Malignant bowel obstruction and intractable diarrhea in advanced cancer are common devastating syndromes.
Apart from disease specific, causative treatment in patients with longer prognosis, there is a
possibility of conservative, non-operative symptom management in terminal phase. A successful control of
intractable vomiting and diarrhea using octreotide in two advanced cancer patients was presented, with
guidance through steps of the management. Pathophysiologic vicious circle of the bowel obstruction and
diarrhoea was described and the management algorithm was proposed. Due to the gut hyposecreting
action, octreotide occurs to be a potent and essential drug in refractory vomiting or diarrhea.Malignant bowel obstruction and intractable diarrhea in advanced cancer are common devastating syndromes.
Apart from disease specific, causative treatment in patients with longer prognosis, there is a
possibility of conservative, non-operative symptom management in terminal phase. A successful control of
intractable vomiting and diarrhea using octreotide in two advanced cancer patients was presented, with
guidance through steps of the management. Pathophysiologic vicious circle of the bowel obstruction and
diarrhoea was described and the management algorithm was proposed. Due to the gut hyposecreting
action, octreotide occurs to be a potent and essential drug in refractory vomiting or diarrhea

Bętkowska, Izabela

Grądalski, Tomasz

English

Via Medica Journals

www.advpm.eu 161Case reportTomasz Grądalski1, 2, Izabela Bętkowska2, 31Pain and Palliative Clinic, Chair of Internal Medicine and Gerontology, Jagiellonian University Collegium Medicum, Krakow, Poland2St. Lazarus Hospice, Krakow, Poland3Division of Family Medicine, Chair of Internal Medicine and Gerontology, Jagiellonian University Collegium Medicum, Krakow,PolandEffectiveness of octreotidein advanced cancer patientswith malignant bowel obstructionand intractable diarrheaAbstractMalignant bowel obstruction and intractable diarrhea in advanced cancer are common devastating syn-dromes. Apart from disease specific, causative treatment in patients with longer prognosis, there is apossibility of conservative, non-operative symptom management in terminal phase. A successful control ofintractable vomiting and diarrhea using octreotide in two advanced cancer patients was presented, withguidance through steps of the management. Pathophysiologic vicious circle of the bowel obstruction anddiarrhoea was described and the management algorithm was proposed. Due to the gut hyposecretingaction, octreotide occurs to be a potent and essential drug in refractory vomiting or diarrhea.Key words: malignant bowel obstruction, intractable diarrhea, octreotideAdv. Pall. Med. 2009; 8, 4: 161–164Address for correspondence: Tomasz GrądalskiPain and Palliative Clinic, Chair of Internal Medicine and GerontologyJagiellonian University Collegium Medicum, Krakow, Polande-mail: tomgr@mp.plAdvances in Palliative Medicine 2009, 8, 161–164Copyright © 2009 Via Medica, ISSN 1898–3863IntroductionIn patients with end-stage disease malignantbowel obstruction (MBO) is a quite common anddevastating complication, which worsens the qual-ity of life and markedly shortens prognosis. Its fre-quency ranges from 5% to 42% in advanced ovari-an cancer and from 4% to 24% in advanced colorec-tal cancer. It may be partial or complete and atsingle or multiple sites; the small bowel is morecommonly involved than the large bowel (61% vs.33% in over 20% of the patients both are involved).Its pathological mechanisms may be benign (morecommon in colorectal cancer, less in gynaecologicalcancers), such as adhesions, post-irradiation boweldamage, inflammatory bowel disease, hernia orfunctional obstruction. Malignant causes are: ex-trinsic, intrinsic or intraluminal gut occlusion andneoplastic or paraneoplastic intestinal motility dis-orders due to infiltration or neuropathy of mesen-tery nerves or celiac plexus [1].Typical clinical symptoms consist of nausea/vom-iting and continuous abdominal pain (90% of pa-tients, less severe in large bowel obstruction) whichinduce colic pain due to gut ineffective motility (ap-prox. 75% of patients). The most pronounced signsare abdominal distension (periodically spontaneous-ly resolving in partial MBO) and high-pitched peri-stalsis or borborygmi [2]. Possible radiological in-vestigations that may be performed in patients withAdvances in Palliative Medicine 2009, vol. 8, no. 4www.advpm.eu162symptoms and signs of MBO like plain/contrast ra-diography or abdominal CT should be consideredonly in patients who will benefit from surgery (goodperformance and nutritional status, no previousabdominal surgery or radiotherapy and acute sin-gle mechanical obstruction). Surgical treatment —which ought to be considered in every case — dueto high risk of mortality (9–40%) and complications(9–90%) is not superior to conservative treatmentand may consist of laparotomy resection or gut by-pass, endoscopy laser resection and endoscopystenting. In inoperable, vomiting and resistant topharmacological therapy patients venting proce-dures [e.g. percutaneous endoscopically placed gas-trostomy (PEG) tube] may be considered. To thevast majority of terminal cancer patients drug ther-apy is the only possible option. It focuses on reliefof nausea, vomiting and pain, sometimes may eventemporally reverse the MBO signs.Diarrhoea in advanced cancer relates to approx.10% of patients can be caused by drugs (laxatives,antibiotics, antacids or chemotherapy), radiothera-py, oncological surgery (e.g. restorative proctocolec-tomy) gastrointestinal tumours, infection, inflam-mation, malabsorption or incorrect diet. Particular-ly in older patients “diarrhea” can also be a sign ofthe overflow fecal incontinence caused by fecal im-paction. Apart from disease specific (causal) man-agement, treatment usually includes opioids (mor-phine or loperamide), pancreatic enzyme replace-ment or probiotics. In intractable or refractory diar-rhoea (ID) gut hypersecretion can play a significantrole [3]. This excessive secretion can be caused bythe damage to the intestinal mucosa including lossof intestinal epithelium, superficial necrosis, and in-flammation of the bowel wall (e.g. due to chemo-therapy) the presence of fistulas or neuroendocrinegastrointestinal tumors (carcinoids or endocrinepancreatic tumors) or paraneoplastic stimulation ofthe gut enzymes [4–6].The aim of this study is to present two cases ofsuccessful management of MBO and ID in terminalcancer patients using somatostatin analogue.Case 1A 75 year old man, with three-year history ofcolon cancer (adenocarcinoma tubulare) was ad-mitted to the hospice. He complained of severe un-restrained vomiting (up to 2 litres a day), weakness,anorexia, abdominal pain and sleep disturbances.Laparotomy revealed relapse of the disease withbowel obstruction (regional 25 cm infiltration ofsigmoid spreading into small intestine and retro-peritoneal space). Performed surgical treatment (par-tial small bowel resection and colostomy) hadbrought no relief. Afterwards gastro-entero anas-tomosis also had not alleviated the symptoms. Onthe contrary his nausea and vomiting had beingmore and more severe in time. Due to his ileus hebecame bed bound and depressive and his socialcontact was scarce. During hospice care he did notrespond to more than 7 days trial of dexametha-sone (8 mg a day i.v.) with metoclopramide. Halo-peridol and levomepromazine benefit was of minorimportance too, with aggravation of depression andconsciousness disturbances. Hyoscine butybromide(up to 180 mg a day) was completely inefficientwith huge discomfort of dry mouth and mental de-terioration. A trial of octreotide was suggested andhis vomiting diminished immediately and was con-trolled on 0,3 mg a day. His sc daily morphine de-mand decreased from 60 to 30 mg. Attempt ofoctreotide withdrawal caused symptoms recurrence.He was stable for seven months, walking with assis-tance, with good appetite, enteral diet and withmood improvement, until peaceful death precededby slow general deterioration.Case 2A 82 year old woman with advanced cervical can-cer after palliative colostomy was suffering of a hugediarrhea because of malignant bowel obstructionsymptoms. It made administering of her colostomysacks almost impossible. In subsequence there was ahuge skin irritation, pruritus and the risk of electro-lytes loss. Odour and shame took effect in avoidingof social contact and exacerbated depression. Onadmission: bed bound, with extensive scorching andburning red inflammatory skin irritation around thecolostomy. She was not hypercalcemic. Her diarrheawas not controlled on high doses of pancreatic en-zymes, loperamide, hyoscine butybromide and mor-phine, with additional notable adverse symptoms asdry mouth. Similarly a trial of steroids did not causeimprovement. Octreotide at a starting dose of 0.1mg a day (in divided doses) was administered, andtitrated to 0.3 mg a day, with eventual diarrhea as-sessment. It enabled colostomy sack administrationand skin irritations healing. In consequence of thistreatment, the patient’s psychological condition andsocial contacts improved and occupational therapybecame possible. A trial of octreotide withdrawalcaused diarrhea recurrence. She remained stable fortwo months and died in comfort.www.advpm.eu 163Tomasz Grądalski, Izabela Bętkowska, Effectiveness of octreotide in advanced cancer patientsPathophysiology of MBO and IDThe most distressing symptoms of MBO are vom-iting, colic or continuous pain; in ID: colic pain anddevastating frequent bowel movements. The in-crease of bowel secretion and contraction seems toplay the crucial role both in the vicious circle ofMBO and ID (Fig. 1).MBO drug therapy comprising analgetics, anti-emetics, and antisecretory drugs without using anasogastric tube was first described by Mary Baineset al. in 1985 [7]. The drugs of choice vary to acertain extent between countries and different cen-ters, based on clinical experience, drug availability,cost and fashion. Medication should be tailored toeach patient with regard to both the drugs to beadministered and the route of administration. Inresistant MBO to anticholinergics a trial of octreotidecan be a valuable option (Fig. 2).ID therapyDiarrhea is a symptom. When possible, the un-derlying disorder should be treated, but symptom-atic treatment is often necessary. Traditional IDsymptomatic management has focused on the useof nonspecific therapy such as atropine, loperam-ide, codeine, and the opium mixture. Alternativenonspecific approaches include anticholinergics,antispasmodics, and adsorbent agents preparations.Opioids exert their antidiarrheal activity on gas-trointestinal cells by their agonistic effects on opio-id receptors, thus decreasing peristaltic movementsand increasing absorption. However, although opi-oids are currently considered as gold standard forID in cancer patients, their effectiveness in control-Figure 1. The importance of bowel secretion andcontraction in MBO/ID pathomechanismsFigure 2. MBO conservative management diagramAdvances in Palliative Medicine 2009, vol. 8, no. 4www.advpm.eu164ling it can be insufficient. Additionally, chronic orhigh-dose opioid treatment may cause serious sideeffects, e.g. loperamide-induced paralytic ileus,which makes close monitoring of patients receivingthis antidiarrheal treatment mandatory. The soma-tostatin can exert its antidiarrheal actions by multi-ple mechanisms.Octreotide is a synthetic analogue of somatosta-tin with a longer duration of action. It inhibits therelease of growth hormone, TSH, prolactin and ACTH,the secretion of insulin, glucagon, gastrin and otherpeptides of the gastro-enteropancreatic system, re-ducing splanchnic blood flow, portal blood flow,gastro-intestinal motility, gastric, pancreatic and smallbowel secretion, and increasing water/electrolyteabsorption. In patients with cancer and inoperablebowel obstruction, octreotide rapidly improves symp-toms in ≥ 75% of patients. In hormone-secretingtumours, octreotide improves symptoms by inhibit-ing hormone secretion, e.g.: 5HT in carcinoid (im-proving flushing and diarrhoea) VIP in VIPomas (im-proving diarrhoea) glucagon in glucagonomas (im-proving rash and diarrhoea). In refractory secretorydiarrhoea it is known to enhance water and sodiumabsorption from the small intestine, it inhibits chlo-ride secretion in the colon and prolongs small intes-tine transit [8]. Octreotide has a direct anticancereffect on solid tumours of the gastro-intestinal tractthus can prolong survival. It is poorly absorbed afteroral administration. After subcutaneous injection itsduration of action can extend up to 12 hours so itshould be given not less frequently than twice a day.The dose should be titrated according to the effect.There are 2-drug compatibility data for octreotide in0.9% saline with diamorphine, haloperidol, hyoscinebutylbromide, midazolam, morphine sulphate andondansetron. Incompatibility may occur with dex-amethasone or levomepromazine [9]. A long-actingformulation (LAR) has been designed to provide long-term controlled release after a singular intramuscu-lar injection. Most side effects encountered with oct-reotide are either local (pain, redness or swelling) orgastrointestinal (anorexia, nausea, vomiting, abdom-inal cramp-like pain). Adverse endocrinological ef-fects are rare. Due to the high acquisition costs (0.1mg ampoule = approx. 30 PLN comparable with forexample hyoscine butylbromide: 20 mg ampoule =approx. 1 PLN), the cost effectiveness of prescribingoctreotide must be considered before commencingtherapy [5].In the case 1 of MBO, both surgical and conser-vative management failed — octreotide due to res-toration of the gut passage and symptom with-drawal — gave the patient seven months of fairlynormal life. In the case 2, ID resistant to causaltreatment, irresponsive to opioid, pancreatic enzymeand probiotic therapy suggested excessive fluid se-cretion. The enrollment of octreotide gave the pa-tient not only restoration of the normal bowel move-ment and possibility to skin lesion healing, but alsoimproved her mood and diminished social isolation.Octreotide occured the valuable option in the man-agement of drug resistant MBO and ID.References1. Ripamonti C., Twycross R., Baines M. et al. Clinical-prac-tice recommendations for the management of bowel ob-struction in patients with end-stage cancer. Support CareCancer 2001; 9: 223–233.2. Ripamonti C. Bowel obstruction. In: Bruera E., Higginson I.J.,Ripamonti C., von Gunter C. (eds.). Textbook of PalliativeMedicine. Edward Arnold Publishers Ltd, London 2006:588–600.3. Fallon M., O’Neill B. ABC of palliative care: Constipationand diarrhea. BMJ 1997; 315: 1293–1296.4. Topkan E., Karaoglu A. Octreotide in the Management ofChemoradiotherapy-Induced Diarrhea Refractory to Lop-eramide in Patients with Rectal Carcinoma. Oncology2006; 71: 354–360.5. Gilbar P.J. The role of octreotide in symptom manage-ment in oncology and palliative care. J. Oncol. Pharm.Practice 2000; 6: 81–91.6. Freeman H.J., Berean K.W. Resolution of paraneoplasticCollagenous enterocollitis after resection of colon can-cer. Can. J. Gastroenterol. 2006; 20: 357–360.7. Baines M., Olivier D.J., Carter L.R. Medical managementof intestinal obstruction in patients with advanced malig-nant disease: a clinical and pathological study. Lancet1985; 2: 990–993.8. Farthing MJG The patient with refractory diarrhoea. BestPractice and Research Clinical Gastroenterology 2007; 21:485–501.9. Available on: http://www.palliativedrugs.com/octreotide.html(28.07.09).

Effectiveness of octreotide in advanced cancer patients with malignant bowel obstruction and intractable diarrhea

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Effectiveness of octreotide in advanced cancer patients with malignant bowel obstruction and intractable diarrhea

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