Skip to main content

Advertisement

SpringerLink
Log in

Platinum salts in advanced breast cancer: a systematic review and meta-analysis of randomized clinical trials

  • Review
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Background

The interest in platinum salts in breast cancer (BC) therapy has been recently renewed as inhibition of DNA damage response may enhance the effects of DNA-damaging agents in BC tumors with high genomic instability. The present systematic review and meta-analysis of randomized trials were performed to assess the efficacy and safety of therapy with platinum salts in patients with locally advanced or metastatic (hereinafter advanced) BC.

Methods

We searched PubMed, EMBASE, SCOPUS, Web of Science, the Cochrane Library, and CINAHL for phase II/III clinical trials that assessed efficacy of platinum-based therapy in patients with advanced BC. Pooled estimates of overall response rate (RR), median progression-free survival (PFS) and overall survival (OS) were computed using random or fixed effects models.

Results

Data on 4625 patients from 23 phase II and III trials (11 with cisplatin, 11 with carboplatin, and 1 with either agents respectively) were analyzed. Estimates for RR, PFS, and OS were obtained from 23, 13, and 15 studies, respectively. Although at the cost of significantly increased fatigue, hematological and gastrointestinal toxicity, compared with non-platinum schemas, cisplatin, and carboplatin prolonged OS (HR 0.91; 95 % CI 0.83–1.00, p = 0.04), PFS (HR 0.84; 95 % CI 0.73–0.97, p = 0.01), and RR (HR 1.27; 95 % CI 1.03–1.57, p = 0.03).

Conclusions

Despite some limitations of the studies examined, including partial information on hormonal receptor and HER2 status, the use of platinum salts significantly prolonged OS, and PFS of patients with advanced BC with no unexpected toxicity.

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
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. McCutcheon S, Cardoso F (2015) Challenges in optimizing care in advanced BC patients: results of an international survey linked to the ABC1 consensus conference. Breast 24:623–629

    Article  PubMed  Google Scholar 

  2. Petrelli F, Coinu A, Borgonovo K, Cabiddu M, Ghilardi M, Lonati V, Barni S (2014) The value of platinum agents as neoadjuvant chemotherapy in triple-negative breast cancers: a systematic review and meta-analysis. Breast Cancer Res Treat 144:223–232

    Article  CAS  PubMed  Google Scholar 

  3. Guan X, Ma F, Fan Y, Zhu W, Hong R, Xu B (2015) Platinum-based chemotherapy in triple-negative breast cancer: a systematic review and meta-analysis of randomized-controlled trials. Anticancer Drugs 26:894–901

    Article  CAS  PubMed  Google Scholar 

  4. Carrick S, Ghersi D, Wilcken N, Simes J (2004) Platinum containing regimens for metastatic breast cancer. Cochrane Database Syst Rev. doi:10.1002/14651858.CD003374.pub3

  5. Hu XC, Zhang J, Xu BH et al (2015) Cisplatin plus gemcitabine versus paclitaxel plus gemcitabine as first-line therapy for metastatic triple-negative breast cancer (CBCSG006): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol 16:436–446. doi:10.1016/S1470-2045(15)70064-1

    Article  CAS  PubMed  Google Scholar 

  6. von Minckwitz G, Schneeweiss A, Loibl S et al (2014) Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol 15:747–756

    Article  Google Scholar 

  7. Ando M, Yamauchi H, Aogi K, Shimizu S, Iwata H, Masuda N, Yamamoto N, Inoue K, Ohono S, Kuroi K, Hamano T, Sukigara T, Fujiwara Y (2014) Randomized phase II study of weekly paclitaxel with and without carboplatin followed by cyclophosphamide/epirubicin/5-fluorouracil as neoadjuvant chemotherapy for stage II/IIIA breast cancer without HER2 overexpression. Breast Cancer Res Treat 145:401–409

    Article  CAS  PubMed  Google Scholar 

  8. Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, Tausch C, Seo JH, Tsai YF, Ratnayake J, McNally V, Ross G, Cortés J (2013) Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 24:2278–2284

    Article  CAS  PubMed  Google Scholar 

  9. Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J, Breast Cancer International Research Group (2011) Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 365:1273–1283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart LA, PRISMA-P Group (2015) Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 349:g7647

    Article  PubMed  Google Scholar 

  11. Higgins JP, Altman DG, Gotzsche PC et al (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343:d5928

    Article  PubMed  PubMed Central  Google Scholar 

  12. https://www.iki.internovi.com/kurve

  13. Deeks JJ, Higgins JP, Altman DG (2011) Analysing data and undertaking meta-analyses. In: Higgins JP, Green S (eds) Cochrane handbook for systematic reviews of interventions. Version 5.1.0. The Cochrane Collaboration, Chichester

    Google Scholar 

  14. Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101

    Article  CAS  PubMed  Google Scholar 

  15. Egger M, Davey Smith G, Schneider M et al (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Creagan ET, Green SJ, Ahmann DL, Ingle JN, Edmonson JH, Marschke RF (1984) A phase III trial comparing the combination cyclophosphamide, adriamycin, cisplatin with cyclophosphamide, 5-fluorouracil, prednisone in patients with advanced breast cancer. J Clin Oncol 2:1260–1265

    CAS  PubMed  Google Scholar 

  17. Cocconi G, Bisagni G, Bacchi M, Boni C, Bartolucci R, Ceci G, Colozza MA, De Lisi V, Lottici R, Mosconi AM, Passalacqua R, Tonato M (1991) Cisplatin and etoposide as first-line chemotherapy for metastatic breast carcinoma: a prospective randomized trial of the Italian Oncology Group for Clinical Research. J Clin Oncol 9:664–669

    CAS  PubMed  Google Scholar 

  18. Cocconi G, Bisagni G, Ceci G, Di Blasio B, De Lisi V, Passalacqua R, Zadro A, Boni C, Morandi P, Savoldi L (1999) Three new active cisplatin-containing combinations in the neoadjuvant treatment of locally advanced and locally recurrent breast carcinoma: a randomized phase II trial. Breast Cancer Res Treat 56:125–132

    Article  CAS  PubMed  Google Scholar 

  19. Costanza ME, Weiss RB, Henderson IC, Norton L, Berry DA, Cirrincione C, Winer E, Wood WC, Frei E, McIntyre OR, Schilsky RL (1999) Safety and efficacy of using a single agent or a phase II agent before instituting standard combination chemotherapy in previously untreated metastatic breast cancer patients: report of a randomized study—Cancer and Leukemia Group B 8642. J Clin Oncol 17:1397–1406

    CAS  PubMed  Google Scholar 

  20. Eisen T, Smith IE, Johnston S, Ellis PA, Prendiville J, Seymour MT, Walsh G, Ashley S (1998) Randomized phase II trial of infusional fluorouracil, epirubicin, and cyclophosphamide versus infusional fluorouracil, epirubicin, and cisplatin in patients with advanced breast cancer. J Clin Oncol 16:1350–1357

    CAS  PubMed  Google Scholar 

  21. Icli F, Akbulut H, Uner A et al (2005) Cisplatin plus oral etoposide (EoP) combination is more effective than paclitaxel in patients with advanced breast cancer pretreated with anthracyclines: a randomized phase III trial of Turkish Oncology Group. Br J Cancer 92:639–644. doi:10.1038/sj.bjc.6602388

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Berruti A, Bitossi R, Gorzegno G et al (2002) Time to progression in metastatic breast cancer patients treated with epirubicin is not improved by the addition of either cisplatin or lonidamine: final results of a phase III study with a factorial design. J Clin Oncol 20:4150–4159. doi:10.1200/JCO.2002.08.012

    Article  CAS  PubMed  Google Scholar 

  23. Fountzilas G, Kalofonos HP, Dafni U et al (2004) Paclitaxel and epirubicin versus paclitaxel and carboplatin as first-line chemotherapy in patients with advanced breast cancer: a phase III study conducted by the Hellenic Cooperative Oncology Group. Ann Oncol 15:1517–1526. doi:10.1093/annonc/mdh395

    Article  CAS  PubMed  Google Scholar 

  24. Nielsen D, Dombernowsky P, Larsen SK, Hansen OP, Skovsgaard T (2000) Epirubicin or epirubicin and cisplatin as first-line therapy in advanced breast cancer. A phase III study. Cancer Chemother Pharmacol 46:459–466

    Article  CAS  PubMed  Google Scholar 

  25. Fountzilas G, Dafni U, Dimopoulos MA et al (2009) A randomized phase III study comparing three anthracycline-free taxane-based regimens, as first line chemotherapy, in metastatic breast cancer. Breast Cancer Res Treat 115:87–99. doi:10.1007/s10549-008-0047-9

    Article  CAS  PubMed  Google Scholar 

  26. Robert N, Leyland-Jones B, Asmar L et al (2006) Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer. J Clin Oncol 24:2786–2792. doi:10.1200/JCO.2005.04.1764

    Article  CAS  PubMed  Google Scholar 

  27. Frasci G, D’Aiuto G, Comella P, Thomas R, Botti G, Di Bonito M, De Rosa V, Iodice G, Rubulotta MR, Comella G (2006) Weekly cisplatin, epirubicin, and paclitaxel with granulocyte colony-stimulating factor support vs triweekly epirubicin and paclitaxel in locally advanced breast cancer: final analysis of a sicog phase III study. Br J Cancer 95:1005–1012. doi:10.1038/sj.bjc.6603395

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Fan Y, Xu BH, Yuan P, Ma F, Wang JY, Ding XY, Zhang P, Li Q, Cai RG (2013) Docetaxel-cisplatin might be superior to docetaxel–capecitabine in the first-line treatment of metastatic triple-negative breast cancer. Ann Oncol 24:1219–1225. doi:10.1093/annonc/mds603

    Article  CAS  PubMed  Google Scholar 

  29. Xu B, Jiang Z, Kim SB, Yu S, Feng J, Malzyner A, del Giglio A, Chung HC, Shen LJ, Pen DLK (2011) Biweekly gemcitabine–paclitaxel, gemcitabine–carboplatin or gemcitabine–cisplatin as first-line treatment in metastatic breast cancer after anthracycline failure: a phase II randomized selection trial. Breast Cancer 18:203–212. doi:10.1007/s12282-011-0260-y

    Article  PubMed  Google Scholar 

  30. Stemmler HJ, diGioia D, Freier W, Tessen HW, Gitsch G, Jonat W, Brugger W, Kettner E, Abenhardt W, Tesch H, Hurtz HJ, Rosel S, Brudler O, Heinemann V (2011) Randomised phase II trial of gemcitabine plus vinorelbine vs gemcitabine plus cisplatin vs gemcitabine plus capecitabine in patients with pretreated metastatic breast cancer. Br J Cancer 104:1071–1078. doi:10.1038/bjc.2011.86

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Valero V, Forbes J, Pegram MD et al (2011) Multicenter phase III randomized trial comparing docetaxel and trastuzumab with docetaxel, carboplatin, and trastuzumab as first-line chemotherapy for patients with HER2-gene-amplified metastatic breast cancer (BCIRG 007 study): two highly active therapeutic regimens. J Clin Oncol 29:149–156. doi:10.1200/JCO.2010.28.6450

    Article  CAS  PubMed  Google Scholar 

  32. Huang L, Chen S, Yang W et al (2015) Efficacy and safety analysis of trastuzumab and paclitaxel based regimen plus carboplatin or epirubicin as neoadjuvant therapy for clinical stage II–III, HER2-positive breast cancer patients: a phase 2, open-label, multicenter, randomized trial. Oncotarget 6:18683–18692

    Article  PubMed  PubMed Central  Google Scholar 

  33. Carey LA, Rugo HS, Marcom PK et al (2012) TBCRC 001: randomized phase II study of cetuximab in combination with carboplatin in stage IV triple-negative breast cancer. J Clin Oncol 30:2615–2623. doi:10.1200/JCO.2010.34.5579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Alba E, Chacon JI, Lluch A et al (2012) A randomized phase II trial of platinum salts in basal-like breast cancer patients in the neoadjuvant setting. Results from the GEICAM/2006-03, multicenter study. Breast Cancer Res Treat 136:487–493. doi:10.1007/s10549-012-2100-y

    Article  CAS  PubMed  Google Scholar 

  35. Dear RF, McGeechan K, Jenkins MC, Barratt A, Tattersall MH, Wilcken N (2013) Combination versus sequential single agent chemotherapy for metastatic breast cancer. Cochrane Database Syst Rev. doi:10.1002/14651858.CD008792.pub2

Download references

Author information

Authors and Affiliations

  1. Medical Oncology Unit, ASST Bergamo Ovest, Piazzale Ospedale 1, 24047, Treviglio, BG, Italy

    Fausto Petrelli & Sandro Barni

  2. Department of Medical Oncology, IRCCS A.O.U. S.Martino-IST, Genoa, Italy

    Giacomo Bregni

  3. University of Milan, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    Filippo de Braud

  4. Division of Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    Serena Di Cosimo

Authors
  1. Fausto Petrelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sandro Barni
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Giacomo Bregni
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Filippo de Braud
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Serena Di Cosimo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fausto Petrelli.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Petrelli, F., Barni, S., Bregni, G. et al. Platinum salts in advanced breast cancer: a systematic review and meta-analysis of randomized clinical trials. Breast Cancer Res Treat 160, 425–437 (2016). https://doi.org/10.1007/s10549-016-4025-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-016-4025-3

Keywords

Search

Navigation