Thermal ablation may improve outcomes in patients with colorectal liver metastasis: a case-control study.

PURPOSE: Local thermal ablation may extend the scope of palliative therapy in patients with colorectal liver metastasis. We performed a retrospective, case-controlled study to compare patients with colorectal liver metastases that were treated with percutaneous radiofrequency (RF) or microwave (MW) thermal ablation, against the control group of chemotherapy alone. METHODS: We described baseline demographics, ablation sessions, procedure duration and related complications. We compared outcomes of percutaneous thermal ablation versus chemotherapy alone (controls) in patients with colorectal liver metastasis. The control group assigned (non-ablated patients) had similar demographics and prior treatment profile when compared to ablated patients. Progression-free survival (PFS) and overall survival (OS) were estimated for the two groups. RESULTS: Twenty-eight cases with 57 baseline hepatic lesions (median age 68 years; male to female ratio 2:1) were evaluated and compared with 48 controls. A total of 55 sessions (52 RF, 3 MW) were performed among the cases, with minimal procedural time (median 8 min), zero mortality and no severe complications (3 cases of local hepatic hematoma not requiring hospitalization). Ablated patients had prolonged median PFS (19.4 months) and OS (27.5 months) when compared against controls (14.0 and 21.4 months, respectively). After adjusting for hepatic involvement, PFS estimates were comparable and OS was better for the ablated group. One and 2-year survival estimates were 0.96 and 0.79 for thermal ablation patients compared with 0.82 and 0.52 for controls (p=0.05 and p=0.07, respectively). CONCLUSION: Percutaneous thermal ablation may delay progression and death in colorectal cancer patients with metastatic liver disease.

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.

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

INTRODUCTION: Chromophobe 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 PRESENTATION: We 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. CONCLUSIONS: Up 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.

Muscle metastasis from hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma is the most common primary tumor of the liver. Disease dissemination occurs through hematogenous routes and frequently involves the lungs, bone, adrenal glands, and pancreas. The patterns of the extrahepatic manifestations are diverse. Soft tissue metastasis is extremely rare and mandates systematic pathological analysis, which may include the use of specific immunohistochemical staining. We report metastasis from a hepatocellular carcinoma, as a discrete subcutaneous mass to the right humerus muscle. MATERIALS AND METHODS: We detail the approach to diagnosis and management of an unusual case of a patient with hepatocellular carcinoma, in whom we found a metastatic lesion as a subcutaneous mass to the right humerus muscle nine years after right hepatectomy. CONCLUSION: This condition poses differential diagnostic problems in the settings of clinical and pathological investigations. Metastasis of hepatocellular carcinoma should be included in the differential diagnosis of rapidly growing lesions.

Trastuzumab plus capecitabine and docetaxel as first-line therapy for HER2-positive metastatic breast cancer: phase II results.

UNLABELLED: In human epidermal growth factor 2 (HER-2)-positive advanced breast cancer, taxanes plus trastuzumab are among the most widely applied options in the first-line setting. The addition of capecitabine to docetaxel significantly improves overall survival in anthracycline-pretreated metastatic breast cancer. We evaluated the efficacy and tolerability of trastuzumab plus capecitabine and docetaxel regimen as first-line therapy. PATIENTS AND METHODS: HER-2-positive patients who had received adjuvant anthracyclines received docetaxel at 75 mg/m(2) on day 1 and capecitabine 950 mg/m(2)/day, days 1-14, every 3 weeks until disease progression or unacceptable toxicity. Trastuzumab was administered at a dose of 6 mg/kg every 3 weeks. Time to progression (TTP) was defined as the primary end point. RESULTS: Twenty-nine patients were evaluable (median age 52, range 34-70 years). The regimen achieved objective responses in 11 patients (38%), including complete response in three (10.3%) and partial response in eight (27.5%). The median overall survival time was 25.5 months, and the median progression-free survival time was 7.8 months. The safety profile of the combination was favorable and predictable, with a low incidence of grade 3/4 adverse events. The most common adverse events were hand-foot syndrome, and gastrointestinal toxicities. Severe myelosuppression was rare and cardiac toxicity did not occur. CONCLUSION: These data confirm that the combination of trastuzumab plus capecitabine and docetaxel is highly active in patients with HER-2-overexpressing anthracycline-pretreated breast cancer, offering a significant survival benefit and is well tolerated.

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

BACKGROUND: Renal 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 PRESENTATION: We present a case of intra-abdominal abscess formation mimicking disease progression, in a patient with metastatic renal cell carcinoma during sunitinib treatment. CONCLUSION: In 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.

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.

Adrenocortical oncocytic carcinoma with recurrent metastases: a case report and review of the literature.

BACKGROUND: Adrenal cortex oncocytic carcinoma (AOC) represents an exceptional pathological entity, since only 22 cases have been documented in the literature so far. CASE PRESENTATION: Our case concerns a 54-year-old man with past medical history of right adrenal excision with partial hepatectomy, due to an adrenocortical carcinoma. The patient was admitted in our hospital to undergo surgical resection of a left lung mass newly detected on chest Computed Tomography scan. The histological and immunohistochemical study revealed a metastatic AOC. Although the patient was given mitotane orally in adjuvant basis, he experienced relapse with multiple metastases in the thorax twice in the next year and was treated with consecutive resections. Two and a half years later, a right hip joint metastasis was found and concurrent chemoradiation was given. Finally, approximately five years post disease onset, the patient died due to massive metastatic disease. A thorough review of AOC and particularly all diagnostic difficulties are extensively stated. CONCLUSION: Histological classification of adrenocortical oncocytic tumours has been so far a matter of debate. There is no officially established histological scoring system regarding these rare neoplasms and therefore many diagnostic difficulties occur for pathologists.

Gemcitabine in combination with vinorelbine for heavily pretreated advanced breast cancer.

PURPOSE: To evaluate the activity and toxicity of gemcitabine and vinorelbine in patients with metastatic breast cancer (MBC), previously treated with anthracyclines alone or with taxanes. PATIENTS AND METHODS: A total of 86 pretreated patients with MBC (median age 62 years), entered the study. Thirty-six patients had been pretreated with anthracyclines and 8 were resistant. The combination of gemcitabine (1000 mg/m2) and vinorelbine (25 mg/m2) was administered on days 1 and 8 every 3 weeks, for a total of 6 cycles. RESULTS: A total of 344 cycles of chemotherapy were administered (median 4 cycles per patient). Partial responses were observed in 31 patients (36.0%; 95% CI: 23-56). The median duration of response was 7 months (range 3-11 months) and the median overall survival was 14 months (range 6-21). The scheme was well tolerated. CONCLUSION: The combination of vinorelbine and gemcitabine is an active scheme in pretreated MBC, demonstrating an acceptable toxicity profile, and may well represent a valuable therapeutic choice after anthracycline/taxane regimens.

Third-line hormonal treatment with exemestane in postmenopausal patients with advanced breast cancer progressing on letrozole or anastrozole. A phase II trial conducted by the Hellenic Group of Oncology (HELGO).

AIMS AND BACKGROUND: The understanding of hormonal therapies in postmenopausal women with metastatic breast cancer has advanced greatly in the past several decades. With the introduction of orally active, potent and selective third-generation aromatase inhibitors (anastrozole, letrozole and exemestane), approaches to the treatment of hormone-sensitive advanced breast cancer are undergoing reevaluation. For treatment of advanced or metastatic disease that has progressed on tamoxifen, all three agents are active. The purpose of the study was to assess the antitumor efficacy and tolerance of exemestane administered as third-line hormonal therapy to postmenopausal women with metastatic breast cancer refractory to letrozole and anastrozole. STUDY DESIGN: Sixty postmenopausal women with stage IV hormone receptor-positive carcinoma of the breast were enrolled in the study. All patients had received two prior hormonal manipulations and had measurable or assessable disease. All adverse events were monitored. RESULTS: Objective tumor response was achieved in 12 (20%) patients (95% CI, 9.6-30.4). The overall clinical benefit was 38.3% (95% CI, 21.2-49.3), and the median duration of objective tumor response was 20 months (range, 9-26). The median time to death was 17.4 months (95% CI, 16.14-18.66). CONCLUSIONS: Exemestane represents an active and well-tolerated treatment option in pretreated patients with advanced breast cancer who have received standard first- and second line hormonal therapies. By extending the sequence of hormonal therapy, disease progression and the need for chemotherapy may be significantly delayed.

Gemcitabine combined with 5-fluorouracil for the treatment of advanced carcinoma of the pancreas.

BACKGROUND: Gemcitabine is an active agent in pancreatic cancer, showing clinical synergy with 5-fluorouracil (5-FU). The aim of the study was to evaluate the safety and efficacy of the combination of gemcitabine and 5-FU in patients with advanced adenocarcinoma of the pancreas. PATIENTS AND METHODS: Forty-two patients (median age, 62 years), with advanced or metastatic pancreatic adenocarcinoma, were enrolled in the study. The combination of gemcitabine (1000 mg/m2) and 5-FU (600 mg/m2) was administered on days 1, 8 and 15 and repeated every 28 days. RESULTS: A total of 168 cycles (median 4 cycles per patient) were administered. Partial responses were observed in 6 patients (14.2%) and stable disease in 11 (26.2%). The overall clinical benefit was 40.4%. Symptom relief and improvement of performance status were observed in 18 (42.8%) patients. The median time to progression, median duration of response and the median overall survival, were 6, 7 and 13 months, respectively. The most common grade 3 to 4 toxicities were neutropenia, anaemia and diarrhoea. CONCLUSION: The combination of gemcitabine and 5-FU is an active regimen for the treatment of advanced pancreatic cancer with an acceptable toxicity profile.

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.

Adjuvant systemic therapy protocol for Dukes' B2 and C resectable colon carcinoma.

AIMS AND BACKGROUND: Trials of adjuvant systemic therapy in high risk patients with Dukes' B2 and C colon cancer utilizing 5-fluorouracil-based regimens have been ongoing since the 1960s. The aim of this study was to compare the combination of 5-FU and leucovorin with the combination of 5-FU and alfa-2b interferon (IFN) in patients who had undergone "curative" resection foronocarcinoma. STUDY DESIGN: A total of 322 patients with histologically proven adenocarcinoma of the colon, Dukes' stage B2 and C, were entered in the study. They were randomized to A) leucovorin 20 mg/m2 rapid intravenous injection and 5-FU 425 mg/m2 IV days 1-5 every 28 days for six cycles or B) 5-FU 600 mg/m2 24-hour infusion for five days, then 600 mg/m2 IV once a week and IFN 5 MU subcutaneously three times a week for six months. RESULTS: There was no statistically significant difference in either disease-free survival or overall survival. Toxicity was the same in the two groups with the exception of flu-like syndrome, which was universal in IFN-treated patients. CONCLUSIONS: There was no difference in disease-free survival or overall survival between the two combinations in any patient subset. Toxicity was greater with the 5-FU+IFN combination because of the flu-like syndrome. These data do not support the use of IFN in combination with 5-FU as systemic adjuvant therapy for patients with locally advanced colon carcinoma.