A phase I study of gemcitabine + dasatinib (gd) or gemcitabine + dasatinib + cetuximab (GDC) in refractory solid tumors.

Purpose: This study was conducted to define the maximum tolerated dose (MTD), recommended phase two dose (RPTD), and toxicities of gemcitabine + dasatinib (GD) and gemcitabine + dasatinib + cetuximab (GDC) in advanced solid tumor patients.

Methods: This study was a standard phase I 3 + 3 dose escalation study evaluating two combination regimens, GD and GDC. Patients with advanced solid tumors were enrolled in cohorts of 3-6 to either GD or GDC.

Biomarker signatures correlate with clinical outcome in refractory metastatic colorectal cancer patients receiving bevacizumab and everolimus.

A novel combination of bevacizumab and everolimus was evaluated in refractory colorectal cancer patients in a phase II trial. In this retrospective analysis, plasma samples from 49 patients were tested for over 40 biomarkers at baseline and after one or two cycles of drug administration. Analyte levels at baseline and change on-treatment were correlated with progression-free survival (PFS) and overall survival (OS) using univariate Cox proportional hazard modeling.

Treatment of palmar-plantar erythrodysesthesia (PPE) with topical sildenafil: a pilot study.

Purpose: Palmar-plantar erythrodysesthesia (PPE) is a common chemotherapy and anti-VEGF multi-kinase inhibitor class-related toxicity that often results in debilitating skin changes and often limits the use of active anti-cancer regimens. Mechanistic and anecdotal clinical evidence suggested that topical application of sildenafil cream may help reduce the severity of PPE. Therefore, we conducted a randomized, double-blind, placebo-controlled pilot study to evaluate the feasibility, safety and efficacy of topical sildenafil cream for the treatment of PPE.

Correlation of angiogenic biomarker signatures with clinical outcomes in metastatic colorectal cancer patients receiving capecitabine, oxaliplatin, and bevacizumab.

A novel combination of capecitabine, oxaliplatin, and bevacizumab was evaluated in colorectal cancer patients enrolled in a phase II clinical trial. In this retrospective analysis, plasma samples from patients receiving capecitabine, oxaliplatin, and bevacizumab were analyzed to investigate biomarkers of clinical benefit. Forty-one protein biomarkers were tested in 38 patients at baseline and after two cycles of drug administration.

A phase II study of oxaliplatin, dose-intense capecitabine, and high-dose bevacizumab in the treatment of metastatic colorectal cancer.

Background: This study was designed to determine the efficacy and tolerability of a novel 2-week regimen of capecitabine, oxaliplatin (OHP), and bevacizumab in patients with chemo-naive advanced colorectal cancer.

Patients And Methods: Nineteen patients with previously untreated advanced colorectal cancer received capecitabine at 1000 mg/m(2) twice a day on days 1-5 and days 8-12 of a 14-day cycle, and OHP at 85 mg/m(2) and bevacizumab at 10 mg/kg every 2 weeks. Because of unacceptable toxicities, the capecitabine dose was reduced to 850 mg/m(2).

A phase II trial of bevacizumab plus everolimus for patients with refractory metastatic colorectal cancer.

Purpose: For patients with metastatic colorectal cancer (mCRC), no standard therapy exists after progression on 5-fluorouracil, oxaliplatin, irinotecan, bevacizumab, and cetuximab or panitumumab. Preclinical data demonstrated that combined vascular endothelial growth factor and mammalian target of rapamycin inhibition has greater antiangiogenic and antitumor activity than either monotherapy. A phase I study of bevacizumab plus everolimus demonstrated that the combination is safe; activity was seen in several patients with refractory mCRC.

A Phase I study of capecitabine, carboplatin, and paclitaxel with external beam radiation therapy for esophageal carcinoma.

Purpose: Concurrent chemotherapy and radiation therapy (RT) are used to treat patients with esophageal cancer. The optimal combination of chemotherapeutic agents with RT is undefined. We evaluated a combination of capecitabine, carboplatin, and paclitaxel with RT in a phase I study.

Long-term treatment with bevacizumab for patients with metastatic colorectal cancer: case report.

Bevacizumab is a monoclonal antibody to vascular endothelial growth factor that has demonstrated increased overall survival when added to standard chemotherapy regimens for metastatic colorectal cancer. Herein we report the cases of 2 patients who demonstrated prolonged survival times of almost 5 and 6 years, respectively, on various chemotherapy regimens that also included bevacizumab. Throughout most of their disease course, these patients maintained a good quality of life, with some adjustments of chemotherapy doses because of side effects.

Increased toxicity with gefitinib, capecitabine, and radiation therapy in pancreatic and rectal cancer: phase I trial results.

Purpose: Overexpression of epidermal growth factor receptor (EGFR) has been associated with aggressive tumor phenotypes, chemotherapy, and radiation resistance, as well as poor survival in preclinical and clinical models. The EGFR inhibitor gefitinib potentiates chemotherapy and radiation tumor cytotoxicity in preclinical models, including pancreatic and colorectal cancer. We initiated two phase I trials assessing the combination of gefitinib, capecitabine, and radiation in patients with localized pancreatic and rectal cancer.

A Phase I trial of preoperative eniluracil plus 5-fluorouracil and radiation for locally advanced or unresectable adenocarcinoma of the rectum and colon.

Purpose: Eniluracil, an effective inactivator of dihydropyrimidine dehydrogenase, allows for oral dosing of 5-fluorouracil (5-FU), which avoids the morbidity of continuous infusion 5-FU. We addressed the safety of oral eniluracil and 5-FU combined with preoperative radiotherapy and determined the recommended Phase II dose and dose-limiting toxicity in patients with locally advanced rectal and colon cancer.

Methods And Materials: Patients with TNM Stage II or III rectal cancer and residual or recurrent colon cancer received eniluracil (starting at 6.