Is treatment with octreotide effective in patients with head-and-neck paraganglioma?

Paraganglioma/glomustumors of the head-and-neck aerea usually grow slowly.
Because of their slow growth velocity, their location in the near presence of
vital structures (large vessels, nerves) and the fact that surgical resection
is frequently complicated by gross morbidity and sometimes mortality, the
current strategy is to wait-and-scan, using MRI-scanning to follow growth
potency. In case of fast growth (>/ 20%/year), locally agressive behaviour or
local complications, surgical treatment follows. Extension of the therapeutic
arsenal with tumor volume reductive therapy is strongly needed. Sometimes,
head-and-neck paraganglioma also produce catecholamines. Head-and-neck
paraganglioma, that express the somatostatin-2 receptor, can usually be made
visible by somatostatin receptor scintigraphy, which is positive in ~94% of
cases. Frequenly, somatostatin receptor scintigraphy is used to visualize
multifocal presence of head-and-neck paraganglioma.
Somatostatin analogues, that bind to somatostatin receptors, are used for many
years in the treatment of neuro-endocrine tumors. Both in vitro and in vivo
antiproliferative effects of somatostatin analogues are described. The effects
are both cytostatic and cytotoxic of nature. Cytostatic effects are brought
about by 4 of 5 somatostatin receptors (sst 1,2,4,5), cytotoxic effects by
sst3. As a result of these effects, somatostatin analogues can reduce tumor
volume and additional hormone production in patients with GH-secernating
pituitary tumors and other neuro-endocrine tumors like carcinoids and
gastrinomas.
Aim of the present study is to evaluate the efficacy of longacting
somatostatin (OCT-LAR) on tumor volume and/or additional catecholamine
overproduction by head of head-and-neck paraganglioma.

Evaluation of the effects of octreotide LAR in head-and-neck paraganglioma on:
1. tumor volume
2. catecholamine produktion
3. clinical and biochemical parameters

30 patients with somatostatinscan positive head-and-neck paraganglioma will be
included in the study, with tumors that grow fast (>/ 20%/year) and/or are
complicated by recent cranial nerve palsy (< 1 year ago) and/or catecholamine
overproduction. Patients will be tested before and after 12 months of treatment
with longacting somatostatin (OCT-LAR). Patients with catecholamine
overproduction by the head-and-neck paraganglioma will get an intravenous
octreotide test as well, versus a controltest using saline, 1 and 2 weeks
before starting OCT-LAR (random 50% of patients start with octreotide 50
microgram iv, after which a wash-out period of 1 week follows, followed by
repeating the test with saline iv, and vice versa).

A prospective intervention study design has been chosen, in which each patient
is her/her own control. The study is not-placebo-controlled, not blinded, since
(in general small) side effects can be expected which will make the nature of
what has been administrated clear for both the patient and the researcher. In
addition, outcome parameters can be measured objectively.

Treatment with long-acting somatostatin (Sandostatin LAR) with monthly
intramuscular injections with a dose of 30 mg during 1 year.

The reseach protocol consists of the following evaluations before and after 6
and 12 month's of the start of the treatment with octreotide LAR: (see also
flow-sheet page 15)
-glomus-related complaints, blood pressure and pulse rate
-blood analysis; ~300 cc blood will be taken during the total study
-urine analysis: patients will be asked to collect 48-hour urine, 5x in case of
no-hormone producing tumor, 9x in case the head-and-neck paraganglioma produces
catecholamines
-before the start of the stduy, and at the end of the study, an abdominal
ultrasound will be performed: in case of the presence of cholelithiasis before
the start of the study, patients will be excluded
-if no octreotide scan has already been performed, this scan will be performed
before the start of the study
-before the start of the study and after 12 months, an MRI of the head-and-neck
region will be performed, in addition to a 24 hour blood pressure registration
-in case of a catecholamine producing head-and-neck paraganglioma, an
intravenous octreotide test versus a saline test will be performed 1 and 2
weeks before starting treatment with octreotide LAR (with 1 week wash-out time
in between tests), during which blood will be sampled during 2 hours at
different time points to measure catecholamine concentrations. In addition,
from 2 days preceeding the test and 2 days after the test, urine will be
collected for the measurement of these hormones.
Octreotide has potential side effects: these are pain, redness and soreness of
the site of injection, and gastrointestinal side effects as anorexia, nausea,
vomiting, flatulence, abdominal cramps, and diarrea. In addition,
cholelithiasis can be aggravated, and be induced, especially during longer
treatment, and glucose intolerance can be induced. Sporadically, hear loss,
acute pancreatitis and acute hepatitis can be induced.

patients will be selected on the basis of a positive octreotide scan, which is
routinely performed in this patient group to evaluate location, multifocal
presence and extension of the head-and-neck paraganglioma. For our research
protocol, therfore, already performed octreotide scans will be used to prevent
unnecessary radiation exposure for patients.