Octreotide (SMS 201-995) for hematopoietic support-dependent high-dose chemotherapy (HSD-HDC)-related diarrhoea: dose finding study and evaluation of efficacy.
Emphasis has been put on the intensification of chemotherapy programs through high-dose chemotherapy regimens. While their myelosuppression is managed through the use of colony-stimulating factors and/or infusion of autologous peripheral blood progenitor cell transfusions (PBPCT), extramedullary dose-limiting toxicities, including gastrointestinal mucosal injury, are a treatment-limiting factor and their management is a critical issue in HSD-HDC. Octreotide is effective in the control of diarrhoea induced by fluoropyrimidines. We have studied its effect on hematopoietic support-dependent high-dose chemotherapy (HSD-HDC) related diarrhoea. HSD-HDC-treated patients were included in the study when they had > or =4 loose stools per day. Diagnostic work-up included physical examination, stool culture, Clostridium difficile toxin assay, abdominal plain films, complete blood counts, liver and renal function tests. Patients were treated with 0.1 mg octreotide, q 8 h, subcutaneously for 48 h. Responding patients (< or =2 loose stools per day) continued treatment at the same dose for an additional 24 h. Lack of response (> or =3 loose stools per day), led to dose escalation by 0.1 mg increments, up to a 0.5 mg/dose and the latter dose was maintained for 24 h. Patients not responding at 0.5 mg/8 h were considered failures. A consecutive cohort of 24 HSD-HDC treated patients was studied. Fourteen (n = 14) (58.33%) patients developed severe diarrhoea with a median number of 7.5 loose stools per day (range, 4-11). Diarrhoea started at a median of 8 days (2-18) from day 0 of the infusion of HSD-HDC. Seven patients (50%) had less than 500 ANC/mm3 (grade 4 neutropenia) simultaneously with the diarrhoea. Twelve of 14 patients (86%) had their diarrhoea controlled, seven of them (50%) at the starting dose level of octreotide. In five of the responding patients (35.7%), octreotide had to be increased to 0.2 mg (one patient), 0.3 mg (two patients) and 0.5 mg (two patients). No toxicity was observed, while one patient had a subcutaneous hematoma at the injection site. We have concluded that octreotide appears to be safe and effective in controlling the diarrhoea induced by HSD-HDC. Prospective controlled trials are needed to confirm its value.
Wasserman
E
E
Division of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain.
Hidalgo
M
M
Hornedo
J
J
Cortés-Funes
H
H
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000150:complications / Q000628:therapy; D003131:Combined Modality Therapy; D003967:Diarrhea / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000150:complications / Q000628:therapy; D015282:Octreotide / Q000627:therapeutic use*; D012512:Sarcoma, Ewing / Q000150:complications / Q000628:therapy; D016896:Treatment Outcome
D005765:Gastrointestinal Agents; D015282:Octreotide