Showing papers by "Ross C. Donehower published in 2010"

Integrated preclinical and clinical development of mTOR inhibitors in pancreatic cancer

Abstract: The purpose of this work was to determine the efficacy of inhibiting mammalian target of rapamycin (mTOR) in pancreatic cancer preclinical models and translate preclinical observations to the clinic. Temsirolimus (20 mg Kg−1 daily) was administered to freshly generated pancreatic cancer xenografts. Tumour growth inhibition was determined after 28 days. Xenografts were characterised at baseline by gene expression and comparative genomic hybridisation. Patients with advanced, gemcitabine-resistant pancreatic cancer were treated with sirolimus (5 mg daily). The primary end point was 6-month survival rate (6mSR). Correlative studies included immunohistochemistry assessment of pathway expression in baseline tumours, drug pharmacokinetics (PKs), response assessment by FDG-PET and pharmacodynamic effects in peripheral-blood mononuclear cells (PBMCs). In all, 4 of 17 xenografts (23%) responded to treatment. Sensitive tumours were characterised by gene copy number variations and overexpression of genes leading to activation of the PI3K/Akt/mTOR pathway. Activation of p70S6K correlated with drug activity in the preclinical studies. Sirolimus was well tolerated in the clinic, showed predictable PKs, exerted pathway inhibition in post-treatment PBMCs and resulted in a 6mSR of 26%. No correlation, however, was found between activated p70S6K in tumour tissues and anti-tumour effects. Sirolimus activity in pancreatic cancer was marginal and not predicted by the selected biomarker.

Make Quality Cancer Survivorship Care Possible in the Era of Workforce Shortage

Abstract: With advances in cancer medicine, patients are living longer. Whether this is measured as an improved cure rate after combined-modality therapy or prolonged survival with a good quality of life, this is an exciting time. As a result of the increasing survival rates after cancer, issues concerning long-term cancer survivorship have become more important in clinical oncology. Many individuals and families continue to face complicated care issues resulting from cancer diagnosis and adverse effects long after completion of their treatments. The growing number of cancer survivors and their unique needs have been challenging our health care system to develop programs that support survivors’ transitions from active treatment to survivorship care. 1-3 After primary treatment, patient follow-up includes screening for recurrence and second primary cancers, management of long-term treatment effects, advice about health promotional strategies, and monitoring and appropriate referral for psychosocial issues.4 Optimal survivorship care must include appropriate general medical care as well, such as routine colonoscopy (for patients with noncolorectal cancer in the right age group) and management of dyslipidemia, hypertension, bone loss, and so on. It is likely to require considerable involvement from primary care providers (PCPs) with ongoing support from oncology specialist teams. 5

A multicenter review of gemcitabine, docetaxel, and capecitabine (GTX) in patients with advanced pancreatic adenocarcinoma.

Abstract: e14580 Background: Combination chemotherapy provides modest benefit in patients with advanced pancreatic adenocarcinoma over single agent gemcitabine. Recent studies have suggested that new regimen...