Prospective Clinical Study of Precision Oncology in Solid Tumors.

Systematic studies evaluating clinical benefit of tumor genomic profiling are lacking. We conducted a prospective study in 250 patients with select solid tumors at the Cleveland Clinic. Eligibility required histopathologic diagnosis, age of 18 years or older, Eastern Cooperative Oncology Group performance status 0-2, and written informed consent.

Predicting early mortality in resectable pancreatic adenocarcinoma: A cohort study.

Background: Survival after surgical resection for pancreatic cancer remains poor. A subgroup of patients die early (<6 months), and understanding factors associated with early mortality may help to identify high-risk patients. The Khorana score has been shown to be associated with early mortality for patients with solid tumors.

Safety and efficacy of sorafenib for the treatment of recurrent hepatocellular carcinoma after liver transplantation.

Introduction: Recurrent hepatocellular carcinoma (HCC) following liver transplantation (LT) carries a poor prognosis. The aim of our study was to assess the safety and efficacy of sorafenib in patients with recurrent HCC following LT.

Methods: A prospectively maintained LT database was retrospectively analyzed for patients with recurrent HCC following LT between 2001 and 2011-34 patients.

Complementary use of resection and radiofrequency ablation for the treatment of colorectal liver metastases: an analysis of 395 patients.

Background: Liver resection and radiofrequency ablation (RFA) are two surgical options in the treatment of patients with colorectal liver metastases (CLM). The aim of this study was to analyze patient characteristics and outcomes after resection and RFA for CLM from a single center.

Methods: Between 2000 and 2010, 395 patients with CLM undergoing RFA (n = 295), liver resection (n = 94) or both (n = 6) were identified from a prospective IRB-approved database.

Predictors of clinical outcomes of resected ampullary adenocarcinoma: a single-institution experience.

Background: In the absence of prospective data, the use of adjuvant therapy in ampullary adenocarcinoma is contingent upon the clinicopathological features which can correlate to 5-year post-operative survival and disease relapse.

Methods: We investigated the factors associated with clinical outcomes among 72 patients who underwent pancreatoduodenectomy at the Cleveland Clinic from 1995 to 2007 for histologically confirmed adenocarcinoma of the ampulla of Vater.

Results: R0 resection was achieved in 96% of patients (median age, 72 years; 58% males, 89% Caucasians).

Clinical implications of acellular mucin pools in resected rectal cancer with pathological complete response to neoadjuvant chemoradiation.

Aim: Approximately 20% of rectal cancers treated with neoadjuvant chemoradiation achieve a pathological complete response (pCR), which is associated with an improved oncological outcome. However, in a proportion of patients with a pCR, acellular pools of mucin are present in the surgical specimen. The aim of this study was to evaluate the clinical implications of acellular mucin pools in patients with rectal adenocarcinoma achieving a pCR after neoadjuvant chemoradiation followed by proctectomy.

A single institution review of adjuvant therapy outcomes for resectable pancreatic adenocarcinoma: outcome and prognostic indicators.

Introduction: A large single-institution series of patients who recently underwent pancreaticoduodenectomy for resectable pancreatic cancer was analyzed to determine prognostic factors for overall survival, including the impact of adjuvant radiation and chemotherapy.

Methods: Medical records were reviewed for 179 consecutive patients treated at The Cleveland Clinic with pancreaticoduodenectomy for resectable pancreatic adenocarcinoma from 1999 to 2006. Clinical data were collected, and Kaplan-Meier method was used to estimate overall survival.

A phase I study of EKB-569 in combination with capecitabine in patients with advanced colorectal cancer.

Purpose: To determine the maximum tolerated dose (MTD), characterize the principal toxicities, and assess the pharmacokinetics of EKB-569, an oral selective irreversible inhibitor of the epidermal growth factor receptor tyrosine kinase, in combination with capecitabine in patients with advanced colorectal cancer.

Experimental Design: Patients were treated with EKB-569 daily for 21 days and capecitabine twice daily for 14 days of a 21-day cycle. The dose levels of EKB-569 (mg/day) and capecitabine (mg/m(2) twice daily) assessed were 25/750, 50/750, 50/1,000 and 75/1,000.

A multi-center phase II study of oxaliplatin, irinotecan, and capecitabine in advanced gastric/gastroesophageal junction carcinoma.

Background: There is no standard first-line therapy for advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma and the prognosis remains poor. Our institution conducted a phase I study of oxaliplatin, irinotecan, and capecitabine given in a novel, weekly schedule. The regimen was tolerated; pharmacodynamic studies revealed no drug interactions, and there was one confirmed response in a gastric cancer patient.

Multidisciplinary management of colorectal brain metastases: a retrospective study.

Background: The incidence of brain metastases (BM) from colorectal cancer (CRC) is increasing, and the management of this previously rare complication at a single institution is reported.

Methods: The records of all patients with BM from 1994 to 2005 were reviewed, and 49 patients (33 men, 16 women) with 102 BM from CRC were identified. Associations between patient and tumor characteristics, treatment modality, and survival were assessed.

Subcutaneous implantable venous access device erosion through the skin in patients treated with anti-vascular endothelial growth factor therapy: a case series.

Subcutaneous implantable venous access devices (IVADs) are commonly used in oncology practice. They facilitate the administration of chemotherapy, fluids and blood products. The incidence of IVAD-related complications is not uncommon, and includes infection, thrombosis and bleeding.

Neoadjuvant therapy for hepatocellular carcinoma: is there an optimal approach?

Hepatocellular carcinoma (HCC) is an aggressive tumor that often occurs in the setting of chronic liver disease and cirrhosis. The incidence of hepatocellular carcinoma is increasing in the United States and worldwide. Orthotopic liver transplantation (OLT) is a viable and potentially curative option for selected patients with HCC.

Calmodulin-androgen receptor (AR) interaction: calcium-dependent, calpain-mediated breakdown of AR in LNCaP prostate cancer cells.

Chemotherapy of prostate cancer targets androgen receptor (AR) by androgen ablation or antiandrogens, but unfortunately, it is not curative. Our attack on prostate cancer envisions the proteolytic elimination of AR, which requires a fuller understanding of AR turnover. We showed previously that calmodulin (CaM) binds to AR with important consequences for AR stability and function.

Phase I trial of three-weekly docetaxel, carboplatin and oral lenalidomide (Revlimid) in patients with advanced solid tumors.

Introduction: Lenalidomide is an immunomodulatory derivative of thalidomide with significantly greater in vitro activity and a different toxicity profile. In preclinical trials it has shown synergy with chemotherapy.

Patients And Methods: Primary objective of this study was to determine the maximum tolerated doses of docetaxel and carboplatin when combined with oral lenalidomide in a standard phase I study design.

Regulatory processes affecting androgen receptor expression, stability, and function: potential targets to treat hormone-refractory prostate cancer.

Prostate cancer cells rely on androgen receptor (AR) for proliferation and survival. Therefore, curing prostate cancer will require elimination of AR. Although androgen is the natural ligand that activates AR, AR activity is also subject to regulation by growth factor/growth factor receptor-stimulated signaling pathways that control the cell cycle.

A phase II study of chloroquinoxaline sulfonamide (CQS) in patients with metastatic colorectal carcinoma (MCRC).

Purpose: Phase II multicenter study investigated the efficacy and toxicity of the novel halogenated derivative of sulfaquixonaline Chloroquinoxaline Sulfonamide (CQS) in metastatic colorectal cancer.

Experimental Design: Eligible patients with metastatic or recurrent colorectal cancer received CQS at a dose schedule of 2000 mg/m2 over an hour weekly for 4 weeks every 42 days. Treatment was continued until unexpected toxicity or disease progression.

Predictors of survival after radiofrequency thermal ablation of colorectal cancer metastases to the liver: a prospective study.

Purpose: The aim of this study was to determine the predictors of survival at the time of radiofrequency thermal ablation (RFA) in patients with colorectal liver metastasis.

Patients And Methods: One hundred thirty-five patients with colorectal liver metastases who were not candidates for resection underwent laparoscopic RFA.

Results: The median Kaplan-Meier survival for all patients was 28.

Molecular characterization of new melanoma cell lines from C3H mice induced by ethanol plus ultraviolet radiation.

A major obstacle in understanding the etiology of malignant melanoma is the lack of mouse models and transplantable cell lines. We have recently developed a model of primary melanoma in C3H mice induced by ethanol and UV light. The present study characterizes three cell lines, SM190.

Randomized phase I trial of recombinant human keratinocyte growth factor plus chemotherapy: potential role as mucosal protectant.

Purpose: To evaluate the safety of recombinant human keratinocyte growth factor (KGF) when administered with fluorouracil (FU) in patients with metastatic colorectal cancer.

Patients And Methods: Patients (N = 81) received KGF by intravenous (IV) bolus on days 1 to 3, followed by FU 425 mg/m2/d IV bolus plus leucovorin 20 mg/m2/d IV on days 4 to 8. KGF dose levels were 1, 10, 20, 40, 60, and 80 microg/kg/d.

Phase I trial of weekly docetaxel and gemcitabine in patients with refractory malignancies.

Background: A Phase I study using weekly docetaxel and gemcitabine was conducted to investigate toxicity; to determine the maximum tolerated dose (MTD) of each agent; and, in a preliminary fashion, to determine the antitumor activity of the combination.

Methods: Docetaxel and gemcitabine were administered intravenously on Days 1, 8, and 15 every 28 days. The dose levels of docetaxel and gemcitabine were as follows: Level I, docetaxel 20 mg/m(2)and gemcitabine 400 mg/m(2); Level II, docetaxel 30 mg/m(2)and gemcitabine 400 mg/m(2); Level III, docetaxel 30 mg/m(2)and gemcitabine 600 mg/m(2); Level IV, docetaxel 36 mg/m(2)and gemcitabine 600 mg/m(2); and Level V, docetaxel 36 mg/m(2)and gemcitabine 800 mg/m(2).

Plants, polysaccharides, and the treatment and prevention of neoplasia.

Plants and Fungi have traditionally been the single largest source of lead compounds for the development of therapeutics by the pharmaceutical industry. Currently mushroom and plant polysaccharides brought to attention by Complementary and Alternative medicine, are undergoing scientific analysis and development to prevent and treat cancer, Two classes of saccharides are under investigation-beta glucan polysaccharides as biological response modifiers for the adjuvant treatment of cancer and "Oligosaccharin"-related oligosaccharides for the prevention of sun-induced skin cancer. Beta glucans already in human trials in the Far East will require mechanistic pharmacologic studies and definition of stucture function relationships before they are ready for clinical trials in the West.

Oxaliplatin: a new agent for colorectal cancer.

For nearly 40 years, the medical treatment of colorectal cancer had been limited to the fluoropyrimidines until the recent development of irinotecan (CPT-11). In the past decade, a new agent has appeared, oxaliplatin. This third-generation platinum compound has synergistic activity with 5-fluorouracil and is non-cross-resistant with 5-fluorouracil, CPT-11, and other platinum agents.

A phase II pharmacodynamic study of pyrazoloacridine in patients with metastatic colorectal cancer.

Purpose: To perform a phase II trial of pyrazoloacridine (PZA), a novel DNA intercalator, in patients with metastatic colorectal carcinoma and no previous therapy.

Methods: PZA was administered at a dose of 750 mg/m2 intravenously over 3 h every 21 days. Pharmacokinetic studies to determine PZA plasma concentrations were performed.

Induction of primary cutaneous melanomas in C3H mice by combined treatment with ultraviolet radiation, ethanol and aloe emodin.

The role of ultraviolet (UV) radiation in the induction of nonmelanoma skin cancer is widely accepted, although its precise contribution to the development of primary cutaneous melanoma skin cancer requires further definition. We found that painting aloe emodin, a trihydroxyanthraquinone from Aloe barbadensis, in ethyl alcohol vehicle on the skin of mice in conjunction with exposure to UVB (280-320 nm) radiation results in the development of melanin-containing skin tumors. C3H/HeN mice were treated thrice weekly with aloe emodin in a 25% ethanol in water vehicle and exposed to 15 kJ/m2 UV radiation.

Phase II trial of liposomal doxorubicin (Doxil) in advanced soft tissue sarcomas.

Purpose: To assess the objective response rate, toxicity experienced, progression-free survival, and overall survival of patients with previously untreated advanced soft tissue sarcomas treated with a liposomal doxorubicin formulation (Doxil).

Methods: Patients with metastatic or recurrent soft tissue sarcoma who had received no prior chemotherapy for advanced disease were treated with liposomal doxorubicin (Doxil) according to a two stage accrual design. Doxil was administered at 50 mg/m2 every 4 weeks.