar approach pioneered by investigators in Brazil clearly shows this to be an effective intervention to decrease early deaths in APL. We believe our experience warrants large scale implementation of our protocol in an attempt to reduce early APL mortality.

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