Dual single‑nucleotide polymorphism biomarker combination for opioid selection to treat cancer pain.

We have been exploring biomarkers that could help physicians select the appropriate opioid for individualized treatment of cancer pain. Recently, we identified a single nucleotide polymorphism (SNP) of (rs17809012) as one such biomarker that was significantly associated with the analgesic effect of morphine. The current study measured the plasma concentrations of chemokines/cytokines in pre-treatment plasma samples of a total of 138 patients who were randomized to receive morphine (n=70) or oxycodone (n=68).

Novel single nucleotide polymorphism biomarkers to predict opioid effects for cancer pain.

There have been few studies on predictive biomarkers that may be useful to select the most suitable opioids to optimize therapeutic efficacy in individual patients with cancer pain. We recently investigated the efficacy of morphine and oxycodone using single nucleotide polymorphisms (SNPs) of the catechol-O-methyltransferase () rs4680 gene as a biomarker (RELIEF study). To explore additional biomarkers that may enable the selection of an appropriate opioid for individual patients with cancer pain, three SNPs were examined: C-C motif chemokine ligand 11 (; rs17809012), histamine N-methyltransferase (; rs1050891) and transient receptor potential V1 (; rs222749), which were screened from 74 pain-related SNPs.

Morphine Versus Oxycodone for Cancer Pain Using a Catechol-O-methyltransferase Genotype Biomarker: A Multicenter, Randomized, Open-Label, Phase III Clinical Trial (RELIEF Study).

Background: We hypothesized that the high-dose opioid requirement in patients carrying the rs4680-GG variant in the COMT gene encoding catechol-O-methyltransferase would be greater for patients taking morphine than for those taking oxycodone, thus providing a much-needed biomarker to inform opioid selection for cancer pain.

Methods: A randomized, multicenter, open-label trial was conducted at a Japanese hospital's palliative care service. Patients with cancer pain treated with regular doses of nonsteroidal anti-inflammatory drugs or acetaminophen were enrolled and randomized (1:1) into morphine (group M) and oxycodone (group O) groups.

Prospective replication study implicates the catechol-O-methyltransferase ValMet polymorphism as a biomarker for the response to morphine in patients with cancer.

Genetic differences in humans cause clinical difficulties in opioid treatment. Previous studies indicate that a single nucleotide polymorphism in the catechol-O-methyltransferase () gene (rs4680; p.ValMet) may present as a predictive biomarker for the response to morphine treatment.

Incidence of carnitine deficiency in patients with cancer pain: A pilot study.

Carnitine deficiency is reportedly associated with increased pain sensation in diabetes mellitus and fibromyalgia, but the association between serum carnitine concentration and cancer pain has not been fully elucidated. We investigated the incidence of carnitine deficiency in patients with cancer pain, and examined the effect of the patients' demographic and clinical characteristics on pain intensity and carnitine deficiency. The serum carnitine concentration was measured in 50 patients with cancer pain receiving non-steroidal anti-inflammatory drugs, but not opioids.

Expectation of a Decrease in Pain Affects the Prognosis of Pain in Cancer Patients: a Prospective Cohort Study of Response to Morphine.

Purpose: Cancer pain is a multidimensional experience that includes physiological, sensory, affective, cognitive, behavioral, and sociocultural dimensions. Few prospective studies have examined the relationship between a patient's expectation of pain improvement and the pain prognosis. The aim of this prospective study was to investigate whether patients' expectation to pain reduction was associated with pain intensity after morphine treatment in opioid treatment-naïve patients with various types of cancer.

Gender differences in cancer-related distress in Japan: a retrospective observation study.

Background: Cancer care is currently the most important medical issue in Japan. Total pain of cancer patients consists of a combination of four factors: physical, psychological, social distress, and spiritual pain. Previous studies showed female cancer patients ask for more psychological support and seem to suffer different types of distress compared with male patients, for example, appearance-related symptoms.

The physical and psychological problems of immigrants to Japan who require psychosomatic care: a retrospective observation study.

Background: As the number of immigrants to Japan increases, the health problems of foreign nationals also have an increasing impact on Japanese medical institutions. The aim of this study was to clarify the Japan-specific health problems related to both the physical and psychological symptoms of foreign nationals from the viewpoint of psychosomatic medicine. The second aim was to clarify the measures that should be taken in Japan and similar countries where immigration may still be considered less than common.

Phase I study of weekly nab-paclitaxel combined with S-1 in patients with human epidermal growth factor receptor type 2-negative metastatic breast cancer.

We conducted a phase I study of a weekly nab-paclitaxel and S-1 combination therapy in patients with human epidermal growth factor receptor type 2-negative metastatic breast cancer. The primary objective was to estimate the maximum tolerated and recommended doses. Each treatment was repeated every 21 days.

Early palliative intervention for patients with advanced cancer.

Background: Early palliative intervention in advanced cancer patients with metastatic non-small-cell-lung cancer has been shown to improve survival time. Possibly, palliative intervention at the time of outpatient care further improves patient survival time.

Objective: We performed a comparative study of late and early referrals of patients with advanced cancer to clarify the appropriate time for palliative intervention and the improvement in survival time.

Pilot study of duloxetine for cancer patients with neuropathic pain non-responsive to pregabalin.

Background: Neuropathic pain frequently occurs in cancer patients, but no drug therapy has been established for this type of disorder. The purpose of this study was to investigate the effect of duloxetine in cancer patients suffering from neuropathic pain.

Patients And Methods: The subjects of the study were 15 cancer patients with neuropathic pain who visited the Kinki University Faculty of Medicine Hospital and met the International Association for the Study of Pain diagnostic criteria for neuropathic pain.

Expression changes in arrestin β 1 and genetic variation in catechol-O-methyltransferase are biomarkers for the response to morphine treatment in cancer patients.

Genetic differences in individuals with regard to opioid-receptor signaling create clinical difficulties for opioid treatment; consequently, useful pharmacodynamic and predictive biomarkers are needed. In this prospective study, we studied gene expression changes in peripheral blood leukocytes using a microarray and real-time RT-PCR analysis to identify pharmacodynamic biomarkers for monitoring the effect of morphine in a cohort of opioid-treatment-naïve cancer patients. We also examined genetic variations in opioid receptor mu 1 (OPRM1, 118A→G) and catechol-O-methyltransferase (COMT, 472G→A) to evaluate predictive biomarkers of the treatment outcome of morphine.

Prospective study evaluating the plasma concentrations of twenty-six cytokines and response to morphine treatment in cancer patients.

Cytokine signaling is involved in pain and opioid-receptor signaling. In this prospective study, we studied the plasma cytokine levels in order to identify candidate biomarkers for predicting resistance to morphine treatment in a cohort of opioid-treatment-naïve cancer patients. We analyzed pain rating and the plasma concentrations of 26 cytokines at baseline and after morphine treatment using a multiplex immunoassay system for the following cytokines: eotaxin, colony stimulating factor, granulocyte (G-CSF), colony stimulating factor granulocyte-macrophage (GM-CSF), interferon α2 (IFN-α2), IFN-γ, interleukin 1α (IL-1α), IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p40), IL-12 (p70), IL-13, IL-15, IL-17, IP-10, monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein 1α (MIP-1α), MIP-1β, tumor necrosis factor-α (TNF-α) and TNF-β.

High-dose dexamethasone plus antihistamine prevents colorectal cancer patients treated with modified FOLFOX6 from hypersensitivity reactions induced by oxaliplatin.

Background: Oxaliplatin is a third-generation platinum compound and a key agent for the management of colorectal cancer. Patients treated with oxaliplatin are at risk for hypersensitivity reactions. We designed a modified premedication regimen to prevent oxaliplatin-related hypersensitivity reactions and assessed if this approach is effective.