Use of Somatostatin Agonists to Treat Medullary Thyroid Carcinoma

1 - 204 . (canceled)

205 . A method of determining the treatment for a patient suffering from medullary thyroid carcinoma comprising the steps of:

a) identifying the change in calcitonin secreted by said medullary thyroid carcinoma in response to a somatostatin agonist or a pharmaceutically acceptable salt thereof; and

b) determining a treatment,

wherein said determining of said treatment is based upon said identified change in calcitonin secretion.

206 . The method according to claim 205 , wherein said somatostatin agonist is an SSTR-2 agonist or a pharmaceutically acceptable salt thereof.

207 . The method according to claim 206 , wherein said SSTR-2 agonist is a selective SSTR-2 agonist or a pharmaceutically acceptable salt thereof.

208 . The method according to claim 207 , wherein said SSTR-2 agonist is D-B-Nal-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Thr-NH 2 .

209 . The method according to claim 207 , wherein said SSTR-2 agonist is D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol.

210 . A method according to claim 205 , wherein said identifying comprises:

a) obtaining a sample of said medullary thyroid carcinoma from said patient;

b) administering a somatostatin agonist or a pharmaceutically acceptable salt thereof to said carcinoma sample; and

c) measuring the change in calcitonin secreted by said sample after said administering.

211 . The method according to claim 210 , wherein said somatostatin agonist is an SSTR-2 agonist or a pharmaceutically acceptable salt thereof.

212 . The method according to claim 211 , wherein said SSTR-2 agonist is a selective SSTR-2 agonist or a pharmaceutically acceptable salt thereof.

213 . The method according to claim 212 , wherein said SSTR-2 agonist is D-B-Nal-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Thr-NH 2 .

214 . The method according to claim 212 , wherein said SSTR-2 agonist is D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol or a pharmaceutically acceptable salt thereof.

215 . The method according to claim 205 , wherein said selection of treatment is based upon a decrease in calcitonin secretion of less than about 15%.

216 . The method according to claim 210 , wherein said selection of treatment is based upon a decrease in calcitonin secretion of less than about 15%.

217 . The method according to claim 205 , wherein said selection of treatment is based upon a decrease in calcitonin secretion of greater than about 15%.

218 . The method according to claim 210 , wherein said selection of treatment is based upon a decrease in calcitonin secretion of greater than about 15%.

219 . A method according to claim 205 , wherein said medullary thyroid carcinoma patient has undergone at least one thyroidectomy.

220 . A method according to claim 210 , wherein said medullary thyroid carcinoma patient has undergone at least one thyroidectomy.

221 . A method of decreasing the secretion of calcitonin from medullary thyroid carcinoma cells which comprises:

contacting medullary thyroid carcinoma cells with an SSTR-1 agonist, an SSTR-2 agonist, an SSTR-5 agonist, or a combination of one or more SSTR-1 agonist and one or more SSTR-2 agonist,

wherein said medullary carcinoma cells are determined to exhibit a decrease in calcitonin secretion of greater than about 15% in response to administration of an SSTR-2 agonist or a pharmaceutically acceptable salt thereof, and

wherein said SSTR-1, SSTR-2 or SSTR-5 agonist optionally comprises a Tyr(I), and

wherein said optional Tyr(I) is 125 I, 127 I or 131 I.

222 . A method according to claim 221 , wherein an SSTR-2 selective agonist, or a pharmaceutically acceptable salt thereof, is used to determine if said medullary carcinoma cells exhibit a decrease in calcitonin secretion of greater than about 15% in response to administration of an SSTR-2 agonist or a pharmaceutically acceptable salt thereof.

223 . A method according to claim 222 , wherein said SSTR-2 agonist or pharmaceutically acceptable salt thereof has a Ki value of less than 5 nM, preferably less than 1 nM.

224 . A method according to claim 222 , wherein said SSTR-2 selective agonist is a compound selected from the group consisting of:

D-β-Nal-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Thr-NH 2 ;

D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol;

Dop2-D-Lys(Dop2)-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]-Thr-NH 2 ;

c[Tic-Tyr-D-Trp-Lys-Abu-Phe];

4-(2-Hydroxyethyl)-1-piperas(inylacetyl-D-Phe-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]-Thr-NH 2 ;

and

4-(2-Hydroxyethyl)-1-piperas(ine-2-ethanesulfonyl-D-Phe-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]-Thr-NH 2 ;

or a pharmaceutically acceptable salt thereof.

225 . A method according to claim 224 , wherein said SSTR-2 agonist is D-β-Nal-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Thr-NH 2 , D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol or a pharmaceutically acceptable salt thereof.

226 . A method according to claim 221 , wherein said contacted medullary thyroid carcinoma cells are contacted with an SSTR-1 selective agonist, an SSTR-2 selective agonist, an SSTR-5 selective agonist, or a combination of one or more SSTR-1 selective agonist and one or more SSTR-2 selective agonist, or pharmaceutically acceptable salts thereof,

wherein, optionally, said SSTR-1 selective agonist has a Ki value of less than 5 nM, preferably less than 1 nM, and

wherein, optionally, said SSTR-2 selective agonist has a Ki value of less than 5 nM, preferably less than 1 nM, and

wherein, optionally, said SSTR-5 selective agonist has a Ki value of less than 5 nM, preferably less than 1 nM.

227 . A method according to claim 222 , wherein said SSTR-1 agonist is selected from the group consisting of:

Caeg-c[D-Cys-3-Pal-D-Trp-Lys-D-Cys]-Thr(Bzl)-Tyr-NH 2 ;

Aaeg-[D-Cys-Pal-D-Trp-Lys-D-Cys]-Thr(Bzl)-Tyr-NH 2 ;

Taeg-c[D-Cys-Phe-D-Trp-Lys-D-Cys]-Thr(Bzl)-Tyr-NH 2 ;

Taeg-c[D-Cys-3-Pal-D-Trp-Lys-D-Cys]-Ser(Bzl)-Tyr-NH 2 ; and

Caeg-c[D-Cys-Phe-D-Trp-Lys-D-Cys]-Thr(Bzl)-Tyr-NH 2 ;

or a pharmaceutically acceptable salt thereof;

228 . A method according to claim 221 , wherein an SSTR-2 agonist or a pharmaceutically acceptable salt thereof is used to contact said contacted medullary thyroid carcinoma cells determined to exhibit a decrease in calcitonin secretion of greater than about 15% in response to administration of an SSTR-2 agonist or a pharmaceutically acceptable salt thereof.

229 . A method according to claim 228 , wherein said SSTR-2 is selected from the group consisting of:

D-β-Nal-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Thr-NH 2 ;

D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol;

Dop2-D-Lys(Dop2)-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]-Thr-NH 2 ;

c[Tic-Tyr-D-Trp-Lys-Abu-Phe];

4-(2-Hydroxyethyl)-1-piperas(inylacetyl-D-Phe-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]-Thr-NH 2 ;

and

4-(2-Hydroxyethyl)-1-piperas(ine-2-ethanesulfonyl-D-Phe-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]-Thr-NH 2 ;

or a pharmaceutically acceptable salt thereof.

230 . A method according to claim 232 , wherein said SSTR-2 agonist is D-β-Nal-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Thr-NH 2 , D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol or a pharmaceutically acceptable salt thereof.

231 . A method according to claim 221 , wherein an SSTR-5 agonist or a pharmaceutically acceptable salt thereof is used to contact said medullary thyroid carcinoma cells determined to exhibit a decrease in calcitonin secretion of greater than about 15% in response to administration of an SSTR-2 agonist or a pharmaceutically acceptable salt thereof.

232 . A method according to claim 231 , wherein said SSTR-5 agonist is

D-Phe-Phe-Trp-D-Trp-Lys-Thr-Phe-Thr-NH 2 ; or

D-Phe-[Cys-Tyr(I)-D-Trp-Lys-Val-Cys]-Thr-NH 2 ;

or a pharmaceutically acceptable salt thereof.

233 . A method according to claim 221 , wherein a combination of an SSTR-1 agonist and an SSTR-2 agonist, or pharmaceutically acceptable salts thereof, is used to contact said medullary thyroid carcinoma cells determined to exhibit a decrease in calcitonin secretion of greater than about 15% in response to administration of an SSTR-2 agonist or a pharmaceutically acceptable salt thereof.

234 . A method according to claim 233 , wherein said SSTR-1 agonist used to contact said medullary thyroid carcinoma cells is selected from the group consisting of:

Caeg-c[D-Cys-3-Pal-D-Trp-Lys-D-Cys]-Thr(Bzl)-Tyr-NH 2 ;

Aaeg-[D-Cys-Pal-D-Trp-Lys-D-Cys]-Thr(Bzl)-Tyr-NH 2 ;

Taeg-c[D-Cys-Phe-D-Trp-Lys-D-Cys]-Thr(Bzl)-Tyr-NH 2 ;

Taeg-c[D-Cys-3-Pal-D-Trp-Lys-D-Cys]-Ser(Bzl)-Tyr-NH 2 ; and

Caeg-c[D-Cys-Phe-D-Trp-Lys-D-Cys]-Thr(Bzl)-Tyr-NH 2 ;

and said SSTR-2 agonist used to contact said medullary thyroid carcinoma cells selected from the group consisting of:

D-β-Nal-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Thr-NH 2 ;

D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol

Dop2-D-Lys(Dop2)-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]-Thr-NH 2 ;

c[Tic-Tyr-D-Trp-Lys-Abu-Phe];

4-(2-Hydroxyethyl)-1-piperas(inylacetyl-D-Phe-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]-Thr-NH 2 ;

and

4-(2-Hydroxyethyl)-1-piperas(ine-2-ethanesulfonyl-D-Phe-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]-Thr-NH 2 ;

or a pharmaceutically acceptable salt thereof.

235 . A method of decreasing the secretion of calcitonin from medullary thyroid carcinoma cells which comprises:

contacting medullary thyroid carcinoma cells with an SSTR-1 agonist,

wherein said medullary carcinoma cells are determined to exhibit a decrease in calcitonin secretion of less than about 15% in response to administration of an SSTR-2 agonist,

wherein said SSTR-1 or SSTR2 agonist optionally comprises a Tyr(I), and

wherein said optional Tyr(I) is 125 I, 127 I or 131 I.

236 . The method according to claim 235 , wherein said SSTR-2 agonist is a selective SSTR-2 agonist, and

wherein said SSTR-1 agonist or pharmaceutically acceptable salt thereof is optionally an SSTR-1 selective agonist; and

wherein said SSTR-1 selective agonist or pharmaceutically acceptable salt thereof has a Ki value of less than 5 nM, preferably less than 1 nM.

237 . The method according to claim 235 , wherein said SSTR-2 agonist is D-β-Nal-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Thr-NH 2 , D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol or a pharmaceutically acceptable salt thereof.

238 . A method according to claim 235 , wherein said SSTR-1 agonist is a compound selected from the group consisting of:

Caeg-c[D-Cys-3-Pal-D-Trp-Lys-D-Cys]-Thr(Bzl)-Tyr-NH 2 ;

Aaeg-[D-Cys-Pal-D-Trp-Lys-D-Cys]-Thr(Bzl)-Tyr-NH 2 ;

Taeg-c[D-Cys-Phe-D-Trp-Lys-D-Cys]-Thr(Bzl)-Tyr-NH 2 ;

Taeg-c[D-Cys-3-Pal-D-Trp-Lys-D-Cys]-Ser(Bzl)-Tyr-NH 2 ; and

Caeg-c[D-Cys-Phe-D-Trp-Lys-D-Cys]-Thr(Bzl)-Tyr-NH 2 ;

or a pharmaceutically acceptable salt thereof.

239 . A method of decreasing the rate of proliferation of medullary thyroid carcinoma cells which comprises contacting medullary thyroid carcinoma cells with an SSTR-2 agonist either alone or in combination with an SSTR-3, SSTR-4 or SSTR-5 agonist, wherein said medullary carcinoma cells are determined to exhibit a decrease in calcitonin secretion of less than about 15% in response to administration of an SSTR-2 agonist or a pharmaceutically acceptable salt thereof,

wherein said SSTR-1, SSTR-2, SSTR-3 or SSTR-4 or SSTR-5 agonist optionally comprises a Tyr(I), and

wherein said optional Tyr(I) is 125 I, 127 I or 131 I.

240 . A method according to claim 239 , wherein said SSTR-2 agonist or pharmaceutically acceptable salt thereof used to contact said medullary thyroid carcinoma cells is an SSTR-2 selective agonist, said SSTR-3 agonist or pharmaceutically acceptable salt thereof used to contact said medullary thyroid carcinoma cells is an SSTR-3 selective agonist, said SSTR-4 agonist or pharmaceutically acceptable salt thereof used to contact said medullary thyroid carcinoma cells is an SSTR-4 selective agonist, and said SSTR-5 agonist or pharmaceutically acceptable salt thereof used to contact said medullary thyroid carcinoma cells is an SSTR-5 selective agonist;

wherein, optionally, said SSTR-2 selective agonist or pharmaceutically acceptable salt thereof used to contact said medullary thyroid carcinoma cells has a Ki value of less than 5 nM, preferably less than 1 nM; and

wherein, optionally, said SSTR-3 selective agonist or pharmaceutically acceptable salt thereof used to contact said medullary thyroid carcinoma cells has a Ki value of less than 5 nM, preferably less than 1 nM; and

wherein, optionally, said SSTR-4 selective agonist or pharmaceutically acceptable salt thereof used to contact said medullary thyroid carcinoma cells has a Ki value of less than 5 nM, preferably less than 1 nM; and

wherein, optionally, said SSTR-5 selective agonist or pharmaceutically acceptable salt thereof used to contact said medullary thyroid carcinoma cells has a Ki value of less than 5 nM, preferably less than 1 nM.

241 . A method according to claim 239 , wherein an SSTR-2 agonist or a pharmaceutically acceptable salt thereof is used to contact said medullary thyroid carcinoma cells determined to exhibit a decrease in calcitonin secretion of less than about 15% in response to administration of an SSTR-2 agonist or a pharmaceutically acceptable salt thereof.

242 . A method according to claim 241 , wherein said SSTR-2 agonist used to contact said medullary thyroid carcinoma cells is selected from the group consisting of:

D-β-Nal-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Thr-NH 2 ;

D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol;

Dop2-D-Lys(Dop2)-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]-Thr-NH 2 ;

c[Tic-Tyr-D-Trp-Lys-Abu-Phe];

4-(2-Hydroxyethyl)-1-piperas(inylacetyl-D-Phe-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]-Thr-NH 2 ; and

4-(2-Hydroxyethyl)-1-piperas(ine-2-ethanesulfonyl-D-Phe-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]-Thr-NH 2 ;

or a pharmaceutically acceptable salt thereof.

243 . A method according to claim 242 , wherein said SSTR-2 agonist is D-β-Nal-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Thr-NH 2 , D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol or a pharmaceutically acceptable salt thereof.

244 . A method according to claim 241 , wherein an SSTR-2 agonist is used to contact said medullary thyroid carcinoma cells in combination with an SSTR-3 agonist or a pharmaceutically acceptable salt thereof.

245 . A method according to claim 241 , wherein an SSTR-2 agonist is used to contact said medullary thyroid carcinoma cells in combination with an SSTR-4 agonist or a pharmaceutically acceptable salt thereof.

246 . A method according to claim 241 , wherein an SSTR-2 agonist or a pharmaceutically acceptable salt thereof, is used in combination with an SSTR-5 agonist or a pharmaceutically acceptable salt thereof, to contact said medullary thyroid carcinoma cells determined to exhibit a decrease in calcitonin secretion of less than about 15% in response to administration of an SSTR-2 agonist or a pharmaceutically acceptable salt thereof.

247 . A method according to claim 246 , wherein said SSTR-5 agonist is a compound selected from the group consisting of:

D-Phe-Phe-Trp-D-Trp-Lys-Thr-Phe-Thr-NH 2 ; and

D-Phe-[Cys-Tyr(1)-D-Trp-Lys-Val-Cys]-Thr-NH 2 ;

or a pharmaceutically acceptable salt thereof, and

wherein said SSTR-2 agonist used to contact said medullary thyroid carcinoma cells in combination with said SSTR-5 agonist is selected from the group consisting of:

D-β-Nal-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Thr-NH 2 ;

D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol;

Dop2-D-Lys(Dop2)-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]-Thr-NH 2 ,

c[Tic-Tyr-D-Trp-Lys-Abu-Phe];

4-(2-Hydroxyethyl)-1-piperas(inylacetyl-D-Phe-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]-Thr-NH 2 ; and

4-(2-Hydroxyethyl)-1-piperas(ine-2-ethanesulfonyl-D-Phe-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]-Thr-NH 2 ;

or a pharmaceutically acceptable salt thereof.

248 . A method according to claim 253 , wherein said SSTR-2 agonist is D-B3-Nal-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Thr-NH 2 , D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol or or a pharmaceutically acceptable salt thereof.

249 . A method of decreasing the rate of proliferation of medullary thyroid carcinoma cells which comprises contacting medullary thyroid carcinoma cells with an SSTR-2 and SSTR-5 somatostatin agonist, or a pharmaceutically acceptable salt thereof,

wherein said SSTR-2 or SSTR-5 agonist optionally comprises a Tyr(I), and

wherein said optional Tyr(I) is 125 I, 127 I or 131 I.

250 . A method according to claim 249 , wherein said somatostatin agonist is D-Phe-[Cys-Tyr(I)-D-Trp-Lys-Val-Cys]-Thr-NH 2 or a pharmaceutically acceptable salt thereof.

251 . A method of treating medullary thyroid carcinoma which comprises administering to a patient in need thereof an effective amount of an SSTR-1 agonist, an SSTR-2 agonist, an SSTR-5 agonist, or a combination of one or more SSTR-1 agonist and one or more SSTR-2 agonist, wherein said medullary carcinoma is determined to exhibit a decrease in calcitonin secretion of greater than about 15% in response to administration of an SSTR-2 agonist,

wherein said SSTR-1, SSTR-2 or SSTR-5 agonist optionally comprises a Tyr(I), and

wherein said optional Tyr(I) is 125 I, 127 I or 131 I.

252 . A method according to claim 251 , wherein said SSTR-1 agonist administered to said patient is an SSTR-1 selective agonist or a pharmaceutically acceptable salt thereof, said SSTR-2 agonist administered to said patient is an SSTR-2 selective agonist or a pharmaceutically acceptable salt thereof, and said SSTR-5 agonist administered to said patient is an SSTR-5 selective agonist or a pharmaceutically acceptable salt thereof;

wherein, optionally, said SSTR-1 selective agonist or pharmaceutically acceptable salt thereof has a Ki value of less than 5 nM, preferably less than 1 nM; and

wherein, optionally, said SSTR-2 selective agonist or pharmaceutically acceptable salt thereof has a Ki value of less than 5 nM, preferably less than 1 nM; and

wherein, optionally, said SSTR-5 selective agonist or pharmaceutically acceptable salt thereof has a Ki value of less than 5 nM, preferably less than 1 nM.

253 . A method according to claim 251 , wherein an SSTR-1 agonist is administered to said medullary thyroid carcinoma patient wherein said medullary carcinoma is determined to exhibit a decrease in calcitonin secretion of greater than about 15% in response to administration of an SSTR-2 agonist.

254 . A method according to claim 253 , wherein said SSTR-1 agonist is a compound selected from the group consisting of:

Caeg-c[D-Cys-3-Pal-D-Trp-Lys-D-Cys]-Thr(Bzl)-Tyr-NH 2 ;

Aaeg-[D-Cys-Pal-D-Trp-Lys-D-Cys]-Thr(Bzl)-Tyr-NH 2 ;

Taeg-c[D-Cys-Phe-D-Trp-Lys-D-Cys]-Thr(Bzl)-Tyr-NH 2 ;

Taeg-c[D-Cys-3-Pal-D-Trp-Lys-D-Cys]-Ser(Bzl)-Tyr-NH 2 ; and

Caeg-c[D-Cys-Phe-D-Trp-Lys-D-Cys]-Thr(Bzl)-Tyr-NH 2 ;

or a pharmaceutically acceptable salt thereof.

255 . A method according to claim 251 , wherein an SSTR-2 agonist or an SSTR-2 selective agonist is administered to said medullary thyroid carcinoma patient wherein said medullary carcinoma is determined to exhibit a decrease in calcitonin secretion of greater than about 15% in response to administration of an SSTR-2 agonist.

256 . A method according to claim 255 , wherein said SSTR-2 agonist used to contact said medullary thyroid carcinoma cells is selected from the group consisting of:

D-β-Nal-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Thr-NH 2 ;

D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol;

Dop2-D-Lys(Dop2)-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]-Thr-NH 2 ;

c[Tic-Tyr-D-Trp-Lys-Abu-Phe];

4-(2-Hydroxyethyl)-1-piperas(inylacetyl-D-Phe-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]-Thr-NH 2 ;

and

4-(2-Hydroxyethyl)-1-piperas(ine-2-ethanesulfonyl-D-Phe-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]-Thr-NH 2 ;

or a pharmaceutically acceptable salt thereof.

257 . A method according to claim 256 , wherein said SSTR-2 agonist administered to said patient is D-β-Nal-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Thr-NH 2 , D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol or a pharmaceutically acceptable salt thereof.

258 . A method according to claim 251 , wherein an SSTR-5 agonist or an SSTR-5 selective agonist is administered to said medullary thyroid carcinoma patient wherein said medullary carcinoma is determined to exhibit a decrease in calcitonin secretion of greater than about 15% in response to administration of an SSTR-2 agonist.

259 . A method according to claim 258 , wherein said SSTR-5 agonist is a compound selected from the group consisting of:

D-Phe-Phe-Trp-D-Trp-Lys-Thr-Phe-Thr-NH 2 ; and

D-Phe-[Cys-Tyr(I)-D-Trp-Lys-Val-Cys]-Thr-NH 2 ;

or a pharmaceutically acceptable salt thereof.

260 . A method according to claim 251 , wherein a combination of SSTR-1 agonist or an SSTR-1 selective agonist and an SSTR-2 agonist, or an SSTR-2 selective agonist, or pharmaceutically acceptable salts thereof, is administered to said medullary thyroid carcinoma patient wherein said medullary carcinoma is determined to exhibit a decrease in calcitonin secretion of greater than about 15% in response to administration of an SSTR-2 agonist.

261 . A method according to claim 260 , wherein said SSTR-1 agonist is a compound selected from the group consisting of:

Caeg-c[D-Cys-3-Pal-D-Trp-Lys-D-Cys]-Thr(Bzl)-Tyr-NH 2 ;

Aaeg-[D-Cys-Pal-D-Trp-Lys-D-Cys]-Thr(Bzl)-Tyr-NH 2 ;

Taeg-c[D-Cys-Phe-D-Trp-Lys-D-Cys]-Thr(Bzl)-Tyr-NH 2 ;

Taeg-c[D-Cys-3-Pal-D-Trp-Lys-D-Cys]-Ser(Bzl)-Tyr-NH 2 ; and

Caeg-c[D-Cys-Phe-D-Trp-Lys-D-Cys]-Thr(Bzl)-Tyr-NH 2 ;

or a pharmaceutically acceptable salt thereof;

and said SSTR-2 agonist administered to said medullary thyroid carcinoma patient is a compound selected from the group consisting of:

D-β-Nal-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Thr-NH 2 ;

D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol;

Dop2-D-Lys(Dop2)-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]-Thr-NH 2 ;

c[Tic-Tyr-D-Trp-Lys-Abu-Phe];

4-(2-Hydroxyethyl)-1-piperas(inylacetyl-D-Phe-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]-Thr-NH 2 ; and

4-(2-Hydroxyethyl)-1-piperas(ine-2-ethanesulfonyl-D-Phe-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]-Thr-NH 2 ;

or a pharmaceutically acceptable salt thereof.

262 . A method according to claim 261 , wherein said SSTR-2 agonist is D-B-Nal-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Thr-NH 2 , D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol or or a pharmaceutically acceptable salt thereof.

263 . A method of treating medullary thyroid carcinoma in a patient which comprises administering to said medullary carcinoma patient in need thereof an effective amount of an SSTR-1 agonist or an SSTR-1 selective agonist, wherein said medullary carcinoma is determined to exhibit a decrease in calcitonin secretion of less than about 15% in response to administration of an SSTR-2 agonist,

wherein said SSTR-1 or SSTR-2 agonist optionally comprises a Tyr(I), and

wherein said optional Tyr(I) is 125 I, 127 I or 131 I,

wherein, optionally, said SSTR-1 selective agonist has a Ki value of less than 5 nM, preferably less than 1 nM.

264 . A method according to claim 263 , wherein said SSTR-2 agonist is a compound selected from the group consisting of

D-β-Nal-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Thr-NH 2 ;

D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol;

Dop2-D-Lys(Dop2)-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]-Thr-NH 2 ;

c[Tic-Tyr-D-Trp-Lys-Abu-Phe];

4-(2-Hydroxyethyl)-1-piperas(inylacetyl-D-Phe-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]-Thr-NH 2 ;

and

4-(2-Hydroxyethyl)-1-piperas(ine-2-ethanesulfonyl-D-Phe-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]-Thr-NH 2 ;

or a pharmaceutically acceptable salt thereof.

265 . A method according to claim 264 , wherein said SSTR-2 agonist is D-B-Nal-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Thr-NH 2 , D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol or or a pharmaceutically acceptable salt thereof.

266 . A method according to claim 263 , wherein said SSTR-1 agonist is a compound selected from the group consisting of:

Caeg-c[D-Cys-3-Pal-D-Trp-Lys-D-Cys]-Thr(Bzl)-Tyr-NH 2 ;

Aaeg-[D-Cys-Pal-D-Trp-Lys-D-Cys]-Thr(Bzl)-Tyr-NH 2 ;

Taeg-c[D-Cys-Phe-D-Trp-Lys-D-Cys]-Thr(Bzl)-Tyr-NH 2 ;

Taeg-c[D-Cys-3-Pal-D-Trp-Lys-D-Cys]-Ser(Bzl)-Tyr-NH 2 ; and

Caeg-c[D-Cys-Phe-D-Trp-Lys-D-Cys]-Thr(Bzl)-Tyr-NH 2 ;

or a pharmaceutically acceptable salt thereof.

267 . A pharmaceutical composition comprising an effective amount of an SSTR-1 agonist, or an SSTR-1 selective agonist, or a pharmaceutically acceptable salt thereof and an effective amount of an SSTR-2 agonist or an SSTR-2 selective agonist, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or diluent.

268 . A pharmaceutical composition according to claim 267 , wherein said SSTR-1 agonist is a compound selected from the group consisting of:

Caeg-c[D-Cys-3-Pal-D-Trp-Lys-D-Cys]-Thr(Bzl)-Tyr-NH 2 ;

Aaeg-[D-Cys-Pal-D-Trp-Lys-D-Cys]-Thr(Bzl)-Tyr-NH 2 ;

Taeg-c[D-Cys-Phe-D-Trp-Lys-D-Cys]-Thr(Bzl)-Tyr-NH 2 ;

Taeg-c[D-Cys-3-Pal-D-Trp-Lys-D-Cys]-Ser(Bzl)-Tyr-NH 2 ; and

Caeg-c[D-Cys-Phe-D-Trp-Lys-D-Cys]-Thr(Bzl)-Tyr-NH 2 ;

or a pharmaceutically acceptable salt thereof; and

said SSTR-2 agonist is a compound selected from the group consisting of:

D-β-Nal-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Thr-NH 2 ;

D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol;

Dop2-D-Lys(Dop2)-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]-Thr-NH 2 ,

c[Tic-Tyr-D-Trp-Lys-Abu-Phe];

4-(2-Hydroxyethyl)-1-piperas(inylacetyl-D-Phe-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]-Thr-NH 2 ;

and

4-(2-Hydroxyethyl)-1-piperas(ine-2-ethanesulfonyl-D-Phe-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]-Thr-NH 2 ;

or a pharmaceutically acceptable salt thereof.

269 . A pharmaceutical composition according to claim 267 , wherein said SSTR-2 agonist is D-β-Nal-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Thr-NH 2 or a pharmaceutically acceptable salt thereof.

270 . A pharmaceutical composition according to claim 267 , wherein said SSTR-2 agonist is D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol or a pharmaceutically acceptable salt thereof.

271 . A pharmaceutical composition according to claim 268 , wherein said pharmaceutical composition is used to treat medullary thyroid carcinoma.

272 . A pharmaceutical composition according to claim 268 , wherein said pharmaceutical composition is used to treat medullary thyroid carcinoma, wherein said medullary carcinoma is determined to exhibit a decrease in calcitonin secretion of greater than about 15% in response to administration of an SSTR-2 agonist.

273 . A pharmaceutical composition according to claim 268 , wherein said pharmaceutical composition is used to treat medullary thyroid carcinoma, wherein said medullary carcinoma is determined to exhibit a decrease in calcitonin secretion of less than about 15% in response to administration of an SSTR-2 agonist.

274 . A pharmaceutical composition comprising an effective amount of an SSTR-1 and SSTR-2 agonist or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or diluent.

275 . A pharmaceutical composition according to claim 274 , wherein said pharmaceutical composition is used to treat medullary thyroid carcinoma.

276 . A pharmaceutical composition according to claim 274 , wherein said pharmaceutical composition is used to treat medullary thyroid carcinoma, wherein said medullary carcinoma is determined to exhibit a decrease in calcitonin secretion of greater than about 15% in response to administration of an SSTR-2 agonist.

277 . A pharmaceutical composition according to claim 274 , wherein said pharmaceutical composition is used to treat medullary thyroid carcinoma, wherein said medullary carcinoma is determined to exhibit a decrease in calcitonin secretion of less than about 15% in response to administration of an SSTR-2 agonist.

278 . A method according to claim 221 , wherein said medullary thyroid carcinoma cells have formed metastases outside the thyroid.

279 . A method according to claim 235 , wherein said medullary thyroid carcinoma cells have formed metastases outside the thyroid.

280 . A method according to claim 239 , wherein said medullary thyroid carcinoma cells have formed metastases outside the thyroid.

281 . A method according to claim 251 , wherein said medullary thyroid carcinoma cells have formed metastases outside the thyroid.

282 . A method according to claim 263 , wherein said medullary thyroid carcinoma cells have formed metastases outside the thyroid.