[Show abstract][Hide abstract] ABSTRACT: Purpose:
The decision to enroll in a clinical trial is complex given the uncertain risks and benefits of new approaches. Many patients also have financial concerns. We sought to characterize the association between financial concerns and the quality of decision making about clinical trials.
We conducted a secondary data analysis of a randomized trial of a Web-based educational tool (Preparatory Education About Clinical Trials) designed to improve the preparation of patients with cancer for making decisions about clinical trial enrollment. Patients completed a baseline questionnaire that included three questions related to financial concerns (five-point Likert scales): "How much of a burden on you is the cost of your medical care?," "I'm afraid that my health insurance won't pay for a clinical trial," and "I'm worried that I wouldn't be able to afford the costs of treatment on a clinical trial." Results were summed, with higher scores indicating greater concerns. We used multiple linear regressions to measure the association between concerns and self-reported measures of self-efficacy, preparation for decision making, distress, and decisional conflict in separate models, controlling for sociodemographic characteristics.
One thousand two hundred eleven patients completed at least one financial concern question. Of these, 27% were 65 years or older, 58% were female, and 24% had a high school education or less. Greater financial concern was associated with lower self-efficacy and preparation for decision making, as well as with greater decisional conflict and distress, even after adjustment for age, race, sex, education, employment, and hospital location (P < .001 for all models).
Financial concerns are associated with several psychological constructs that may negatively influence decision quality regarding clinical trials. Greater attention to patients' financial needs and concerns may reduce distress and improve patient decision making.
Full-text · Article · Dec 2015 · Journal of Clinical Oncology
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Lack of knowledge and negative attitudes have been identified as barriers to participation in clinical trials by patients with cancer. We developed Preparatory Education About Clinical Trials (PRE-ACT), a theory-guided, Web-based, interactive computer program, to deliver tailored video educational content to patients in an effort to overcome barriers to considering clinical trials as a treatment option.
Patients and methods:
A prospective, randomized clinical trial compared PRE-ACT with a control condition that provided general clinical trials information produced by the National Cancer Institute (NCI) in text format. One thousand two hundred fifty-five patients with cancer were randomly allocated before their initial visit with an oncologist to PRE-ACT (n = 623) or control (n = 632). PRE-ACT had three main components: assessment of clinical trials knowledge and attitudinal barriers, values assessment with clarification back to patients, and provision of a video library tailored to address each patient's barriers. Outcomes included knowledge and attitudes and preparation for decision making about clinical trials.
Both PRE-ACT and control interventions improved knowledge and attitudes (all P < .001) compared with baseline. Patients randomly allocated to PRE-ACT showed a significantly greater increase in knowledge (P < .001) and a significantly greater decrease in attitudinal barriers (P < .001) than did their control (text-only) counterparts. Participants in both arms significantly increased their preparedness to consider clinical trials (P < .001), and there was a trend favoring the PRE-ACT group (P < .09). PRE-ACT was also associated with greater patient satisfaction than was NCI text alone.
These data show that patient education before the first oncologist visit improves knowledge, attitudes, and preparation for decision making about clinical trials. Both text and tailored video were effective. The PRE-ACT interactive video program was more effective than NCI text in improving knowledge and reducing attitudinal barriers.
No preview · Article · Dec 2015 · Journal of Clinical Oncology
[Show abstract][Hide abstract] ABSTRACT: Background:
Very little is known about the pharmacokinetics of chemotherapeutic agents in patients also being treated with continuous ambulatory peritoneal dialysis. We sought to evaluate the pharmacokinetics of cisplatin and 5-fluorouracil in plasma and peritoneal dialysate in a patient being treated for esophageal adenocarcinoma.
A single patient with esophageal adenocarcinoma and on peritoneal dialysis for end-stage renal disease was treated with cisplatin 25 mg/m(2) on day 1 of weeks 1 and 5 and continuous infusional 5-fluorouracil 1000 mg/m(2)/day on days 1-4 of weeks 1 and 5 along with daily radiation therapy. Intense plasma and dialysate sampling was performed during the week 5 administration, followed by quantitation of platinum by atomic absorption spectrophotometry and 5-fluorouracil by LC-MS/MS.
Following systemic administration, clearance of ultrafilterable (active) platinum over the first 6 h was 20.8 L/h, which is lower than previously reported clearance levels of ultrafilterable platinum. Total platinum AUC was 131 μg h/mL, also higher than an AUC previously reported for total platinum in patients with normal renal function. Platinum-related material was detected in the peritoneal cavity, but this is likely inactive. 5-Fluorouracil penetrated the intraperitoneal cavity, but the contribution of peritoneal dialysis to drug clearance was negligible at 0.072 %.
Administration of intravenous cisplatin and 5-fluorouracil chemotherapy to a patient treated with continuous ambulatory peritoneal dialysis is feasible, but clearance in dialysate is nominal, thus suggesting that dose reduction is indicated for cisplatin. Systemic drug administration results in limited intraperitoneal penetration of 5-fluorouracil and inactive platinum species.
No preview · Article · Dec 2015 · Cancer Chemotherapy and Pharmacology
[Show abstract][Hide abstract] ABSTRACT: Pancreatic cancer remains the fourth leading cause of cancer deaths in the United States with a dismal prognosis and a 5-year survival of less than 5% across all stages.(1) In 2014, there were approximately 46,420 new cases of pancreatic cancer with only 9% of patients having localized disease.(2) Given that the vast majority of patients present with advanced disease, much of the focus for drug development has been in the metastatic setting, which is evident with the advent of two combination chemotherapy regimens for this indication. Although conventional cytotoxic chemotherapy remains the standard of care, an ongoing search for novel therapeutic approaches continues. We will highlight several new approaches here, with a particular emphasis on immunotherapeutic strategies. We will also introduce concepts regarding the potential economic effects associated with the development and implementation of new treatments in pancreatic cancer.
[Show abstract][Hide abstract] ABSTRACT: Combination therapy with trabectedin and docetaxel was evaluated in patients with advanced malignancies.
In this open-label phase 1 study, docetaxel (60 or 75 mg/m(2); 1-h intravenous infusion) was given on day 1 of a 21-day cycle in combination with escalating doses of trabectedin (0.4-1.3 mg/m(2) by 3-h intravenous infusion, 1 h after docetaxel) and prophylactic granulocyte colony-stimulating factor (G-CSF). Maximum tolerated dose (MTD) as primary objective and safety, plasma pharmacokinetics, and antitumor activity as secondary objectives were assessed.
Patients (N = 49) received a median of four cycles of treatment. MTD was 1.3 mg/m(2) trabectedin and 60 mg/m(2) docetaxel for patients with limited and 1.1 mg/m(2) trabectedin and 60 mg/m(2) docetaxel for patients with unlimited prior chemotherapy. Dose-limiting toxicities (during cycle 1) included elevated alanine aminotransferase (ALT) and fatigue in patients with limited prior chemotherapy and elevated ALT and febrile neutropenia in those with unlimited prior chemotherapy. The most common drug-related adverse events were nausea (65 %), fatigue (63 %), and neutropenia (53 %). One patient achieved a complete response. Thirty patients had stable disease, and 11 had stable disease for ≥6 months. Pharmacokinetic results for trabectedin plus docetaxel were similar to those previously reported for the single agents.
In patients with previously treated, advanced malignancies, the combination of therapeutic doses of trabectedin and docetaxel showed clinical activity and was tolerable with prophylactic G-CSF, with no evidence of clinically important drug interactions.
Preview · Article · Mar 2015 · Cancer Chemotherapy and Pharmacology
[Show abstract][Hide abstract] ABSTRACT: Sunitinib is approved worldwide for treatment of advanced pancreatic neuroendocrine tumours (pNET), but no validated markers exist to predict response. This analysis explored biomarkers associated with sunitinib activity and clinical benefit in patients with pNET and carcinoid tumours in a phase II study.
Plasma was assessed for vascular endothelial growth factor (VEGF)-A, soluble VEGF receptor (sVEGFR)-2, sVEGFR-3, interleukin (IL)-8 (n=105), and stromal cell-derived factor (SDF)-1α (n=28). Pre-treatment levels were compared between tumour types and correlated with response, progression-free (PFS), and overall survival (OS). Changes in circulating myelomonocytic and endothelial cells were also analysed.
Stromal cell-derived factor-1α and sVEGFR-2 levels were higher in pNET than in carcinoid (P=0.003 and 0.041, respectively). High (above-median) baseline SDF-1α was associated with worse PFS, OS, and response in pNET, and high sVEGFR-2 with longer OS (P⩽0.05). For carcinoid, high IL-8, sVEGFR-3, and SDF-1α were associated with shorter PFS and OS, and high IL-8 and SDF-1α with worse response (P⩽0.05). Among circulating cell types, monocytes showed the largest on-treatment decrease, particularly CD14+ monocytes co-expressing VEGFR-1 or CXCR4.
Interleukin-8, sVEGFR-3, and SDF-1α were identified as predictors of sunitinib clinical outcome. Putative pro-tumorigenic CXCR4+ and VEGFR-1+ monocytes represent novel candidate markers and biologically relevant targets explaining the activity of sunitinib.British Journal of Cancer advance online publication 10 March 2015; doi:10.1038/bjc.2015.73 www.bjcancer.com.
No preview · Article · Mar 2015 · British Journal of Cancer
[Show abstract][Hide abstract] ABSTRACT: Cancer is responsible for approximately 7.6 million deaths per year worldwide. A 2012 survey in the United Kingdom found dramatic improvement in survival rates for childhood cancer because of increased participation in clinical trials. Unfortunately, overall patient participation in cancer clinical studies is low. A key logistical barrier to patient and physician participation is the time required for identification of appropriate clinical trials for individual patients. We introduce the Trial Prospector tool that supports end-to-end management of cancer clinical trial recruitment workflow with (a) structured entry of trial eligibility criteria, (b) automated extraction of patient data from multiple sources, (c) a scalable matching algorithm, and (d) interactive user interface (UI) for physicians with both matching results and a detailed explanation of causes for ineligibility of available trials. We report the results from deployment of Trial Prospector at the National Cancer Institute (NCI)-designated Case Comprehensive Cancer Center (Case CCC) with 1,367 clinical trial eligibility evaluations performed with 100% accuracy.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Gemcitabine (G) has been shown to sensitize pancreatic cancer to radiotherapy but requires lower doses of G and thus delays aggressive systemic treatment, potentially leading to distant failure. We initiated a phase I trial combining ultra-fractionated low-dose radiotherapy with full dose G and erlotinib in the treatment of patients with advanced pancreatic cancer.
Patients with locally advanced or metastatic pancreatic cancer confined to the abdomen and an ECOG performance status (PS) of 0-1 who had received 0-1 prior regimens (without G or E) and no prior radiotherapy were eligible. Patients were treated in 21 day cycles with G IV days 1 & 8, E once PO QD, and twice daily RT fractions separated by at least 4h on days 1, 2, 8, and 9. Whole abdominal RT fields were used. Primary endpoint was to define dose limiting toxicity (DLT) and the maximum tolerated dose (MTD).
27 patients (median age 64 years and 15 male) were enrolled between 11/24/08 and 4/12/12. 1 patient withdrew consent prior to receiving any protocol therapy. 17 patients had a PS of 1. The majority of patients were stage IV. One DLT was noted out of 7 patients at dose level (DL) 1. Subsequently no DLTs were noted in 3 patients each enrolled at DL2-4 or 11 patients in the expansion cohort. The majority of grade 3 toxicities were hematologic with 1 grade 5 bowel perforation in dose level 1 in cycle 4. Best response in 24 evaluable patients: PR (8), stable (15), PD 1. Median survival for the entire group was 9.1 months.
This phase I study combining low-dose ultra-fractionated RT as a sensitizer to full dose G plus E was well tolerated with encouraging efficacy. This represents a novel strategy worthy of further investigation in advanced pancreatic cancer patients.
No preview · Article · Oct 2014 · Radiotherapy and Oncology
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Although initially approved for metastatic colorectal cancer (mCRC) tumors with epidermal growth factor receptor (EGFR) overexpression, the use of anti-EGFR antibodies is now restricted to wild-type KRAS tumors. Little is known about prescribers' response to new clinical data, practice guidelines, and US Food and Drug Administration (FDA) label change with regard to the use of anti-EGFR antibodies in clinical practice.
Commercially insured patients with mCRC who received second-line therapy between 2004 and 2010 were identified by dusing the LifeLink Health Plan Claims Database. We calculated the fraction of patients receiving anti-EGFR antibody in 2-month intervals. χ(2) tests were used to compare treatment rates at four time points: time 1: June 2008, ASCO presentation of clinical data; time 2: February 2009, ASCO guidelines publication; time 3: August 2009, FDA label change; time 4: April 2010 to 8 months after FDA label change.
Five thousand eighty-nine patients received second-line therapy; of these, 2,599 patients received an anti-EGFR antibody. Median age was 60 years (range, 20 to 97), with 57% male sex. The majority of patients (59.4%) received an anti-EGFR antibody at time 1, with significant decrease at each of the subsequent time points (time 2: 46.2% [P = .019]; time 3: 35.2% [P < .001]; Time 4: 16.2% [P < .001]). Multivariable logistic regression did not show any affect of age, sex, comorbidities, or region of the country on this pattern.
The use of anti-EGFR antibodies for mCRC decreased after the presentation of clinical trial data, ASCO guidelines publication, and FDA label change. These data suggest that oncologists respond rapidly to new evidence and professional guidelines, and readily incorporate predictive biomarkers into clinical practice.
Full-text · Article · Jul 2014 · Journal of Oncology Practice
[Show abstract][Hide abstract] ABSTRACT: Objective:
This article describes the rigorous development process and initial feedback of the PRE-ACT (Preparatory Education About Clinical Trials) web-based- intervention designed to improve preparation for decision making in cancer clinical trials.
The multi-step process included stakeholder input, formative research, user testing and feedback. Diverse teams (researchers, advocates and developers) participated including content refinement, identification of actors, and development of video scripts. Patient feedback was provided in the final production period and through a vanguard group (N=100) from the randomized trial.
Patients/advocates confirmed barriers to cancer clinical trial participation, including lack of awareness and knowledge, fear of side effects, logistical concerns, and mistrust. Patients indicated they liked the tool's user-friendly nature, the organized and comprehensive presentation of the subject matter, and the clarity of the videos.
The development process serves as an example of operationalizing best practice approaches and highlights the value of a multi-disciplinary team to develop a theory-based, sophisticated tool that patients found useful in their decision making process. Practice implications Best practice approaches can be addressed and are important to ensure evidence-based tools that are of value to patients and supports the usefulness of a process map in the development of e-health tools.
[Show abstract][Hide abstract] ABSTRACT: Background:
This was a prospective single-centre, phase I study to document the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and the recommended phase II dose for future study of capecitabine in combination with radioembolization.
Patients with advanced unresectable liver-dominant cancer were enrolled in a 3+3 design with escalating doses of capecitabine (375–1000 mg/m2 b.i.d.) for 14 days every 21 days. Radioembolization with 90Y-resin microspheres was administered using a sequential lobar approach with two cycles of capecitabine.
Twenty-four patients (17 colorectal) were enrolled. The MTD was not reached. Haematologic events were generally mild. Common grade 1/2 non-haematologic toxicities included transient transaminitis/alkaline phosphatase elevation (9 (37.5%) patients), nausea (9 (37.5%)), abdominal pain (7 (29.0%)), fatigue (7 (29.0%)), and hand-foot syndrome or rash/desquamation (7 (29.0%)). One patient experienced a partial gastric antral perforation with a capecitabine dose of 750 mg/m2. The best response was partial response in four (16.7%) patients, stable disease in 17 (70.8%) and progression in three (12.5%). Median time to progression and overall survival of the metastatic colorectal cancer cohort was 6.4 and 8.1 months, respectively.
This combined modality treatment was generally well tolerated with encouraging clinical activity. Capecitabine 1000 mg/m2 b.i.d. is recommended for phase II study with sequential lobar radioembolization.
Full-text · Article · Jul 2014 · British Journal of Cancer
[Show abstract][Hide abstract] ABSTRACT: Background
Patients with advanced biliary tract cancers have limited therapeutic options. Preclinical data suggest proteasome inhibition may be an effective therapeutic strategy. We thus evaluated the clinical efficacy of bortezomib in advanced biliary tract cancers.
Patients and Methods
Patients with locally advanced or metastatic cholangiocarcinoma or gallbladder adenocarcinoma who had received 0-2 prior therapies received bortezomib 1.3 mg/m2 days 1, 4, 8, and 11 of a 21-day cycle. The primary endpoint was objective response rate. A Simon two-stage design was employed (null response rate of < 5% and response rate of ≥ 20% of interest).
Twenty patients enrolled: bile duct/gallbladder cancer (14/6), prior treatments 0/1/2 (10/6/3). The trial was discontinued early due to lack of confirmed partial responses. No unanticipated adverse events were noted. There was one unconfirmed partial response. Ten patients achieved stable disease as best response. Median time to progression was 5.8 months (95% CI 0.7-77.6 months). Median survival was 9 months (95% CI 4.6-18.5 months). The 6-month and 1-year survival rates were 70% and 38%. There was no difference in survival based on primary disease site.
Single agent bortezomib does not result in objective responses in biliary tract cancers. However, the rate of stable disease and time to progression benchmark is encouraging. Further development of bortezomib in combination with other therapies in this disease setting should be considered.
No preview · Article · Jun 2014 · Clinical Colorectal Cancer
[Show abstract][Hide abstract] ABSTRACT: The decision regarding adjuvant therapy for patients with stage II colon cancer remains a challenge. In contrast to stage III colon cancer, for which compelling clinical data support the use of adjuvant chemotherapy, the clinical benefit of systemic therapy in unselected patients with stage II disease is modest at best. Risk stratification based on clinicopathologic features and DNA mismatch repair status is commonly used in adjuvant therapy decisions, but these factors do not have a desired level of precision in identifying patients at high risk. Recently, gene expression platforms have been developed to further define risk and to assist in therapeutic decision making for patients with stage II disease. This review describes those platforms that are furthest along in clinical development, in an effort to place their potential clinical application in context.