Octreotide (SMS 201–995) for hematopoietic support-dependent high-dose chemotherapy (HSD-HDC)-related diarrhoea: dose finding study and evaluation of efficacy

Abstract

Summary:diarrhoea induced by HSD-HDC. Prospective controlled trials are needed to confirm its value. Keywords: diarrhoea; high-dose chemotherapy; octreoEmphasis has been put on the intensification of chemotherapy programs through high-dose chemotherapy tide acetate regimens. While their myelosuppression is managed through the use of colony-stimulating factors and/or infusion of autologous peripheral blood progenitor cell Chemotherapy-related diarrhoea is a very common problem transfusions (PBPCT), extramedullary dose-limiting in cancer patients. Although diarrhoea has been reported toxicities, including gastrointestinal mucosal injury, are with many antineoplastic drugs, this adverse effect is usua treatment-limiting factor and their management is a ally associated with 5-FU, 1 CDDP 2 and most recently with critical issue in HSD-HDC. Octreotide is effective in the CPT 11. 3 The diarrhoea associated with high-dose chemocontrol of diarrhoea induced by fluoropyrimidines. We therapy is not only a quality of life issue, but often a lifehave studied its effect on hematopoietic support-depenthreatening toxicity. Mucosal injuries associated with dent high-dose chemotherapy (HSD-HDC) related diawatery diarrhoea result in dehydration, electrolyte disorders rrhoea. HSD-HDC-treated patients were included in the and can be a harbinger of sepsis and neutropenic infections, study when they had у4 loose stools per day. Diagnostic all events which may prolong hospitalization. The successwork-up included physical examination, stool culture, ful management of this toxicity will facilitate the developClostridium difficile toxin assay, abdominal plain films, ment of outpatient intensive chemotherapy programs. complete blood counts, liver and renal function tests.Octreotide acetate (Sandostatin; Sandoz Pharmaceutical, Patients were treated with 0.1 mg octreotide, q 8 h, subHanover, NJ, USA), a synthetic polypeptide analog of somcutaneously for 48 h. Responding patients (р2 loose atostatin, has proven to be safe and effective in the treatstools per day) continued treatment at the same dose ment of secretory diarrhoea associated with the Zollingerfor an additional 24 h. Lack of response (у3 loose stools Ellison syndrome, the carcinoid syndrome, the Vernerper day), led to dose escalation by 0.1 mg increments, Morrison syndrome, AIDS and graft-versus-host disease. 4-8up to a 0.5 mg/dose and the latter dose was maintained Furthermore, impressive results have been reported with for 24 h. Patients not responding at 0.5 mg/8 h were octreotide acetate in several studies involving 5-fluorouraconsidered failures. A consecutive cohort of 24 HSDcil 9,10 and cisplatin 11 -induced diarrhoea. In a randomized HDC treated patients was studied. Fourteen (n = 14) study in solid tumour patients treated with 5-fluorouracil (58.33%) patients developed severe diarrhoea with a who developed severe diarrhoea, octreotide showed superimedian number of 7.5 loose stools per day (range, 4-ority over loperamide. mg (two patients). No toxicity wasFourteen consecuti...

Control of irinotecan-induced diarrhea by octreotide after loperamide failure

“…The dosage of 0.5 mg every 8 h is in accordance with previous studies [8,11], where higher doses of octreotide were more effective than the lower doses of 100-200 mg.…”

“…It has been shown to be effective in the control of diarrhea caused by fluoropyrimidine or by the high-dose chemotherapy regimens [6,8] used in bone marrow transplantation.…”

Sequential cycles of high-dose chemotherapy with dose escalation of carboplatin with or without paclitaxel supported by G-CSF mobilized peripheral blood progenitor cells: a phase I/II study in advanced ovarian cancer

“…This transient well-known side-effect of high-dose carboplatin is correctable in part by oral opium tincture or octreotide at 0.3 to 1.5 mg/day administered i.v. as a continuous infusion, or s.c. every 8 h. 14,25,30,38 Mucositis was seen exclusively after cycle 4 which was clearly attributed to the combination of high-dose etoposide and melphalan.…”

Review: Chemotherapy-induced diarrhea: pathophysiology, frequency and guideline-based management

“…Current treatment guidelines recommend a starting dose of 100150 mg subcutaneously (sc) or intravenously (iv) three times a day. Doses could be escalated to 500 mg sc/iv three times a day or by continuous iv infusion 2550 mg/hr showing a dose-response relationship without significant toxicities [Wadler et al 1995;Wasserman et al 1997b]. …”