Journal of Cancer Research and Clinical Oncology

, Volume 137, Issue 6, pp 1005–1013 | Cite as

A literature-based meta-analysis taxane-based doublet versus single-agent taxane chemotherapy in patients with advanced breast cancer

  • Hong-Bin Xu
  • Qing Xu
  • Ling Li
Original Paper



Clinical trials have reported conflicting results as to whether taxane-based doublet improves outcome over single-agent taxane in patients with advanced breast cancer.


We performed a meta-analysis comparing primary and secondary end points of taxane-based doublet with single-agent taxane chemotherapy in patients with advanced breast cancer and prior anthracycline treatment. The event-based relative risk ratio (RR) with 95% confidence intervals (95% CI) was derived, and a test of heterogeneity was applied.


Four eligible trials (2,343 patients) were selected from 488 studies that initially were identified. A significant difference in favoring taxane-based doublet over single-agent taxane was observed in progression-free survival (PFS) (RR, 1.33; 95% CI, 1.02–1.75; P = 0.039) and partial response (PR) (RR, 1.43; 95% CI, 1.10–1.86; P = 0.008). The ORR was higher for patients receiving taxane-based doublet, although not statistically significant (RR, 1.17; 95% CI, 0.91–1.50; P = 0.220). Whereas there was no difference in 1-year survival rate (1-year SR) (RR, 1.05; 95% CI, 0.94–1.17; P = 0.422), clinical benefit (CB) (RR, 1.02; 95% CI, 0.95–1.09; P = 0.642), and complete response (CR) (RR, 0.75; 95% CI, 0.31–1.79; P = 0.512). Toxicities did not differ significantly except stomatitis and diarrhea.


Taxane-based doublet appeared to improve PFS and PR compared with single-agent taxane in the treatment of patients with advanced breast cancer. Further prospective, randomized, controlled trials will be necessary.


Meta-analysis Taxane Breast cancer Doublet regimen Advanced 


Conflict of interest

We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work; there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled, “A literature-based meta-analysis of taxane-based doublet versus single-agent taxane chemotherapy in patients with advanced breast cancer”.


  1. Aihara T, Kim Y, Takatsuka Y (2002) Phase II study of weekly docetaxel in patients with metastatic breast cancer. Ann Oncol 13:286–292PubMedCrossRefGoogle Scholar
  2. Albain KS, Nag SM, Calderillo-Ruiz G, Jordaan JP, Llombart AC, Janusz Rolski AP, Melemed AS, Reyes-Vidal JM, Sekhon JS, Simms L, O’Shaughnessy J (2008) Gemcitabine plus Paclitaxel versus Paclitaxel monotherapy in patients with metastatic breast cancer and prior anthracycline treatment. J Clin Oncol 26:3950–3957PubMedCrossRefGoogle Scholar
  3. Baltali E, Altundag K, Ozisik Y, Guler N, Tekuzman G (2004) Weekly paclitaxel in pretreated metastatic breast cancer: retrospective analysis of 52 patients. Tohoku J Exp Med 203:205–210PubMedCrossRefGoogle Scholar
  4. Bergh J, Jonsson PE, Glimelius B, Nygren P (2001) A systematic overview of chemotherapy effects in breast cancer. Acta Oncol 40:253–281PubMedCrossRefGoogle Scholar
  5. Bonneterre J, Roche H, Monnier A, Guastalla JP, Namer M, Fargeot P, Assadourian S (2002) Docetaxel vs 5-fluorouracil plus vinorelbine in metastatic breast cancer after anthracycline therapy failure. Br J Cancer 87:1210–1215PubMedCrossRefGoogle Scholar
  6. Bontenbal M, Creemers GJ, Braun HJ, de Boer AC, Janssen JT, Leys RB, Ruit JB, Goey SH, van der Velden PC, Kerkhofs LG, Schothorst KL, Schmitz PI, Bokma HJ, Verweij J, Seynaeve C (2005) Phase II to III study comparing doxorubicin and docetaxel with fluorouracil, doxorubicin, and cyclophosphamide as first-line chemotherapy in patients with metastatic breast cancer: results of a dutch community setting trial for the Clinical Trial Group of the Comprehensive Cancer Centre. J Clin Oncol 23:7081–7088PubMedCrossRefGoogle Scholar
  7. Bria E, Giannarelli D, Felici A, Peter WP, Nistico C, Vanni B, Cuppone F, Cognetti F, Terzoli E (2005) Taxanes with anthracyclines as first-line chemotherapy for metastatic breast carcinoma. Cancer 103:672–679PubMedCrossRefGoogle Scholar
  8. Bullock K, Blackwell K (2008) Clinical efficacy of taxane-trastuzumab combination regimen for HER-2-positive metastatic breast cancer. Oncologist 13:515–525PubMedCrossRefGoogle Scholar
  9. Burstein HJ, Manola J, Younger J, Parker LM, Bunnell CA, Scheib R, Matulonis UA, Garber JE, Clarke KD, Shulman LN, Winer EP (2000) Docetaxel administered on a weekly basis for metastatic breast cancer. J Clin Oncol 18:1212–1219PubMedGoogle Scholar
  10. Case LD, Kimmick G, Paskett ED, Lohman K, Tucker R (2002) Interpreting measures of treatment effect in cancer clinical trials. Oncologist 7:181–187PubMedCrossRefGoogle Scholar
  11. Chan S, Friedrichs K, Noel D, Pintér T, Van Belle S, Vorobiof D, Duarte R, Gil Gil M, Bodrogi I, Murray E, Yelle L, von Minckwitz G, Korec S, Simmonds P, Buzzi F, González Mancha R, Richardson G, Walpole E, Ronzoni M, Murawsky M, Alakl M, Riva A, Crown J (1999) Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer. J Clin Oncol 17:2341–2354PubMedGoogle Scholar
  12. D’Hondt R, Paridaens R, Wildiers H, Pauwelyn K, Thomas J, Dumez H, Van O, Allan T (2004) Safety and efficacy of weekly docetaxel in frail and/or elderly patients with metastatic breast cancer: a phase II study. Anticancer Drugs 15:341–346PubMedCrossRefGoogle Scholar
  13. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188PubMedCrossRefGoogle Scholar
  14. Di Leo A, Gomez HL, Aziz Z, Zvirbule Z, Bines J, Arbushites MC, Guerrera SF, Koehler M, Oliva C, Stein SH, Williams LS, Dering J, Finn RS, Press MF (2008) Phase III, double-blind, randomized study comparing lapatinib plus paclitaxel with placebo plus paclitaxel as first-line treatment for metastatic breast cancer. J Clin Oncol 26:5544–5552PubMedCrossRefGoogle Scholar
  15. Fountzilas G, Dafni U, Dimopoulos MA, Koutras A, Skarlos D, Papakostas P, Gogas H, Bafaloukos D, Kalogera-Fountzila A, Samantas E, Briasoulis E, Pectasides D, Maniadakis N, Matsiakou F, Aravantinos G, Papadimitriou C, Karina M, Christodoulou C, Kosmidis P, Kalofonos HP (2009) A randomized phase III study comparing three anthracycline-free taxane-based regimens, as first line chemotherapy, in metastatic breast cancer: a Hellenic Cooperative Oncology Group study. Breast Cancer Res Treat 115:87–99PubMedCrossRefGoogle Scholar
  16. Fumoleau P, Seidman AD, Trudeau ME, Chevallier B, Huinink WWTB (1997) Docetaxel: a new active agent in the therapy of metastatic breast cancer. Expert Opin Investing Drugs 6:1853–1865CrossRefGoogle Scholar
  17. Gennari A, Conte P, Rosso R, Orlandini C, Bruzzi P (2005) Survival of metastatic breast carcinoma patients over a 20-year period: a retrospective analysis based on individual patient data from six consecutive studies. Cancer 104:1742–1750PubMedCrossRefGoogle Scholar
  18. Gori S, Mosconi AM, Basurtol C, Cherubinil R, DeAngelis V, Tonato M, Colozza M (2002) Weekly paclitaxel in metastatic breast cancer patients: a phase II study. Tumori 88:470–473PubMedGoogle Scholar
  19. Hainsworth JD, Burris HA, Yardley DA, Bradof JE, Grimaldi M, Kalman LA, Sullivan T, Baker M, Erland JB, Greco FA (2001) Weekly docetaxel in the treatment of elderly patients with advanced breast cancer: a Minnie Pearl Cancer Research Network phase II trial. J Clin Oncol 19:3500–3505PubMedGoogle Scholar
  20. Horiguchi J, Oyama T, Koibuchi Y, Yokoe T, Takata D, Ikeda F, Nagaoka H, Rokutanda N, Nagaoka R, Ishikawa Y, Odawara H, Kikuchi M, Sato A, Iino Y, Takeyoshi I (2009) Neoadjuvant weekly paclitaxel with and without trastuzumab in locally advanced or metastatic breast cancer. Anticancer Res 29:517–524PubMedGoogle Scholar
  21. Icli E, Akbulut h, Uner A (2002) Paclitaxel (T) vs cisplatin + VP-16 (EP) in metastatic breast cancer patients treated with anthracyclines: a phase III randomized study. Turkish Oncology Group. Ann Oncol 13(Suppl 5):47Google Scholar
  22. Icli F, Akbulut H, Uner A, Yalcin B, Baltali E, Altinbas M, Coşkun S, Komurcu S, Erkisi M, Demirkazik A, Senler FC, Sencan O, Büyükcelik A, Boruban C, Onur H, Zengin N, Sak SD (2005) Cisplatin plus oral etoposide (EoP) combination is more effective than paclitaxel in patients with advanced breast cancer pretreated with anthracyclines: a randomised phase III trial of Turkish Oncology Group. Br J Cancer 92:639–644PubMedCrossRefGoogle Scholar
  23. Jackisch C, Eibach H, Knuth A (2000) Phase II trial of docetaxel weekly as dose dense treatment in metastatic breast cancer (MBC). Proc Am Soc Clin Oncol 18:417aGoogle Scholar
  24. Jensen BV (2006) Cardiotoxic consequences of anthracycline-containing therapy in patients with breast cancer. Semin Oncol 33(suppl 8):15–21CrossRefGoogle Scholar
  25. Kuroi K, Bando H, Saji S, Toi M (2003) Protracted administration of weekly docetaxel in metastatic breast cancer. Oncol Rep 10:1479–1484PubMedGoogle Scholar
  26. Lombardi D, Crivellari D, Scuderi C, Magri MD, Spazzapan S, Sorio R, DiLauro V, Scalone S, Veronesi A (2004) Long-term, weekly one-hour infusion of paclitaxel in patients with metastatic breast cancer: a phase II monoinstitutional study. Tumori 90:285–288PubMedGoogle Scholar
  27. Maisano R, Mare M, Zavattieri M, Caristi N, Mesiti M, Scisca C, Latorre F (2003) Is weekly docetaxel an active and gentle chemotherapy in the treatment of metastatic breast cancer? Anticancer Res 23:1923–1926PubMedGoogle Scholar
  28. Mey U, Gorschluter M, Ziske C, Kleinschmidt R, Glasmacher A, Schmidt-Wolf IGH (2003) Weekly docetaxel in patients with pretreated metastatic breast cancer: a phase II trial. Anticancer Drugs 14:233–238PubMedCrossRefGoogle Scholar
  29. Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, Shenkier T, Cella D, Davidson NE (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357:2666–2676PubMedCrossRefGoogle Scholar
  30. Nabholtz JM, Thuerlimann B, Bezwoda WR, Melnychuk D, Dounma J, Vandenberg TA, Rapoport B, Rosso R, Trillet Lenoir V, Drbal J, Aapro MA, Alaki M, Murawsky M, Allesandro R (1997) Docetaxel vs mitomycin plus vinblastine in anthracycline-resistant metastatic breast cancer. Oncology (Williston Park) 11(Suppl 8):25–30Google Scholar
  31. Nabholtz JM, Senn HJ, Bezwoda W, Melnychuk D, Deschênes L, Douma J, Vandenberg TA, Rapoport B, Rosso R, Trillet-Lenoir V, Drbal J, Molino A, Nortier JW, Richel DJ, Nagykalnai T, Siedlecki P, Wilking N, Genot JY, Hupperets PS, Pannuti F, Skarlos D, Tomiak EM, Murawsky M, Alakl M, Aapro M (1999) Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. 304 Study Group. J Clin Oncol 17:1413–1424PubMedGoogle Scholar
  32. O’Shaughnessy J, Miles D, Vukelja S, Moiseyenko V, Ayoub JP, Cervantes G, Fumoleau P, Jones S, Lui WY, Mauriac L, Twelves C, Hazel GV, Verma S, Leonard R (2002) Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. J Clin Oncol 20:2812–2823PubMedCrossRefGoogle Scholar
  33. Perez EA, Vogel CL, Irwin DH, Kirshner JJ, Patel R (2001) Multicenter phase II trial of weekly paclitaxel in women with metastatic breast cancer. J Clin Oncol 19:4216–4223PubMedGoogle Scholar
  34. Ramos M, Gonzalez-Ageitos A, Amenedo M, Gonzalez-quintas A, Gamzo JL, Togores P, Losada G, Almanza C, Romero C, Gomez-martin C (2003) Weekly docetaxel as second-line therapy for patients with advanced breast cancer resistant to previous anthracycline treatment. J Chemother 15:192–197PubMedGoogle Scholar
  35. Sato K, Inoue K, Saito T, Kai T, Mihara H, Okubo K, Koh J, Mochizuki H, Tabei T (2003) Multicenter phase II trial of weekly paclitaxel for advanced or metastatic breast cancer: the Saitama Breast Cancer Clinical Study Group (SBCCSG-01). Jpn J Clin Oncol 33:371–376PubMedCrossRefGoogle Scholar
  36. Sawada N, Ishikawa T, Fukase Y et al (1998) Induction of thymidine phosphorylase activity and enhancement of capecitabine efficacy by Taxol/Taxotere in human cancer xenografts. Clin Cancer Res 4:1013–1019PubMedGoogle Scholar
  37. Seidman AD, Hudis CA, Albanel J, Tong W, Tepler I, Currie V, Moynaha ME, Theodoulou M, Gollub M, Baselga J, Norton L (1998) Dose-dense therapy with weekly 1-hour paclitaxel infusions in the treatment of metastatic breast cancer. J Clin Oncol 16:3353–3361PubMedGoogle Scholar
  38. Sjostrom J, Blomqvist C, Mouridsen H, Pluzanska A, Ottosson Lonn S, Bengtsson NO, Ostenstad B, Mjaaland I, Palm Sjovall M, Wist E, Valvere V, Anderson H, Bergh J (1999) Docetaxel compared with sequential methotrexate and 5-fluorouracil in patients with advanced breast cancer after anthracycline failure: a randomised phase III study with crossover on progression by the Scandinavian Breast Group. Eur J Cancer 35:1194–1201PubMedCrossRefGoogle Scholar
  39. Sparano JA, Makhson AN, Semiglazov VF, Tjulandin SA, Balashova OI, Bondarenko IN, Bogdanova NV, Manikhas GM, Oliynychenko GP, Chatikhine VA, Zhuang SH, Xiu L, Yuan ZL, Rackoff WR (2009) Pegylated liposomal doxorubicin plus docetaxel significantly improves time to progression without additive cardiotoxicity compared with docetaxel monotherapy in patients with advanced breast cancer previously treated with neoadjuvant-adjuvant anthracycline therapy: results from a randomized phase III study. J Clin Oncol 27:4522–4529PubMedCrossRefGoogle Scholar
  40. Trudeau ME, Eisenhauer EA, Higgins BP, Letendre F, Lofters WS, Norris BD, Vandenberg TA, Delorme F, Muldal AM (1996) Docetaxel in patients with metastatic breast cancer: a phase II study of the National Cancer Institute of Canada-Clinical Trials Group. J Clin Oncol 14:422–428PubMedGoogle Scholar
  41. Verma S, Maraninchi D, O’Shaughnessy J, Jamieson C, Jones S, Martin M, Mckendrick J, Miles D, Twelves C, Hornberger J (2005) Capecitabine plus docetaxel combination therapy. Cancer 103:2455–2465PubMedCrossRefGoogle Scholar
  42. Verma S, Dent S, Chow BJ, Rayson D, Safra T (2008) Metastatic breast cancer: the role of pegylated liposomal doxorubicin after conventional anthracyclines. Cancer Treat Rev 34:391–406PubMedCrossRefGoogle Scholar
  43. Von Hoff DD, Layard MW, Basa P, Davis HL Jr, Von Hoff AL, Rozencweig M, Muggia FM (1979) Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med 91:710–717Google Scholar
  44. Wist EA, Sommer HH, Ostenstad B, Risberg T, Fjaestad K (2004) Weekly one-hour paclitaxel as first-line chemotherapy for metastatic breast cancer. Acta Oncol 43:11–14PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Department of Clinical PharmacyShanghai Tenth People’s Hospital, Tongji University School of MedicineShanghaiChina
  2. 2.Department of OncologyShanghai Tenth People’s Hospital, Tongji University School of MedicineShanghaiChina

Personalised recommendations