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1.  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
2.  The Effect of Oral Methadone on the QTc Interval in Advanced Cancer Patients: A Prospective Pilot Study 
Journal of Palliative Medicine  2010;13(1):33-38.
Recent reports suggest that high doses of methadone may prolong QTc interval and occasionally cause torsades de pointes; however, few of these studies involved the palliative care population.
The purpose of this study was to determine the effect of initiation of methadone on QTc interval in patients with cancer pain seen at the palliative care setting.
We enrolled 100 patients with cancer in this prospective study. Patients were followed clinically and electrocardiographically for QTc changes at baseline, 2, 4, and 8 weeks. Contributing factors for QTc prolongation such as medications, cardiovascular diseases, and electrolytes disturbances were documented. QTc prolongation was defined as greater than 430 ms in males and greater than 450 ms in females, and significant QTc prolongation was defined as QTc interval greater than 25% increase from baseline or 500 ms or more.
Electrocardiographic (ECG) assessments were available for 100, 64, 41, and 27 patients at baseline, 2-, 4-, and 8-week follow-up, respectively. At baseline prior to initiation of methadone, 28 (28%) patients had QTc prolongation. Clinically significant increase in QTc occurred in only 1 of 64 (1.6%) patients at week 2, and none at weeks 4 and 8. There was no clinical evidence of torsades de pointes, ventricular fibrillation, or sudden death. QTc prolongation was more frequent among patients with increased baseline QTc interval.
Baseline QTc prolongation was common, whereas significant QTc interval 500 ms or more after methadone initiation rarely occurred, with no evidence of clinically significant arrhythmias. This study supports the safety of methadone use for pain control in patients with advanced cancer in the palliative care setting.
PMCID: PMC2939847  PMID: 19824814
3.  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 1-3 (3)