Constantine Gennatas

Successful treatment with the mTOR inhibitor everolimus in a patient with Perivascular epithelioid cell tumor

Perivascular epithelioid cell tumor (PEComa) is an extremely rare neoplasm that appears to arise most commonly at visceral (especially gastrointestinal and uterine), retroperitoneal, and abdominopelvic sites. Malignant PEComas exist but are very rare. These tumors represent a family of mesenchymal neoplasms, mechanistically linked through activation of the mTOR signaling pathway. Metastatic PEComa is a rare form of sarcoma for which no effective therapy has been described previously and that has a uniformly fatal outcome. Although there is no known effective therapy, the molecular pathophysiology of aberrant mTOR signaling provides a scientific rationale to target this pathway therapeutically. The difficulty in determining optimal therapy, owing to the sparse literature available, led us to present this case. On this basis, we report a case of metastatic retroperitoneal PEComa treated with an oral mTOR inhibitor, with everolimus achieving significant clinical response.

Isolated Talus Metastasis from Breast Carcinoma: A Case Report and Review of the Literature

Background: Acrometastases are very rare and have been identified in only a few cases on the foot. At the onset, they might be misdiagnosed as arthritis. Case Report: A 59-year-old woman with isolated metastasis to the talus, originating from breast carcinoma was treated by radiotherapy, letrazole, and intravenous bisphosphonates. Results: The review of the literature revealed that this is the first case of an isolated metastasis to the bone of talus from a breast carcinoma, while there are a few cases originating from other organs. The differential diagnosis of acrometastases may be difficult. Conclusion: Pain in the foot or hand of a patient with a known history of malignancy should be considered as potential metastasis.

The Role of Capecitabine in the Management of Tumors of the Digestive System

Capecitabine has been developed as a prodrug of FU, with the goal of improving tolerability and intratumor drug concentration through tumor-specific conversion to the active drug. The purpose of this article is to review the available information on capecitabine with respect to clinical efficacy for tumors of the digestive tract, adverse-effect profile, documented drug interactions, dosage and administration, and future directions of ongoing research. Relevant English-language literature was identified through searches of NCI, PubMed, ASCO.org and ESMO, ECCO meetings proceedings.

A randomized phase II trial of aminoglutethimide and hydrocortisone versus combined aminoglutethimide, hydrocortisone and fluoxymesterone in advanced breast cancer

Fifty postmenopausal women with advanced breast cancer were included in the following randomized phase II trial: 25 patients received aminoglutethimide 1000 mg and hydrocortisone 40 mg daily. Twenty-five patients received aminoglutethimide 1000 mg, hydrocortisone 40 mg and fluoxymesterone 20 mg daily. The two groups of patients were comparable in respect to the most important pretreatment characteristics. The majority of patients in both groups had bone lesions. There was a history of response to tamoxifen in all the cases and 17 patients had positive estrogen and progesterone receptors. The evaluation of response was based on the system adopted by the UICC. In the aminoglutethimide-hydrocortisone group, 16 (64%) patients obtained a partial remission, 3 (12%) remained stable and 6 (24%) had progressive disease. In the combination treatment group, 17 (68%) patients obtained a partial remission, 3 (12%) remained stable and 5 (20%) developed progressive disease. The median duration of partial remission and stabilization of the disease was 9 and 7 months respectively in both groups.

Abscess formation mimicking disease progression, in a patient with metastatic renal cell carcinoma during sunitinib treatment

BackgroundRenal cell carcinoma (RCC) represents approximately 3% of all adult cancers and is more common in males. Systemic treatment for RCC has improved following the introduction of tyrosine kinase inhibitors, such as sunitinib. The molecular targets of sunitinib are receptor tyrosine kinases (RTKs). Moreover, sunitinib has an additional anti-angiogenic effect through its inhibition of the vascular endothelial growth factor receptor activation.Case presentationWe present a case of intra-abdominal abscess formation mimicking disease progression, in a patient with metastatic renal cell carcinoma during sunitinib treatment.ConclusionIn the advancing era of molecular therapy of solid tumours, sunitinib has demonstrated significant efficacy in the post-cytokine setting treatment of metastatic renal cancer. Concurrently, however, increasing evidence has emerged to indicate that this class of drugs exert profound immunomodulatory effects on T cells and play major roles in immune tumor surveillance.

Chromophobe renal cell carcinoma with prolonged response to targeted therapy: a case report

IntroductionChromophobe renal cell carcinoma is universally accepted as a distinct subtype of renal cell carcinoma. There are conflicting reports on prognosis, and few data on response to treatment exist. Currently, we do not have any effective treatment for the metastatic disease apart from surgical procedures. Current strategies are based on results obtained in the context of clear cell-type renal cell carcinoma. Separate trials for rare histologies seem unfeasible and are unlikely to be performed. For these cases, clinical observations are an important part for advancing therapeutic insight. In recent years, novel tyrosine kinase inhibitors have been shown to have significant clinical benefit in advanced renal cell carcinoma.Case presentationWe present the case of a 43-year-old Caucasian man with advanced chromophobe renal cell carcinoma treated with the tyrosine kinase inhibitor sunitinib and subsequently with sorafenib and the mammalian target of the rapamycin inhibitor everolimus, achieving a prolonged response and significant clinical benefit. We report an unexpectedly high efficacy of everolimus as a third-line treatment in a patient with metastatic chromophobe renal cell carcinoma.ConclusionsUp to now, no published data from randomized clinical studies have addressed the question of efficacy of everolimus as a third-line treatment after failure of tyrosine kinase inhibitors. To the best of our knowledge, this case is the first report of chromophobe renal cell carcinoma treated successfully with sequential tyrosine kinase and mammalian target of rapamycin inhibitor therapy. Notably, the time on treatment with sunitinib exceeded four years. The case presented here implies that everolimus could be a viable option for patients with metastatic chromophobe renal cell carcinoma.