Search tips
Search criteria

Results 1-20 (20)

Clipboard (0)

Select a Filter Below

more »
Year of Publication
Document Types
1.  The effects of curcumin (diferuloylmethane) on body composition of patients with advanced pancreatic cancer 
Oncotarget  2016;7(15):20293-20304.
Curcumin is a natural product that is often explored by patients with cancer. Weight loss due to fat and muscle depletion is a hallmark of pancreatic cancer and is associated with worse outcomes. Studies of curcumin's effects on muscularity show conflicting results in animal models.
Methods and results
Retrospective matched 1:2 case-control study to evaluate the effects of curcumin on body composition (determined by computerized tomography) of 66 patients with advanced pancreatic cancer (22 treated,44 controls). Average age (SEM) was 63(1.8) years, 30/66(45%) women, median number of prior therapies was 2, median (IQR) time from advanced pancreatic cancer diagnosis to baseline image was 7(2-13.5) months (p>0.2, all variables). All patients lost weight (3.3% and 1.3%, treated vs. control, p=0.13). Treated patients lost more muscle (median [IQR] percent change −4.8[−9.1,-0.1] vs. −0.05%[−4.2, 2.6] in controls,p<0.001) and fat (median [IQR] percent change −6.8%[−15,-0.6] vs. −4.0%[−7.6, 1.3] in controls,p=0.04). Subcutaneous fat was more affected in the treated patients. Sarcopenic patients treated with curcumin(n=15) had survival of 169(115-223) days vs. 299(229-369) sarcopenic controls(p=0.024). No survival difference was found amongst non-sarcopenic patients.
Patients with advanced pancreatic cancer treated with curcumin showed significantly greater loss of subcutaneous fat and muscle than matched untreated controls.
PMCID: PMC4991455  PMID: 26934122
pancreatic neoplasms; curcumin; body composition; inflammation
2.  Family caregiver preferences for patient decisional control among Hispanics in the United States and Latin America 
Palliative medicine  2013;27(7):692-698.
Understanding family caregivers’ decisional role preferences is important for communication, quality of care, and patient and family satisfaction. The family caregiver has an important role in a patient’s decisional role preferences. There are limited studies on family caregivers’ preferences of the patient’s decisional control at the end of life among Hispanics.
To identify Hispanic caregivers’ preferences of the decision control of patients with advanced cancer and to compare the preferences of caregivers in Latin America (HLA) and Hispanic American (HUSA) caregivers.
We surveyed patients and their family caregivers referred to outpatient palliative care clinics in the United States, Chile, Argentina, and Guatemala. Caregiver preferences of patient’s decisional control were evaluated using the Control Preference Scale. Caregivers’ and patients’ socio-demographic variables, patient performance status, and HUSA patient acculturation level was also collected.
A total of 387 caregivers were surveyed: 100 (26%) in Chile, 99 (26%) in Argentina, 97 (25%) in Guatemala, and 91 (24%) in the United States. The median age was 56 years, and 59% were female.
Caregiver preference of patients decisions control was passive, shared, and active by 10 (11%), 45 (52%) and 32 (37%) HUSA caregivers and 54 (19%), 178 (62%) and 55 (19%) HLA caregivers (p=0.0023). Caregiver acculturation level did not affect the preferences of the HUSA sample (p=0.60).
Most Hispanic family caregivers preferred the patient to make shared decisions. HLA caregivers preferred more frequently patients to assume a passive decisional role. Acculturation did not influence the preferences of HUSA caregivers.
PMCID: PMC3742314  PMID: 23670718
Decisional role preferences; family caregivers; palliative care; Hispanics; Latinos
3.  Concepts and definitions for “supportive care,” “best supportive care,” “palliative care,” and “hospice care” in the published literature, dictionaries, and textbooks 
Commonly used terms such as “supportive care,” “best supportive care,” “palliative care,” and “hospice care” were rarely and inconsistently defined in the palliative oncology literature. We conducted a systematic review of the literature to further identify concepts and definitions for these terms.
We searched MEDLINE, PsycInfo, EMBASE, and CINAHL for published peer-reviewed articles from 1948 to 2011 that conceptualized, defined, or examined these terms. Two researchers independently reviewed each citation for inclusion and then extracted the concepts/definitions when available. Dictionaries/textbooks were also searched.
Nine of 32 “SC/BSC,” 25 of 182 “PC,” and 12 of 42 “HC” articles focused on providing a conceptual framework/definition. Common concepts for all three terms were symptom control and quality-of-life for patients with life-limiting illness. “SC” focused more on patients on active treatment compared to other categories (9/9 vs. 8/37) and less often involved interdisciplinary care (4/9 vs. 31/37). In contrast, “HC” focused more on volunteers (6/12 vs. 6/34), bereavement care (9/12 vs. 7/34), and community care (9/12 vs. 6/34). Both “PC” and “SC/BSC” were applicable earlier in the disease trajectory (16/34 vs. 0/9). We found 13, 24, and 17 different definitions for “SC/BSC,” “PC,” and “HC,” respectively. “SC/BSC” was the most variably defined, ranging from symptom management during cancer therapy to survivorship care. Dictionaries/textbooks showed similar findings.
We identified defining concepts for “SC/BSC,” “PC,” and “HC” and developed a preliminary conceptual framework unifying these terms along the continuum of care to help build consensus toward standardized definitions.
PMCID: PMC3781012  PMID: 22936493
Supportive care; Best supportive care; Palliative care; Hospice care; Definitions; Concepts; Terminology
4.  Frequency and Predictors of Patient Deviation from Prescribed Opioids and Barriers to Opioid Pain Management in Patients with Advanced Cancer 
Journal of pain and symptom management  2012;45(3):10.1016/j.jpainsymman.2012.02.023.
Approximately 80% of patients with advanced cancer report pain and receive opioids. Information is limited about deviations from prescribed opioid doses and barriers to pain control, but poor opioid adherence has been reported in 49%–70% of patients.
To evaluate the frequency and severity of self-reported opioid deviation and barriers to opioid pain management in outpatients with advanced cancer.
We surveyed 198 patients and collected pain scores (0–10), prescribed opioid dose, confidential patient-reported opioid prescription dose and intake (as long as there was no severe opioid deviation), barriers to pain management (Barriers Questionnaire-II [BQ-II]) scores, and adherence scores. Opioid deviation was defined as <70% or >130% of the prescribed dose.
Median patient age was 55 years; 91 (46%) were female. Median pain intensity and morphine equivalent daily dose were 4 (interquartile range [IQR]=3–7) and 120 mg (IQR=45–270mg), respectively. Prescribed and patient-reported prescribed doses were highly correlated for regular (r=0.90, P<0.001) and regular plus breakthrough opioid intake (r=0.94, P<0.001). Nineteen (9.6%) patients deviated. Deviation was more frequent in males (P=0.039) and non-Whites (P=0.0270). Non-White patients had higher scores on the BQ-II than White patients (P=0.038). Low adherence scores were significantly associated with higher BQ-II scores (1.99±0.80) for lower motivation score vs. 1.61±0.77 for higher score, P=0.007; and 2.13±0.79 for lower knowledge score vs. 1.57±0.72 for higher score, P=0.001.
Very few patients reported dose deviations, which were mostly towards lower dose. More research is necessary to better characterize the frequency and predictors of opioid deviation in this population.
PMCID: PMC3856203  PMID: 22940562
opioid analgesics; pain management; deviation; advanced cancer; palliative care
5.  Reporting of Funding Sources and Conflict of Interest in the Supportive and Palliative Oncology Literature 
The reporting of funding support and conflict of interest has not been examined in the supportive/palliative oncology literature.
We examined the frequency of funding and conflict of interest reporting and various study characteristics associated with such reporting.
We systematically searched MEDLINE PubMed, PsycInfo, EMBASE, ISI Web of Science, and CINAHL for original studies related to palliative care and cancer in the first six months of 2004 and 2009. For each article, we reviewed the study design, research topic, journal type, and reporting of funding and conflict of interest.
Three hundred forty-four (41%) and 504 (59%) of 848 articles were from 2004 and 2009, respectively. Five hundred two of 848 (59%) studies reported no funding sources, whereas 216 (26%), 70 (8%), 34 (4%), and 26 (3%) reported one, two, three, and four or more sources, respectively. Key funding sources included governmental agencies (n = 182/848, 21%), philanthropic foundations (n = 163/848, 19%), university departments (n = 76/848, 9%), and industry (n = 27/848, 3%). Conflict of interest was not reported in 436 of 848 (51%) studies, and only 94 of 848 (11%) explicitly stated no conflict of interest. Other than extramural funding, conflict of interest reporting of any kind was extremely rare (mostly less than 1%). Conflict of interest reporting increased between 2004 and 2009 (39% vs. 55%, P < 0.001). Both funding and conflict of interest reporting were associated with prospective studies, larger sample sizes, nontherapeutic studies, North American authors, and publication in palliative care/oncology journals (P ≤ 0.008 for all comparisons).
A majority of supportive/palliative oncology studies did not report funding sources and conflict of interest, raising the need for standardization.
PMCID: PMC3905444  PMID: 22771126
Neoplasms; palliative care; literature; funding; conflict of interest
6.  Evaluation of the Clinical Relevance of Body Composition Parameters in Patients with Cancer Metastatic to the Liver Treated with Hepatic Arterial Infusion Chemotherapy 
Nutrition and cancer  2012;64(2):10.1080/01635581.2012.638433.
The association between body composition parameters and toxicity associated with hepatic arterial infusion (HAI) chemotherapy regimens has not been analyzed. We analyzed data from patients with advanced cancer and liver metastases treated on a clinical trial of HAI oxaliplatin combination regimen. Patient characteristics, response and toxicities were analyzed in relevance with body composition data from CT images. Forty-eight of 57 patients (mean age 57 years; 60% women) had available CT scans. The most common diagnosis was colorectal cancer (22/48, 46%); 30/48 patients (63%) had body mass index (BMI) ≥ 25 kg/m2. Twenty of 48 patients were sarcopenic (42%). Grade 3–4 adverse events did not differ among patients with and without sarcopeniaor according to BMI. The median survival (95% confidence interval [CI]) was 167 (128–206) days for sarcopenic and 280 (214–346) days for non-sarcopenic patients (p=0.271). Among patients treated at the maximum tolerated dose, the median survival was 103 days for sarcopenic and 312 days for non-sarcopenic patients (p=0.173). Sarcopenia was present in 30% (6/20) of patients with reduction in tumor size post-treatment, and in 52% (14/27) of patients with increased tumor size (p=0.171). In conclusion, body composition was not associated with toxicities. Sarcopenia might be associated with shorter survival.
PMCID: PMC3886552  PMID: 22229660
neoplasms; antineoplastic combined chemotherapy protocols; adverse effects; treatment outcome; survival; sarcopenia
7.  A pilot study of temsirolimus and body composition 
Body weight and composition play a role in cancer etiology, prognosis, and treatment response. Therefore, we analyzed the weight, body composition changes, and outcome in patients treated with temsirolimus, an mTor inhibitor that has weight loss as one of its side effects.
Patients and methods
Sixteen patients with advanced solid tumors treated with temsirolimus were studied; body composition was evaluated utilizing computerized tomography images. Sarcopenia was defined as skeletal muscle index lower than 38.5 cm2/m2 for women and 52.4 cm2/m2 for men.
Five of 16 patients (31 %) were men; median age, 60 years. Forty-four percent (7/16) of patients were sarcopenic. Fatigue, anemia, hyperglycemia, and hyperlipidemia were common. Baseline sarcopenia and body composition did not correlate with worse toxicity or treatment outcome. However, there was a trend for greater loss of adipose area (p = 0.07), fat mass (p = 0.09), and adipose index (p = 0.07) for patients with grade 3 or 4 toxicities versus those with grade 1 and 2 side effects.
Patients with higher grade toxicities tended to lose more body fat, suggesting a possible end-organ metabolic effect of temsirolimus. These observations merit exploration in a larger cohort of patients.
PMCID: PMC3830004  PMID: 23893509
Temsirolimus; Body composition; Sarcopenia; Toxicity
8.  The Lack of Standard Definitions in the Supportive and Palliative Oncology Literature 
Journal of pain and symptom management  2011;43(3):10.1016/j.jpainsymman.2011.04.016.
Multiple organizations have raised concerns about the lack of standard definitions for terminology in the supportive and palliative oncology literature.
We aimed to determine: 1) the frequency of 10 commonly used terms in the supportive and palliative oncology literature; 2) the proportion of articles that provided definitions for each term; and 3) how each term was defined.
We systematically searched MEDLINE, PubMed, PsycINFO, the Cochrane Library, Embase, ISI Web of Science, and CINAHL for original studies, review articles and systematic reviews related to palliative care and cancer in the first six months of 2004 and 2009. We counted the number of occurrences for “palliative care,” “supportive care,” “best supportive care,” “hospice care,” “terminal care,” “end-of-life,” “terminally ill,” “goals of care,” “actively dying,” and “transition of care” in each article, reviewed them for the presence of definitions, and documented the journal characteristics.
Among the 1213 articles found, 678 (56%) were from 2009. “Palliative care” and “end-of-life” were the most frequently used terms. “Palliative care,” “end-of-life” and “terminally ill” appeared more frequently in palliative care journals, while “supportive care” and “best supportive care” were used more often in oncology journals (P<0.001). Among 35 of 601 (6%) articles with a definition for “palliative care,” there were 16 different variations (21 of 35 articles used the World Health Organization definition). “Hospice care” had 13 definitions among 13 of 151 (9%) articles. “Supportive care” and other terms were rarely defined (less than 5% of articles that used the term).
Our findings highlight the lack of definitional clarity for many important terms in the supportive and palliative oncology literature. Standard definitions are needed to improve administrative, clinical and research operations.
PMCID: PMC3818788  PMID: 22104619
Palliative care; supportive care; neoplasms; literature; terminology; definitions
9.  The Relationship Between Body Composition and Response to Neoadjuvant Chemotherapy in Women with Operable Breast Cancer 
The Oncologist  2012;17(10):1240-1245.
Breast cancer patients with a pathologic complete response (pCR) to neoadjuvant chemotherapy were compared with nonresponding controls to evaluate associations among a pCR, survival outcomes, and sarcopenia as well as the combination of sarcopenia and a high body mass index (BMI). Overweight patients had a lower pCR rate and shorter progression-free survival time. Among patients with a normal BMI, the pCR rate was better in sarcopenic patients.
Overweight women diagnosed with breast cancer have greater recurrence and mortality risks. Recent studies in advanced cancer showed that the combination of sarcopenia and an overweight or obese body mass index (BMI) is associated with poor clinical outcomes.
To compare pathological complete response (pCR) cases with controls and evaluate associations among a pCR, survival outcome, and sarcopenia as well as the combination of both sarcopenia and a BMI ≥25 kg/m2.
Sixty-seven breast cancer patients with a pCR to neoadjuvant chemotherapy (NC) were matched with controls who did not have a pCR to NC. Patients were matched by age, Black's nuclear grading system, clinical cancer stage, and estrogen receptor and progesterone receptor status. Body composition was analyzed using computed tomography images taken prior to NC.
BMI was associated with pCR. Among normal weight patients, the pCR rate was higher in sarcopenic patients and the progression-free survival (PFS) interval was significantly longer than in overweight or obese BMI patients. The death hazard was 2% higher for each unit higher skeletal muscle index and 0.6% higher for each unit higher visceral adipose tissue.
Overweight patients treated with NC had a lower pCR rate and shorter PFS time. Among patients with a normal BMI, the pCR rate was better in sarcopenic patients. More research is required to evaluate the negative impact of sarcopenic obesity on prognosis and the contributors to better response rates in operable, normal weight breast cancer patients with sarcopenia.
PMCID: PMC3481889  PMID: 22903527
Breast cancer; Body composition; Clinical outcome
10.  Undocumented Alcoholism and its Relationship with Tobacco and Illegal Drug Use in Advanced Cancer Patients 
Cancer  2011;117(19):4551-4556.
The purpose of our retrospective study was to determine the frequency of undiagnosed alcoholism among advanced cancer patients referred to palliative care and explore the relationship with alcoholism, tobacco abuse, and use of illegal drugs.
We reviewed 665 consecutive charts and identified 598 patients (90%) who completed the CAGE questionnaire (Cut down, Annoyed, Guilty, Eye-opener) and 100 consecutive CAGE positive (CAGE+) and negative (CAGE−) patients. Tobacco and illegal drug use, Edmonton Symptom Assessment Scale, and Morphine Equivalent Daily Dose (MEDD) were collected.
Frequency of CAGE+ in our palliative care population was 100/598 (17%). Only 13/100 (13%) among these CAGE+ patients were documented to have been identified as alcoholics prior to palliative care consultation. CAGE+ patients were younger (58.6 versus 61.3 years, p=0.07), predominantly male (68/100 versus 51/100, p=0.021), more likely to have a history of tobacco use (86/100 versus 48/100, p<0.001), be actively using nicotine (33/100 versus 9/100, p=0.02), and have a history of illegal recreational drug use (17/100 versus 1/100, p<0.001). Pain and dyspnea were worse in patients with a history of nicotine use. Both CAGE+ patients and patients with a history of tobacco use were more frequently on strong opioids at the time of palliative care consultation.
Our findings suggest that alcoholism is highly prevalent and frequently under-diagnosed in patients with advanced cancer. CAGE+ patients were more likely to have a history of, or actively engage in, smoking and illegal recreational drug use placing them at risk for inappropriate opioid escalation and abuse.
PMCID: PMC3128208  PMID: 21446042
Alcoholism; Opioid Analgesics; Tobacco Use Disorder; Cancer; Substance Abuse
11.  The Influence of Tumor Necrosis Factor-α –308 G/A and IL-6 –174 G/C on Pain and Analgesia Response in Lung Cancer Patients Receiving Supportive Care 
We previously showed that select cytokine gene polymorphisms are a significant predictor for pain reported at initial presentation in 446 white patients newly diagnosed with non–small cell lung cancer. This follow-up study explores the extent to which polymorphisms in tumor necrosis factor-α (TNF- α-308 G/A), interleukin (IL)-6 −174G/C, and IL-8 −251T/A could explain variability in pain and analgesic response among those patients (n = 140) subsequently referred for pain treatment.
Pain severity (0, no pain; 10, worst pain) was assessed at initial consultation and at follow-up visit. The total dose of opioids at the time of first-follow up visit (30 days postconsult) was converted to an equivalent dose of parenteral morphine.
Forty-one percent (57 of 140) of the patients reported severe pain (score >7/10) at initial consultation (mean, 5.5), which significantly decreased to 25% (mean, 4) at first follow-up visit (McNemar = P < 0.001). Polymorphisms in TNF and IL-6 were significantly associated with pain severity (for TNF GG, 4.12; GA, 5.38; AA, 5.50; P = 0.04) and with morphine equivalent daily dose (IL-6 GG, 69.61; GC, 73.17; CC, 181.67; P = 0.004), respectively. Adjusting for demographic and clinical variables, variant alleles in TNFα −308 G/A remained significantly associated with pain severity (b = 0.226; P = 0.036) and carriers of the IL-6 −174C/C genotypes required 4.7 times higher dose of opioids for pain relief (odds ratio, 4.7; 95% confidence interval, 1.2;15.0) relative to GG and GC genotypes.
We provide preliminary evidence of the influence of cytokine genes on pain and response to analgesia in lung cancer patients. Additional studies are needed to validate our findings. The long-term application is to tailored pain therapies.
PMCID: PMC3398799  PMID: 18990769
12.  Quantity, Design, and Scope of the Palliative Oncology Literature 
The Oncologist  2011;16(5):694-703.
The quantity, research design, and research topics of palliative oncology publications in the first 6 months of 2004 and 2009 were reviewed, and significant deficiencies were identified.
The current state of the palliative oncology literature is unclear. We examined and compared the quantity, research design, and research topics of palliative oncology publications in the first 6 months of 2004 with the first 6 months of 2009. We systematically searched MEDLINE, PsychInfo, EMBASE, ISI Web of Science, and CINAHL for original studies, review articles, and systematic reviews related to “palliative care” and “cancer” during the first 6 months of 2004 and 2009. Two physicians reviewed the literature independently and coded the study characteristics with high inter-rater reliability. We found a consistent decrease in the proportion of oncology studies related to palliative care between 2004 and 2009, despite an absolute increase in the total number of palliative oncology studies. Combining the two time periods, the most common original study designs were case report/series, cross-sectional studies, and qualitative studies. Randomized controlled trials comprised 6% of all original studies. The most common topics were physical symptoms, health services research, and psychosocial issues. Communication, decision making, spirituality, education, and research methodologies all represented <5% of the literature. Comparing 2004 with 2009, we found an increase in the proportion of original studies among all palliative oncology publications but no significant difference in study design or research topic. We identified significant deficiencies in the quantity, design, and scope of the palliative oncology literature. Further effort and resources are necessary to improve the evidence base for this important field.
PMCID: PMC3228194  PMID: 21471275
Literature; Neoplasms; Palliative care; Research design
13.  Outcomes of Patients with Advanced Non-Small Cell Lung Cancer Treated in a Phase I Clinic 
The Oncologist  2011;16(3):327-335.
The presenting characteristics and outcomes of patients with advanced/metastatic non-small cell lung cancer treated in MD Anderson Cancer Center phase I clinical studies are reported.
The outcomes of patients with advanced non-small cell lung cancer (NSCLC) treated in phase I clinical trials have not been systematically analyzed.
We reviewed the records of consecutive patients with advanced/metastatic NSCLC who were treated in the Phase I Clinical Trials Program at MD Anderson from August 2004 to May 2009.
Eighty-five patients (51 men, 34 women) treated on various phase I protocols were identified. The median age was 62 years (range, 30–85). The median number of previous systemic therapies was two (range, 0–5). A partial response was observed in eight patients (9.5%) and stable disease lasting >4 months was observed in 16 patients (19%). The median overall survival time was 10.6 months and median progression-free survival (PFS) time was 2.8 months, which was 0.6 months shorter than the median PFS of 3.4 months following prior second-line therapy. Factors predicting longer survival in the univariate analysis were an Eastern Cooperative Oncology Group performance status (PS) score of 0–1, no prior smoking, two or fewer organ systems involved, a hemoglobin level ≥12 g/dL, liver metastases, a history of thromboembolism, and a platelets count > 440 × 109/L. In the multivariate analysis, a PS score of 0–1 and history negative for smoking predicted longer survival. Sixty-two (73%) patients had grade ≤2 toxicity, and there were no treatment-related deaths.
Phase I clinical trials were well tolerated by selected patients with advanced NSCLC treated at M.D. Anderson. Nonsmokers and patients with a good PS survived longer. PFS in our population was shorter in smokers/ex-smokers and patients with a PS score of 2. It is reasonable to refer pretreated patients with a good PS to phase I clinical trials.
PMCID: PMC3228100  PMID: 21339262
Phase I; Non-small cell lung cancer; Survival
14.  Body Composition, Symptoms, and Survival in Advanced Cancer Patients Referred to a Phase I Service 
PLoS ONE  2012;7(1):e29330.
Body weight and body composition are relevant to the outcomes of cancer and antineoplastic therapy. However, their role in Phase I clinical trial patients is unknown.
We reviewed symptom burden, body composition, and survival in 104 patients with advanced cancer referred to a Phase I oncology service. Symptom burden was analyzed using the MD Anderson Symptom Assessment Inventory(MDASI); body composition was evaluated utilizing computerized tomography(CT) images. A body mass index (BMI)≥25 kg/m2 was considered overweight. Sarcopenia, severe muscle depletion, was assessed using CT-based criteria.
Most patients were overweight (n = 65, 63%); 53 patients were sarcopenic (51%), including 79% of patients with a BMI<25 kg/m2 and 34% of those with BMI≥25 kg/m2. Sarcopenic patients were older and less frequently African-American. Symptom burden did not differ among patients classified according to BMI and presence of sarcopenia. Median (95% confidence interval) survival (days) varied according to body composition: 215 (71–358) (BMI<25 kg/m2; sarcopenic), 271 (99–443) (BMI<25 kg/m2; non-sarcopenic), 484 (286–681) (BMI≥25 kg/m2; sarcopenic); 501 d (309–693) (BMI≥25 kg/m2; non-sarcopenic). Higher muscle index and gastrointestinal cancer diagnosis predicted longer survival in multivariate analysis after controlling for age, gender, performance status, and fat index.
Patients referred to a Phase I clinic had a high frequency of sarcopenia and a BMI≥25 kg/m2, independent of symptom burden. Body composition variables were predictive of clinically relevant survival differences, which is potentially important in developing Phase I studies.
PMCID: PMC3250428  PMID: 22235285
15.  R1507, an Anti-Insulin-Like Growth Factor-1 Receptor (IGF-1R) Antibody, and EWS/FLI-1 siRNA in Ewing's Sarcoma: Convergence at the IGF/IGFR/Akt Axis 
PLoS ONE  2011;6(10):e26060.
A subset of patients with Ewing's sarcoma responds to anti-insulin-like growth factor-1 receptor (IGF-1R) antibodies. Mechanisms of sensitivity and resistance are unknown. We investigated whether an anti-IGF-1R antibody acts via a pathway that could also be suppressed by small interfering (si) RNA against the EWS/FLI-1 fusion protein, the hallmark of Ewing's sarcoma. The growth of two Ewing's sarcoma cell lines (TC-32 and TC-71) was inhibited by the fully human anti-IGF-1R antibody, R1507 (clonogenic and MTT assays). TC-32 and TC-71 cells express high levels of IGF-2, while RD-ES and A4573 Ewing's cell lines, which were less responsive to R1507 in our assays, express low or undetectable IGF-2, respectively. TC-71 cells also expressed high levels of IGF-1R, and R1507 decreased steady-state levels of this receptor by internalization/degradation, an effect which was associated with a decrease in p-IGF-1R, p-IRS-1, and p-Akt. EWS/FLI-1 siRNA also decreased p-Akt, due to its ability to increase IGF-BP3 levels and subsequently decrease IGF-1 and IGF-2 levels, thus inhibiting signaling through p-IGF-1R. This inhibition correlated with growth suppression and apoptosis. The attenuation of Akt activation was confirmed in TC-71 and HEK-293 (human embryonic kidney) cells by transfecting them with IGF-1R siRNA. We conclude that antibodies and siRNA to IGF-1R, as well as siRNA to EWS/FLI-1, act via intersecting IGF/IGF-1R signals that suppress a common point in this pathway, namely the phosphorylation of Akt.
PMCID: PMC3191161  PMID: 22022506
16.  Timing of Palliative Care Referral and Symptom Burden in Phase I Cancer Patients: A Retrospective Cohort Study 
Cancer  2010;116(18):4402-4409.
Phase I trials offer advanced cancer patients the opportunity to pursue life-prolonging cancer treatments. In this study, we compared the timing of referral and symptom burden between patients referred to palliative care by Phase I oncologists and those referred by non-Phase I oncologists.
All 57 patients with advanced solid tumors referred by Phase I to our palliative care outpatient clinic in 2007/2008 were included. The comparison cohort consisted of 114 non-Phase I patients stratified by age, sex and cancer diagnosis in a 1:2 ratio. We retrieved information regarding patient characteristics, Edmonton Symptom Assessment Scale (ESAS), timing of referral and survival.
Both cohorts had the following matched characteristics: average age 57, female 44% and gastrointestinal cancers 47%. At the time of palliative care consultation, Phase I patients were more likely than non-Phase I patients to have a better performance status (ECOG 0-1, 61% vs. 36%, P=0.003). ESAS was not different except for better well-being in the Phase I cohort (mean 4.5 vs. 5.5, p=0.03). No difference was found for the duration between M.D. Anderson registration and palliative care consult (13 vs. 11 months, P=0.41) and overall survival from time of palliative care consult (5 vs. 4 months, P=0.69).
Phase I outpatients referred to palliative care had a better performance status but similar symptom burden as non-Phase I patients. Phase I involvement did not delay palliative care referral compared to non-Phase I. This supports the development of a simultaneous care model.
PMCID: PMC2936661  PMID: 20564164
Advanced cancer; Palliative Care; Phase I; Referral timing; Simultaneous care; Symptoms
17.  Placebo and nocebo effects in randomized double blind clinical trials of agents for the treatment of fatigue in advanced cancer patients 
Cancer  2010;116(3):766-774.
We have previously reported significant response to placebo in randomized controlled trials of treatments for cancer related fatigue (CRF). We conducted a retrospective study to determine the frequency and predictors of response to placebo effect and nocebo effect in patients with CRF treated in those trials.
We reviewed the records of 105 patients who received placebo in two previous randomized clinical trials conducted by our group and determined the proportion of patients who demonstrated clinical response to fatigue, defined as an increase in FACIT-F score of 7 or greater from baseline to day 8, and the proportion of patients with a nocebo effect, defined as those reporting >2 side effects. Baseline patient characteristics and symptoms recorded using the Edmonton Symptom Assessment Scale (ESAS) were analyzed to determine their association with placebo and nocebo effects.
59 (56%) patients had a placebo response. Worse baseline anxiety and well-being subscale score (univariate) and well-being (multivariate) were significantly associated with placebo response. Common side effects reported were insomnia (79%), anorexia (53%), nausea (38%) and restlessness (34%). Multivariate analysis showed that worse baseline (ESAS) sleep, appetite, and nausea were associated with increased reporting of the corresponding side effects.
More than half of advanced cancer patients enrolled in CRF trials had a placebo response. Worse baseline physical well-being score was associated with placebo response. Patients experiencing specific symptoms at baseline were more likely to report these as side effects of the medication. These findings should be considered in the design of future CFR trials.
PMCID: PMC2815077  PMID: 19918921
fatigue; placebo; nocebo; neoplasms
Cancer  2010;116(2):520-528.
Methadone is an effective and inexpensive opioid for cancer pain treatment. It has been reported as difficult to use in the outpatient setting due to its variable relative potency and long half-life. The purpose of this study was to determine the outcome of methadone initiation or rotation for cancer pain treatment in outpatient settings.
Chart review of 189 consecutive patients who underwent methadone initiation or rotation in our palliative care outpatient center. Data were collected regarding demographic and clinical characteristics, symptoms, and opioid side effects at baseline and for 2 follow up visits(F1,F2). Failure was defined as methadone discontinuation by the palliative care physician or patient's hospitalization for uncontrolled pain or methadone-related side effects at F1.
100(53%) initiations and 89(47%) rotations were conducted. Success rates for methadone initiation and rotation were 82/89(92%) and 85/100(84%) respectively. Mean(standard deviation) age was 60(11) years. 100(53%) patients were female, 138(73%) white, 182(96%) had solid cancers. The main reason for rotation was pain (65/89 patients, 47%). Median(interquartile range, IR) pain scores (Edmonton Symptom Assessment System/0–10) were 6(5–8), 4(3–6), and 3(2–5) at baseline, F1, and F2, respectively(p<0.0001). Median(IR) daily methadone dose for initiation and rotation was 10(5–15)mg and 15(10–30)mg at F1(p<0.0001) and 10(8–15)mg and 18(10–30)mg at F2(p<0.0001), respectively. Constipation and nausea improved (p<0.005) after initiation/rotation to methadone. Frequency of sedation, hallucinations, myoclonus, and delirium did not increase after initiation/rotation to methadone.
Outpatient methadone initiation and rotation for cancer pain treatment were safe, with high success rate and low side effect profile.
PMCID: PMC2811764  PMID: 19924788
methadone; pain; neoplasms; outpatients; palliative care
20.  Alcoholism Screening in Patients with Advanced Cancer: Impact on Symptom Burden and Opioid Use 
Journal of Palliative Medicine  2008;11(7):964-968.
Alcoholism is a devastating disease that can cause patient and family suffering and is frequently underdiagnosed. Preliminary studies suggest that it is associated with increased symptom expression and opioid dose escalation. The CAGE questionnaire is a widely used tool for alcoholism screening. The purpose of this study was to determine the frequency and characteristics of patients who screen positive for alcoholism in a palliative care outpatient clinic (PCOC).
We reviewed 665 consecutive charts of patients referred to the PCOC and collected data regarding age, gender, and type of cancer. For the first 100 consecutive CAGE positive (CAGE+) and 100 consecutive CAGE negative (CAGE−) patients, time from advanced cancer diagnosis (AC) to PCOC was calculated, and symptoms (Edmonton Symptom Assessment Scale, ESAS) and Morphine Equivalent Daily Dose (MEDD) were collected.
CAGE was available for 598 of 665 (90%) patients. Of 598 patients, 100 (17%) were CAGE+. CAGE+ patients were younger (58 versus 60 years, p < 0.05), predominantly male (68% versus 47%, p < 0.0001), and with head/neck malignancies (24% versus 9%, p < 0.05). CAGE+ patients were referred earlier (5 ± 19 versus 13 ± 27 months after AC, p < 0.0001). At baseline, pain, sleep, dyspnea, well-being, and total symptom distress were significantly worse among CAGE+ patients. Both groups showed similar improvement in symptoms. CAGE+ patients were more frequently on opioids upon referral (47/100 versus 29/100, p < 0.05) and follow-up (27/65 versus 16/68, p < 0.05). At follow-up, opioid doses did not show significant changes.
Seventeen percent of the patients were CAGE+. These patients were referred earlier to palliative care, had more symptom expression, and were more frequently on opioids. The palliative care team successfully improved symptom control in both groups without opioid dose escalation.
PMCID: PMC2988458  PMID: 18788955

Results 1-20 (20)