The use of new somatostatin analogues, lanreotide and octastatin, in neuroendocrine gastro-intestinal tumours.
In an open phase III study, octastatin was given as a continuous subcutaneous (s.c.) infusion to 35 patients (mean age 62 years) with malignant neuroendocrine gastro-intestinal tumours and the carcinoid syndrome. The wash-out was often incomplete because of the advanced stage of disease. The starting dose of 1.5 mg/24 h was increased up to 3.0 mg/24 h at 3 months in some patients. The carcinoid syndrome disappeared in 20% of patients at 3 months and in 23% at 6 months, with 43 and 45% of patients, respectively, experiencing an improvement. The mean Karnovsky index increased by > 10% in 40% of patients at 3 and 6 months. Urinary 5-hydroxyindoleacetic acid (U-5-HIAA) levels at 3 months normalised in 1 patient, fell in 20% (by > 50%; p = 0.0021) and stabilised in 66%. The respective values at 6 months were 1, 17% (p = 0.023) and 60%. There was also a significant decrease in plasma chromogranin levels at 3 months (p = 0.042), which did not persist at 6 months. Tumour size fell (by > 50%) in 1 patient by 6 months but this patient had undergone chemoembolisation one month prior to the start of the study. Most patients had tumour size stabilisation (76 and 68%) or progression (20 and 24%) at 3 and 6 months, respectively. Dose escalation from 1.5 to 3.0 mg did not significantly improve clinical, biochemical or tumour responses. The treatment was well tolerated with minor adverse events. In an open pilot phase II study of 19 patients (mean age 58 years), patients were given high dose somatuline with a maintenance dose of 12,000 mg/day in 4 divided s.c. injections. U-5-HIAA, which was elevated in 13 patients with a mean of 444 mumol/day before the start, was reduced to 58% of baseline at 3 months, 68% at 6 months (p = 0.04), 66% at 9 months and 75% at 12 months (p = 0.14). P-chromogranin was elevated in 18 patients, with a mean of 5,300 micrograms/l before the start, and was reduced to 52, 55, 63 and 64% of the baseline at 3, 6 (p = 0.039), 9 and 12 (p = 0.013) months, respectively. In the responding patients, apoptosis was induced.
Eriksson
B
B
Department of Internal Medicine, University Hospital, Uppsala, Sweden.
Janson
E T
ET
Bax
N D
ND
Mignon
M
M
Morant
R
R
Opolon
P
P
Rougier
P
P
Oberg
K E
KE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D015408:Gastrinoma / Q000000981:diagnostic imaging / Q000188:drug therapy*; D005935:Glucagonoma / Q000000981:diagnostic imaging / Q000188:drug therapy*; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000652:urine; D008303:Malignant Carcinoid Syndrome / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*; D010456:Peptides, Cyclic / Q000009:adverse effects / Q000627:therapeutic use*; D013004:Somatostatin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*; D014055:Tomography, Emission-Computed
D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D010456:Peptides, Cyclic; C060347:lanreotide; C051458:vapreotide; D013004:Somatostatin; D006897:Hydroxyindoleacetic Acid