Medical Oncology

, Volume 29, Issue 3, pp 1421–1428 | Cite as

GEMOX regimen in the treatment of metastatic differentiated refractory thyroid carcinoma

  • Jean-Philippe SpanoEmail author
  • Y. Vano
  • S. Vignot
  • T. De La Motte Rouge
  • L. Hassani
  • R. Mouawad
  • F. Menegaux
  • D. Khayat
  • L. Leenhardt
Original Paper


Treatment options for radioiodine resistant metastatic thyroid cancer patients are limited, and chemotherapy is considered an outdated therapeutic method for differentiated thyroid carcinoma. In this study, we evaluated the activity and safety of gemcitabine and oxaliplatin combination which is considered an out of label therapeutic method in patients with differentiated metastatic thyroid cancer refractory to 131-I treatment. Fourteen refractory patients (8 papillary, 6 follicular), six men/eight women with median age of 63 years and performance status (0–3) were included. Patients received gemcitabine (1,000 mg/m2) plus oxaliplatin (100 mg/m2) every 2 weeks until 12-cycles and each cycle correspond to 2 weeks treatment. This protocol was approved by the local Institutional Review Boards. Response rate was assessed every four cycles. Progression-free and overall survivals were calculated. Median treatment was 9.5 cycles (range 2–17) with 22 weeks duration. Overall response rate was 57%, with 7% achieving a complete response (1/14), 50% a partial response (7/14), and 28% with a stable disease. All patients with follicular subtype showed objective responses. Eleven patients progressed at a median time of 10.1 months; 10 of 14 patients still alive and the median survival was not reached (median follow-up of 19.8 months). The combination was generally well tolerated. No deaths occurred due to therapy and no grade IV toxicity was recorded. The most common treatment-related adverse events grade 1/3 includes asthenia, peripheral neuropathy, diarrhea, anemia, thrombocytopenia, and neutropenia. In conclusion, the GEMOX regimen is well tolerated and effective in advanced differentiated thyroid cancer. However, this retrospective data on a small sample size are considered preliminary and needs to be evaluated prospectively in a higher number of patients in a clinical trial.


Gemcitabine Oxaliplatin Refractory thyroid carcinoma Relevant therapy 



This work was supported by the Foundation Delattre, Foundation Charles Aznavour, and the Association pour la Vie-Espoir contre le Cancer (A.V.E.C).

Conflict of interest

The authors declare no conflict of interest with this paper is to be disclosed.


  1. 1.
    Colonna M, Grande E, Jonasson JG, Eurocare Working G. Variation in relative survival of thyroid cancers in Europe: results from the analysis on 21 countries over the period 1983–1994 (eurocare-3 study). Eur J Cancer. 2006;42:2598–608.PubMedCrossRefGoogle Scholar
  2. 2.
    Kilfoy BA, Zheng T, Holford TR, Han X, Ward MH, Sjodin A, Zhang Y, Bai Y, Zhu C, Guo GL, Rothman N. International patterns and trends in thyroid cancer incidence, 1973–2002. Cancer Causes Control. 2009;20:525–31.PubMedCrossRefGoogle Scholar
  3. 3.
    Leenhardt L, Grosclaude P, Cherie-Challine L. Increased incidence of thyroid carcinoma in France: a true epidemic or thyroid nodule management effects? Report from the French thyroid cancer committee. Thyroid. 2004;14:1056–60.PubMedCrossRefGoogle Scholar
  4. 4.
    Sherman SI. Thyroid carcinoma. Lancet. 2003;361:501–11.PubMedCrossRefGoogle Scholar
  5. 5.
    Baudin E, Schlumberger M. New therapeutic approaches for metastatic thyroid carcinoma. Lancet Oncol. 2007;8:148–56.PubMedCrossRefGoogle Scholar
  6. 6.
    Durante C, Haddy N, Baudin E, Leboulleux S, Hartl D, Travagli JP, Caillou B, Ricard M, Lumbroso JD, De Vathaire F, Schlumberger M. Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. J Clin Endocrinol Metab. 2006;91:2892–9.PubMedCrossRefGoogle Scholar
  7. 7.
    O’Neill CJ, Oucharek J, Learoyd D, Sidhu SB. Standard and emerging therapies for metastatic differentiated thyroid cancer. Oncologist. 2010;15:146–56.PubMedCrossRefGoogle Scholar
  8. 8.
    Ahuja S, Ernst H. Chemotherapy of thyroid carcinoma. J Endocrinol Invest. 1987;10:303–10.PubMedGoogle Scholar
  9. 9.
    Gottlieb JA, Hill CS Jr. Chemotherapy of thyroid cancer with adriamycin. Experience with 30 patients. N Engl J Med. 1974;290:193–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Matuszczyk A, Petersenn S, Bockisch A, Gorges R, Sheu SY, Veit P, Mann K. Chemotherapy with doxorubicin in progressive medullary and thyroid carcinoma of the follicular epithelium. Horm Metab Res. 2008;40:210–3.PubMedCrossRefGoogle Scholar
  11. 11.
    Shimaoka K, Schoenfeld DA, DeWys WD, Creech RH, DeConti R. A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma. Cancer. 1985;56:2155–60.PubMedCrossRefGoogle Scholar
  12. 12.
    Gupta-Abramson V, Troxel AB, Nellore A, Puttaswamy K, Redlinger M, Ransone K, Mandel SJ, Flaherty KT, Loevner LA, O’Dwyer PJ, Brose MS. Phase II trial of sorafenib in advanced thyroid cancer. J Clin Oncol. 2008;26:4714–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Cohen EE, Rosen LS, Vokes EE, Kies MS, Forastiere AA, Worden FP, Kane MA, Sherman E, Kim S, Bycott P, Tortorici M, Shalinsky DR, Liau KF, Cohen KF. Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase ii study. J Clin Oncol. 2008;26:4708–13.PubMedCrossRefGoogle Scholar
  14. 14.
    Bible KC, Suman VJ, Molina JR, Smallridge RC, Maples WJ, Menefee ME, Rubin J, Sideras K, Morris JC 3rd, McIver B, Burton JK, Webster KP, Bieber C, Traynor AM, Flynn PJ, Goh BC, Tang H, Ivy SP, Erlichman C. Efficacy of pazopanib in progressive, radioiodine-refractory, metastatic differentiated thyroid cancers: results of a phase 2 consortium study. Lancet Oncol. 2010;11:962–72.PubMedCrossRefGoogle Scholar
  15. 15.
    Hoftijzer H, Heemstra KA, Morreau H, Stokkel MP, Corssmit EP, Gelderblom H, Weijers K, Pereira AM, Huijberts M, Kapiteijn E, Romijn JA, Smit JW. Beneficial effects of sorafenib on tumor progression, but not on radioiodine uptake, in patients with differentiated thyroid carcinoma. Eur J Endocrinol. 2009;161:923–31.PubMedCrossRefGoogle Scholar
  16. 16.
    Kloos RT, Ringel MD, Knopp MV, Hall NC, King M, Stevens R, Liang J, Wakely PE Jr, Vasko VV, Saji M, Rittenberry J, Wei L, Arbogast D, Collamore M, Wright JJ, Grever M, Shah MH. Phase II trial of sorafenib in metastatic thyroid cancer. J Clin Oncol. 2009;27:1675–84.PubMedCrossRefGoogle Scholar
  17. 17.
    Soh EY, Eigelberger MS, Kim KJ, Wong MG, Young DM, Clark OH, Duh QY. Neutralizing vascular endothelial growth factor activity inhibits thyroid cancer growth in vivo. Surgery. 2000;128:1059–65. discussion 1065–1056.PubMedCrossRefGoogle Scholar
  18. 18.
    Raymond E, Faivre S, Woynarowski JM, Chaney SG. Oxaliplatin: mechanism of action and antineoplastic activity. Semin Oncol. 1998;25:4–12.PubMedGoogle Scholar
  19. 19.
    Faivre S, Raymond E, Woynarowski JM, Cvitkovic E. Supraadditive effect of 2′,2′-difluorodeoxycytidine (gemcitabine) in combination with oxaliplatin in human cancer cell lines. Cancer Chemother Pharmacol. 1999;44:117–23.PubMedCrossRefGoogle Scholar
  20. 20.
    Cancer therapy evaluation program. Common toxicity criteria, version 2.0.2. dctd, nci, nih, dhhs. NIH; 1998.
  21. 21.
    Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised recist guideline (version 1.1). Eur J Cancer. 2009;45:228–47.PubMedCrossRefGoogle Scholar
  22. 22.
    Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. Am StatAssoc J. 1958;53:457–81.CrossRefGoogle Scholar
  23. 23.
    Louvet C, Labianca R, Hammel P, Lledo G, Zampino MG, Andre T, Zaniboni A, Ducreux M, Aitini E, Taieb J, Faroux R, Lepere C, De Gramont A. Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a gercor and giscad phase III trial. J Clin Oncol. 2005;23:3509–16.PubMedCrossRefGoogle Scholar
  24. 24.
    Andre T, Tournigand C, Rosmorduc O, Provent S, Maindrault-Goebel F, Avenin D, Selle F, Paye F, Hannoun L, Houry S, Gayet B, Lotz JP, de Gramont A, Louvet C. Gemcitabine combined with oxaliplatin (gemox) in advanced biliary tract adenocarcinoma: a gercor study. Ann Oncol. 2004;15:1339–43.PubMedCrossRefGoogle Scholar
  25. 25.
    Faivre S, Le Chevalier T, Monnerat C, Lokiec F, Novello S, Taieb J, Pautier P, Lhomme C, Ruffie P, Kayitalire L, Armand JP, Raymond E. Phase I-II and pharmacokinetic study of gemcitabine combined with oxaliplatin in patients with advanced non-small-cell lung cancer and ovarian carcinoma. Ann Oncol. 2002;13:1479–89.PubMedCrossRefGoogle Scholar
  26. 26.
    Louafi S, Boige V, Ducreux M, Bonyhay L, Mansourbakht T, de Baere T, Asnacios A, Hannoun L, Poynard T, Taieb J. Gemcitabine plus oxaliplatin (gemox) in patients with advanced hepatocellular carcinoma (hcc): results of a phase II study. Cancer. 2007;109:1384–90.PubMedCrossRefGoogle Scholar
  27. 27.
    Afchain P, Chibaudel B, Lledo G, Selle F, Bengrine-Lefevre L, Nguyen S, Paitel JF, Mineur L, Artru P, Andre T, Louvet C. First-line simplified gemox (s-gemox) versus classical gemox in metastatic pancreatic cancer (mpa): results of a gercor randomized phase ii study. Bull Cancer. 2009;96:E18–22.PubMedGoogle Scholar
  28. 28.
    Santini F, Bottici V, Elisei R, Montanelli L, Mazzeo S, Basolo F, Pinchera A, Pacini F. Cytotoxic effects of carboplatinum and epirubicin in the setting of an elevated serum thyrotropin for advanced poorly differentiated thyroid cancer. J Clin Endocrinol Metab. 2002;87:4160–5.PubMedCrossRefGoogle Scholar
  29. 29.
    Fenton C, Patel A, Dinauer C, Robie DK, Tuttle RM, Francis GL. The expression of vascular endothelial growth factor and the type 1 vascular endothelial growth factor receptor correlate with the size of papillary thyroid carcinoma in children and young adults. Thyroid. 2000;10:349–57.PubMedCrossRefGoogle Scholar
  30. 30.
    Sherman SI, Wirth LJ, Droz JP, Hofmann M, Bastholt L, Martins RG, Licitra L, Eschenberg MJ, Sun YN, Juan T, Stepan DE, Schlumberger MJ. Motesanib diphosphate in progressive differentiated thyroid cancer. N Engl J Med. 2008;359:31–42.PubMedCrossRefGoogle Scholar
  31. 31.
    Cabanillas ME, Waguespack SG, Bronstein Y, Williams MD, Feng L, Hernandez M, Lopez A, Sherman SI, Busaidy NL. Treatment with tyrosine kinase inhibitors for patients with differentiated thyroid cancer: The m. D. Anderson experience. J Clin Endocrinol Metab. 2010;95:2588–95.PubMedCrossRefGoogle Scholar
  32. 32.
    Leboulleux S, Bastholt L, Krause TM, et al. Vandetanib in locally advanced or metastatic differentiated thyroid cancer: a randomised double blind phase II trial. International thyroid conference, Paris, France; 2010, Abstr OC-023.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Jean-Philippe Spano
    • 1
    • 5
    Email author
  • Y. Vano
    • 1
  • S. Vignot
    • 1
  • T. De La Motte Rouge
    • 1
  • L. Hassani
    • 2
  • R. Mouawad
    • 1
  • F. Menegaux
    • 3
  • D. Khayat
    • 1
  • L. Leenhardt
    • 4
  1. 1.Medical Oncology DepartmentGH Pitié-SalpêtrièreParisFrance
  2. 2.Pharmacy DepartmentGH Pitié-SalpêtrièreParisFrance
  3. 3.Department of General, Digestive and Endocrine SurgeryGH Pitié-SalpêtrièreParisFrance
  4. 4.Department of Nuclear MedicineGH Pitié-SalpêtrièreParisFrance
  5. 5.Medical Oncology DepartmentPitie-Salpêtrière HospitalParisFrance

Personalised recommendations