Complete and Durable Responses in Primary Central Nervous System Posttransplant Lymphoproliferative Disorder with Zidovudine, Ganciclovir, Rituximab, and Dexamethasone.

Primary central nervous system posttransplant lymphoproliferative disorder (PCNS-PTLD) is a complication of solid organ transplantation with a poor prognosis and typically associated with Epstein-Barr virus (EBV). We hypothesized EBV lytic-phase protein expression would allow successful treatment with antiviral therapy. Thirteen patients were treated with zidovudine (AZT), ganciclovir (GCV), dexamethasone, and rituximab in EBV PCNS-PTLD.

Hyperthermic Intraperitoneal Chemotherapy Following Cytoreductive Surgery Improves Outcome in Patients With Primary Appendiceal Mucinous Adenocarcinoma: A Pooled Analysis From Three Tertiary Care Centers.

Purpose: Appendiceal mucinous neoplasms (AMN) are a rare heterogeneous group of diseases. In the absence of randomized trials, AMN management is controversial. The goal of this study was to evaluate the impact of hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery on survival in AMN patients.

Treatment-related Hypertension as a Pharmacodynamic Biomarker for the Efficacy of Bevacizumab in Advanced Pancreas Cancer: A Pooled Analysis of 4 Prospective Trials of Gemcitabine-based Therapy With Bevacizumab.

Purpose: Phase III studies of bevacizumab in advanced pancreas cancer (APCA) demonstrated no improvement in outcome. No validated biomarkers for bevacizumab efficacy exist. We evaluated bevacizumab-related hypertension (B-HTN) as a biomarker in APCA patients in a pooled analysis from 4 prospective clinical trials of gemcitabine-based therapy combined with bevacizumab.

Baseline serum albumin is a predictive biomarker for patients with advanced pancreatic cancer treated with bevacizumab: a pooled analysis of 7 prospective trials of gemcitabine-based therapy with or without bevacizumab.

Background: Phase 3 studies of bevacizumab in patients with advanced pancreatic cancer (APCA) demonstrated no improvement in outcome. To the authors' knowledge, no validated predictive biomarkers for bevacizumab exist, although emerging data suggest that subsets of patients with APCA may benefit from treatment with bevacizumab. The authors evaluated baseline serum albumin (b-alb) as a predictive biomarker in a pooled analysis from 7 prospective clinical trials of gemcitabine-based therapy with or without bevacizumab.

Should combination chemotherapy serve as the backbone in clinical trials of advanced pancreatic cancer? A pooled analysis of phase II trials of gemcitabine-containing doublets plus bevacizumab.

Objective: The objective of this study was to evaluate whether building upon multidrug chemotherapy regimens represents a viable strategy in pancreatic cancer clinical trial design.

Methods: We performed a pooled analysis of all single-arm phase II studies in which a specific targeted agent (the anti-vascular endothelial growth factor monoclonal antibody bevacizumab) was added to gemcitabine-based cytotoxic doublets. The primary end point was overall survival (OS).

Genetic validation of the protein arginine methyltransferase PRMT5 as a candidate therapeutic target in glioblastoma.

Glioblastoma is the most common and aggressive histologic subtype of brain cancer with poor outcomes and limited treatment options. Here, we report the selective overexpression of the protein arginine methyltransferase PRMT5 as a novel candidate theranostic target in this disease. PRMT5 silences the transcription of regulatory genes by catalyzing symmetric dimethylation of arginine residues on histone tails.

A phase I dose escalation and pharmacodynamic study of SU5416 (semaxanib) combined with weekly cisplatin and irinotecan in patients with advanced solid tumors.

Background: This phase I study evaluated the safety of SU5416, a potent and selective inhibitor of the vascular endothelial growth factor (VEGF) receptor tyrosine kinase Flk-1, in combination with weekly cisplatin and irinotecan in patients with advanced solid tumors.

Methods: The patients received cisplatin 30 mg/m² and irinotecan 50 mg/m² weekly from week 1 to week 4, with SU5416 at either 65 mg/m² (dose level (DL)1) or 85 mg/m² (DL2) twice weekly for 6 weeks (1 cycle). Serial ¹⁸fluorodeoxyglucose-positron emission tomography (¹⁸FDG-PET) and ¹⁵O-H₂O-PET scans were obtained.

The addition of radiation to chemotherapy does not improve outcome when compared to chemotherapy in the treatment of resected pancreas cancer: the results of a single-institution experience.

Background: Pancreas cancer is highly lethal even at early stages. Adjuvant therapy with chemotherapy (CT) or chemoradiation (CRT) is standard following surgery to delay recurrence and improve survival. There is no consensus on the added value of radiotherapy (RT).

Optimizing neoadjuvant therapy for rectal cancer with oxaliplatin.

Neoadjuvant chemoradiation (CRT) is standard treatment for stage II-III rectal cancer. Fluoropyrimidine-based CRT prolongs disease-free survival over adjuvant CRT and improves local control over both adjuvant CRT and neoadjuvant radiotherapy alone, but does not prolong overall survival. New approaches to neoadjuvant therapy may improve outcome in this disease.

Management of venous thromboembolism in patients with advanced gastrointestinal cancers: what is the role of novel oral anticoagulants?

Venous thromboembolism (VTE) is a frequent complication of gastrointestinal cancers that increases morbidity and may impact mortality. Low-molecular-weight heparins (LMWHs) and vitamin K antagonists (VKAs) are standard anticoagulation options for the ambulatory gastrointestinal cancer patient with VTE, but both of these agents are challenging to use for various reasons. Novel oral anticoagulants (NOAs) are new, orally available anticoagulants designed to be easier to administer with more reliable pharmacokinetics that eliminate the need for frequent monitoring of various laboratory parameters.

Photodynamic therapy (PDT) may provide effective palliation in the treatment of primary tracheal carcinoma: a small case series.

Objective: The purpose of this study was to evaluate the role of photodynamic therapy (PDT) in primary tracheal carcinomas.

Methods: Data were obtained from patients treated with Photofrin(®) PDT for primary tracheal carcinoma at the Ohio State University. Demographic data as well as survival and response were collected.

A phase I study of prolonged infusion of triapine in combination with fixed dose rate gemcitabine in patients with advanced solid tumors.

Purpose: Prolonged exposure of cancer cells to triapine, an inhibitor of ribonucleotide reductase, followed by gemcitabine enhances gemcitabine activity in vitro. Fixed-dose-rate gemcitabine (FDR-G) has improved efficacy compared to standard-dose. We conducted a phase I trial to determine the maximum tolerated dose (MTD), safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of prolonged triapine infusion followed by FDR-G.

A dose escalation and pharmacodynamic study of triapine and radiation in patients with locally advanced pancreas cancer.

Purpose: Triapine, a novel inhibitor of the M2 subunit of ribonucleotide reductase (RR), is a potent radiosensitizer. This phase 1 study, sponsored by the National Cancer Institute Cancer Therapy Evaluation Program, assessed the safety and tolerability of triapine in combination with radiation (RT) in patients with locally advanced pancreas cancer (LAPCA).

Methods And Materials: We evaluated 3 dosage levels of triapine (24 mg/m2, 48 mg/m2, 72 mg/m2) administered with 50.

Elevated baseline CA19-9 levels correlate with adverse prognosis in patients with early- or advanced-stage pancreas cancer.

CA19-9 is the most specific biomarker for pancreas cancer. We investigated the prognostic significance of normal (≤ 37 U/mL) versus elevated (>37 U/mL) CA19-9 levels in patients with resected and advanced pancreas cancer. Relevant data were obtained from patients treated for early-stage or advanced pancreatic adenocarcinoma at our institution.

Influence of KRAS mutation status in metachronous and synchronous metastatic colorectal adenocarcinoma.

Background: Mutations in the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) are present in approximately 30% to 40% of colorectal adenocarcinomas. Wild-type (WT) KRAS mutation status is predictive of tumor response with epidermal growth factor receptor-directed therapies, but the results from studies evaluating the prognostic value of KRAS status in localized disease have been contradictory. The prognostic value of KRAS in metastatic disease, specifically according to whether patients have synchronous or metachronous disease at presentation, is less understood.

Yttrium-90 radioembolization as salvage therapy for colorectal cancer with liver metastases.

Background: Few patients with metastatic colorectal cancer (mCRC) are candidates for resection of their hepatic disease. Yttrium-90 ((90)Y) radioembolization has promise in the treatment of unresectable mCRC. We conducted a retrospective study to assess the efficacy in patients with refractory mCRC who underwent (90)Y radioembolization.