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Malignant salivary gland tumors: Treatment of recurrent and metastatic disease

Scott A Laurie, MD, FRCPC
Bradley Schiff, MD
Section Editors
Bruce E Brockstein, MD
Marshall R Posner, MD
David M Brizel, MD
Marvin P Fried, MD, FACS
Deputy Editor
Michael E Ross, MD


Salivary glands produce and secrete saliva from a glandular structure, the secretory acinus, the ducts, and the myoepithelial and basal cells. Salivary gland tumors can be benign or malignant (table 1). These tumors can arise from either the major salivary glands (parotid, submandibular, and sublingual (figure 1)) or the minor salivary glands, which are located throughout the submucosa of the mouth and upper aerodigestive tract, including the oral cavity (especially the palate), paranasal sinuses, larynx, and pharynx.

Salivary gland tumors are rare, and information on management is based mainly upon retrospective series, although in the last few years, a concerted effort has led to the completion of several prospective phase II trials, particularly in adenoid cystic carcinoma. The most common malignant salivary gland tumors include mucoepidermoid carcinoma, adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma, carcinoma ex pleomorphic adenoma, acinic cell carcinoma, and adenocarcinoma not otherwise specified.

The treatment of locoregionally recurrent and metastatic salivary gland tumors is reviewed here. The initial treatment of locoregional disease and the epidemiology, risk factors, pathology, and clinical features of these tumors are discussed separately. (See "Salivary gland tumors: Treatment of locoregional disease" and "Salivary gland tumors: Epidemiology, diagnosis, evaluation, and staging".)


Treatment options for recurrent salivary gland tumors, as with recurrent head and neck cancer in general, are limited by the previous therapy received and the potential resectability of recurrent disease. (See "Treatment of locally recurrent squamous cell carcinoma of the head and neck".)

Treatment of recurrent pleomorphic adenoma (benign mixed tumor) is discussed separately. (See "Salivary gland tumors: Treatment of locoregional disease", section on 'Pleomorphic adenoma'.)


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Literature review current through: Jul 2017. | This topic last updated: Sep 19, 2016.
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  1. Dai D. Postoperative irradiation in malignant tumors of submandibular gland. Cancer Invest 1999; 17:36.
  2. Mücke T, Tannapfel A, Kesting MR, et al. Adenoid cystic carcinomas of minor salivary glands. Auris Nasus Larynx 2010; 37:615.
  3. Laramore GE. Role of particle radiotherapy in the management of head and neck cancer. Curr Opin Oncol 2009; 21:224.
  4. Chen AM, Garcia J, Bucci MK, et al. Recurrent salivary gland carcinomas treated by surgery with or without intraoperative radiation therapy. Head Neck 2008; 30:2.
  5. Haddad RI, Posner MR, Busse PM, et al. Chemoradiotherapy for adenoid cystic carcinoma: preliminary results of an organ sparing approach. Am J Clin Oncol 2006; 29:153.
  6. Barnett TA, Kapp DS, Goffinet DR. Adenoid cystic carcinoma of the salivary glands. Management of recurrent, advanced, or persistent disease with hyperthermia and radiation therapy. Cancer 1990; 65:2648.
  7. Gabriele P, Amichetti M, Orecchia R, Valdagni R. Hyperthermia and radiation therapy for inoperable or recurrent parotid carcinoma. A phase I/II study. Cancer 1995; 75:908.
  8. Pederson AW, Haraf DJ, Blair EA, et al. Chemoreirradiation for recurrent salivary gland malignancies. Radiother Oncol 2010; 95:308.
  9. Hill ME, Constenla DO, A'Hern RP, et al. Cisplatin and 5-fluorouracil for symptom control in advanced salivary adenoid cystic carcinoma. Oral Oncol 1997; 33:275.
  10. Spiro RH. Distant metastasis in adenoid cystic carcinoma of salivary origin. Am J Surg 1997; 174:495.
  11. Sung MW, Kim KH, Kim JW, et al. Clinicopathologic predictors and impact of distant metastasis from adenoid cystic carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg 2003; 129:1193.
  12. van der Wal JE, Becking AG, Snow GB, van der Waal I. Distant metastases of adenoid cystic carcinoma of the salivary glands and the value of diagnostic examinations during follow-up. Head Neck 2002; 24:779.
  13. Sur RK, Donde B, Levin V, et al. Adenoid cystic carcinoma of the salivary glands: a review of 10 years. Laryngoscope 1997; 107:1276.
  14. Yu T, Gao QH, Wang XY, et al. Malignant sublingual gland tumors: a retrospective clinicopathologic study of 28 cases. Oncology 2007; 72:39.
  15. Laurie SA, Ho AL, Fury MG, et al. Systemic therapy in the management of metastatic or locally recurrent adenoid cystic carcinoma of the salivary glands: a systematic review. Lancet Oncol 2011; 12:815.
  16. Gilbert J, Li Y, Pinto HA, et al. Phase II trial of taxol in salivary gland malignancies (E1394): a trial of the Eastern Cooperative Oncology Group. Head Neck 2006; 28:197.
  17. Licitra L, Marchini S, Spinazzè S, et al. Cisplatin in advanced salivary gland carcinoma. A phase II study of 25 patients. Cancer 1991; 68:1874.
  18. Schramm VL Jr, Srodes C, Myers EN. Cisplatin therapy for adenoid cystic carcinoma. Arch Otolaryngol 1981; 107:739.
  19. Verweij J, de Mulder PH, de Graeff A, et al. Phase II study on mitoxantrone in adenoid cystic carcinomas of the head and neck. EORTC Head and Neck Cancer Cooperative Group. Ann Oncol 1996; 7:867.
  20. Vermorken JB, Verweij J, de Mulder PH, et al. Epirubicin in patients with advanced or recurrent adenoid cystic carcinoma of the head and neck: a phase II study of the EORTC Head and Neck Cancer Cooperative Group. Ann Oncol 1993; 4:785.
  21. Airoldi M, Pedani F, Succo G, et al. Phase II randomized trial comparing vinorelbine versus vinorelbine plus cisplatin in patients with recurrent salivary gland malignancies. Cancer 2001; 91:541.
  22. Dreyfuss AI, Clark JR, Fallon BG, et al. Cyclophosphamide, doxorubicin, and cisplatin combination chemotherapy for advanced carcinomas of salivary gland origin. Cancer 1987; 60:2869.
  23. Kaplan MJ, Johns ME, Cantrell RW. Chemotherapy for salivary gland cancer. Otolaryngol Head Neck Surg 1986; 95:165.
  24. Licitra L, Cavina R, Grandi C, et al. Cisplatin, doxorubicin and cyclophosphamide in advanced salivary gland carcinoma. A phase II trial of 22 patients. Ann Oncol 1996; 7:640.
  25. Creagan ET, Woods JE, Rubin J, Schaid DJ. Cisplatin-based chemotherapy for neoplasms arising from salivary glands and contiguous structures in the head and neck. Cancer 1988; 62:2313.
  26. Alberts DS, Manning MR, Coulthard SW, et al. Adriamycin/cis-platinum/cyclophosphamide combination chemotherapy for advanced carcinoma of the parotid gland. Cancer 1981; 47:645.
  27. Belani CP, Eisenberger MA, Gray WC. Preliminary experience with chemotherapy in advanced salivary gland neoplasms. Med Pediatr Oncol 1988; 16:197.
  28. Tsukuda M, Kokatsu T, Ito K, et al. Chemotherapy for recurrent adeno- and adenoidcystic carcinomas in the head and neck. J Cancer Res Clin Oncol 1993; 119:756.
  29. Dimery IW, Legha SS, Shirinian M, Hong WK. Fluorouracil, doxorubicin, cyclophosphamide, and cisplatin combination chemotherapy in advanced or recurrent salivary gland carcinoma. J Clin Oncol 1990; 8:1056.
  30. Venook AP, Tseng A Jr, Meyers FJ, et al. Cisplatin, doxorubicin, and 5-fluorouracil chemotherapy for salivary gland malignancies: a pilot study of the Northern California Oncology Group. J Clin Oncol 1987; 5:951.
  31. Airoldi M, Pedani F, Brando V, et al. Cisplatin, epirubicin and 5-fluorouracil combination chemotherapy for recurrent carcinoma of the salivary gland. Tumori 1989; 75:252.
  32. Farhat F, Kattan J, Culine S, et al. [Efficacy of the combination of 5 fluorouracil, adriamycin and cisplatin (FAP protocol) in the treatment of metastatic cylindroma. Apropos of a case with review of the literature]. Bull Cancer 1994; 81:47.
  33. Gedlicka C, Schüll B, Formanek M, et al. Mitoxantrone and cisplatin in recurrent and/or metastatic salivary gland malignancies. Anticancer Drugs 2002; 13:491.
  34. Laurie SA, Siu LL, Winquist E, et al. A phase 2 study of platinum and gemcitabine in patients with advanced salivary gland cancer: a trial of the NCIC Clinical Trials Group. Cancer 2010; 116:362.
  35. Airoldi M, Fornari G, Pedani F, et al. Paclitaxel and carboplatin for recurrent salivary gland malignancies. Anticancer Res 2000; 20:3781.
  36. Ruzich JC, Ciesla MC, Clark JI. Response to paclitaxel and carboplatin in metastatic salivary gland cancer: a case report. Head Neck 2002; 24:406.
  37. Posner MR, Ervin TJ, Weichselbaum RR, et al. Chemotherapy of advanced salivary gland neoplasms. Cancer 1982; 50:2261.
  38. de Haan LD, De Mulder PH, Vermorken JB, et al. Cisplatin-based chemotherapy in advanced adenoid cystic carcinoma of the head and neck. Head Neck 1992; 14:273.
  39. Weed DT, Gomez-Fernandez C, Pacheco J, et al. MUC4 and ERBB2 expression in major and minor salivary gland mucoepidermoid carcinoma. Head Neck 2004; 26:353.
  40. Glisson B, Colevas AD, Haddad R, et al. HER2 expression in salivary gland carcinomas: dependence on histological subtype. Clin Cancer Res 2004; 10:944.
  41. Jaehne M, Roeser K, Jaekel T, et al. Clinical and immunohistologic typing of salivary duct carcinoma: a report of 50 cases. Cancer 2005; 103:2526.
  42. Press MF, Pike MC, Hung G, et al. Amplification and overexpression of HER-2/neu in carcinomas of the salivary gland: correlation with poor prognosis. Cancer Res 1994; 54:5675.
  43. Nabili V, Tan JW, Bhuta S, et al. Salivary duct carcinoma: a clinical and histologic review with implications for trastuzumab therapy. Head Neck 2007; 29:907.
  44. Dori S, Vered M, David R, Buchner A. HER2/neu expression in adenoid cystic carcinoma of salivary gland origin: an immunohistochemical study. J Oral Pathol Med 2002; 31:463.
  45. Agulnik M, Cohen EW, Cohen RB, et al. Phase II study of lapatinib in recurrent or metastatic epidermal growth factor receptor and/or erbB2 expressing adenoid cystic carcinoma and non adenoid cystic carcinoma malignant tumors of the salivary glands. J Clin Oncol 2007; 25:3978.
  46. Haddad R, Colevas AD, Krane JF, et al. Herceptin in patients with advanced or metastatic salivary gland carcinomas. A phase II study. Oral Oncol 2003; 39:724.
  47. Prat A, Parera M, Reyes V, et al. Successful treatment of pulmonary metastatic salivary ductal carcinoma with trastuzumab-based therapy. Head Neck 2008; 30:680.
  48. Nashed M, Casasola RJ. Biological therapy of salivary duct carcinoma. J Laryngol Otol 2009; 123:250.
  49. Kaidar-Person O, Billan S, Kuten A. Targeted therapy with trastuzumab for advanced salivary ductal carcinoma: case report and literature review. Med Oncol 2012; 29:704.
  50. Limaye SA, Posner MR, Krane JF, et al. Trastuzumab for the treatment of salivary duct carcinoma. Oncologist 2013; 18:294.
  51. Mino M, Pilch BZ, Faquin WC. Expression of KIT (CD117) in neoplasms of the head and neck: an ancillary marker for adenoid cystic carcinoma. Mod Pathol 2003; 16:1224.
  52. Pfeffer MR, Talmi Y, Catane R, et al. A phase II study of Imatinib for advanced adenoid cystic carcinoma of head and neck salivary glands. Oral Oncol 2007; 43:33.
  53. Wong SJ, Karrison T, Hayes DN, et al. Phase II trial of dasatinib for recurrent or metastatic c-KIT expressing adenoid cystic carcinoma and for nonadenoid cystic malignant salivary tumors. Ann Oncol 2016; 27:318.
  54. Laurie SA, Licitra L. Systemic therapy in the palliative management of advanced salivary gland cancers. J Clin Oncol 2006; 24:2673.
  55. Jakob JA, Kies MS, Glisson BS, et al. Phase II study of gefitinib in patients with advanced salivary gland cancers. Head Neck 2015; 37:644.
  56. Locati LD, Bossi P, Perrone F, et al. Cetuximab in recurrent and/or metastatic salivary gland carcinomas: A phase II study. Oral Oncol 2009; 45:574.
  57. Hitre E, Budai B, Takácsi-Nagy Z, et al. Cetuximab and platinum-based chemoradio- or chemotherapy of patients with epidermal growth factor receptor expressing adenoid cystic carcinoma: a phase II trial. Br J Cancer 2013; 109:1117.
  58. Zhang J, Peng B, Chen X. Expressions of nuclear factor kappaB, inducible nitric oxide synthase, and vascular endothelial growth factor in adenoid cystic carcinoma of salivary glands: correlations with the angiogenesis and clinical outcome. Clin Cancer Res 2005; 11:7334.
  59. Argiris A, Ghebremichael M, Burtness B, et al. A phase 2 trial of bortezomib followed by the addition of doxorubicin at progression in patients with recurrent or metastatic adenoid cystic carcinoma of the head and neck: a trial of the Eastern Cooperative Oncology Group (E1303). Cancer 2011; 117:3374.
  60. Kim DW, Oh DY, Shin SH, et al. A multicenter phase II study of everolimus in patients with progressive unresectable adenoid cystic carcinoma. BMC Cancer 2014; 14:795.
  61. Chau NG, Hotte SJ, Chen EX, et al. A phase II study of sunitinib in recurrent and/or metastatic adenoid cystic carcinoma (ACC) of the salivary glands: current progress and challenges in evaluating molecularly targeted agents in ACC. Ann Oncol 2012; 23:1562.
  62. Thomson DJ, Silva P, Denton K, et al. Phase II trial of sorafenib in advanced salivary adenoid cystic carcinoma of the head and neck. Head Neck 2015; 37:182.
  63. Ho AL, Dunn L, Sherman EJ, et al. A phase II study of axitinib (AG-013736) in patients with incurable adenoid cystic carcinoma. Ann Oncol 2016; 27:1902.
  64. Fan CY, Melhem MF, Hosal AS, et al. Expression of androgen receptor, epidermal growth factor receptor, and transforming growth factor alpha in salivary duct carcinoma. Arch Otolaryngol Head Neck Surg 2001; 127:1075.
  65. Shadaba A, Gaze MN, Grant HR. The response of adenoid cystic carcinoma to tamoxifen. J Laryngol Otol 1997; 111:1186.
  66. Elkin AD, Jacobs CD. Tamoxifen for salivary gland adenoid cystic carcinoma: report of two cases. J Cancer Res Clin Oncol 2008; 134:1151.
  67. Locati LD, Quattrone P, Bossi P, et al. A complete remission with androgen-deprivation therapy in a recurrent androgen receptor-expressing adenocarcinoma of the parotid gland. Ann Oncol 2003; 14:1327.
  68. van der Hulst RW, van Krieken JH, van der Kwast TH, et al. Partial remission of parotid gland carcinoma after goserelin. Lancet 1994; 344:817.
  69. Jaspers HC, Verbist BM, Schoffelen R, et al. Androgen receptor-positive salivary duct carcinoma: a disease entity with promising new treatment options. J Clin Oncol 2011; 29:e473.
  70. Locati LD, Guzzo M, Bossi P, et al. Lung metastasectomy in adenoid cystic carcinoma (ACC) of salivary gland. Oral Oncol 2005; 41:890.
  71. Qureshi SS, Nadkarni MS, Shrikhande SV, et al. Hepatic resection for metastasis from adenoid cystic carcinoma of parotid gland. Indian J Gastroenterol 2005; 24:29.
  72. Gruttadauria S, Marino G, Catalano F, et al. Secondary carcinoma of the liver from parotid gland tumor. Chir Ital 2000; 52:179.
  73. Ishihama H, Kobayashi S, Ikeda Y, et al. [Surgical treatment for pulmonary metastasis from submandibular gland cancer]. Kyobu Geka 2003; 56:51.
  74. Sidhu GS, Forrester EM. Acinic cell carcinoma: long-term survival after pulmonary metastases: light and electron microscopic study. Cancer 1977; 40:756.
  75. Liu D, Labow DM, Dang N, et al. Pulmonary metastasectomy for head and neck cancers. Ann Surg Oncol 1999; 6:572.