Pharmacogenetics-Guided Phase I Study of Capecitabine on an Intermittent Schedule in Patients with Advanced or Metastatic Solid Tumours.

The FDA-approved starting dosage of capecitabine is 1,250 mg/m(2), and market research indicates that U.S. physicians routinely prescribe 1,000 mg/m(2).

Tumour pharmacodynamics and circulating cell free DNA in patients with refractory colorectal carcinoma treated with regorafenib.

Background: Regorafenib, a multi-kinase inhibitor, is used in the treatment of patients with metastatic colorectal cancer refractory to standard therapy. However, this benefit was limited to 1.4 months improvement in overall survival, with more than half of patients experiencing grade 3 to 4 adverse events.

Evaluation of hypertension and proteinuria as markers of efficacy in antiangiogenic therapy for metastatic colorectal cancer.

Background: The vascular endothelial growth factor pathway is strongly implicated in cancer-related angiogenesis. Antiangiogenic agents such as bevacizumab commonly cause hypertension (HTN) and proteinuria (PTN), which may be biomarkers of response and clinical outcome.

Study: We conducted a retrospective analysis of patients with histologically proven metastatic colorectal cancer (mCRC) treated with either bevacizumab or a tyrosine kinase inhibitor in combination with chemotherapy at The Christie Hospital from January 2006 to September 2009.

Glucuronidation by UGT1A1 is the dominant pathway of the metabolic disposition of belinostat in liver cancer patients.

Unlabelled: Belinostat is a hydroxamate class HDAC inhibitor that has demonstrated activity in peripheral T-cell lymphoma and is undergoing clinical trials for non-hematologic malignancies. We studied the pharmacokinetics of belinostat in hepatocellular carcinoma patients to determine the main pathway of metabolism of belinostat. The pharmacokinetics of belinostat in liver cancer patients were characterized by rapid plasma clearance of belinostat with extensive metabolism with more than 4-fold greater relative systemic exposure of major metabolite, belinostat glucuronide than that of belinostat.

Pharmacologic modulation strategies to reduce dose requirements of anticancer therapy while preserving clinical efficacy.

Drug interactions may be exploited to overcome pharmacokinetic issues in order to improve the therapeutic index of a drug, with clinical goals of reducing the dose of the active drug while preserving efficacy or reducing toxicity. This strategy has been used in infectious disease and transplant medicine, and, more recently, in oncology. Pharmacologic modulation strategies range from coadministration of either a drug that inhibits a metabolizing enzyme that would inactivate the drug of interest, a drug that induces an enzyme that activates the drug of interest or a drug that inhibits transporters that affect the uptake or elimination of the drug of interest.

Unusual Merkel cell carcinoma of the eyelid.

Merkel cell carcinoma of the eyelid is a rare tumor with less than 100 reported cases worldwide. We describe an unusual presentation of Merkel cell carcinoma of the eyelid in a 60 year old Asian male. He presented with multiple left lower lid conjunctival nodules, intense conjunctival erythema, as well as ipsilateral cervical lymphadenopathy.

Outcomes after multiple lines of chemotherapy for platinum-resistant epithelial cancers of the ovary, peritoneum, and fallopian tube.

Background: Platinum-resistant and refractory cancers of the ovary, fallopian tube, and peritoneum have a poor prognosis, yet in some cases, they can respond to multiple lines of chemotherapy. Uncertainty remains over optimal drug choice and when therapeutic focus should be switched from active therapy to supportive care.

Methods: A retrospective case note review was performed on 274 women treated for platinum-resistant/refractory ovarian, fallopian tube, or peritoneal carcinoma at the Christie Hospital between 2004 and 2008.

Imaging angiogenesis of genitourinary tumors.

Angiogenesis is a key process in the growth and metastasis of cancer, and genitourinary tumors are no exception. The evolution of angiogenesis as an important target for novel anticancer therapeutics has brought with it new challenges for in vivo imaging. Most imaging techniques quantify physiological parameters, such as blood volume and capillary endothelial permeability.