9068 Background: Palliative cancer care is the integration into cancer care of therapies that address multiple issues that cause suffering for patients and their families and impact their life quality. Challenges and barriers continue to hinder the integration of palliative care into comprehensive, ambulatory oncology care. This paper aims to describe how symptoms, distress, and quality of life (QOL) data from the usual care phase of a NCI-supported Program Project (P01) informed the development of an interdisciplinary palliative care intervention for patients with metastatic non-small-cell lung cancer (NSCLC). Methods: Patients receiving usual care for metastatic NSCLC were recruited into this prospective longitudinal study. A total of 130 patients with stage IV NSCLC were accrued, and 114 patients had evaluable data. Upon informed consent, patients completed outcome measures that assessed physical function/cognitive status, social activities and support, symptom characteristics, psychological distress, and overall QOL. Patient-reported outcomes were completed at baseline, 6, 12, and 24 weeks post-accrual. Results: Subjects were primarily female (64%), ranged in age from 40-84 years, and 39% were ethnic minorities. The majority were former smokers (66%). KPS, IADL, and Cognitive scores deteriorated significantly over time (p=.001, .009, and .042, respectively). Patients reported higher severity scores with symptoms such as dyspnea, fatigue, insomnia, lack of appetite, peripheral neuropathy, pain, dry skin, nail changes, and problems with sexual interest in all four time periods. Global Symptom Distress Index and Total Symptom score both significantly worsened at 24 weeks (p=.003 and .017, respectively). Physical Well-Being worsened significantly (p=.036), while overall QOL, spiritual well-being, and psychological distress scores remained statistically stable over time. Conclusions: Patients with metastatic NSCLC continue to experience high symptom burden and diminished physical well-being over time while receiving treatments. An interdisciplinary palliative care intervention is currently being tested to improve symptom burden and overall QOL.

Background: This NCI funded program project (P01) is an interdisciplinary research project focused on palliative care, quality of life (QOL), and symptom control in lung cancer. The purpose of this study is to test usual care versus integration of palliative care encompassing four dimensions of QOL.

The gut is a neurological organ, which implies that many neuroactive drugs such as opioid analgesics can seriously disturb gastrointestinal function, because many of the transmitters and transmitter receptors present in the brain are also found in the enteric nervous system. One of the most common manifestations of opioid-induced bowel dysfunction is constipation which results from blockade of peristalsis and intestinal fluid secretion. The discovery of opioid receptor antagonists with a peripherally restricted site of action, such as N-methylnaltrexone and alvimopan, makes it possible to normalize bowel function in opiate-treated patients without compromising central opioid analgesia. There is emerging evidence that opioid receptor antagonists may also have prokinetic actions, reversing pathological states of gastrointestinal hypomotility that are due to overactivity of the enteric opioid system.

Background: Patients with advanced illness (AI), receiving opioids for pain control, often experience laxative-unresponsive, severe opioid-induced constipation (OIC) that is distressing and complicates pain management. Methylnaltrexone (MNTX) is a quaternary methyl derivative of the pure opioid antagonist naltrexone. MNTX does not cross the blood-brain barrier and thus may antagonize the peripheral effects of opioids without affecting centrally mediated analgesia. Previous results of a phase III trial in AI patients demonstrated significant activity of single subcutaneous (SC) doses of both 0.15 mg/kg and 0.30 mg/kg compared to placebo in inducing laxation within 4 hours and 24 hours, without causing reversal of pain control or symptoms of withdrawal. The present phase III study was designed to assess the efficacy and safety of MNTX (0.15 mg/kg, SC) versus placebo administered every other day (QOD) for 2 weeks in AI patients with OIC. Methods: This was a multicenter, double-blind, randomized, placebo-controlled study of SC MNTX for OIC in AI patients in hospice, nursing homes, and palliative care programs. Eligible patients had a life expectancy of < 6 months and OIC (< 3 laxations in the prior week, or no laxation in 48 hours). Patients were on stable laxatives and opioids. Patients were randomized to either placebo or MNTX 0.15 mg/kg QOD for 2 weeks. No rescue laxatives were allowed within 4 hours of dosing. Patients were able to double their blinded dose in week 2 if there were ≤ 2 laxations in the first week (unrelated to rescue laxatives). Co-primary endpoints were laxation within 4 hours of the first dose and laxations occurring within 4 hours of at least 2 of the first 4 doses. The intent-to-treat population was analyzed using a Cochran-Mantel-Haenszel test. Results: 133 patients were randomized. Within 4 hours of the first dose 48.4% of MNTX patients vs. 15.5% of placebo patients achieved laxation (P < .0001). Laxation within 4 hours of dosing for at least 2 of the first 4 doses occurred in 51.6% of MNTX patients vs. 8.5% of placebo patients (P < .0001). Over 70% of patients had a laxation response within 4 hours after at least 1 of the first 4 doses of MNTX. For those who responded to MNTX the median time to laxation was 30 minutes. MNTX was well tolerated with transient abdominal cramping and flatulence being the most common adverse events, as previously reported. There were no reports of systemic opioid withdrawal or loss of analgesia due to study medication. Conclusions: MNTX can reverse constipation due to opioids in AI patients when given every other day for a 2-week period. This drug was well tolerated and has the potential to meet a significant unmet medical need.

LBA8003 Background: Constipation is a common and distressing side effect of opioid treatment. Patients with AMI commonly experience severe OIC unresponsive to laxatives which can significantly complicate pain management. MNTX is a quaternary derivative of the pure opioid antagonist naltrexone formed by the addition of a methyl group to the ring nitrogen. MNTX does not cross the blood-brain barrier; hence it has the potential to antagonize the peripheral effects of opioids while sparing centrally mediated analgesia. MNTX has been shown to reverse OIC in chronic methadone users and we have previously reported positive results of a phase II trial of MNTX for relief of OIC in hospice patients without evidence of withdrawal or worsened pain (Thomas, et al. ProcASCO, 2003). The present phase III study was initiated to confirm the findings of phase II and assess the safety and efficacy of MNTX in treating OIC in patients with AMI. Methods: This is a multi-center, double-blind, randomized, placebo-controlled study of subcutaneous MNTX for OIC in AMI patients in hospice or palliative care programs. Patients must have a life expectancy of 1 to 6 months, no laxation for 48 hours, on stable opioids for pain and stable laxatives. Patients are randomized to either placebo, MNTX 0.15 mg/kg, or MNTX 0.30 mg/kg. 24 hours after a single subcutaneous dose of study drug, patients may receive open label MNTX, as needed over the next 4 weeks, titrated to effect and tolerability. Total accrual will be approximately 150 patients (50 per group). The primary endpoint is the efficacy of single-dose MNTX (0.15 mg/kg or 0.30 mg/kg vs. placebo) to induce laxation within 4 hours of dosing. We will also measure laxation over 24 hours and adverse events, pain scores, and opioid withdrawal symptoms. The primary analysis will be intent-to-treat and include all randomized patients using a Cochran-Mantel-Haenszel test of placebo against each MNTX dose level. Results: 150 patients have been enrolled as of 12/2/04 and enrollment will be closed on 12/15/04. Analysis of the primary and secondary endpoints and a summary of the demographics will be presented for all patients. Conclusions: To be reached after data becomes available. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Progenics Progenics Progenics