Skip to main content
SpringerLink
Log in

Treatment of Disseminated CUP

  • Chapter
Cancer of Unknown Primary

  • 1035 Accesses

Abstract

Advanced CUP (cancer of unknown primary) as defined by disseminated involvement of several organs is the typical manifestation of the disease, making up 75–85 % of the patients. In a small share, the prognosis is favorable and specific therapeutic options are available (see Chap. 10). Empiric chemotherapy is the standard treatment for the vast majority of patients. A combination of platinum and taxane is the best documented option, yielding a median survival of 8–11 months, a 1-year survival rate of 37–45 %, and a 2-year survival rate of 18–26 %. Gemcitabine and irinotecan also proved to be effective in first-line treatment. Individual patient-specific and prognostic factors have to be considered for the choice of therapy. In many cases, single compound treatment is feasible; in some cases, the therapy should be limited to symptomatic treatment as defined by palliative care. Second-line therapy is not well documented but may be effective in selected patients. New treatment options are expected to result from gene expression profiling and recent developments in immunotherapy (see Chaps. 11 and 12).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Deuel H. Primäre Halsgeschwülste und deren Differentialdiagnose gegenüber Lymphknotenmetastasen. Radiol Clin. 1942;11:297–316.

    Google Scholar 

  2. Martin H, Morfit HM. Cervical lymph node metastasis as the first symptom of cancer. Surg Gynecol Obstet. 1944;78:133–59.

    Google Scholar 

  3. Fenster LF, Klatskin G. Manifestations of metastatic tumors of the liver. Am J Med. 1961;31:238–48.

    Article  CAS  PubMed  Google Scholar 

  4. Johnson RO, Castro R, Ansfield FJ. Response of primary unknown cancers to treatment with 5-fluorouracil. Cancer Chemother Rep. 1964;38:63–4.

    CAS  PubMed  Google Scholar 

  5. Didolkar MS, Fanous N, Elias EG, Moore RH. Metastatic carcinomas from occult primary tumors. A study of 254 patients. Ann Surg. 1977;186:625–30.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Hübner G, Tamme C, Wildfang I, Schöber C, Schmoll H-J. Management of patients with carcinoma of unknown primary (CUP-Syndrome). J Cancer Res Clin Oncol. 1990;116(Suppl Part I):190.

    Google Scholar 

  7. Altman E, Cadman E. An analysis of 1539 patients with cancer of unknown primary site. Cancer. 1986;57:120–4.

    Article  CAS  PubMed  Google Scholar 

  8. Muir C. Cancer of unknown primary site. Cancer. 1995;75(1 Suppl):353–6.

    Article  CAS  PubMed  Google Scholar 

  9. Snee MP, Vyramuthu N. Metastatic carcinoma from unknown primary site: the experience of a large oncology centre. Br J Radiol. 1985;58:1091–5.

    Article  CAS  PubMed  Google Scholar 

  10. Le Chevalier T, Cvitkovic E, Caille P, Harvey J, Contesso G, Spielmann M, et al. Early metastatic cancer of unknown primary origin at presentation. A clinical study of 302 consecutive autopsied patients. Arch Intern Med. 1988;148:2035–9.

    Article  PubMed  Google Scholar 

  11. Nystrom JS, Weiner JM, Wolf RM, Bateman JR, Viola MV. Identifying the primary site in metastatic cancer of unknown origin Inadequacy of roentgenographic procedures. JAMA. 1979;241:381–3.

    Article  CAS  PubMed  Google Scholar 

  12. McMillan JH, Levine E, Stephens RH. Computed tomography in the evaluation of metastatic adenocarcinoma from an unknown primary site. A retrospective study. Radiology. 1982;143:143–6.

    Article  CAS  PubMed  Google Scholar 

  13. Yi JH, La CY, Lee SJ, Ahn HK, Baek KK, Lim T, et al. Clinical presentation of carcinoma of unknown primary: 14 years of experience. Tumour Biol. 2011;32(1):45–51.

    Article  PubMed  Google Scholar 

  14. Hübner G, Link H, Kohne CH, Stahl M, Kretzschmar A, Steinbach S, et al. Paclitaxel and carboplatin vs gemcitabine and vinorelbine in patients with adeno- or undifferentiated carcinoma of unknown primary: a randomised prospective phase II trial. Br J Cancer. 2009;100:44–9.

    Article  Google Scholar 

  15. Hess KR, Abbruzzese MC, Lenzi R, Raber MN, Abbruzzese JL. Classification and regression tree analysis of 1000 consecutive patients with unknown primary carcinoma. Clin Cancer Res. 1999;5(11):3403–10.

    CAS  PubMed  Google Scholar 

  16. Greco FA, Burris III HA, Litchy S, Barton JH, Bradof JE, Richards P, et al. Gemcitabine, Carboplatin, and Paclitaxel for patients with carcinoma of unknown primary site: a minnie pearl cancer research network study. J Clin Oncol. 2002;20(6):1651–6.

    Article  CAS  PubMed  Google Scholar 

  17. Culine S, Lortholary A, Voigt JJ, Bugat R, Theodore C, Priou F, et al. Cisplatin in combination with either gemcitabine or irinotecan in carcinomas of unknown primary site: results of a randomized phase II study–trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). J Clin Oncol. 2003;21(18):3479–82.

    Article  CAS  PubMed  Google Scholar 

  18. Lee J, Hahn S, Kim DW, Kim J, Kang SN, Rha SY, et al. Evaluation of survival benefits by platinums and taxanes for an unfavourable subset of carcinoma of unknown primary: a systematic review and meta-analysis. Br J Cancer. 2013;108(1):39–48.

    Article  PubMed Central  PubMed  Google Scholar 

  19. Greco FA, Spigel DR, Yardley DA, Erlander MG, Ma XJ, Hainsworth JD. Molecular profiling in unknown primary cancer: accuracy of tissue of origin prediction. Oncologist. 2010;15(5):500–6.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Moertel CG, Reitemeier RJ, Schutt AJ, Hahn RG. Treatment of the patient with adenocarcinoma of unknown origin. Cancer. 1972;30:1469–72.

    Article  CAS  PubMed  Google Scholar 

  21. Bedikian AY, Bodey GP, Valdivieso M, Burgess MA. Sequential chemotherapy for adenocarcinoma of unknown primary. Am J Clin Oncol. 1983;6:219–24.

    Article  CAS  PubMed  Google Scholar 

  22. Fiore JJ, Kelsen DP, Gralla RJ, Casper ES, Magill G, Cheng E, et al. Adenocarcinoma of unknown primary origin: treatment with vindesine and doxorubicin. Cancer Treat Rep. 1985;69:591–4.

    CAS  PubMed  Google Scholar 

  23. Kelsen D, Coit D, Houston C, Martin D, Sawyer R, Colofiore J. Phase II trial of pala, methotrexate (Mtx), fluorouracil (FU), and leucovorin (L) in adenocarcinoma of unknown primary site (ACUP). Proc ASCO. 1989;8:A1141.

    Google Scholar 

  24. Bécouarn Y, Brunet R, Barbe-Gaston C. Fluorouracil, doxorubicin, cisplatin and altretamine in the treatment of metastatic carcinoma of unknown primary. Eur J Cancer Clin Oncol. 1989;25:861–5.

    Article  PubMed  Google Scholar 

  25. Hainsworth JD, Erland JB, Kalman LA, Schreeder MT, Greco FA. Carcinoma of unknown primary site: treatment with 1-hour paclitaxel, carboplatin, and extended-schedule etoposide. J Clin Oncol. 1997;15(6):2385–93.

    CAS  PubMed  Google Scholar 

  26. Briasoulis E, Kalofonos H, Bafaloukos D, Samantas E, Fountzilas G, Xiros N, et al. Carboplatin plus paclitaxel in unknown primary carcinoma: a phase II hellenic cooperative oncology group study. J Clin Oncol. 2000;18(17):3101–7.

    CAS  PubMed  Google Scholar 

  27. Munoz A, Barcelo JR, Lopez-Vivanco G. Gemcitabine and docetaxel as front-line chemotherapy in patients with carcinoma of an unknown primary site. Cancer. 2004;101(3):653–4.

    Article  PubMed  Google Scholar 

  28. Park YH, Ryoo BY, Choi SJ, Yang SH, Kim HT. A phase II study of paclitaxel plus cisplatin chemotherapy in an unfavourable group of patients with cancer of unknown primary site. Jpn J Clin Oncol. 2004;34(11):681–5.

    Article  PubMed  Google Scholar 

  29. Woods RL, Fox RM, Tattersall MH, Levi JA, Brodie GN. Metastatic adenocarcinomas of unknown primary site: a randomized study of two combination-chemotherapy regimens. N Engl J Med. 1980;303:87–9.

    Article  CAS  PubMed  Google Scholar 

  30. Eagan RT, Therneau TM, Rubin J, Long HJ, Schutt AJ. Lack of value for cisplatin added to mitomycin-doxorubicin combination chemotherapy for carcinoma of unknown primary site. A randomized trial. Am J Clin Oncol. 1987;10:82–5.

    Article  CAS  PubMed  Google Scholar 

  31. Milliken ST, Tattersall MH, Woods RL, Coates AS, Levi JA, Fox RM, et al. Metastatic adenocarcinoma of unknown primary site. A randomized study of two combination chemotherapy regimens. Eur J Cancer Clin Oncol. 1987;23:1645–8.

    Article  CAS  PubMed  Google Scholar 

  32. Falkson CI, Cohen GL. Mitomycin C, epirubicin and cisplatin versus mitomycin C alone as therapy for carcinoma of unknown primary origin. Oncology. 1998;55:116–21.

    Article  CAS  PubMed  Google Scholar 

  33. Dowell JE, Garrett AM, Shyr Y, Johnson DH, Hande KR. A randomized phase II trial in patients with carcinoma of an unknown primary site. Cancer. 2001;91(3):592–7.

    Article  CAS  PubMed  Google Scholar 

  34. Assersohn L, Norman AR, Cunningham D, Iveson T, Seymour M, Hickish T, et al. A randomised study of protracted venous infusion of 5-fluorouracil (5-FU) with or without bolus mitomycin C (MMC) in patients with carcinoma of unknown primary. Eur J Cancer. 2003;39(8):1121–8.

    Article  CAS  PubMed  Google Scholar 

  35. Palmeri S, Lorusso V, Palmeri L, Vaglica M, Porta C, Nortilli R, et al. Cisplatin and gemcitabine with either vinorelbine or paclitaxel in the treatment of carcinomas of unknown primary site: results of an Italian multicenter, randomized, phase II study. Cancer. 2006;107(12):2898–905.

    Article  CAS  PubMed  Google Scholar 

  36. Hainsworth JD, Spigel DR, Clark BL, Shipley D, Thompson DS, Farley C, et al. Paclitaxel/carboplatin/etoposide versus gemcitabine/irinotecan in the first-line treatment of patients with carcinoma of unknown primary site: a randomized, phase III Sarah Cannon Oncology Research Consortium Trial. Cancer J. 2010;16(1):70–5.

    Article  CAS  PubMed  Google Scholar 

  37. Gross-Goupil M, Fourcade A, Blot E, Penel N, Negrier S, Culine S, et al. Cisplatin alone or combined with gemcitabine in carcinomas of unknown primary: results of the randomised GEFCAPI 02 trial. Eur J Cancer. 2012;48(5):721–7.

    Article  CAS  PubMed  Google Scholar 

  38. Hainsworth JD, Daugaard G, Lesimple T, Hübner G, Greco FA, Stahl MJ, et al. Paclitaxel/carboplatin with or without belinostat as empiric first-line treatment for patients with carcinoma of unknown primary site: a randomized, phase 2 trial. Cancer. 2015;121:1654–61.

    Article  CAS  PubMed  Google Scholar 

  39. Briasoulis E, Fountzilas G, Bamias A, Dimopoulos MA, Xiros N, Aravantinos G, et al. Multicenter phase-II trial of irinotecan plus oxaliplatin [IROX regimen] in patients with poor-prognosis cancer of unknown primary: a hellenic cooperative oncology group study. Cancer Chemother Pharmacol. 2008;62(2):277–84.

    Article  CAS  PubMed  Google Scholar 

  40. Schuette K, Folprecht G, Kretzschmar A, Link H, Koehne CH, Gruenwald V, et al. Phase II trial of capecitabine and oxaliplatin in patients with adeno- and undifferentiated carcinoma of unknown primary. Onkologie. 2009;32(4):162–6.

    Article  CAS  PubMed  Google Scholar 

  41. Culine S, Ychou M, Fabbro M, Romieu G, Cupissol D. 5-fluorouracil and leucovorin as second-line chemotherapy in carcinomas of unknown primary site. Anticancer Res. 2001;21(2B):1455–7.

    CAS  PubMed  Google Scholar 

  42. Hainsworth JD, Burris III HA, Calvert SW, Willcutt NT, Scullin Jr DC, Bramham J, et al. Gemcitabine in the second-line therapy of patients with carcinoma of unknown primary site: a phase II trial of the Minnie Pearl Cancer Research Network. Cancer Invest. 2001;19(4):335–9.

    Article  CAS  PubMed  Google Scholar 

  43. Pouessel D, Culine S, Becht C, Romieu G, Fabbro M, Ychou M, et al. Gemcitabine and docetaxel after failure of cisplatin-based chemotherapy in patients with carcinoma of unknown primary site. Anticancer Res. 2003;23(3C):2801–4.

    CAS  PubMed  Google Scholar 

  44. Hainsworth JD, Spigel DR, Raefsky EL, Kuzur ME, Yost K, Kommor M, et al. Combination chemotherapy with gemcitabine and irinotecan in patients with previously treated carcinoma of an unknown primary site: a Minnie Pearl Cancer Research Network Phase II trial. Cancer. 2005;104(9):1992–7.

    Article  CAS  PubMed  Google Scholar 

  45. Hainsworth JD, Spigel DR, Farley C, Thompson DS, Shipley DL, Greco FA. Phase II trial of bevacizumab and erlotinib in carcinomas of unknown primary site: the Minnie Pearl Cancer Research Network. J Clin Oncol. 2007;25(13):1747–52.

    Article  CAS  PubMed  Google Scholar 

  46. Moller AK, Pedersen KD, Abildgaard J, Petersen BL, Daugaard G. Capecitabine and oxaliplatin as second-line treatment in patients with carcinoma of unknown primary site. Acta Oncol. 2010;49(4):431–5.

    Article  PubMed  Google Scholar 

  47. Hainsworth JD, Spigel DR, Burris III HA, Shipley D, Farley C, Dias-Perez IM, et al. Oxaliplatin and capecitabine in the treatment of patients with recurrent or refractory carcinoma of unknown primary site: a phase 2 trial of the Sarah Cannon Oncology Research Consortium. Cancer. 2010;116(10):2448–54.

    CAS  PubMed  Google Scholar 

  48. Fizazi K, Greco FA, Pavlidis N, Pentheroudakis G. Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2011;22 Suppl 6:vi64–8.

    PubMed  Google Scholar 

  49. Hübner G, Borner M, Neben K, Stöger H (2014) Onkopedia Leitlinien: CUP-Syndrom – Krebserkrankungen mit unbekanntem Primärtumor. https://www.dgho-onkopediade/de/onkopedia/leitlinien/cup-syndrom-krebserkrankungen-mit-unbekanntem

  50. NCCN Guidelines (2015) Occult primary. https://www.nccnorg/store/login/loginaspx?ReturnURL=http://www.nccnorg/professionals/physician_gls/pdf/occultpdf; 1.205

Download references

Potential Conflicts of Interests

Within the last 15 years, the corresponding author has received grants for the conduction of clinical and experimental studies in CUP syndrome by Lilly Oncology, Bristol-Myers-Squibb, Sanofi-Aventis, Roche Oncology, and Agendia BV. He is or has been member of advisory boards of Roche Oncology, Boehringer Ingelheim, and Teva Pharmaceutical.

He confirms that he has no financial relationships to any firm relevant to the treatment of CUP syndrome. The presentation of the topic is independent, and the contents of the chapter are free of any influences from third parties including pharmaceutical firms.

Author information

Authors and Affiliations

  1. Department of Hematology and Medical Oncology, Sana Kliniken Ostholstein GmbH, Eutin/Oldenburg/Holstein, Germany

    Gerdt Hübner MD

Authors
  1. Gerdt Hübner MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gerdt Hübner MD .

Editor information

Editors and Affiliations

  1. German Cancer Research Center (DKFZ) and University of Heidelberg, Clinical Cooperation Unit Molecular, Hematology/Oncology, Heidelberg, Germany

    Alwin Krämer

  2. German Cancer Research Center (DKFZ) and University of Heidelberg, Clinical Cooperation Unit Molecular, Hematology/Oncology, Heidelberg, Germany

    Harald Löffler

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Hübner, G. (2016). Treatment of Disseminated CUP. In: Krämer, A., Löffler, H. (eds) Cancer of Unknown Primary. Springer, Cham. https://doi.org/10.1007/978-3-319-22581-4_8

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-22581-4_8

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-22580-7

  • Online ISBN: 978-3-319-22581-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation