Skip to main content

Advertisement

SpringerLink
Log in

Phase II trials in patients with carcinoma of unknown primary: a pooled data analysis

  • PHASE II STUDIES
  • Published:
Investigational New Drugs Aims and scope Submit manuscript

Summary

Background The management of carcinoma of unknown primary site remains debatable. The literature data consists of about 29 phase-II studies investigating 38 regimens, providing a broad range of response rates (RR). Methods We performed a pooled published data analysis to identify the factors influencing RR in these 29 studies. Results In front-line treatment, the overall RR was 31% (430/1,380). At least nine factors significantly influenced the reported RR, excluding drugs under investigation, such as the impact factor of the journal, single-centre study, some eligibility criteria, central radiological review, sample size calculation based on statistical hypothesis and stratification. Two drugs seem to improve RR: cisplatin and doxorubicin. Two drugs seem to be associated with a worse RR: irinotecan and carboplatin. Conclusions This pooled data analysis illustrates that in a phase II trial setting, it is impossible to attribute the variation in RR solely to the modification of drugs under investigation.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Pavlidis N (2007) Forty years experience of treating cancer of unknown primary. Acta Oncol (Madr) 46:592–601. doi:10.1080/02841860701243095

    Article  Google Scholar 

  2. Varadhachary GR, Talantov D, Raber MV, Meng C, Hess KR, Jatkoe T et al (2008) Molecular profiling of carcinoma of unknown primary and correlation with clinical evaluation. J Clin Oncol 26:4442–4448. doi:10.1200/JCO.2007.14.4378

    Article  CAS  PubMed  Google Scholar 

  3. Harlings HM, Van Laar RK, Kerst JM, Helgasar HM, Wessling J, Van der Hoeven JJ et al (2008) Gene expression profiling to identify the histogenetic origin of metastases adenocarcinoma of unknown primary. J Clin Oncol 26:4435–4441. doi:10.1200/JCO.2007.14.6969

    Article  Google Scholar 

  4. Culine S, Lhortolary A, Voigt JJ, Bugat R, Théodore C, Priou F, Kaminisky MC et al (2003) 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 21:3479–3482. doi:10.1200/JCO.2003.12.104

    Article  CAS  PubMed  Google Scholar 

  5. Palmeri S, Lorusso V, Palmeri L, Vaglica M, Porta C, Nortilli R et al (2006) Cisplatin and gemcitabine with either vinorelebine or paclitaxel in the treatment of carcinomas of unknown primary. Cancer 107:2898–2905. doi:10.1002/cncr.22379

    Article  CAS  PubMed  Google Scholar 

  6. Hainsworth JD, Spigel DR, Farley C, Thompson DS, Shipley DL, Greco A (2007) Phase II trial of bavacizumab and erlotinib in carcinomas of unknown primary site: the Minne Pearl cancer research network. J Clin Oncol 25:1747–1752. doi:10.1200/JCO.2006.09.3047

    Article  CAS  PubMed  Google Scholar 

  7. Pittman KB, Olver IN, Koczwara B, Kotsek D, Patterson WK, Keefe DM et al (2006) Gemcitabine and carboplatin in carcinoma of unknown primary site: a phase 2 Adelaide cancer trials and education collaborative study. Br J Cancer 2002 95(10):1309–1313

    Article  CAS  Google Scholar 

  8. Hainsworth JD, Spigel DR, Raefsky EL, Kuzur ME, Yost K, Kommor M et al (2005) Combination chemotherapy with gemcitabine in patients with previously treated carcinoma of unknown primary site. Cancer 104:1992–1997. doi:10.1002/cncr.21416

    Article  CAS  PubMed  Google Scholar 

  9. Park YH, Ryoo BY, Choi SJ, Yang SH, Kim HT (2004) 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 34:681–685. doi:10.1093/jjco/hyh124

    Article  PubMed  Google Scholar 

  10. Greco FA, Rodriguez GI, Shaffer DW, Hermann R, Litchy S, Yardley DA et al (2004) Carcinoma of unknown primary site: sequential treatment with paclitaxel/Carboplatin/Etoposide and Gemcitabine/Irinotecan: a Minnie Pearl cancer research network phase II trial. Oncologist 9:644–652. doi:10.1634/theoncologist.9-6-644

    Article  CAS  PubMed  Google Scholar 

  11. Piga A, Nortilli R, Cetto GL, Cardelli N, Fedelli N, Fiorentini G et al (2004) Carboplatin, doxorubicin and etoposide in the treatment of tumours of unknown primary site. Br J Cancer 90:1898–1904. doi:10.1038/sj.bjc.6601785

    Article  CAS  PubMed  Google Scholar 

  12. Pouessel D, Culine S, Becht C, Ychou M, Romieu G, Fabbro M et al (2004) Gemcitabine and docetaxel s front-line chemotherapy in patients with carcinoma of an unknown primary site. Cancer 100:1257–1261. doi:10.1002/cncr.20100

    Article  CAS  PubMed  Google Scholar 

  13. Balana C, Manzano JL, Moreno I, Cirauqui B, Abad A, Font A et al (2003) A phase II study of cisplatin, etoposide and gemcitabine in an unfavourable group of patients with carcinoma of unknown primary site. Ann Oncol 14:1425–1429. doi:10.1093/annonc/mdg361

    Article  CAS  PubMed  Google Scholar 

  14. Asserhorn L, Norman AR, Cunningham D, Iveson T, Seymour M, Hickissh T et al (2003) A randomised study of protracted venous infusion of 5-fluorourcil (5-FU) with or without bolus mitomycin C (MMC) in patients with carcinoma of unknown primary. Eur J Cancer 39:1121–1128. doi:10.1016/S0959-8049(03)00150-3

    Article  Google Scholar 

  15. Greco FA, Burris HA, Litchy S, Barton JH, Bradaf JE, Richards P et al (2002) Gemcitabine, Carboplatin, and Paclitaxel for patients with carcinoma of unknown primary site: a Minnie Pearl cancer research network study. J Clin Oncol 20:1651–1656. doi:10.1200/JCO.20.6.1651

    Article  CAS  PubMed  Google Scholar 

  16. Culine S, Fabbro M, Ychou M, Romieu G, Cupissol D, Pinguet F (2002) Alternative bimonthly cycles of doxorubicin, cyclophosphaide, and etoposide, cisplatin with hematopoietic growth factor support in patients with carcinoma of unknown primary site. Cancer 94:840–846. doi:10.1002/cncr.10264

    Article  CAS  PubMed  Google Scholar 

  17. Dowell JE, Garrett AM, Shyr Y, Johnson DH, Hande KR (2001) A randomized phase II trial in patients with carcinoma of an unknown primary site. Cancer 91:592–597. doi:10.1002/1097-0142(20010201) 91:3<592::AID-CNCR1039>3.0.CO;2-5

    Article  CAS  PubMed  Google Scholar 

  18. Briasoulis E, Klofonos H, Bafaloukos D, Epaminondas S, Fountzilas G, Xiros N et al (2000) Carboplatin plus pacliaxel in unknown primary carcinoma: a phase II Hellenic cooperative oncology group study. J Clin Oncol 18:3101–3107

    CAS  PubMed  Google Scholar 

  19. Greco FA, Erland JB, Morrissey LH, Burris HA III, Hermann RC, Steis R et al (2000) Carcinoma of unknown primary site: phase II trials with docetaxel plus cisplatin or carboplatin. Ann Oncol 11:211–215. doi:10.1023/A:1008369812295

    Article  CAS  PubMed  Google Scholar 

  20. Falkson CI, Cohen GL, Mitomycin C (1998) Epirubicin and cisplatin versus mitomycin C alone as therapy for carcinoma of unknown primary origin. Oncology 55:116–121. doi:10.1159/000011845

    Article  CAS  PubMed  Google Scholar 

  21. Hainsworth JD, Burris HA III, Calvert SW, Willcutt NT, Scullin DC, Bramham J et al (2001) 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 19:335–339. doi:10.1081/CNV-100103127

    Article  CAS  PubMed  Google Scholar 

  22. Hainsworth JD, Erlnd JB, Kalman LA, Schreeder MT, Greco FA (1997) Carcinoma of unknown primary site: treatment with 1-hour paclitaxel, carboplatin, and extended-schedule etoposide. J Clin Oncol 15:2385–2393

    CAS  PubMed  Google Scholar 

  23. Saghatchian M, Fizazi K, Borel C, Ducreux M, Ruffié P, Le Chevalier T et al (2001) Carcinoma of an unknown primary site: a chemotherapy strategy based on histological differentiation—results of a prospective study. Ann Oncol 12:535–540. doi:10.1023/A:1011129429499

    Article  CAS  PubMed  Google Scholar 

  24. Culine S, Fabbro M, Ychou M, Romieu G, Cupissol D, Pujol H (1999) Chemotherapy in carcinomas of unknown primary site : high-dose intensity policy. Ann Oncol 10:569–575. doi:10.1023/A:1026478009050

    Article  CAS  PubMed  Google Scholar 

  25. Guardiola E, Pivot X, Tchicknavorian X, Magne N, Otto J, Thyss A et al (2001) Combination of cisplatin-doxorubicin-cyclophosphamide in adenocarcinoma of unknown primary site. A phase II trial. Am J Clin Oncol 24:372–375. doi:10.1097/00000421-200108000-00012

    Article  CAS  PubMed  Google Scholar 

  26. Voog E, Merrouche Y, Trillet-Lenoir V, Lasset C, Peaud PY, Rebattu P et al (2000) Multicentric phase II study of cisplatin and etoposide in patients with metastatic carcinoma of unknown primary. Am J Clin Oncol 23:614–616. doi:10.1097/00000421-200012000-00018

    Article  CAS  PubMed  Google Scholar 

  27. Schneider BJ, El-Rayes B, Muler JH, Philip PA, Kalemkerian GP, Griffith KA et al (2007) Phase II trial of carboplatin, gemcitabine, and capeticabine in patients with carcinoma of unknown primary site. Cancer 110:770–775. doi:10.1002/cncr.22857

    Article  CAS  PubMed  Google Scholar 

  28. Parnis FX, Olver IN, Kotasek D, Norman J, Taylor A, Russell J et al (2000) Phase II study of epirubicin, cisplatin and continuous infusion 5-fluorouracil (ECF) for carcinoma of unknown primary site. Ann Oncol 11:883–884. doi:10.1023/A:1008311919633

    Article  CAS  PubMed  Google Scholar 

  29. Berry W, Elkory M, O’Rourke M, Kahn M, Asmar L (2007) Results of a phase II study with weekly paclitaxel plus carboplatin in advanced carcinoma of unknown primary origin: a reasonable regimen for the community-based clinic? Cancer Invest 25:27–1. doi:10.1080/07357900601130656

    Article  CAS  PubMed  Google Scholar 

  30. El-Rayes BF, Shields AF, Zalupski M, Heilbrun LK, Jain V, Terry D et al (2005) A phase II study of carboplatin and paclitaxel in adenocarcinoma of unknown primary. Am J Clin Oncol 28:152–156. doi:10.1097/01.coc.0000142590.70472.e2

    Article  PubMed  Google Scholar 

  31. McDonald AG, Nicolson MC, Samuel LM, Hutcheon AW, Ahmed FY (2002) A phase II study of mitomycin C, cisplatin and continuous infusion 5-fluorouracil (MCF) in the treatment of patients with carcinoma of unknown primary site. Br J Cancer 86:1238–1242. doi:10.1038/sj.bjc.6600258

    Article  Google Scholar 

  32. Warner E, Goel R, Chang J, Chow W, Verma S, Dancey J et al (1998) A multicentre phase II study of carboplatin and prolonged oral etoposide in the treatment of cancer of unknown primary site (CUPS). Br J Cancer 77(12):2376–2380

    CAS  PubMed  Google Scholar 

  33. Simon R (1989) Optimal two-stage designs for phase II clinical trials. Control Clin Trials 10:1–10. doi:10.1016/0197-2456(89)90015-9

    Article  CAS  PubMed  Google Scholar 

  34. Morris JA, Gardner MJ (1988) Calculating confidence intervals for relative risks (odds ratios) and standardised ratios and rates. BMJ 296:1313–1316. doi:10.1136/bmj.296.6632.1313

    Article  CAS  PubMed  Google Scholar 

  35. Gwyther S, Bolis G, Gore M, Ten Bokkel Huinink W, Verweij J, Hudson IR et al (1997) Experience with independent radiological review during a Topotecan trial in ovarian cancer. Ann Oncol 8:463–468. doi:10.1023/A:1008241127883

    Article  CAS  PubMed  Google Scholar 

  36. Penel N, Bui BN, Bay JO, Cupissol D, Ray-Coquard I, Piperno-Neumann S et al (2008) Phase II trial of weekly paclitaxel for unresectable angiosarcoma. The ANGIOTAX study. J Clin Oncol 26:5269–5274. doi:10.1200/JCO.2008.17.3146

    Article  CAS  PubMed  Google Scholar 

  37. Penel N, Adenis A (2009) Publication biases and phase II investigating anticancer targeted therapies. Invest New Drugs 27(3):287–88

    Article  PubMed  Google Scholar 

Download references

Acknowledgement

Support for this study was provided by Chugai-Pharma France.

Author information

Authors and Affiliations

  1. Département de Cancérologie Digestive et Urologique, Centre Oscar Lambret, Lille, France

    Antoine Adenis & Charles Ferté

  2. Département de Cancérologie Générale, Centre Oscar Lambret, 3, Rue F Combemale, Lille, France

    Charles Ferté & Nicolas Penel

  3. Equipe d’accueil 2694 : Santé Publique, Epidémiologie et modélisation des maladies chroniques, Université de Lille II, Lille, France

    Nicolas Penel

Authors
  1. Antoine Adenis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Charles Ferté
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nicolas Penel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nicolas Penel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Adenis, A., Ferté, C. & Penel, N. Phase II trials in patients with carcinoma of unknown primary: a pooled data analysis. Invest New Drugs 28, 178–184 (2010). https://doi.org/10.1007/s10637-009-9261-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10637-009-9261-5

Keywords

Search

Navigation