Download PDF
Horm Metab Res 2009; 41(9): 687-696
DOI: 10.1055/s-0029-1231025
Review

© Georg Thieme Verlag KG Stuttgart · New York

Treatment of Malignant Pheochromocytoma

R. Adjallé 1 , P. F. Plouin 2 , K. Pacak 3 , H. Lehnert 1
  • 11st Department of Medicine, University of Lübeck, Lübeck, Germany
  • 2Hypertension Unit, European Hospital Georges Pompidou, University of Paris Descartes, Paris, France
  • 3Endocrinology Branch, NICHD, NIH, Bethesda, MD, USA
Further Information

Publication History

received 26.03.2009

accepted 15.06.2009

Publication Date:
11 August 2009 (online)

Also available at
    Permissions and Reprints

Abstract

Pheochromocytoma (PCC) is a rare disease, mainly sporadic, but also associated with some familial disorders, with a malignancy frequency of approximately 10%. Only the presence of distant metastases, derived from large pleomorphic chromaffin cells, is widely accepted as a criterion of malignancy. Variable symptoms may be caused by production and release of catecholamines. Since there is no curative treatment for malignant PCC and due to its unfavorable prognosis, assuring quality of life is one of the main therapeutic objectives. Besides a long-term medical treatment of symptoms using selective α-1 blockers and nonselective, noncompetitive α- and/or β-blockers, debulking surgery is the first treatment step. In case of a sufficient uptake of 123I-MIBG treatment with targeted radiation therapy, use of 131I-MIBG is an option as an adjuvant therapy, following debulking surgery. Chemotherapy should be applied to patients without positive MIBG-scan, with no response to 131I-MIBG or progression after radionuclide treatment, and especially in cases with high proliferation index. The most effective chemotherapy regimen appears to be the CVD-scheme, including cyclophosphamide, vincristine, and dacarbazine. The so-called targeted molecular therapies with treatment combinations of temozolomide and thalidomide, or sunitinib monotherapy, and novel therapeutic somatostatin analogues have shown promising results and should thus encourage clinical trials to improve the prognosis of metastatic PCC. Within this review the current treatment modalities and novel molecular strategies in the management of this disease are discussed and a treatment algorithm is suggested.

Key words

pheochromocytoma - paraganglioma - adrenal mass

References

  • 1 Manger WM. An overview of pheochromocytoma: history, current concepts, vagaries, and diagnostic challenges.  Ann N Y Acad Sci. 2006;  1073 1-20
    Google Scholar
  • 2 McNeil AR, Blok BH, Koelmeyer TD, Burke MP, Hilton JM. Phaeochromocytomas discovered during coronial autopsies in Sydney, Melbourne and Auckland.  Aust N Z J Med. 2000;  30 648-652
    Google Scholar
  • 3 Neumann HP, Bausch B, McWhinney SR, Bender BU, Gimm O, Franke G, Schipper J, Klisch J, Altehoefer C, Zerres K, Januszewicz A, Eng C, Smith WM, Munk R, Manz T, Glaesker S, Apel TW, Treier M, Reineke M, Walz MK, Hoang-Vu C, Brauckhoff M, Klein-Franke A, Klose P, Schmidt H, Maier-Woelfle M, Peczkowska M, Szmigielski C. Germ-line mutations in nonsyndromic pheochromocytoma.  N Engl J Med. 2002;  346 1459-1466
    Google Scholar
  • 4 Tischler AS. Pheochromocytoma and extra-adrenal paraganglioma: updates.  Arch Pathol Lab Med. 2008;  132 1272-1284
    Google Scholar
  • 5 Strong VE, Kennedy T, Al Ahmadie H, Tang L, Coleman J, Fong Y, Brennan M, Ghossein RA. Prognostic indicators of malignancy in adrenal pheochromocytomas: clinical, histopathologic, and cell cycle/apoptosis gene expression analysis.  Surgery. 2008;  143 759-768
    Google Scholar
  • 6 Thompson LD. Pheochromocytoma of the Adrenal gland Scaled Score (PASS) to separate benign from malignant neoplasms: a clinicopathologic and immunophenotypic study of 100 cases.  Am J Surg Pathol. 2002;  26 551-566
    Google Scholar
  • 7 Wu LT, Dicpinigaitis P, Bruckner H, Manger W, Averbuch S. Hypertensive crises induced by treatment of malignant pheochromocytoma with a combination of cyclophosphamide, vincristine, and dacarbazine.  Med Pediatr Oncol. 1994;  22 389-392
    Google Scholar
  • 8 Goldstein RE, O’Neill  JA  Jr, Holcomb GW, Morgan WM III, Neblett WW, Oates JA, Brown N, Nadeau J, Smith B, Page DL, Abumrad NN, Scott Jr HW. Clinical experience over 48 years with pheochromocytoma.  Ann Surg. 1999;  229 755-764
    Google Scholar
  • 9 Scholz T, Schulz C, Klose S, Lehnert H. Diagnostic management of benign and malignant pheochromocytoma.  Exp Clin Endocrinol Diabetes. 2007;  115 155-159
    Google Scholar
  • 10 Favier J, Plouin PF, Corvol P, Gasc JM. Angiogenesis and vascular architecture in pheochromocytomas: distinctive traits in malignant tumors.  Am J Pathol. 2002;  161 1235-1246
    Google Scholar
  • 11 Salmenkivi K, Haglund C, Arola J, Heikkila P. Increased expression of tenascin in pheochromocytomas correlates with malignancy.  Am J Surg Pathol. 2001;  25 1419-1423
    Google Scholar
  • 12 Salmenkivi K, Heikkila P, Liu J, Haglund C, Arola J. VEGF in 105 pheochromocytomas: enhanced expression correlates with malignant outcome.  APMIS. 2003;  111 458-464
    Google Scholar
  • 13 Amar L, Bertherat J, Baudin E, Ajzenberg C, Bressac-de Paillerets B, Chabre O, Chamontin B, Delemer B, Giraud S, Murat A, Niccoli-Sire P, Richard S, Rohmer V, Sadoul JL, Strompf L, Schlumberger M, Bertagna X, Plouin PF, Jeunemaitre X, Gimenez-Roqueplo AP. Genetic testing in pheochromocytoma or functional paraganglioma.  J Clin Oncol. 2005;  23 8812-8818
    Google Scholar
  • 14 Rao F, Keiser HR, O’Conner DT. Malignant pheochromocytoma. Chromaffin granule transmitters and response to treatment.  Hypertension. 2000;  36 1045-1052
    Google Scholar
  • 15 Capella C, Riva C, Cornaggia M, Chiaravalli AM, Frigerio B, Solcia E. Histopathology, cytology and cytochemistry of pheochromocytomas and paragangliomas including chemodectomas.  Pathol Res Pract. 1988;  183 176-187
    Google Scholar
  • 16 Eisenhofer G, Bornstein SR, Brouwers FM, Cheung NK, Dahia PL, de Krijger RR, Giordano TJ, Greene LA, Goldstein DS, Lehnert H, Manger WM, Maris JM, Neumann HP, Pacak K, Shulkin BL, Smith DI, Tischler AS, Young   WF. Malignant pheochromocytoma: current status and initiatives for future progress.  Endocr Relat Cancer. 2004;  11 423-436
    Google Scholar
  • 17 Neumann HP, Berger DP, Sigmund G, Blum U, Schmidt D, Parmer RJ, Volk B, Kirste G. Pheochromocytomas, multiple endocrine neoplasia type 2, and von Hippel-Lindau disease.  N Engl J Med. 1993;  329 1531-1538
    Google Scholar
  • 18 Tanaka S, Ito T, Tomoda J, Higashi T, Yamada G, Tsuji T. Malignant pheochromocytoma with hepatic metastasis diagnosed 20 years after resection of the primary adrenal lesion.  Intern Med. 1993;  32 789-794
    Google Scholar
  • 19 Pommier RF, Vetto JT, Billingsly K, Woltering EA, Brennan MF. Comparison of adrenal and extraadrenal pheochromocytomas.  Surgery. 1993;  114 1160-1165
    Google Scholar
  • 20 Sclafani LM, Woodruff JM, Brennan MF. Extraadrenal retroperitoneal paragangliomas: natural history and response to treatment.  Surgery. 1990;  108 1124-1129
    Google Scholar
  • 21 Whalen RK, Althausen AF, Daniels GH. Extra-adrenal pheochromocytoma.  J Urol. 1992;  147 1-10
    Google Scholar
  • 22 Loh KC, Fitzgerald PA, Matthay KK, Yeo PP, Price DC. The treatment of malignant pheochromocytoma with iodine-131 metaiodobenzylguanidine (131I-MIBG): a comprehensive review of 116 reported patients.  J Endocrinol Invest. 1997;  20 648-658
    Google Scholar
  • 23 Eisenhofer G, Siegert G, Kotzerke J, Bornstein SR, Pacak K. Current progress and future challenges in the biochemical diagnosis and treatment of pheochromocytomas and paragangliomas.  Horm Metab Res. 2008;  40 329-337
    Google Scholar
  • 24 Lenders JW, Keiser HR, Goldstein DS, Willemsen JJ, Friberg P, Jacobs MC, Kloppenborg PW, Thien T, Eisenhofer G. Plasma metanephrines in the diagnosis of pheochromocytoma.  Ann Intern Med. 1995;  123 101-109
    Google Scholar
  • 25 Sjoberg RJ, Simcic KJ, Kidd GS. The clonidine suppression test for pheochromocytoma. A review of its utility and pitfalls.  Arch Intern Med. 1992;  152 1193-1197
    Google Scholar
  • 26 Cleary S, Phillips JK, Huynh TT, Pacak K, Fliedner S, Elkahloun AG, Munson P, Worrell RA, Eisenhofer G. Chromogranin a expression in phaeochromocytomas associated with von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2.  Horm Metab Res. 2007;  39 876-883
    Google Scholar
  • 27 Grossrubatscher E, Dalino P, Vignati F, Gambacorta M, Pugliese R, Boniardi M, Rossetti O, Marocchi A, Bertuzzi M, Loli P. The role of chromogranin A in the management of patients with phaeochromocytoma.  Clin Endocrinol (Oxf). 2006;  65 287-293
    Google Scholar
  • 28 Havekes B, Lai EW, Corssmit EP, Romijn JA, Timmers HJ, Pacak K. Detection and treatment of pheochromocytomas and paragangliomas: current standing of MIBG scintigraphy and future role of PET imaging.  Q J Nucl Med Mol Imaging. 2008;  52 419-429
    Google Scholar
  • 29 Takano A, Oriuchi N, Tsushima Y, Taketomi-Takahashi A, Nakajima T, Arisaka Y, Higuchi T, Amanuma M, Endo K. Detection of metastatic lesions from malignant pheochromocytoma and paraganglioma with diffusion-weighted magnetic resonance imaging: comparison with 18F-FDG positron emission tomography and 123I-MIBG scintigraphy.  Ann Nucl Med. 2008;  22 395-401
    Google Scholar
  • 30 Ilias I, Chen CC, Carrasquillo JA, Whatley M, Ling A, Lazurova I, Adams KT, Perera S, Pacak K. Comparison of 6–18F-fluorodopamine PET with 123I-metaiodobenzylguanidine and 111In-pentetreotide scintigraphy in localization of nonmetastatic and metastatic pheochromocytoma.  J Nucl Med. 2008;  49 1613-1619
    Google Scholar
  • 31 Timmers HJ, Eisenhofer G, Carrasquillo JA, Chen CC, Whatley M, Ling A, Adams KT, Pacak K. Use of 6-[18F]-fluorodopamine positron emission tomography as first-line investigation for the diagnosis and localization of non-metastatic and metastatic pheochromocytoma.  Clin Endocrinol (Oxf). 2008 Dec 5;  , Epub ahead of print]
    Google Scholar
  • 32 Hoegerle S, Nitzsche E, Altehoefer C, Chen CC, Whatley M, Ling A, Adams KT, Pacak K. Pheochromocytomas: detection with 18F DOPA whole body PET–initial results.  Radiology. 2002;  222 507-512
    Google Scholar
  • 33 Pacak K, Ilias I, Adams KT, Eisenhofer G. Biochemical diagnosis, localization and management of pheochromocytoma: focus on multiple endocrine neoplasia type 2 in relation to other hereditary syndromes and sporadic forms of the tumour.  J Intern Med. 2005;  257 60-68
    Google Scholar
  • 34 Takahashi K, Ashizawa N, Minami T, Suzuki S, Sakamoto I, Hayashi K, Tomiyasu S, Sumikawa K, Kitamura K, Eto T, Yano K. Malignant pheochromocytoma with multiple hepatic metastases treated by chemotherapy and transcatheter arterial embolization.  Intern Med. 1999;  38 349-354
    Google Scholar
  • 35 Tada K, Okuda Y, Yamashita K. Three cases of malignant pheochromocytoma treated with cyclophosphamide, vincristine, and dacarbazine combination chemotherapy and alpha-methyl-p-tyrosine to control hypercatecholaminemia.  Horm Res. 1998;  49 295-297
    Google Scholar
  • 36 Nonaka K, Makuuchi H, Naruse Y, Kobayashi T, Goto M. Surgical excision of malignant pheochromocytoma in the left atrium.  Jpn J Thorac Cardiovasc Surg. 2000;  48 126-128
    Google Scholar
  • 37 Huang KH, Chung SD, Chen SC, Chueh SC, Pu YS, Lai MK, Lin WC. Clinical and pathological data of 10 malignant pheochromocytomas: long-term follow up in a single institute.  Int J Urol. 2007;  14 181-185
    Google Scholar
  • 38 Ahlman H. Malignant pheochromocytoma: state of the field with future projections.  Ann N Y Acad Sci. 2006;  1073 449-464
    Google Scholar
  • 39 Mannelli M. Management and treatment of pheochromocytomas and paragangliomas.  Ann N Y Acad Sci. 2006;  1073 405-416
    Google Scholar
  • 40 Brauckhoff M, Gimm O, Dralle H. Preoperative and surgical therapy in sporadic and familial pheochromocytoma.  Front Horm Res. 2004;  31 121-144
    Google Scholar
  • 41 Lehnert H, Mundschenk J, Hahn K. Malignant pheochromocytoma.  Front Horm Res. 2004;  31 155-162
    Google Scholar
  • 42 Jaroszewski DE, Tessier DJ, Schlinkert RT, Grant CS, Thompson GB, van Heerden JA, Farley DR, Smith SL, Hinder RA. Laparoscopic adrenalectomy for pheochromocytoma.  Mayo Clin Proc. 2003;  78 1501-1504
    Google Scholar
  • 43 Joseph L. Malignant phaochromocytoma of the organ of Zuckerkandl with functioning metastases.  Br J Urol. 1967;  39 221-225
    Google Scholar
  • 44 Mukherjee JJ, Kaltsas GA, Islam N, Plowman PN, Foley R, Hikmat J, Britton KE, Jenkins PJ, Chew SL, Monson JP, Besser GM, Grossman AB. Treatment of metastatic carcinoid tumours, phaeochromocytoma, paraganglioma and medullary carcinoma of the thyroid with (131)I-meta-iodobenzylguanidine [(131)I-mIBG].  Clin Endocrinol (Oxf). 2001;  55 47-60
    Google Scholar
  • 45 van der HE, de Herder WW, Bruining HA, Bonjer HJ, de Krijger RR, Lamberts SW, van de Meiracker AH, Boomsma F, Stijnen T, Krenning EP, Bosman FT, Kwekkeboom DJ. [(123)I]metaiodobenzylguanidine and [(111)In]octreotide uptake in benign and malignant pheochromocytomas.  J Clin Endocrinol Metab. 2001;  86 685-693
    Google Scholar
  • 46 Sisson JC, Shapiro B, Beierwaltes WH, Glowniak JV, Nakajo M, Mangner TJ, Carey JE, Swanson DP, Copp JE, Satterlee WG. Radiopharmaceutical treatment of malignant pheochromocytoma.  J Nucl Med. 1984;  25 197-206
    Google Scholar
  • 47 Gedik GK, Hoefnagel CA, Bais E, Olmos RA. 131I-MIBG therapy in metastatic phaeochromocytoma and paraganglioma.  Eur J Nucl Med Mol Imaging. 2008;  35 725-733
    Google Scholar
  • 48 Kaltsas GA, Mukherjee JJ, Foley R, Britton KE, Grossman AB. Treatment of Metastatic Pheochromocytoma and Paraganglioma With 131I-Meta-Iodobenzylguanidine (MIBG).  Endocrinologist. 2001;  13 321-333
    Google Scholar
  • 49 Shapiro B, Sisson JC, Wieland DM, Mangner TJ, Zempel SM, Mudgett E, Gross MD, Carey JE, Zasadny KR, Beierwaltes WH. Radiopharmaceutical therapy of malignant pheochromocytoma with 131I-metaiodobenzylguanidine: results from ten years of experience.  J Nucl Biol Med. 1991;  35 269-276
    Google Scholar
  • 50 Troncone L, Rufini V. 131I-MIBG therapy of neural crest tumours (review).  Anticancer Res. 1997;  17 1823-1831
    Google Scholar
  • 51 Rose B, Matthay KK, Price D, Huberty J, Klencke B, Norton JA, Fitzgerald PA. High-dose 131I-metaiodobenzylguanidine therapy for 12 patients with malignant pheochromocytoma.  Cancer. 2009;  98 239-248
    Google Scholar
  • 52 Matthay KK, DeSantes K, Hasegawa B, Huberty J, Hattner RS, Ablin A, Reynolds CP, Seeger RC, Weinberg VK, Price D. Phase I dose escalation of 131I-metaiodobenzylguanidine with autologous bone marrow support in refractory neuroblastoma.  J Clin Oncol. 1998;  16 229-236
    Google Scholar
  • 53 Fitzgerald PA, Goldsby RE, Huberty JP, Price DC, Hawkins RA, Veatch JJ, Dela Cruz F, Jahan TM, Linker CA, Damon L, Matthay KK. Malignant pheochromocytomas and paragangliomas: a phase II study of therapy with high-dose 131I-metaiodobenzylguanidine (131I-MIBG).  Ann N Y Acad Sci. 2006;  1073 465-490
    Google Scholar
  • 54 Hartley A, Spooner D, Brunt AM. Management of malignant phaeochromocytoma: a retrospective review of the use of MIBG and chemotherapy in the West Midlands.  Clin Oncol (R Coll Radiol). 2001;  361-366
    Google Scholar
  • 55 Weckbecker G, Raulf F, Stolz B, Bruns C. Somatostatin analogs for diagnosis and treatment of cancer.  Pharmacol Ther. 1993;  60 245-264
    Google Scholar
  • 56 Patel YC. Somatostatin and its receptor family.  Front Neuroendocrinol. 1999;  20 157-198
    Google Scholar
  • 57 Frilling A, Weber F, Saner F, Bockisch A, Hofmann M, Mueller-Brand J, Broelsch CE. Treatment with (90)Y- and (177)Lu-DOTATOC in patients with metastatic neuroendocrine tumors.  Surgery. 2006;  140 968-976
    Google Scholar
  • 58 Hubalewska-Dydejczyk A, Trofimiuk M, Sowa-Staszczak A, Gilis-Januszewska A, Wierzchowski W, Pach D, Budzynski A, Karcz D. Somatostatin receptors expression (SSTR1-SSTR5) in pheochromocytomas.  Przegl Lek. 2008;  65 405-407
    Google Scholar
  • 59 Invitti C, De MI, Bolla GB, Pecori Giraldi F, Maestri E, Leonetti G, Cavagnini F. Effect of octreotide on catecholamine plasma levels in patients with chromaffin cell tumors.  Horm Res. 1993;  40 156-160
    Google Scholar
  • 60 Mundschenk J, Unger N, Schulz S, Hollt V, Schulz S, Steinke R, Lehnert H. Somatostatin receptor subtypes in human pheochromocytoma: subcellular expression pattern and functional relevance for octreotide scintigraphy.  J Clin Endocrinol Metab. 2003;  88 5150-5157
    Google Scholar
  • 61 Arnold R, Trautmann ME, Creutzfeldt W, Benning R, Benning M, Neuhaus C, Jurgensen R, Stein K, Schafer H, Bruns C, Dennler HJ. Somatostatin analogue octreotide and inhibition of tumour growth in metastatic endocrine gastroenteropancreatic tumours.  Gut. 1996;  38 430-438
    Google Scholar
  • 62 Koopmans KP, Jager PL, Kema IP, Kerstens MN, Albers F, Dullaart RP. 111In-octreotide is superior to 123I-metaiodobenzylguanidine for scintigraphic detection of head and neck paragangliomas.  J Nucl Med. 2008;  49 1232-1237
    Google Scholar
  • 63 Shulkin BL, Ilias I, Sisson JC, Pacak K. Current trends in functional imaging of pheochromocytomas and paragangliomas.  Ann N Y Acad Sci. 2006;  1073 374-382
    Google Scholar
  • 64 Lamarre-Cliche M, Gimenez-Roqueplo AP, Billaud E, Baudin E, Luton JP, Plouin PF. Effects of slow-release octreotide on urinary metanephrine excretion and plasma chromogranin A and catecholamine levels in patients with malignant or recurrent phaeochromocytoma.  Clin Endocrinol (Oxf). 2002;  57 629-634
    Google Scholar
  • 65 Plouin PF, Bertherat J, Chatellier G, Billaud E, Azizi M, Grouzmann E, Epelbaum J. Short-term effects of octreotide on blood pressure and plasma catecholamines and neuropeptide Y levels in patients with phaeochromocytoma: a placebo-controlled trial.  Clin Endocrinol (Oxf). 1995;  42 289-294
    Google Scholar
  • 66 Forrer F, Riedweg I, Maecke HR, Mueller-Brand J. Radiolabeled DOTATOC in patients with advanced paraganglioma and pheochromocytoma.  Q J Nucl Med Mol Imaging. 2008;  52 334-340
    Google Scholar
  • 67 Bruns C, Lewis I, Briner U, Meno-Tetang G, Weckbecker G. SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile.  Eur J Endocrinol. 2002;  146 707-716
    Google Scholar
  • 68 Pasquali D, Rossi V, Conzo G, Pannone G, Bufo P, De Bellis A, Renzullo A, Bellastella G, Colao A, Vallone G, Bellastella A, Sinisi AA. Effects of somatostatin analog SOM230 on cell proliferation, apoptosis, and catecholamine levels in cultured pheochromocytoma cells.  J Mol Endocrinol. 2008;  40 263-271
    Google Scholar
  • 69 Scharf Y, Ben Arieh Y, Gellei B. Orbital metastases from extra-adrenal pheochromocytoma.  Am J Ophthalmol. 1970;  69 638-640
    Google Scholar
  • 70 Philipps AF, McMurtry RJ, Taubman J. Malignant pheochromocytoma in childhood.  Am J Dis Child. 1976;  130 1252-1255
    Google Scholar
  • 71 Hamilton BP, Cheikh IE, Rivera LE. Attempted treatment of inoperable pheochromocytoma with streptozocin.  Arch Intern Med. 1977;  137 762-765
    Google Scholar
  • 72 Feldman JM. Treatment of metastatic pheochromocytoma with streptozocin.  Arch Intern Med. 1983;  143 1799-1800
    Google Scholar
  • 73 Herrera LO, Hossain ZM, Rafal HS, Frelick RW, Ashley PF, Lopez GE. Malignant pheochromocytoma (paraganglioma) of the organ of Zuckerkandl: a study of two cases.  J Surg Oncol. 1980;  14 133-145
    Google Scholar
  • 74 Bukowski RM, Vidt DG. Chemotherapy trials in malignant pheochromocytoma: report of two patients and review of the literature.  J Surg Oncol. 1984;  27 89-92
    Google Scholar
  • 75 Srimuninnimit V, Wampler GL. Case report of metastatic familial pheochromocytoma treated with cisplatin and 5-fluorouracil.  Cancer Chemother Pharmacol. 1991;  28 217-219
    Google Scholar
  • 76 Jirari A, Charpentier A, Popescu S, Boidin P, Eisenmann B. A malignant primary cardiac pheochromocytoma.  Ann Thorac Surg. 1999;  68 565-566
    Google Scholar
  • 77 Keiser HR, Goldstein DS, Wade JL, Douglas FL, Averbuch SD. Treatment of malignant pheochromocytoma with combination chemotherapy.  Hypertension. 1985;  7 I18-I24
    Google Scholar
  • 78 Edstrom EE, Hjelm Skog AL, Hoog A, Hamberger B. The management of benign and malignant pheochromocytoma and abdominal paraganglioma.  Eur J Surg Oncol. 2003;  29 278-283
    Google Scholar
  • 79 Naoi Y, Tamaki Y, Ooka M, Tsukamoto F, Miyoshi Y, Tanji Y, Taguchi T, Noguchi S. A case of metastatic pheochromocytoma with remarkable response to combination of cyclophosphamide, vincristine and dacarbazine.  Gan To Kagaku Ryoho. 2003;  30 145-149
    Google Scholar
  • 80 Wu D, Tischler AS, Lloyd RV, Delellis RA, de Krijger R, van Nederveen F, Nose V. Observer Variation in the Application of the Pheochromocytoma of the Adrenal Gland Scaled Score.  Am J Surg Pathol. 2009;  33 599-608
    Google Scholar
  • 81 Huang H, Abraham J, Hung E, Averbuch S, Merino M, Steinberg SM, Pacak K, Fojo T. Treatment of malignant pheochromocytoma/paraganglioma with cyclophosphamide, vincristine, and dacarbazine: recommendation from a 22-year follow-up of 18 patients.  Cancer. 2008;  113 2020-2028
    Google Scholar
  • 82 Kulke MH, Stuart K, Enzinger PC, Ryan DP, Clark JW, Muzikansky A, Vincitore M, Michelini A, Fuchs CS. Phase II study of temozolomide and thalidomide in patients with metastatic neuroendocrine tumors.  J Clin Oncol. 2006;  24 401-406
    Google Scholar
  • 83 Newlands ES, Stevens MF, Wedge SR, Wheelhouse RT, Brock C. Temozolomide: a review of its discovery, chemical properties, pre-clinical development and clinical trials.  Cancer Treat Rev. 1997;  23 35-61
    Google Scholar
  • 84 Ekeblad S, Sundin A, Janson ET, Welin S, Granberg D, Kindmark H, Dunder K, Kozlovacki G, Orlefors H, Sigurd M, Oberg K, Eriksson B, Skogseid B. Temozolomide as monotherapy is effective in treatment of advanced malignant neuroendocrine tumors.  Clin Cancer Res. 2007;  13 2986-2991
    Google Scholar
  • 85 Chrisoulidou A, Kaltsas G, Ilias I, Grossman AB. The diagnosis and management of malignant phaeochromocytoma and paraganglioma.  Endocr Relat Cancer. 2007;  14 569-585
    Google Scholar
  • 86 Patel PH, Chaganti RS, Motzer RJ. Targeted therapy for metastatic renal cell carcinoma.  Br J Cancer. 2006;  94 614-619
    Google Scholar
  • 87 Jimenez C, Cabanillas ME, Santarpia L, Jonasch E, Kyle KL, Lano EA, Matin SF, Nunez RF, Perrier ND, Phan A, Rich TA, Shah B, Williams MD, Waguespack SG. Use of the tyrosine kinase inhibitor sunitinib in a patient with von Hippel-Lindau disease: Targeting angiogenic factors in pheochromocytoma and other von Hippel-Lindau disease-related tumors.  J Clin Endocrinol Metab. 2009;  94 386-391
    Google Scholar
  • 88 Joshua AM, Ezzat S, Asa SL, Evans A, Broom R, Freeman M, Knox JJ. Rationale and evidence for sunitinib in the treatment of malignant paraganglioma/pheochromocytoma.  J Clin Endocrinol Metab. 2009;  94 5-9
    Google Scholar
  • 89 Gross DJ, Munter G, Bitan M, Siegal T, Gabizon A, Weitzen R, Merimsky O, Ackerstein A, Salmon A, Sella A, Slavin S. The role of imatinib mesylate (Glivec) for treatment of patients with malignant endocrine tumors positive for c-kit or PDGF-R.  Endocr Relat Cancer. 2006;  13 535-540
    Google Scholar
  • 90 Yao JC, Phan AT, Chang DZ, Wolff RA, Hess K, Gupta S, Jacobs C, Mares JE, Landgraf AN, Rashid A, Meric-Bernstam F. Efficacy of RAD001 (everolimus) and octreotide LAR in advanced low- to intermediate-grade neuroendocrine tumors: results of a phase II study.  J Clin Oncol. 2008;  26 4311-4318
    Google Scholar
  • 91 Sausville EA, Tomaszewski JE, Ivy P. Clinical development of 17-allylamino, 17-demethoxygeldanamycin.  Curr Cancer Drug Targets. 2003;  3 377-383
    Google Scholar
  • 92 Averbuch SD, Steakley CS, Young RC, Gelmann EP, Goldstein DS, Stull R, Keiser HR. Malignant pheochromocytoma: effective treatment with a combination of cyclophosphamide, vincristine, and dacarbazine.  Ann Intern Med. 1988;  109 267-273
    Google Scholar

Correspondence

Prof. H. Lehnert

1st Medical Department

University of Lübeck

Ratzeburger Allee 160

23538 Lübeck

Germany

Phone: +49/451/500 23 06

Fax: 49/451/500 33 39

Email: Hendrik.Lehnert@uk-sh.de

      >