30 research outputs found
Targeted therapy of advanced gallbladder cancer and cholangiocarcinoma with aggressive biology: eliciting early response signals from phase 1 trials.
PurposePatients with advanced cholangiocarcinoma (CC) and gallbladder carcinoma (GC) have few therapeutic options for relapsed disease. methods: Given the overall poor prognosis in this population and the availability of novel targeted therapies, we systematically analyzed the characteristics and outcomes for GC and CC patients treated on phase I trials with an emphasis on targeted agents and locoregional therapies.ResultsOf 40 treated patients (GC=6; CC=34; median age, 60 years), 8 (20%) had stable disease (SD) > 6 months, 3 (8%) partial response (PR), on protocols with hepatic arterial drug infusion and anti-angiogenic, anti-HER-2/neu or novel MAPK/ERK kinase (MEK) inhibitors. Median progression-free survival (PFS) on phase I trials was 2.0 months (95% CI 1.7, 2.8) versus 3.0 months (95% CI 2.4, 5.0), 3.0 months (95% CI 2.3, 4.6), and 3.0 months (95% CI 2.4, 3.9) for their first-, second-, and last-line FDA-approved therapy. In univariate analysis, >3 metastatic sites, elevated alanine aminotransferase (ALT) (>56IU/L), serum creatinine (>1.6mg/dL), and CA19-9 (>35U/mL) were associated with a shorter PFS. Mutational analysis revealed mutation in the KRAS oncogene in 2 of 11 patients (18%). The SD >6 months/PR rate of 28% was seen with hepatic arterial infusion of oxaliplatin, and inhibitors of angiogenesis, HER-2/neu or MEK.ConclusionsThe PFS in phase I trials was similar to that of the first, second, and last-line therapy (P=0.95, 0.98, 0.76, respectively) with FDA-approved agents given in the advanced setting, emphasizing a role for targeted agents in a clinical trials setting as potentially valuable therapeutic options for these patients
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Biological predictors of chemotherapy-induced peripheral neuropathy (CIPN): MASCC neurological complications working group overview.
Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating condition associated with a number of chemotherapeutic agents. Drugs commonly implicated in the development of CIPN include platinum agents, taxanes, vinca alkaloids, bortezomib, and thalidomide analogues. As a drug response can vary between individuals, it is hypothesized that an individual's specific genetic variants could impact the regulation of genes involved in drug pharmacokinetics, ion channel functioning, neurotoxicity, and DNA repair, which in turn affect CIPN development and severity. Variations of other molecular markers may also affect the incidence and severity of CIPN. Hence, the objective of this review was to summarize the known biological (molecular and genomic) predictors of CIPN and discuss the means to facilitate progress in this field
Exploring response signals and targets in aggressive unresectable hepatocellular carcinoma: an analysis of targeted therapy phase 1 trials
Targeted therapy of advanced gallbladder cancer and cholangiocarcinoma with aggressive biology: eliciting early response signals from phase 1 trials.
Expanding enrollment of underrepresented populations on early phase clinical trials: An analysis of participation among adolescent and young adults (AYA) with advanced cancers on phase I clinical trials.
Analysis of patient related and trial related factors leading to non-participation of patients with advanced cancer in immunotherapy clinical trials: Implications for modifying eligibility criteria.
Participation and response assessment of older adults with advanced cancer treated on phase I trials as compared to middle age and AYA patients: An analysis of 1489 patients.
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Older adults in phase I clinical trials: a comparative analysis of participation and clinical benefit rate among older adults versus middle age and AYA patients on phase I clinical trials with VEGF/VEGFR inhibitors
BackgroundOlder adults aged 65 years and above remain underrepresented in cancer clinical trials. We hypothesized that older participation in early phase trials with VEGF/VEGFR (VEGF/R) inhibitors was lower than cancer prevalence in this group and lower than other age groups (middle age, adolescent/young adults [AYA]).ResultsOf 1489 patients, 278 were older adults (18%, median age 68.9y), 220 AYA (15%, median age 32.6 y), 991 middle age (67%, median age 53.8 y). Common malignancies included gastrointestinal (n = 438, 29%), gynecologic (n = 234, 16%), and thoracic/head/neck (n = 216, 15%). Median time to treatment failure did not vary significantly between the 3 age-based cohorts (3m in older adults, 3.5 m middle age, 3.3 m AYA). OR of achieving clinical benefit in older adults vs middle age (OR 1.10, p 0.19 [two-tailed], p 0.09 [one-tailed]) and AYA vs middle age (OR 0.85, p 0.31 [proportions z-test, two tailed], p 0.15 [one-tailed]) showed no significant differences.ConclusionsOlder adults accounted for <20% of participants on phase I clinical trials with VEGF/R inhibitors but those who participated were just as likely to achieve a clinical benefit as AYA and middle age patients. These findings merit further exploration into patient selection for early phase trials.MethodsWe identified and separated patients treated on VEGF/R-inhibitor-based phase I trials from 12/1/2004-07/31/2013 into 3 age-based cohorts, AYA (15-39y), middle age (40-64 y), older adults (65 y+). We analyzed clinical/treatment characteristics and response outcomes, calculating the odds ratios (OR) of clinical benefit (defined as SD ≥ 6months, PR, CR) for older adults and AYAs versus middle age participants