Phase I and Pharmacology Study of Ropidoxuridine (IPdR) as Prodrug for Iododeoxyuridine-Mediated Tumor Radiosensitization in Advanced GI Cancer Undergoing Radiation.

Purpose: Iododeoxyuridine (IUdR) is a potent radiosensitizer; however, its clinical utility is limited by dose-limiting systemic toxicities and the need for prolonged continuous infusion. 5-Iodo-2-pyrimidinone-2'-deoxyribose (IPdR) is an oral prodrug of IUdR that, compared with IUdR, is easier to administer and less toxic, with a more favorable therapeutic index in preclinical studies. Here, we report the clinical and pharmacologic results of a first-in-human phase I dose escalation study of IPdR + concurrent radiation therapy (RT) in patients with advanced metastatic gastrointestinal (GI) cancers.

Impact of Primary Tumor Location on First-line Bevacizumab or Cetuximab in Metastatic Colorectal Cancer.

Background: Colorectal cancer is one of the most common malignancies in the United States, with a large proportion of patients presenting with metastatic disease or developing a recurrence. Systemic chemotherapy is the mainstay of therapy in this setting. There is a clear benefit in the addition of bevacizumab or cetuximab (for rat sarcoma [RAS] wild type tumors) to oxaliplatin- and irinotecan-based regimens which can be considered for first-line therapy.

Effect of the Addition of Cetuximab to Paclitaxel, Cisplatin, and Radiation Therapy for Patients With Esophageal Cancer: The NRG Oncology RTOG 0436 Phase 3 Randomized Clinical Trial.

Importance: The role of epidermal growth factor receptor (EGFR) inhibition in chemoradiation strategies in the nonoperative treatment of patients with esophageal cancer remains uncertain.

Objective: To evaluate the benefit of cetuximab added to concurrent chemoradiation therapy for patients undergoing nonoperative treatment of esophageal carcinoma.

Design, Setting, And Participants: A National Cancer Institute (NCI) sponsored, multicenter, phase 3, randomized clinical trial open to patients with biopsy-proven carcinoma of the esophagus.

RECQ1 A159C Polymorphism Is Associated With Overall Survival of Patients With Resected Pancreatic Cancer: A Replication Study in NRG Oncology Radiation Therapy Oncology Group 9704.

Purpose: To confirm whether a previously observed association between RECQ1 A159C variant and clinical outcome of resectable pancreatic cancer patients treated with preoperative chemoradiation is reproducible in another patient population prospectively treated with postoperative chemoradiation.

Methods And Materials: Patients were selected, according to tissue availability, from eligible patients with resected pancreatic cancer who were enrolled on the NRG Oncology Radiation Therapy Oncology Group 9704 trial of 5-fluorouacil (5-FU)-based chemoradiation preceded and followed by 5-FU or gemcitabine. Deoxyribonucleic acid was extracted from paraffin-embedded tissue sections, and genotype was determined using the Taqman method.

Updates in Tumor Profiling in Gastrointestinal Cancers.

In the last decade there has been a focus on biomarkers that play a critical role in understanding molecular and cellular mechanisms which drive tumor initiation, maintenance and progression of cancers. Characterization of genomes by next-generation sequencing (NGS) has permitted significant advances in gastrointestinal cancer care. These discoveries have fueled the development of novel therapeutics and have laid the groundwork for the development of new treatment strategies.

Mutation Profiling of Clinically Advanced Cancers Using Next-Generation Sequencing for Targeted Therapy: A Lifespan Experience.

The application of modern molecular tests such as next-generation sequencing (NGS) to human malignancies has led to better understanding of tumor biology and the design of targeted molecular therapies. In the research setting, important genomic alterations in tumors have been discovered with potential therapeutic implications but data regarding the impact of this technology in a real world oncology practice is limited. As a result, we decided to review the results of NGS in 144 advanced-stage cancer patients referred to the oncology practices of Lifespan-affiliated centers in Rhode Island.

Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial.

Background: Vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2)-mediated signalling and angiogenesis can contribute to the pathogenesis and progression of gastric cancer. We aimed to assess whether ramucirumab, a monoclonal antibody VEGFR-2 antagonist, prolonged survival in patients with advanced gastric cancer.

Methods: We did an international, randomised, double-blind, placebo-controlled, phase 3 trial between Oct 6, 2009, and Jan 26, 2012, at 119 centres in 29 countries in North America, Central and South America, Europe, Asia, Australia, and Africa.

Lenalidomide for second-line treatment of advanced hepatocellular cancer: a Brown University oncology group phase II study.

Purpose: To assess the activity and toxicity of lenalidomide for patients with advanced hepatocellular cancer (HCC) previously treated with sorafenib.

Materials And Methods: Patients with advanced HCC who progressed on or were intolerant to sorafenib were eligible. Patients received lenalidomide 25 mg orally for 1 to 21 days in a 28-day cycle until disease progression or unacceptable toxicities.

Paclitaxel poliglumex, temozolomide, and radiation for newly diagnosed high-grade glioma: a Brown University Oncology Group Study.

Objectives: Paclitaxel poliglumex (PPX), a drug conjugate that links paclitaxel to poly-L-glutamic acid, is a potent radiation sensitizer. Prior studies in esophageal cancer have demonstrated that PPX (50 mg/m/wk) can be administered with concurrent radiation with acceptable toxicity. The primary objective of this study was to determine the safety of the combination of PPX with temozolomide and concurrent radiation for high-grade gliomas.

Cetuximab, paclitaxel, carboplatin, and radiation for head and neck cancer: a survival analysis of a Brown University Oncology Group phase II study.

Objectives: To assess the effect on progression-free and overall survival from the addition of cetuximab to paclitaxel-based chemoradiation for patients with squamous cell head and neck cancer from Brown University Oncology Group studies.

Methods: BrUOG HN-204 patients with stage III or IV locally advanced squamous cell cancer of the head and neck without distant organ metastases received 4 weeks of induction cetuximab followed by weekly cetuximab, paclitaxel, carboplatin, and concurrent radiation. Recurrence and survival data were compared with previous Brown University studies utilizing the same paclitaxel-based chemoradiation with and without induction chemotherapy.

A randomized, placebo-controlled phase 2 study of ganitumab (AMG 479) or conatumumab (AMG 655) in combination with gemcitabine in patients with metastatic pancreatic cancer.

Background: We evaluated the efficacy and safety of ganitumab (a mAb antagonist of insulin-like growth factor 1 receptor) or conatumumab (a mAb agonist of human death receptor 5) combined with gemcitabine in a randomized phase 2 trial in patients with metastatic pancreatic cancer.

Patients And Methods: Patients with a previously untreated metastatic pancreatic adenocarcinoma and an Eastern Cooperative Oncology Group (ECOG) performance status ≤1 were randomized 1 : 1 : 1 to i.v.

A Phase I Study of Dasatinib with Concurrent Chemoradiation for Stage III Non-Small Cell Lung Cancer.

Objectives: Src family kinases (SFKs) are expressed in non-small cell lung cancer (NSCLC) and may be involved in tumor growth and metastases. Inhibition of SFK may also enhance radiation. The purpose of this study was to evaluate if a maximum dose of 100 mg of dasatinib could be safely administered with concurrent chemoradiation and then continued as maintenance for patients with newly diagnosed stage III NSCLC.

Pathologic response after neoadjuvant carboplatin and weekly paclitaxel for early-stage lung cancer: a Brown University oncology group phase II study.

Introduction: Pathologic complete response (pCR) to neoadjuvant chemotherapy is associated with improved survival in solid tumors. Southwest Oncology Group 9,900 demonstrated a 9% pCR after three cycles of paclitaxel/carboplatin every 21 days. We evaluated pCR rate with intensive weekly paclitaxel in a phase II study.

Neoadjuvant paclitaxel poliglumex, cisplatin, and radiation for esophageal cancer: a phase 2 trial.

Purpose: To evaluate the pathologic complete response (CR) rate and safety of paclitaxel poliglumex (PPX), cisplatin, and concurrent radiation for patients with esophageal cancer.

Patients And Methods: Patients with adenocarcinoma or squamous cell carcinoma of the esophagus or gastroesophageal junction with no evidence of distant metastasis received PPX (50 mg/m(2)/wk) and cisplatin (25 mg/m(2)/wk) for 6 weeks with 50.4 Gy concurrent radiation.

Weekly paclitaxel and carboplatin induction chemotherapy followed by concurrent chemoradiotherapy in locally advanced squamous cell carcinoma of the head and neck.

Objective: To perform a phase II trial evaluating dose dense induction chemotherapy for locally advanced head and neck cancer.

Patients And Methods: Thirty-five patients received 6 weekly doses of carboplatin (area under the curve=2) and paclitaxel (135 mg/m) followed by concurrent weekly paclitaxel (40 mg/m) and carboplatin (area under the curve=1) and daily radiation (66-72 Gy).

Results: There was 1 induction death from neutropenic sepsis and 1 sudden death during chemoradiotherapy.

Neoadjuvant bevacizumab, oxaliplatin, 5-fluorouracil, and radiation for rectal cancer.

Purpose: To evaluate the feasibility and pathologic complete response rate of induction bevacizumab + modified infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) 6 regimen followed by concurrent bevacizumab, oxaliplatin, continuous infusion 5-fluorouracil (5-FU), and radiation for patients with rectal cancer.

Methods And Materials: Eligible patients received 1 month of induction bevacizumab and mFOLFOX6. Patients then received 50.

Pneumonectomy after neoadjuvant chemotherapy and radiation for advanced-stage lung cancer.

Background: Intergroup 0139 Trial suggests an increase in mortality after pneumonectomy in patients receiving preoperative chemotherapy and radiation. We evaluate our outcomes with pneumonectomy after neoadjuvant chemotherapy and radiation.

Methods: Neoadjuvant chemotherapy and radiation consisted of cisplatin 50 mg/m2 on days 1, 8, 29, and 36 and etoposide 50 mg/m2 on days 1-5 and 29-33 given concurrently with 5,040 cGy radiation.

Cetuximab, paclitaxel, carboplatin, and radiation for head and neck cancer: a toxicity analysis.

Objective: To determine the feasibility and toxicity of the addition of cetuximab to paclitaxel, carboplatin, and concurrent radiation for patients with head and neck cancer.

Materials And Methods: Patients with stage III or IV locally advanced squamous cell cancer of the head and neck, without distant organ metastases, were eligible. Patients received 4 weeks of induction cetuximab followed by weekly cetuximab, paclitaxel, carboplatin, and concurrent radiation.

Lapatinib/gemcitabine and lapatinib/gemcitabine/oxaliplatin: a phase I study for advanced pancreaticobiliary cancer.

Objective: To evaluate the safety/tolerability and potential antitumor activity of lapatinib, at dose ranges of 1000 to 1500 mg/d, in combination with gemcitabine and gemcitabine/oxaliplatin (GEMOX) in patients with advanced pancreaticobiliary cancer.

Materials And Methods: Patients with advanced pancreaticobiliary cancer were assigned to 1 of 4 cohorts of lapatinib administered once daily. Toxicities, response, and survival were assessed.

Cetuximab with concurrent chemoradiation for esophagogastric cancer: assessment of toxicity.

Purpose: To determine the feasibility and toxicity of the addition of cetuximab with paclitaxel, carboplatin, and radiation for patients with esophagogastric cancer on a Phase II study.

Methods And Materials: Patients with locoregional esophageal and proximal gastric cancer without distant organ metastases were eligible. All patients received cetuximab, paclitaxel, and carboplatin weekly for 6 weeks with 50.

Docetaxel, capecitabine and carboplatin in metastatic esophagogastric cancer: a phase II study.

Purpose: A Phase I investigation of docetaxel, carboplatin, and capecitabine at our institution demonstrated the safety and tolerability of this regimen in patients with metastatic esophagogastric cancer. The objectives of this Phase II study were to determine the response rate, toxicity, and survival for patients with metastatic esophagogastric cancer treated with this regimen.

Materials And Methods: Chemotherapy naïve patients with metastatic esophageal or gastric cancer received a regimen comprised of docetaxel 40 mg/m(2), days 1 and 8, carboplatin AUC = 2, Days 1 and 8, and capecitabine 2000 mg/m(2), Days 1-10 in 21-Day cycles.

A phase I study of docetaxel, oxaliplatin, and capecitabine in patients with metastatic gastroesophageal cancer.

Objectives: Docetaxel, capecitabine, and oxaliplatin are important new agents in esophagogastric cancer. The Brown University Oncology Group initiated a phase I study to determine the maximum tolerated dose of weekly docetaxel, oxaliplatin, and capecitabine.

Methods: Patients with metastatic esophageal and gastric cancers received docetaxel and oxaliplatin on days 1 and 8 and capecitabine in divided doses, twice daily, on days 1 to 10, with each cycle repeated every 21 days.

HER family inhibitors in pancreatic cancer: current status and future directions.

Pancreatic cancer is characterized by multiple genetic abnormalities that can be used as targets for specific therapeutics. The HER family consists of four transmembrane growth factor receptors. Targeting HER1 with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib demonstrated a survival advantage for patients with advanced pancreatic cancer.