Physical and Psychosocial Symptoms of Young Adult Patients Referred to the Supportive Care Mobile Team.

Young adult (YA) aged cancer patients have unique psychosocial needs with studies indicating more symptoms and emotional distress compared to older patients. Our study aimed to compare clinical characteristics and symptom distress between YAs and older adults. We retrospectively studied 896 randomly selected patients across 3 age groups: 18-39 YAs (n = 297), 40-64 (n = 300), and 65 and older (n = 299). We compared medical, psychosocial history, Morphine Equivalent Daily Dose (MEDD), Edmonton Symptom Assessment Scale (ESAS) scores, and Eastern Cooperative Oncology Group (ECOG) scores at the time of initial inpatient consultation with supportive care. YAs were more frequently female and white, with higher ECOG scores, had more self-reported psychiatric history and worse ESAS sleep scores compared to the other age cohort groups. YAs had higher pain expression than those of 65 years and older. YAs were more likely to have children younger than 18 years old, which was associated with worse pain, sleep, and financial distress. In general, YAs did not report higher symptoms distress, with the exception of insomnia and self-reported psychiatric history. Importantly, YAs with children was associated with higher ratings of pain, sleep difficulties, and financial distress. Overall, results suggest YAs may benefit from specialized services to address their unique psychosocial needs.

The Conversion Ratio From Intravenous Hydromorphone to Oral Opioids in Cancer Patients.

CONTEXT: The lack of knowledge of the accurate conversion ratio (CR) between intravenous (IV) and oral hydromorphone and opioid rotation ratio (ORR) between IV hydromorphone and oral morphine equivalent daily dose (MEDD) may lead to poorly controlled pain or overdosing in cancer inpatients. OBJECTIVES: We aimed to determine the CR and ORR from IV hydromorphone to oral hydromorphone and MEDD (obtained from oral morphine and oxycodone). METHODS: A total of 4745 consecutive inpatient palliative care consults during 2010-14 were reviewed for conversions from IV hydromorphone to oral hydromorphone, morphine or oxycodone. Patient characteristics, symptoms, and opioid doses were determined in patients successfully discharged on oral opioids without readmission within one week. Linear regression analysis was used to estimate the CR or ORR between the 24 hour IV hydromorphone mg dose before conversion and the oral opioid mg dose used before discharge. RESULTS: Among 394 patients on IV hydromorphone, 147 underwent conversion to oral hydromorphone and 247 underwent rotation to oral morphine (163) or oxycodone (84). The median (interquartile range) CR from IV to PO hydromorphone was 2.5 (2.14-2.75) with correlation of 0.95 (P < 0.0001). The median ORR (interquartile range) from IV hydromorphone to MEDD was 11.46 (9.84-13.00) with correlation of 0.93(P < 0.0001). The median ORR was 11.54 in patients receiving <30 mg of IV hydromorphone/day and 9.86 in patients receiving ≥30 mg (P = 0.0004). CONCLUSION: Our study found that 1 mg of IV hydromorphone is equivalent to 2.5 mg of oral hydromorphone and 11.46 mg of MEDD. Hydromorphone at doses ≥30 mg/day may require a lower ORR to other opioids.

Transgenic expression of aflatoxin aldehyde reductase (AKR7A1) modulates aflatoxin B1 metabolism but not hepatic carcinogenesis in the rat.

In both experimental animals and humans, aflatoxin B(1) (AFB(1)) is a potent hepatic toxin and carcinogen against which a variety of antioxidants and experimental or therapeutic drugs (e.g., oltipraz, related dithiolethiones, and various triterpenoids) protect from both acute toxicity and carcinogenesis. These agents induce several hepatic glutathione S-transferases (GST) as well as aldo-keto reductases (AKR) which are thought to contribute to protection. Studies were undertaken in transgenic rats to examine the role of one inducible enzyme, AKR7A1, for protection against acute and chronic actions of AFB(1) by enhancing detoxication of a reactive metabolite, AFB(1) dialdehyde, by reduction to alcohols. The AFB(1) dialdehyde forms adducts with protein amino groups by a Schiff base mechanism and these adducts have been theorized to be at least one cause of the acute toxicity of AFB(1) and to enhance carcinogenesis. A liver-specific AKR7A1 transgenic rat was constructed in the Sprague-Dawley strain and two lines, AKR7A1(Tg2) and AKR7A1(Tg5), were found to overexpress AKR7A1 by 18- and 8-fold, respectively. Rates of formation of AFB(1) alcohols, both in hepatic cytosols and as urinary excretion products, increased in the transgenic lines with AKR7A1(Tg2) being the highest. Neither line offered protection against acute AFB(1)-induced bile duct proliferation, a functional assessment of acute hepatotoxicity by AFB(1), nor did they protect against the formation of GST-P positive putative preneoplastic foci as a result of chronic exposure to AFB(1). These results imply that the prevention of protein adducts mediated by AKR are not critical to protection against AFB(1) tumorigenicity.

A novel acetylenic tricyclic bis-(cyano enone) potently induces phase 2 cytoprotective pathways and blocks liver carcinogenesis induced by aflatoxin.

A novel acetylenic tricyclic bis-(cyano enone), TBE-31, is a lead compound in a series of tricyclic compounds with enone functionalities in rings A and C. Nanomolar concentrations of this potent multifunctional molecule suppress the induction of the inflammatory protein, inducible nitric oxide synthase, activate phase 2 cytoprotective enzymes in vitro and in vivo, block cell proliferation, and induce differentiation and apoptosis of leukemia cells. Oral administration of TBE-31 also significantly reduces formation of aflatoxin-DNA adducts and decreases size and number of aflatoxin-induced preneoplastic hepatic lesions in rats by >90%. Because of the two cyano enones in rings A and C, TBE-31 may directly interact with DTT and protein targets such as Keap1 that contain reactive cysteine residues. The above findings suggest that TBE-31 should also be tested for chemoprevention and chemotherapy in relevant models of cancer and against other chronic, degenerative diseases in which inflammation and oxidative stress contribute to disease pathogenesis.

A multicenter phase II trial of intrathecal topotecan in patients with meningeal malignancies.

To determine the therapeutic efficacy (13-week and 26-week CNS progression-free survival [PFS], response rate, and overall survival) and safety of intraventricular (IVent) topotecan in patients with neoplastic meningitis (NM), we conducted a phase II, open-label, nonrandomized, single-arm trial of IVent topotecan in patients with NM using 400 mug of topotecan IVent twice weekly for 6 weeks, followed by evaluation with imaging, cerebrospinal fluid (CSF), and physical examinations. In the absence of disease progression, patients were then treated with IVent topotecan weekly for 6 weeks, twice monthly for 4 months, and monthly thereafter. Sixty-two patients (23 males and 39 females) were enrolled from April 2001 through March 2006. Median age and KPS at enrollment were 56 (range 5-83) and 80 (range 60-100), respectively. Primary cancers included breast (19), lung (13), CNS (14), and others (16). Forty patients (65%) completed the 6-week induction period, among whom 13 (21%) had CSF clearance of malignant cells. Kaplan-Meier estimates of PFS at 13 and 26 weeks were 30% (95% confidence interval [CI], 20%-45%) and 19% (95% CI, 11%-34%). Overall median survival (50 deaths) was 15 weeks (95% CI, 13-24 weeks). The most common side effect was chemical meningitis in 32% of patients (5% grade 3); 32% experienced no drug side effects. IVent topotecan is well tolerated, but provides no added benefit over other IVent therapies. Because of its modest side effect profile, combining IVent topotecan with other IVent or systemic interventions should be considered.

Complementary and alternative medicine use and quality of life in patients with primary brain tumors.

This study explored the use of complementary and alternative medicine (CAM) approaches and their relationship with demographic and disease characteristics and quality of life (QOL) in the primary brain tumor (PBT) population. One hundred one PBT patients were enrolled in this study. The results showed that 34% of patients reported using CAM. Forty-one percent reported using more than one type of CAM. The average cost of each CAM used per month was 69 dollars, with 20% of patients spending more than 100 dollars per month. The majority (74%) reported that their physicians were unaware of their use of CAM. Data analysis found a higher performance status to be the only factor significantly related to use of CAM therapy (P < 0.005). There was no difference in patient report of QOL between users and nonusers of CAM therapies. The high number of patients who do not report CAM use has potential implications for evaluation of symptoms and response to therapy in this population. This may be especially relevant in those patients with higher functional status participating in clinical trials.

Potent protection against aflatoxin-induced tumorigenesis through induction of Nrf2-regulated pathways by the triterpenoid 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole.

Synthetic triterpenoid analogues of oleanolic acid are potent inducers of the phase 2 response as well as inhibitors of inflammation. We show that the triterpenoid, 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im), is a highly potent chemopreventive agent that inhibits aflatoxin-induced tumorigenesis in rat liver. The chemopreventive potency of CDDO-Im was evaluated by measuring inhibition of formation of putative preneoplastic lesions (glutathione S-transferase P positive foci) in the liver of rats exposed to aflatoxin B1. CDDO-Im produces an 85% reduction in the hepatic focal burden of preneoplastic lesions at 1 micromol/kg body weight and a >99% reduction at 100 micromol/kg body weight. CDDO-Im treatment reduces levels of aflatoxin-DNA adducts by approximately 40% to 90% over the range of 1 to 100 micromol/kg body weight. Additionally, changes in mRNA levels of genes involved in aflatoxin metabolism were measured in rat liver following a single dose of CDDO-Im. GSTA2, GSTA5, AFAR, and EPHX1 transcripts are elevated 6 hours following a 1 micromol/kg body weight dose of CDDO-Im. Microarray analysis using wild-type and Nrf2 knockout mice confirms that many phase 2 and antioxidant genes are induced in an Nrf2-dependent manner in mouse liver following treatment with CDDO-Im. Thus, low-micromole doses of CDDO-Im induce cytoprotective genes, inhibit DNA adduct formation, and dramatically block hepatic tumorigenesis. As a point of reference, oltipraz, an established modulator of aflatoxin metabolism in humans, is 100-fold weaker than CDDO-Im in this rat antitumorigenesis model. The unparalleled potency of CDDO-Im in vivo highlights the chemopreventive promise of targeting Nrf2 pathways with triterpenoids.

Neurocognitive changes in cancer patients.

OBJECTIVES: To review the neurocognitive changes in patients with cancer. This will include and overview of signs and symptoms, diagnostic tests, nursing interventions, and supportive pharmacologic measures for the treatment of acute and chronic changes in cognition. DATA SOURCES: Published articles and reference books. CONCLUSION: The treatment modalities used for individuals with cancer can produce cognitive deficits that may negatively affect quality of life. The clinician's consistent assessment and evaluation of contributing factors such as co-morbidities, medications, age, and metabolic abnormalities assists in identifying the etiology for cognitive changes and guiding appropriate interventions. IMPLICATIONS FOR NURSING PRACTICE: Understanding the need for assessment of changes in cognition and the direct and indirect factors that contribute to these changes is critical for the oncology nurse caring for patients with cancer to provide an appropriate plan of care.

Evaluation of the cancer chemopreventive potency of dithiolethione analogs of oltipraz.

Oltipraz and related dithiolethiones constitute an important class of chemopreventive agents that enhance the expression of carcinogen detoxication and antioxidant genes. Dose-response studies were undertaken to characterize the cancer chemopreventive activities of several dithiolethiones that are at least as active as oltipraz as inducers. Inhibition of formation of pre-neoplastic lesions and formation of DNA adducts in livers of rats exposed to aflatoxin B1 (AFB1) was monitored. In the tumorigenesis experiment, the dithiolethiones were orally gavaged 3 days/week for 3 successive weeks and at four doses ranging from 0.03 to 0.3 mmol/kg body wt. AFB1 was gavaged beginning 1 week after the start of the dithiolethiones and for two successive weeks. The burden of AFB1-induced putative pre-neoplastic lesions (glutathione S-transferase-placental isoform positive foci) was quantified by light microscopy. Reduction in AFB-DNA adduct burden was assessed 24 h following the first dose of AFB1. Both the parent 1,2-dithiole-3-thione (D3T) and its 5-tert-butyl derivative were more potent inhibitors than oltipraz against these endpoints, while two of the seven tested analogs were slightly less inhibitory. D3T, the most potent dithiolethione of this series, was examined by microarray analysis for induction of hepatic genes at an intermediate chemopreventive dose (0.1 mmol/kg). Transcript levels of eight genes, including two known to detoxify aflatoxin, namely, glutathione S-transferase A5 (GSTA5) and AFB1 aldehyde reductase (AFAR) were elevated. Western analysis indicated that induction of hepatic GSTA5 and AFAR were directly related to the dose of D3T. At the highest dose of D3T (0.3 mmol/kg), protein levels of GSTA5 and AFAR were induced by 7- and 27-fold, respectively. While efficacy in humans has yet to be tested, D3T is clearly more potent than oltipraz and serves as a useful molecular probe for determining the key events associated with protection by this class of agents.