Clinical evaluation of the efficacy of methylnaltrexone in resolving constipation induced by different opioid subtypes combined with laboratory analysis of immunomodulatory and antiangiogenic effects of methylnaltrexone

. Age >/= 18 years 2. Receiving palliative care 3. Life expectancy > 2 weeks 4. Able to give informed consent 5. Receiving opioid treatment with either morphine sulphate, oxycodone or fentanyl 6. Opioid treatment, both a) On a regular schedule (not just as needed or rescue doses) for the control of pain or dyspnea for at least 2 weeks before the first dose of methylnaltrexone, and b) On a stable opioid regimen for at least 3 days before the first dose of methylnaltrexone. This is defined as no dose reduction of >/= 50%, dose increases are permitted. 7. If a subject uses a combination of short- and long-acting (including continuous administration) opioids, the short-acting opioid should preferably be of the same type as the long-acting opioid. If the subject uses a different type of short-acting opioid than the long-acting opioid, the subject is allowed to enter the study if he/she has used this short-acting opioid /= 3 days before the first dose of methylnaltrexone. This is defined as at least one type of laxative in an adequate dosing regimen, (e.g. macrogol 2 packets daily, magnesium(hydr)oxide 500 mg three times daily, bisacodyl 10 mg daily or sennoside A+B 10 ml daily) or at least two types of laxatives in a suboptimal dose with patient characteristics hampering optimal treatment. 11. If the subject is a woman with presumed child bearing potential; negative urine pregnancy test at screening 12. Surgically sterile or agrees to use a medically acceptable method of birth control or practice sexual abstinence for the duration of the methylnaltrexone treatment and the following 15 days. ~ * including laxation after rescue laxative or enema ~ not necessary for postmenopausal women

1. Previous treatment with methylnaltrexone 2. Known or suspected mechanical gastrointestinal obstruction 3. Presence of an other cause of bowel dysfunction that is considered to be a major contribution to the constipation according to investigator 4. Presence of a peritoneal catheter for intraperitoneal chemotherapy or dialysis 5. Clinically relevant active diverticular disease 6. History of bowel surgery within 10 days before first dose of methylnaltrexone 7. Fecal ostomy 8. Use of vinca alkaloids within previous 4 months 9. Body weight <38 kg 10. Renal failure defined as EGFR <30 ml/min per 1.73m2 or requires dialysis. 11. Known or suspected allergy to methylnaltrexone or similar compounds (e.g. naltrexone or naloxone) 12. Participation in a study with investigational products within 30 days before first dose of methylnaltrexone. 13. Pregnant or nursing 14. Clinically important abnormalities that may interfere with participation or compliance to the study, determined by investigator Additional exclusion criteria for the immunologic and angiogenic analysis part of the study: 15. Chemotherapy or treatment with tyrosine kinase inhibitor during 4 weeks before inclusion or treatment scheduled during participation in this study. 16. Treatment with high dose corticosteroids during 2 weeks before inclusion in this study. This is defined as the equivalent of 30 mg of prednisone per day for >/= 2 consecutive days.