Allolio, B

Arlt, W

Deuss, U

Reincke, M

Siekmann, L

Winkelmann, W

English

B ALLOLIO

Crossref

SURAMIN FOR TREATMENT OF ADRENOCORTICAL CARCINOMA

University of Birmingham Research Portal

Suramin for treatment of adrenocortical carcinoma

Allolio, B.

Reincke, Martin

Arlt, W.

Deuß, U.

Winkelmann, W.

Open Access LMU ( Ludwig-Maximilians-Univ. München)

277respond to metoclopramide, domperidone, ranitidine, amantadine,levodopa, carbamazepine, clonidine, prazosin, haloperidol,methysergide, or metoprolol. He improved slightly with theapplication of scopolamine patches, which had to be stoppedbecause of side-effects. Intramuscular chlorpromazine (25 mg)would sometimes prevent attacks for up to a week. He wasprescribed baclofen 10 mg, three times daily, after which his hiccupsceased for five days. When they recurred, baclofen dose wasincreased to 20 mg three times daily which has been successful, withonly an occasional solitary hiccup. When he ran out of tablets fortwo days, the hiccups returned with their former ferocity. He hasnow remained under control on this medication for three months,has gained weight, and is feeling well for the first time in 30 years.The family history suggests transmission by an autosomaldominant gene.Department of Neurology,Prince Henry Hospital,Sydney, NSW 2036, AustraliaRichmond, NSWJAMES W. LANCEGERALD T. BASSIL1. Williamson BWA, Macintyre IMC. Management of intractable hiccup. Br Med J1977; ii: 501-03.2. Jacobson PL, Messenheimer JA, Farmer TW. Treatment of intractable hiccups withvalproic acid. Neurology 1981; 31: 1458-60.3. Burke AM, White AB. Baclofen for intractable hiccups N Engl J Med 1988; 319: 1354.TETRACYCLINES FOR DYSTROPHICEPIDERMOLYSIS BULLOSASIR,-Dr White (April 29, p 966) reports the beneficial effects ofminocycline in the treatment of dystrophic epidermolysis bullosa.Evidence that tetracyclines may inhibit excessive collagenaseactivity in skin from conventional and germ-free rats1 suggests newtherapeutic possibilities for these drugs, especially in cutaneousconditions such as recessive dystrophic epidermolysis bullosa,where collagenase activity is increased. To assess the activity oftetracycline on the dermal-epidermal junction, we investigated theeffects of tetracycline chlorhydrate in hairless rats2 with the suctionblister method.3 Our results indicated that tetracycline may play animportant part in increasing the cohesion of the epidermis to thedermis. Tetracyclines may thus prove useful in treating bullous skindiseases with a high collagenase activity.Department of Dermatology,Centre Hospitalier Universitaire,25030 Besancon, FranceP. HUMBERTA. RENAUDR. LAURENTP. AGACHE1. Golub LM, Ramamurthy NS, McNamara TF. Tetracyclines inhibit tissuecollagenase activity. J Periodont Res 1984; 19: 651-55.2. Humbert P, Renaud A, Millet J, et al. Evaluation of the effect of heparin andtetracycline on the cohesion of the dermal-epidermal junction. Acta DermatolVenereol (in press).3. Kiistala U. Suction blister device for separation of viale epidermia from dermis.J Invest Dermatol 1968; 50: 129-37.SURAMIN FOR TREATMENT OFADRENOCORTICAL CARCINOMASIR,-Dr Vierhapper and colleagues (May 27, p 1207) report thebeneficial effect of suramin in adrenocortical carcinoma. However,their patient had shown a reduction of metastases duringadministration of mitotane, and an additional effect of suraminremains uncertain.We have now used suramin in three male and two female patients(aged 23-62 years) with metastatic adrenal carcinoma notresponding to mitotane. Suramin was given in a dose of 1-0-1 5 mgintravenously at weekly intervals. Plasma suramin concentrationswere monitored by high pressure liquid chromatography. In threepatients no response to suramin was seen. One patient showed atransient disease stabilisation, and one had complete resolution ofmultiple pulmonary metastases for 5 months.1 In none of thenon-responders did suramin reach the target concentration of200 J.1g/ml/ whereas in the patient with tumour regressionconcentrations above 300 J.1g/ml were noted. Thus close monitoringof drug levels may be important in these patients. AlthoughVierhapper and colleagues did not report suramin concentrations, atotal dose of 5 g is unlikely to be sufficient to induce suraminconcentrations above 200 J.1g/ml. It may therefore be possible thatless suramin is required for an additional beneficial action inmitotane responders.Suramin is active not only against adrenocortical carcinoma butalso against various other malignancies On the other handnumerous side-effects have been reported during treatment withhigh doses of suramin, including proteinuria, thrombocytopenia,.coagulopathy, liver test abnormalities, vortex keratopathy, andreversible acute demyelinating polyneuropathy. 1-3 We thereforebelieve that the use of suramin for malignant diseases should berestricted to carefully planned studies, and we invite others toparticipate in our phase II trial investigating the effect of suramin inadrenocortical carcinoma not responding to conventional therapy.Medicine Clinic II and Polyclinic,University of Cologne,5000 Cologne 41, West GermanyB. ALLOLIOM. REINCKEW. ARLTU. DEUSSW. WINKELMANNDepartment of Clinical Biochemistry,University of Bonn L. SIEKMANN1. Allolio B, Jaursch-Hancke C, Reincke M, Arlt W, Metzler U, Winkelmann W.Behandlung des metastasierten Nebennierencarcinoms mit Suramin. Dtsch MedWochenschr 1989; 114: 381-84.2. Stem CA, La Rocca RV, Thomas R, McAtee N, Myers CE. Suramin: an anticancerdrug with a unique mechanism of action. J Clin Oncol 1989; 7: 499-508.3. Hawking F. Suramin: with special reference to onchocerciasis. Adv PharmacolChemother 1978; 15: 289-322.DEATHS AFTER TOTAL LYMPHOID IRRADIATIONFOR MULTIPLE SCLEROSISSIR,-In a double-blind randomised prospective trial weobserved transient functional stabilisation of patients with chronicprogressive multiple sclerosis (MS) after total lymphoid irradiation(TLI) at 1980 cGy, limited to patients with mean lymphocytecounts below 850-900/)il during the 3 month period post-therapy.1-3 Beneficial effects in this subgroup of patients persisted for up to 6years post-therapy, as compared with chronic progressive patientswith higher lymphocyte counts post-TLI or with sham-irradiatedpatients (figure).54 patients have been treated with TLI-24 as part of ourdouble-blind study, the remainder in an open pilot study in whichmost also received low-dose prednisone (30 mg per day or less). 30patients have been followed up for 2 years or longer. Althoughside-effects of TLI have generally not been severe, 5 patients whoV 11 1 1 v IV VV IMONTHSKaplan-Meier curves comparing MS patients with low mean bloodcounts during 3 months post-TLI with patients with highercounts, and sham irradiated patients..0. vs :. (p = 0-0035); " vs - (p = 0,(08); -- vs - (NS).End-point is time to two-point deterioration in Troiano functional statusscale after TLI or sham TLI.

Universität München: Elektronischen Publikationen

277
respond to metoclopramide, domperidone, ranitidine, amantadine,
levodopa, carbamazepine, clonidine, prazosin, haloperidol,
methysergide, or metoprolol. He improved slightly with the
application of scopolamine patches, which had to be stopped
because of side-effects. Intramuscular chlorpromazine (25 mg)
would sometimes prevent attacks for up to a week. He was
prescribed baclofen 10 mg, three times daily, after which his hiccups
ceased for five days. When they recurred, baclofen dose was
increased to 20 mg three times daily which has been successful, with
only an occasional solitary hiccup. When he ran out of tablets for
two days, the hiccups returned with their former ferocity. He has
now remained under control on this medication for three months,
has gained weight, and is feeling well for the first time in 30 years.
The family history suggests transmission by an autosomal
dominant gene.
Department of Neurology,
Prince Henry Hospital,
Sydney, NSW 2036, Australia
Richmond, NSW
JAMES W. LANCE
GERALD T. BASSIL
1. Williamson BWA, Macintyre IMC. Management of intractable hiccup. Br Med J
1977; ii: 501-03.
2. Jacobson PL, Messenheimer JA, Farmer TW. Treatment of intractable hiccups with
valproic acid. Neurology 1981; 31: 1458-60.
3. Burke AM, White AB. Baclofen for intractable hiccups N Engl J Med 1988; 319: 1354.
TETRACYCLINES FOR DYSTROPHIC
EPIDERMOLYSIS BULLOSA
SIR,-Dr White (April 29, p 966) reports the beneficial effects of
minocycline in the treatment of dystrophic epidermolysis bullosa.
Evidence that tetracyclines may inhibit excessive collagenase
activity in skin from conventional and germ-free rats1 suggests new
therapeutic possibilities for these drugs, especially in cutaneous
conditions such as recessive dystrophic epidermolysis bullosa,
where collagenase activity is increased. To assess the activity of
tetracycline on the dermal-epidermal junction, we investigated the
effects of tetracycline chlorhydrate in hairless rats2 with the suction
blister method.3 Our results indicated that tetracycline may play an
important part in increasing the cohesion of the epidermis to the
dermis. Tetracyclines may thus prove useful in treating bullous skin
diseases with a high collagenase activity.
Department of Dermatology,
Centre Hospitalier Universitaire,
25030 Besancon, France
P. HUMBERT
A. RENAUD
R. LAURENT
P. AGACHE
1. Golub LM, Ramamurthy NS, McNamara TF. Tetracyclines inhibit tissue
collagenase activity. J Periodont Res 1984; 19: 651-55.
2. Humbert P, Renaud A, Millet J, et al. Evaluation of the effect of heparin and
tetracycline on the cohesion of the dermal-epidermal junction. Acta Dermatol
Venereol (in press).
3. Kiistala U. Suction blister device for separation of viale epidermia from dermis.
J Invest Dermatol 1968; 50: 129-37.
SURAMIN FOR TREATMENT OF
ADRENOCORTICAL CARCINOMA
SIR,-Dr Vierhapper and colleagues (May 27, p 1207) report the
beneficial effect of suramin in adrenocortical carcinoma. However,
their patient had shown a reduction of metastases during
administration of mitotane, and an additional effect of suramin
remains uncertain.
We have now used suramin in three male and two female patients
(aged 23-62 years) with metastatic adrenal carcinoma not
responding to mitotane. Suramin was given in a dose of 1-0-1 5 mg
intravenously at weekly intervals. Plasma suramin concentrations
were monitored by high pressure liquid chromatography. In three
patients no response to suramin was seen. One patient showed a
transient disease stabilisation, and one had complete resolution of
multiple pulmonary metastases for 5 months.1 In none of the
non-responders did suramin reach the target concentration of
200 J.1g/ml/ whereas in the patient with tumour regression
concentrations above 300 J.1g/ml were noted. Thus close monitoring
of drug levels may be important in these patients. Although
Vierhapper and colleagues did not report suramin concentrations, a
total dose of 5 g is unlikely to be sufficient to induce suramin
concentrations above 200 J.1g/ml. It may therefore be possible that
less suramin is required for an additional beneficial action in
mitotane responders.
Suramin is active not only against adrenocortical carcinoma but
also against various other malignancies On the other hand
numerous side-effects have been reported during treatment with
high doses of suramin, including proteinuria, thrombocytopenia,.
coagulopathy, liver test abnormalities, vortex keratopathy, and
reversible acute demyelinating polyneuropathy. 1-3 We therefore
believe that the use of suramin for malignant diseases should be
restricted to carefully planned studies, and we invite others to
participate in our phase II trial investigating the effect of suramin in
adrenocortical carcinoma not responding to conventional therapy.
Medicine Clinic II and Polyclinic,
University of Cologne,
5000 Cologne 41, West Germany
B. ALLOLIO
M. REINCKE
W. ARLT
U. DEUSS
W. WINKELMANN
Department of Clinical Biochemistry,
University of Bonn L. SIEKMANN
1. Allolio B, Jaursch-Hancke C, Reincke M, Arlt W, Metzler U, Winkelmann W.
Behandlung des metastasierten Nebennierencarcinoms mit Suramin. Dtsch Med
Wochenschr 1989; 114: 381-84.
2. Stem CA, La Rocca RV, Thomas R, McAtee N, Myers CE. Suramin: an anticancer
drug with a unique mechanism of action. J Clin Oncol 1989; 7: 499-508.
3. Hawking F. Suramin: with special reference to onchocerciasis. Adv Pharmacol
Chemother 1978; 15: 289-322.
DEATHS AFTER TOTAL LYMPHOID IRRADIATION
FOR MULTIPLE SCLEROSIS
SIR,-In a double-blind randomised prospective trial we
observed transient functional stabilisation of patients with chronic
progressive multiple sclerosis (MS) after total lymphoid irradiation
(TLI) at 1980 cGy, limited to patients with mean lymphocyte
counts below 850-900/)il during the 3 month period post-therapy.1-
3 Beneficial effects in this subgroup of patients persisted for up to 6
years post-therapy, as compared with chronic progressive patients
with higher lymphocyte counts post-TLI or with sham-irradiated
patients (figure).
54 patients have been treated with TLI-24 as part of our
double-blind study, the remainder in an open pilot study in which
most also received low-dose prednisone (30 mg per day or less). 30
patients have been followed up for 2 years or longer. Although
side-effects of TLI have generally not been severe, 5 patients who
V 11 1 1 v IV VV I
MONTHS
Kaplan-Meier curves comparing MS patients with low mean blood
counts during 3 months post-TLI with patients with higher
counts, and sham irradiated patients.
.0. vs :. (p = 0-0035); " vs - (p = 0,(08); -- vs - (NS).
End-point is time to two-point deterioration in Troiano functional status
scale after TLI or sham TLI.


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Suramin for treatment of adrenocortical carcinoma

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