Richard L Schilsky

..It has demonstrated efficacy in patients with advanced colorectal carcinoma, and studies are ongoing in other tumor types...

..The goals of this phase I study were to determine the maximum-tolerated doses of capecitabine and gemcitabine in patients with advanced cancer and to describe the dose-limiting toxicities (DLT) and safety profile of this combination...

..Bone marrow suppression, which may be cumulative, is the dose-limiting toxicity of the combination. Prolonged AGT suppression is likely attributable primarily to the effect of O6-benzyl-8-oxoguanine...

..To evaluate the safety and efficacy of a five-day regimen of oral 5-fluorouracil (5-FU) plus eniluracil (776C85) in patients with metastatic colorectal cancer (CRC)...

..Eniluracil is a promising drug, which permits reliable and safe administration of oral 5-FU and has the potential to overcome 5-FU resistance mediated by overexpression of DPD...

..The development and use of such agents in biomarker-defined populations enables a more personalized approach to cancer treatment than previously possible and has the potential to reduce the cost of cancer care...

..Explored in this Commentary are challenges of and potential solutions for the clinical testing of modern cancer therapies...

..It is anticipated that the results of the current studies will contribute significantly to the goal of individualizing cancer treatment...

..CONCLUSION: Safety profiles of both treatments were acceptable. Although antitumor activity was observed, EU/5-FU did not meet the protocol-specified statistical criteria for equivalence to 5-FU/LV in terms of OS...

..Hence, this study was designed to evaluate if pharmacokinetic modulation of oral etoposide with ketoconazole could lead to a favorable alteration of etoposide pharmacokinetics, and to assess the feasibility and safety of this approach...

..ZD9331 seems to have a manageable toxicity profile, although it should be used with caution in patients with renal impairment...

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..Five partial responses were observed. Pharmacokinetic modulation of irinotecan with cyclosporine and phenobarbital has been demonstrated; further studies are necessary to evaluate whether this strategy improves the therapeutic index...

..These encouraging data led Cancer and Leukemia Group B (CALGB) to conduct a double-blind, placebo-controlled, randomized phase III trial of gemcitabine/bevacizumab versus gemcitabine/placebo in advanced pancreatic cancer patients...

..Here, we review the data on the clinical development of molecular markers to individualize adjuvant therapy in colon cancer...

..Further investigation of the incorporation of population pharmacokinetic approaches in food effect studies is warranted...

..The evidence of antitumor activity suggests that additional clinical development is warranted, with a focus on tumors that express high levels of CanAg and which are known to be sensitive to antimicrotubule agents...

..This article presents the Agents Developmental Pathway and discusses key challenges associated with the processes described...

..The purpose of this study was to determine the maximum tolerated dose and toxicity profile of gemcitabine given on a weekly schedule with continuous infusion 5-fluorouracil...

..ASCO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of ASCO's PCOs, or for any errors or omissions...

..The purpose of this study was to determine the toxicity of escalating doses of trastuzumab when combined with a fixed dose regimen of interleukin (IL)-2...

..CA Cancer J Clin 2011. © 2011 American Cancer Society...

..The main purpose of this analysis was to assess the amount of safety and concomitant medication data collected to determine a more optimal approach in the collection of these data when used in support of supplemental applications...

..To determine the efficacy of fluorouracil (5-FU) plus eniluracil when administered to patients with previously untreated metastatic colorectal cancer...

..Indeed, aspects of the phase 0 design lend themselves well to chemoprevention research, suggesting that this approach will become more common in the near future...

..75). CONCLUSION: HD-CPB with stem-cell support was not superior to ID-CPB for event-free or overall survival among all randomized women with high-risk primary breast cancer...

..Patients with hepatic or renal dysfunction are often treated with 5-fluorouracil (5-FU), but there are few data to confirm the safety of this practice...

..CONCLUSIONS: The recommended phase II dose is 6 mg/m2 (or 10 mg) of CI-994 in combination with capecitabine 2000 mg/m2/day for 2 weeks of a 3-week cycle...

..The goal of this article is to review the features of the main oral 5-FU prodrugs, which include capecitabine, uracil and tegafur (UFT)/leucovorin, S-1, and BOF-A2 and to describe their potential efficacy in treating colorectal cancer...

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..Curiously, an increase in alkaline phosphatase was associated with an increase in the platelet nadir (P = 0.02). If PZDH continues to be developed as an antineoplastic agent, further studies of these relationships are suggested...

..The objective of this study was to determine the pharmacokinetics and metabolic fate of O6-Benzylguanine in humans and its effect on AGT activity in peripheral-blood mononuclear cells (PBMCs)...

..CONCLUSION: The recommended dose for ZD9331 on this schedule is 25 mg/d. Neutropenia, thrombocytopenia, and rash were dose-limiting, and efficacy studies in colorectal cancer are indicated...

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..To examine the ethical, scientific, and regulatory issues in the design and conduct of placebo-controlled cancer clinical trials...

..UFT 300 mg/m2/day and leucovorin 90 mg/day could be administered safely to patients with advanced biliary cancer with good performance status; however, this combination and schedule of 28-day administration has no activity in this disease...

..We undertook a prospective, randomized phase III trial to evaluate the safety and efficacy of using a phase II agent before initiating therapy with standard combination chemotherapy in metastatic breast cancer patients...

..We explore the consequences (both good and bad) of foregoing randomized phase III trials and propose criteria that might be used to select drugs for consideration of such an approach...

..We prospectively collected germline DNA and conducted a genome-wide association study (GWAS) using overall survival (OS) as the endpoint...

..Criterion validation studies with an external gold standard should be pursued to determine the sensitivity and specificity of chemotherapy codes in the Medicare NCH files...

..The risks of both cognitive dysfunction and most cancers increase with age. A literature review was undertaken to identify how cognitive issues in older patients were being assessed in the oncology literature...

..There is now a validated predictive biomarker to guide use of adjuvant chemotherapy in patients with stage II colon cancer...

..Further studies to characterize the pharmacodynamics and pharmacogenetics of TAS-103 are warranted...

..CONCLUSIONS: The recommended dose of GTI-2040 given on this infusion schedule is 185 mg/m(2)/day. GTI-2040 appears to have a manageable toxicity profile and is generally well tolerated as a single agent...

..In view of the high doses of leucovorin given clinically and the slow clearance of the unnatural isomer, our observations suggest that leucovorin may have important direct inhibitory effects on folate-requiring enzymes...

..A Phase III trial is now being conducted randomizing untreated, metastatic clear cell RCC patients to IFN-alpha alone or IFN-alpha plus Avastin...

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..This report provides a mature analysis of Cancer and Leukemia Group B (CALGB) 9633, the only RCT designed specifically for stage IB NSCLC...

..To describe both minimum requirements for a site conducting quality clinical trials and attributes of an exemplary site...

..Regular physical activity reduces the risk of developing colon cancer, however, its influence on patients with established disease is unknown...

..We examine the processes and document the calendar time required to activate such studies opened by the Cancer and Leukemia Group B (CALGB)...

..This report demonstrates the essential role of clinical cancer research in finding new and better ways to treat, diagnose, and prevent a group of diseases that strike half of men and one-third of women in the United States...

..This study was designed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a standard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival...

..The development of new and reliable methods for the assessment of CIPN as well as safe and effective treatments to prevent this complication of treatment would represent important medical advancements for cancer patients...

..I hope you find it useful. Sincerely, Nancy E. Davidson, MD President American Society of Clinical Oncology...

..This editorial will review commonly used clinical trial end points and describe their potential advantages and disadvantages to expedite the drug approval process required in the United States...

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..Future studies should consider sharing trial results with patients and evaluating the process and its effect on both patients and clinicians...

..Administrative Medicare claims data appear to be a valid source of information for chemotherapy administered to elderly Medicare beneficiaries with cancer...

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..Because the elderly are underrepresented on clinical trials, physicians have few sources of information to estimate the risks (ie, toxicities) and benefits of chemotherapy administration to the elderly...

..A new activity in Cancer Imaging will be initiated during the coming grant period in an effort to better integrate novel imaging science into cancer treatment studies. ..

..A new activity in Cancer Imaging will be initiated during the coming grant period in an effort to better integrate novel imaging science into cancer treatment studies. ..

..To collaborate with qualified investigators in the conduct of outstanding translational research projects that utilize the CALGB specimen repositories and associated clinical data. ..

..This well integrated project provides a multidisciplinary approach that will address many issues relevant to the treatment of elderly women with breast cancer. ..

..A new activity in Cancer Imaging will be initiated during the coming grant period in an effort to better integrate novel imaging science into cancer treatment studies. ..