Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2009 Apr 15;2009(2):CD003372.
doi: 10.1002/14651858.CD003372.pub3.

Single agent versus combination chemotherapy for metastatic breast cancer

Sue Carrick  1 , Sharon Parker, Charlene E Thornton, Davina Ghersi, John Simes, Nicholas Wilcken
Affiliations
Meta-Analysis

Single agent versus combination chemotherapy for metastatic breast cancer

Sue Carrick et al. Cochrane Database Syst Rev. .

Abstract

Background: Combination chemotherapy regimens are frequently favoured over single agents for the treatment of metastatic breast cancer, in an attempt to achieve superior tumour response rates. It is not known however whether giving more intensive chemotherapy regimens results in better health outcomes, when both survival and toxicity are considered, and whether better response rates and rates of progression free survival actually translate to better overall survival.

Objectives: To compare single agent with combination chemotherapy for the treatment of metastatic breast cancer.

Search strategy: We searched the Cochrane Breast Cancer Group Specialised Register November 2008. Handsearching of recent conference proceedings was also undertaken.

Selection criteria: Randomised trials of single agent chemotherapy compared to combination therapy in metastatic breast cancer.

Data collection and analysis: Two authors independently assessed trials for eligibility and quality, and extracted data. Hazard ratios were derived for reported time-to-event outcomes.Response rates were analysed as dichotomous variables. Toxicity and quality of life data were extracted where present.

Main results: Forty three eligible trials (48 comparisons) were identified. These included 9742 women, 55% of whom were receiving first-line treatment for metastatic disease. For overall survival there was a statistically significant difference in favour of the combination regimens with no heterogeneity (HR 0.88, 95% CI 0.83-0.93, p<0.00001). Results were very similar when trials of first-line treatment were analysed, and for analyses where the single agent was also included in the combination regimen. Combination regimens showed a statistically significant advantage for survival over single agent taxane (HR 0.82; 95% CI 0.75-0.89, p<0.00001), but not anthracycline (HR 0.94.86-1.02, p=0.15).Combination regimens were also associated with significantly better time to progression (HR 0.78, 95% CI 0.74 - 0.82, p<0.00001) and response (RR 1.29, 95% CI 1.14 -1.45, p<0.0001) although heterogeneity was statistically significant in both instances and probably due to clinical diversity of the participants and interventions.Women receiving combination regimens experienced a statistically significant detrimental effect on white cell count, increased alopecia and nausea and vomiting.

Authors' conclusions: Combination chemotherapy regimens show a statistically significant advantage for survival, tumor response and time to progression in women with metastatic breast cancer but they also produce more toxicity. An unresolved question is whether combination regimens are more effective than single agents given sequentially.

PubMed Disclaimer

Conflict of interest statement

Nil conflict of interest

Figures

1
1
Quorum flow chart
2
2
Summary of included trials with extractable data Q1
3
3
Summary of included trials with extractable data Q2
4
4
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
5
5
Summary of regimens Q1
6
6
Summary of regimens Q2
1.1
1.1. Analysis
Comparison 1: Overall survival, Outcome 1: Overall survival ‐ randomised patients ‐ all trials
1.2
1.2. Analysis
Comparison 1: Overall survival, Outcome 2: Overall survival ‐ randomised patients ‐ first line
1.3
1.3. Analysis
Comparison 1: Overall survival, Outcome 3: Overall survival ‐ Question 1 ‐ Regimen A versus A + other ‐ randomised patients
1.4
1.4. Analysis
Comparison 1: Overall survival, Outcome 4: Overall survival ‐ Question 2 ‐ Regimen A versus Regimen C ‐ randomised patients
1.5
1.5. Analysis
Comparison 1: Overall survival, Outcome 5: Overall survival ‐ single agent taxane versus all combination
1.6
1.6. Analysis
Comparison 1: Overall survival, Outcome 6: Overall survival ‐ single agent anthracycline versus all combinations
2.1
2.1. Analysis
Comparison 2: Time to progression, Outcome 1: Time to progression ‐ randomised patients ‐ all trials
2.2
2.2. Analysis
Comparison 2: Time to progression, Outcome 2: Time to progression ‐ randomised patients ‐ first line
2.3
2.3. Analysis
Comparison 2: Time to progression, Outcome 3: Time to progression ‐ Question 1 ‐ Regimen A versus A + other ‐ randomised patients
2.4
2.4. Analysis
Comparison 2: Time to progression, Outcome 4: Time to progression ‐ Question 2 ‐ Regimen A versus Regimen C ‐ randomised patients
2.5
2.5. Analysis
Comparison 2: Time to progression, Outcome 5: Time to progression ‐ single agent taxane versus all combinations
2.6
2.6. Analysis
Comparison 2: Time to progression, Outcome 6: Time to progression ‐ Single agent anthracycline versus all combinations
3.1
3.1. Analysis
Comparison 3: Overall response, Outcome 1: Overall response ‐ assessable patients‐all trials
3.2
3.2. Analysis
Comparison 3: Overall response, Outcome 2: Overall response ‐ assessable patients first line
3.3
3.3. Analysis
Comparison 3: Overall response, Outcome 3: Overall response ‐ Question 1 ‐ Regimen A versus A + other ‐ assessable patients
3.4
3.4. Analysis
Comparison 3: Overall response, Outcome 4: Overall response ‐ Question 2 ‐ Regimen A versus Regimen C ‐ assessable patients
3.5
3.5. Analysis
Comparison 3: Overall response, Outcome 5: Overall response ‐ single agent taxane versus all combinations
3.6
3.6. Analysis
Comparison 3: Overall response, Outcome 6: Overall response ‐ single agent anthracycline versus all combinations
4.1
4.1. Analysis
Comparison 4: Toxicity ‐ Nausea and vomiting, Outcome 1: Nausea and vomiting ‐ asssessable patients ‐ all trials
4.2
4.2. Analysis
Comparison 4: Toxicity ‐ Nausea and vomiting, Outcome 2: Nausea and vomiting ‐ Question 1 ‐ Regimen A versus A + other ‐ assessable patients
4.3
4.3. Analysis
Comparison 4: Toxicity ‐ Nausea and vomiting, Outcome 3: Nausea and vomiting ‐ Question 2 ‐ Regimen A versus Regimen C ‐ assessable patients
5.1
5.1. Analysis
Comparison 5: Toxicity ‐ White cell count, Outcome 1: WCC ‐ assessable patients ‐ all trials
5.2
5.2. Analysis
Comparison 5: Toxicity ‐ White cell count, Outcome 2: WCC ‐ Question 1 ‐ Regimen A versus A + other ‐ assessable patients
5.3
5.3. Analysis
Comparison 5: Toxicity ‐ White cell count, Outcome 3: WCC ‐ Question 2 ‐ Regimen A versus Regimen C ‐ assessable patients
6.1
6.1. Analysis
Comparison 6: Toxicity ‐ Alopecia, Outcome 1: Alopecia ‐ assessable patients ‐ all trials
6.2
6.2. Analysis
Comparison 6: Toxicity ‐ Alopecia, Outcome 2: Alopecia ‐ Question 1 ‐ Regimen A versus A + other ‐ assessable patients
6.3
6.3. Analysis
Comparison 6: Toxicity ‐ Alopecia, Outcome 3: Alopecia ‐ Question 2 ‐ Regimen A versus Regimen C ‐assessable patients
7.1
7.1. Analysis
Comparison 7: Treatment related death, Outcome 1: Treatment related death ‐ assessable patients ‐ all trials
See this image and copyright information in PMC

Update of

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

References to studies included in this review

Ahmann DL 1974(1) {published data only}
    1. Ahmann DL, Bisel HF, Hahn RG. A phase 2 evaluation of 1 (2 chloroethyl) 3 (4 methylcyclohexyl) 1 nitrosourea (NSC 95441) in. Cancer Research 1974;34:27-30. - PubMed
    1. Ahmann DL, Schaid DJ, Bisel HF, Hahn RG, Edmonson JH, Ingle JN. The effect on survival of initial chemotherapy in advanced breast cancer: polychemotherapy. Journal Clinical Oncology 1987;5:1928-32. - PubMed
Ahmann DL 1974(2) {published data only}
    1. Ahmann DL, Bisel HF, Hahn RG. Phase II clinical trial of isophosphamide (NSC-109724) in patients with advances breast cancer. Cancer Chemotherapy Reports - Part 1 1974;58(6):861-5. - PubMed
    1. Ahmann DL, Schaid DJ, Bisel HF, Hahn RG, Edmonson JH, Ingle JN. The effect on survival of initial chemotherapy in advanced breast cancer: polychemotherapy. J Clin Oncol 1987;5:1928-1932. - PubMed
Ahmann DL 1974(3) {published data only}
    1. Ahmann DL, Bisel HF, Eagan RT, Edmonson JH, Hahn RG. Controlled evaluation of adriamycin (NSC-123127) in patients with disseminated breast cancer. Cancer Chemotherapy Reports 1974;58:877-82. - PubMed
    1. Ahmann DL, Schaid DJ, Bisel HF, Hahn RG, Edmonson JH, Ingle JN. The effect on survival of initial chemotherapy in advanced breast cancer: polychemotherapy. Journal of Clinical Oncology 1987;5:1928-32. - PubMed
Albain KS 2004 {published data only}
    1. Albain KS, Nag S, Calderillo-Ruiz G, Jordaan JP, Llombart A, Pluzanska A, Pawlicki M, Melemed AS, O'Shaughnessy J, Teyes JM. Global Phase III study of gemcitabine plus paclitaxel versus paclitaxel as frontline therapy for metastatic breast cancer.. In: Proceedings of the American Society of Clinical Oncolcogy. 2004:Abstract 510.
    1. Moinpour, C, Wu, J, Donaldson, G, Liepa, A, Melemed, A, Oshaughnessy, J, Rappold, E, Albain, K Moinpour, C, Wu, J, Donaldson, G, Liepa, A, Melemed, A, Oshaughnessy, J, Rappold, E, Albain, K. Gemcitabine plus paclitaxel (GT) versus paclitaxel (T) as first-line treatment for anthracycline pre-treated metastatic breast cancer (MBC): Quality of life (QoL) and pain palliation results from the global phase III study. In: ASCO. Vol. 22. 2004.
Andersson M 1986 {published data only}
    1. Andersson M, Daugaard S, Maase H, Mouridsen HT. Doxorubicin versus mitomycin versus doxorubicin plus mitomycin in advanced breast cancer: a randomized study. Cancer Treat Rep 1986;70(10):1181-6. - PubMed
ANZBCTG 2001 {unpublished data only}
    1. Australia and New Zealand Breast Cancer Trials Group. Phase III randomised trial to evaluate single agent (MTZ) versus combination (CMFp) cytotoxic therapy in advanced breast cancer. Annual Scientific Report 2001.
    1. Simes, RJ, Gebski, V, Coates, AS, Forbes, J, Harvey, V, Van Hazel, G, Tattersall, MHN, Abdi, E, Brigham, B. Quality of life (QOL) with single agent mitozantrone (MTZ) or combination chemotherapy (CMFP) for advanced breast cancer: a randomised trial. Proceedings of the American Society of Clinical Oncology 1994;13:73.
Berruti D 2002 {published data only}
    1. Berruti D 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. Journal of Clinical Oncology 15-10-2002;20(20):4150-59. - PubMed
Bishop J 1999 {published data only}
    1. Bishop J 1999. Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast cancer. Journal of Clinical Oncology 1999;17(8):2355-64. - PubMed
Bonneterre J 2002 {published data only}
    1. Bonneterre J 2002. Docetaxel vs 5-fluorouracil plus vinorelbine in metastatic breast cancer after anthracycline therapy failure. British Journal of Cancer 18-11-2002;87(11):1210-15. - PMC - PubMed
Canellos GP 1976 {published data only}
    1. Canellos GP, Pocock SJ, Taylor SG, Sears ME, Klaasen DJ, Band PR. Combination chemotherapy for metastatic breast carcinoma. Prospective comparison of. Cancer 1976;38:1882-6. - PubMed
Carmo‐Pereira 1980 {published data only}
    1. Carmo-Pereira J, Costa FO, Henriques E. Single-drug vs combination cytotoxic chemotherapy in advanced breast cancer: a randomized. European Journal of Cancer 1980;16(12):1621-5. - PubMed
Eagan RT 1976 {published data only}
    1. Eagan RT 1976. Evaluation of VP-16 and the combination of adriamycin and vincristine in advanced breast cancer. Oncology 1976;33:146-8. - PubMed
Ejlertsen B 2004 {published data only}
    1. Ejlertsen B, Mouridsen HT, Langkjer ST, Andersen J, Sjostrom J, Kjaer M. Phase III study of intravenous vinorelbine in combination with epirubicin versus epirubicin alone in patients with advanced breast cancer: A Scandinavian Breast Group Trial (SBG9403). Journal of Clincal Oncology 2004;27:2313-20. - PubMed
    1. Ejlertsen B. Phase III randomised study of epirubicin/vinorelbine vs epirubicin alone for advanced breast cancer. PDQ 1996.
Erkisi M 1997 {published data only}
    1. Erkisi M, Bilkay BC, Seyrek E, Hazar B, Burgut R. Refractory breast cancer: a comparison of two different chemotherapy regimens. Journal Chemotherapy 1997;9:442-5. - PubMed
Falkson G 1990 {published data only}
    1. Falkson G, Falkson HC, Glidewell O, Weinberg V, Leone L, Holland JF. Improved remission rates and remission duration in young women with metastatic breast cancer following combined oophorectomy and chemotherapy. A study by cancer and leukemia group B. Cancer 1979;43:2215-22. - PubMed
    1. Falkson G 1990. Survival of premenopausal women with metastatic breast cancer. Long-term follow-up of Eastern Cooperative Group and Cancer and Leukemia Group B studies. Cancer 1990;66(7):1621-9. - PubMed
Fraser S 1993 {published data only}
    1. Fraser SC, Ramirez AJ, Ebbs SR, Fallowfield LJ, Dobbs HJ, Richards MA, Bates T, Baum M. A daily diary for quality of life measurement in advanced breast cancer trials. British Journal of Cancer 1993;67(2):341-6. - PMC - PubMed
    1. Fraser SC Dobbs HJ, Ebbs SR, Fallowfield LJ, Bates T, Baum M. Combination or mild single agent chemotherapy for advanced breast cancer? CMF vs. British Journal of Cancer 1993;67(2):402-6. - PMC - PubMed
French Epi (A) 1991 {published data only}
    1. French Epirubicin Study Group. A prospective randomized trial comparing epirubicin monochemotherapy to two fluorouracil, cyclophosphamide, and epirubicin regimens differing in epirubicin dose in advanced breast cancer patients. The French Epirubicin Study Group [see comments]. Journal of Clinical Oncology 1991;9(2):305-12. - PubMed
French Epi (B) 1991 {published data only}
    1. French Epirubicin Study Group. A prospective randomized trial comparing epirubicin monochemotherapy to two fluorouracil, cyclophosphamide, and epirubicin regimens differing in epirubicin dose in advanced breast cancer patients. The French Epirubicin Study Group [see comments]. Journal of Clinical Oncology 1991;9(2):305-12. - PubMed
GEICAM 2007 {published data only}
    1. Miguel Martín, Amparo Ruiz, Monserrat Muñoz, Ana Balil, Jesús García-Mata, Lourdes Calvo, Eva Carrasco, Esther Mahillo, Antonio Casado, José Ángel García-Saenz, M José Escudero, Vicente Guillem, Carlos Jara, Nuria Ribelles, Fernando Salas, Celia Soto, Flavia Morales-Vasquez, César A Rodríguez, Encarna Adrover, José Ramón Mel. Gemcitabine plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer previously treated with anthracyclines and taxanes: final results of the phase III Spanish Breast Cancer Research Group (GEICAM) trial. The Lancet 2007;8:219-225. - PubMed
Gundersen S 1986 {published data only}
    1. Gundersen S, Kvinnsland S, Klepp O, Kvaloy S, Lund E, Host H. Weekly adriamycin versus VAC in advanced breast cancer. A randomized trial. European Journal of Cancer & Clinical Oncology 1986;22(12):1431-4. - PubMed
Heidemann E 2002 {published data only}
    1. Heidemann EStoeger et al. Is first-line single-agent mitoxantrone in the treatment of high-risk metastatic breast cancer patients as effective as combination chemotherapy? No difference in survival but higher quality of life were found in a multicenter randomized trial. Annals of Oncology 2002;13(11):1717-29. - PubMed
Heidemann E 2004 {unpublished data only}
    1. Else Heidemann, Norbert Holländer, Gunter von Minckwitz, Rainer Souchon, Michael R Clemens, Martina Mahlke, Brigitte Eggeling, Manfred Schulze, Anton Scharl, Axel Hefti, Peter F Tauber, Martin Schumacher, Manfred Kaufmann. Mitoxantrone (M) versus Mitoxantrone plus Docetaxel (MDoc) as First-Line Therapy for Patients with High-Risk Metastatic Breast Cancer: Results of a Multicenter Randomized Trial Mitoxantrone (M) versus Mitoxantrone plus Docetaxel (MDoc) as First-Line Therapy for Patients with High-Risk Metastatic Breast Cancer: Results of a Multicenter Randomized Trial First-Line Therapy for Patients with High-Risk Metastatic Breast Cancer: Results of a Multicenter Randomized Trial. Unpublished manuscript 2004.
Hoogstraten B(A)1976 {published data only}
    1. Hoogstraten B, George SL, Samal B, Rivkin SE, Costanzi JJ, Bonnet JD, Thigpen T, Braine H. Combination chemotherapy and adriamycin in patients with advanced breast cancer. A. Cancer 1976;38:13-20. - PubMed
Hoogstraten B(B)1976 {published data only}
    1. Hoogstraten B, George SL, Samal B, Rivkin SE, Costanzi JJ, Bonnet JD, Thigpen T, Braine H. Combination chemotherapy and adriamycin in patients with advanced breast cancer. A. Cancer 1976;38:13-20. - PubMed
Icli F 2005 {published data only}
    1. Icli, F, Akbulut, H, Uner, A, Bulent, Y, Altinbas, M, Baltali, E, Komurcu, S, Erkisi, M, Demirkazik, A, Cay Senler, F. Paclitaxel (T) vs cisplatin + VP-16 (EP) in metastatic breast cancer patients treated with anthracyclines: A phase III randomized study, Turkish Oncology Group.. Annals of Oncology 2002;13:47.
    1. Icli, F Akbulut, H Uner, A Baltali, E Altinbas, M Coskun, S Komurcu, S Erkisi, M Demirkazik, A Cay Senler, F Sencan, O Buyukcelik, A Boruban, C Onue, H Zengin, NSak, SD. Paclitaxel (T) vs cisplatin + VP-16 (EP) in metastatic breast cancer patients treated with anthracyclinesCisplatin plus oral etoposide (EOP) combination is more effective than paclitaxel in patients with advacned breast cancer pretreated with anthracycline. British Journal of Cancer 2005;92:639. - PMC - PubMed
Ingle J 1985 {published data only}
    1. Ingle JN, Pfeifle DM, Green SJ, Kvols LK, Brunk SF, Reuter NF, Krook, JE, Laurie JA, . Randomized clinical trial of doxorubicin alone or combined with mitolactol in women with. American Journal of Clinical Oncology 1985;8(4):275-82. - PubMed
Ingle J 1989 {published data only}
    1. Ingle JN, Mailliard JA, Schaid DJ, Krook JE, Gerstner JB, Pfeifle DM, Marschke RF Jr, Long. Randomized trial of doxorubicin alone or combined with vincristine and mitomycin C in women with Metastatic Breast Cancer. American Journal of Clinical Oncology 1989;12(6):474-80. - PubMed
Joensuu H 1998 {published data only}
    1. Joensuu H, Holli K, Heikkinen M, Suonio E, Aro AR, Hietanen P, Huovinen, R. Combination chemotherapy versus single-agent therapy as first- and second-line treatment in. Journal of Clinical Oncology 1998;16(12):3720-30. - PubMed
Mouridsen HT 1977 {published data only}
    1. Mouridsen HT, Palshof T, Brahm M, Rahbek I. Evaluation of single-drug versus multiple-drug chemotherapy in the treatment of advanced. Cancer Treat Rep 1977;61(1):47-50. - PubMed
Nabholtz JM 1999 {published data only}
    1. Nabholtz JM, Senn HJ, Bezwoda WR, Melnychuk D, Deschenes L, Douma J, Vandenberg. Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with. Journal of Clinical Oncology 1999;17(5):1413-1424. - PubMed
Nielsen D 2000 {published data only}
    1. Nielsen D, Dombernowsky P, Larsen SK, Hansen OP, Skovsgaard T. Epirubicin or epirubicin and cisplatin as first-line therapy in advanced breast cancer. A phase III. Cancer Chemotherapy & Pharmacology 2000;46(6):459-66. - PubMed
Nielson D 1990 {published data only}
    1. Nielsen D, Dombernowsky P, Skovsgaard T, Jensen J, Andersen E, Engelholm SA, Hansen. Epirubicin or epirubicin and vindesine in advanced breast cancer. A phase III study. Annals of Oncology 1990;1(4):275-80. - PubMed
Norris B 2000 {published data only}
    1. Norris B, Pritchard KI, Myles JJ, Bennett K, Marlin S, Skillings J, Findlay B, Vandenberg T, Goss P, Latrielle J, Rudinskas L, Lofters W, Trudeau M, Osaba D, Rodgers A. Phase III comparative study of vinorelbine combined with doxorubicin versus doxorubicin alone in disseminated metastic/recurrent breast cancer: National cancer institute of Canada Clinical Trials Group Study MA8. Journal of Clinical Oncology 2000;18:2385-94. - PubMed
O'Shaughnessy J 2001 {published data only}
    1. O'Shaughnessy JA, Blum J, Moiseyenko V, Jones SE, Miles D, Bell D, Rosso R, Mauriac L, Osterwalder B, Burger HU, Laws S. Randomised, open-label, phase II trial of oral capecitabine vs. a reference arm of intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) as first-line therapy for advanced breast cancer. Annals of Oncology 2001;12:1247-54. - PubMed
O'Shaughnessy J 2002 {published data only}
    1. Miles D, Vukelja S, Moiseyenko V, Cervantes G, Mauriac l, Van Hazel G, Liu W, Ayoub JP, O'Shaughnesy JA. Survival benefit with capecitabine/docetaxel versus docetaxel alone: Analysis of therapy in a randomised Pahe III trial.. Clinical Breast Cancer 2004;Not stated:273-78. - PubMed
    1. O'Shaughnessy, J, Miles, D, Vukelja, S, Moiseyenko, V, Ayoub, JP, Cervantes, G, Fumoleau, P, Jones, S, Lui, WY, Mauriac, L, Twelves, C, Van Hazel, G, Verma, S, Leonard, R. Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. Journal of Clinical Oncology 2002;20(12):2812-23. - PubMed
Rubens RD 1975 {published data only}
    1. Rubens RD, Knight RK, Hayward JL. Chemotherapy of advanced breast cancer: a controlled randomised trial of cyclophosphamide. British Journal of Cancer 1975;32:730-36. - PMC - PubMed
Sjostrom J 1999 {published data only}
    1. Sjostrom J, Blomqvist C, Mouridsen H, Pluzanska A, Ottosson-Lonn S, Bengtsson NO, . Docetaxel compared with sequential methotrexate and 5-fluorouracil in patients with advanced. European Journal of Cancer 1999;35(8):1194-1201. - PubMed
Sledge G(A) 2003 {published data only}
    1. Sledge GW, Neuberg D, Bernardo P, Ingle J, Martino S, Rowinsky EK, Wood W. Phase III trials of Doxorubicin, Paclitaxel, and the Combination of Doxorubicin and Paclitaxel as Front-Line Chemotherapy for Metastatic Breast Cancer: An Intergroup Trial (EII93). Journal of Clinical Oncology 2003;21(4):588-92. - PubMed
Sledge G(B) 2003 {published data only}
    1. Sledge GW, Neuberg D, Bernardo P, Ingle J, Martino S, Rowinsky EK, Wood W. Phase III trials of Doxorubicin, Paclitaxel, and the Combination of Doxorubicin and Paclitaxel as Front-Line Chemotherapy for Metastatic Breast Cancer: An Intergroup Trial (EII93). Journal of Clinical Oncology 2003;21(4):588-92. - PubMed
Steiner R 1983 {published data only}
    1. Steiner R, Stewart JF, Cantwell BM, Minton MJ, Knight RK, Rubens RD. Adriamycin alone or combined with vincristine in the treatment of advanced breast cancer. European Journal of Cancer & Clinical Oncology 1983;19(11):1553-57. - PubMed
Stockler M 2006 {published data only}
    1. Stockler MR, Sourjina T, Harvey V, Francis P, Byrne M, Hazel G, Fitzharris B, Ackland S, Finch K, Lindsay D, Kato-Foong A, Paksec L, Gebski V, Simes RJ, Coates AS, Forbes J. A randomized trial of capecitabine given intermittently versus continuously versus classical CMF as first line chemotherapy for women with advanced breast cancer unsuited to more intensive treatment. In: Proceedings of the American Society of Clinical Oncolcogy. Vol. Abstract 6066. 2006.
Takayama T(A) 2000 {published data only}
    1. Takayama T, Nomura Y. [A double-blind randomized comparative study of oral 5-fluorouracil (5-FU), cyclophosphamide. Gan to Kagaku Ryoho [Japanese Journal of Cancer & Chemotherapy] 2000;27(1):73-80. - PubMed
Takayama T(B) 2000 {published data only}
    1. Takayama T, Nomura Y. [A double-blind randomized comparative study of oral 5-fluorouracil (5-FU), cyclophosphamide. Gan to Kagaku Ryoho [Japanese Journal of Cancer & Chemotherapy] 2000;27(1):73-80. - PubMed
Tashiro H 1994 {published data only}
    1. Tashiro H, Nomura Y, Ohsaki A. A double blind comparative study of tegafur (FT) and UFT (a combination of Tegafur and. Japanese Journal of Clinical Oncology 1994;24(4):212-17. - PubMed
Thomas E 2008 {published data only}
    1. Eva S Thomas, Henry L Gomez, Rubi K Li, Hyun-Cheol Chung, Luis E Fein, Valorie F Chan, Jacek Jassem, Xavier B Pivot, Judith V Klimovsky, Fernando Hurtado de Mendoza, Binghe Xu, Mario Campone, Guillermo L Lerzo, Ronald A Peck, Pralay Mukhopadhyay, Linda T Vahdat, and Henri H Roché. Ixabepilone Plus Capecitabine for Metastatic Breast Cancer Progressing After Anthracycline and Taxane Treatment Ixabepilone Plus Capecitabine for Metastatic Breast Cancer Progressing After Anthracycline and Taxane Treatment. Journal of Clinical Oncology 2008;25(33):5210-17. - PubMed
Vaughn CB 1988 {published data only}
    1. Vaughn CB, Green SJ, O'Bryan R, Reed M, Grozea PN, Fletcher WS, Green JB, Metch B, . VP-16 + adriamycin vs. adriamycin alone in advanced adenocarcinoma of the breast, phase II,. Medical & Pediatric Oncology 1988;16(5):312-19. - PubMed
Venturino A(A) 2000 {published data only}
    1. Venturino A, Comandini D, Simoni C, Merlini L, Naso C, Palumbo R, Fusco V, Porcile G, . Is salvage chemotherapy for metastatic breast cancer always effective and well tolerated? A. Breast Cancer Research & Treatment 2000;60(3):195-200. - PubMed
Venturino A (B) 2000 {published data only}
    1. Venturino A, Comandini D, Simoni C, Merlini L, Naso C, Palumbo R, Fusco V, Porcile G, . Is salvage chemotherapy for metastatic breast cancer always effective and well tolerated? A. Breast Cancer Research & Treatment 2000;60(3):195-200. - PubMed

References to studies excluded from this review

Anonymous 2002 {published data only}
    1. Anonymous. Combination versus mild single agent chemotherapy for advanced breast cancer. Trial register 2002.
Doroshow 1997 {unpublished data only}
    1. Doroshow. Phase II randomised study of paclitaxel versus paclitaxel and PSC 833 in advanced breast cancer (recurring less than 6 months since adjuvant or as second line for advanced disease). PDQ 1997.
Jackisch C 1999 {published data only}
    1. Jackisch. Single vs. tandem high-dose chemotherapy (HDC) for chemotherapy-sensitive metastatic breast cancer (MBC) - interim results from an ongoing phase-III trial. In: 22nd Annual San Antonio Breast Cancer Symposium. 57 edition. Vol. 57. 1999:66.
Kaufman PA 1998 {published data only}
    1. Kaufman, PA, Harris, R, Skillings, J, Walde, D, Hong, A, Verma, S, Guevin, R, Joseph, J, Finizio, M. Losoxantrone + Paclitaxel versus Paclitaxel alone as first line chemotherapy for metastatic breast cancer (MBC): Final results of a Phase III randomized trial. In: Proceedings of the American Society of Clinical Oncology. 1988.
Keller AM 2004 {published data only}
    1. Keller AM, Mennel RG, Georgoulias VA, Nabholtz JM, Erazo A, Lluch A, Vogel CL et al. Randomized phase III trial of pegylated liposomal doxorubicin versus vinorelbine or mitomycin C plus vinblastine in women with taxane-refractory advanced breast cancer. Journal of Clincal Oncology 2004;22(19):3893-3901. - PubMed
    1. Keller AM, Mennel RG, Nabholtz JM, Georgoulias VA, Emmanuel DJ, Tendler CL. Phase III trial of pegylated liposomal doxorubicin (Caelyx/Doxil) for the treatment of patients with advanced breast cancer who have failed a prior taxane containing chemotherapy. In: American Society of Clinical Oncology. Vol. Abstract 115. 2001.
Legha, 1979 {published data only}
    1. Legha SS, Buzdar AU, Hortobagyi GN, et al. Phase II study of hexamethylmelamine alone and in combination with mitomycin C and. Cancer Treat Rep 1979;63(11-12):2053-6. - PubMed
Liu T 1986 {published data only}
    1. Liu TJ. Dynamic hormonal chemotherapy in advanced metastatic breast carcinoma. Journal of the Formosan Medical Association 1986;85(4):376-83. - PubMed
Mann GB 1985 {published data only}
    1. Mann GB, Hortobagyi GN, Buzdar AU, Yap HY, Valdivieso M. A comparative study of PALA, PALA plus 5-FU, and 5-FU in advanced breast cancer. Cancer 1985;56(6):1320-24. - PubMed
Nemoto T. 1978 {published data only}
    1. Nemoto, T, Rosner, D, Diaz, R, Dao, T, Sponzo, R, Cunningham, T, Horton, J, Simon, R. Combination chemotherapy for metastatic breast cancer: comparison of multiple drug therapy with 5-fluorouracil, cytoxan and prednisone with adriamycin or adrenalectomy. Cancer 1978;41:2073-77. - PubMed
Perez E 2001 {published data only}
    1. Perez E. Phase III randomized study of paclitaxel with or without carboplatin as first line chemotherapy in elderly women with metastatic breast cancer. Trial register 2001.

References to ongoing studies

Burzynski 1999 {unpublished data only}
    1. Burzynski. Phase II randomised study of methotrexate with or without antineoplaston A10 capsules in women with advanced breast cancer. Trial register 1999.
Butler FO 2004 {published data only}
    1. Butler FO, Weitman L. A study of docetaxel monotherapy or DOXIL/CAAELYX and docetaxel in patients with advanced breast cancer.. PDQ 2004.
Heidemann E 2001 {published data only}
    1. Heidemann. Phase III randomized study of Mitoxantrone vs cyclophosphamide methotrexate/fluorouracil (CMF) chemotherapy for good-risk metastatic breast cancer. Trial register 2001.
Yunus F. 2000 {published data only}
    1. Yunus F. Phase III randomized study of paclitaxel with or without gemcitabine in women with. Trial register 2000.

Additional references

Cardoso 2002
    1. F Cardoso, A Di Leo, C Lohrisch, C Bernard, F Ferreira & MJ Piccart. Second and subsequent lines of chemotherapy for metastatic breast cancer: what did we learn in the last two decades? Annals of Oncology 2002;13:197-207. - PubMed
Colozza 2007
    1. Mariantonietta Colozza, Evandro de Azambuja, Nicola Personeni, Fabienne Lebrun, Martine J Piccart, Fatima Cardoso. Achievements in systemic therapies in the pregenomic era in metastatic breast cancer. Oncologist 2007;12:253-70. - PubMed
Crown 2004
    1. John Crown, Michael O'Leary, Wei-Seong Ooi. Docetaxel and paclitaxel in the treatment of breast cancer:a review of clinical experience. The Oncologist 2004;9(suppl 2):24-32. - PubMed
Ferlay 2002
    1. J Ferlay, F Bray, P Pisani, DM Parkin. Cancer Incidence, Mortality and Prevalence Worldwide. GLOBOCAN, Version 2.0. IARC CancerBase No. 5. 2002:http://www-dep.iarc.fr/globocan/globocan.html.
Fossati 1998
    1. Fossati R, Confalonierir C, Torri V, Ghislandi E, Penna A, Pistotti V, Tinazzi A, Liberati A. Cytotoxic and hormonal treatment for metastatic breast cancer: a systematic review of published randomized trials involving 31,510 women. Journal of Clinical Oncology 1998;16(10):3439-3460. - PubMed
Hortobagyi 1996
    1. Hortobagyi GN, Piccart-Gebhart MJ. Current Management of Advanced Breast Cancer.. Seminars in Oncology 1996;23(Suppl 11):1-5. - PubMed
Hryniuk 1987
    1. Hryniuk WA, Figueredo A, Goodyear M. Applications of dose intensity to problems in chemotherapy of breast and colorectal cancer.. Seminare in Oncology 1987;11(Suppl 4):3-11. - PubMed
Martín 2007
    1. Miguel Martín, Amparo Ruiz, Monserrat Muñoz, Ana Balil, Jesús García-Mata, Lourdes Calvo, Eva Carrasco, Esther Mahillo, Antonio Casado, José Ángel García-Saenz, M José Escudero, Vicente Guillem, Carlos Jara, Nuria Ribelles, Fernando Salas, Celia Soto, Flavia Morales-Vasquez, César A Rodríguez, Encarna Adrover, José Ramón Mel. Gemcitabine plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer previously treated with anthracyclines and taxanes: final results of the phase III Spanish Breast Cancer Research Group (GEICAM) trial. The Lancet 2007;8:219-225. - PubMed
Nabholtz 2002
    1. Jean-Marc Nabholtz, David Reese, Mary-Anne Lindsay. Evidence for the use of chemotherapy in breast cancer. International Journal of Clinical Oncology 2002;7:254-64. - PubMed
NBCC 2007
    1. National Breast Cancer Centre. Recommendations for use of Trastuzumab (Herceptin®) for the treatment of HER2-positive breast cancer. http://www.nbcc.org.au/resources/resource.php?code=HERG 2007.
O'Shaughnessy 2002
    1. Joyce O'Shaughnessy, Chris Twelves, Matti Aapro. Treatment for anthracycline-pretreated metastatic breast cancer. Oncologist 2002;7:4-12. - PubMed
O'Shaughnessy 2005
    1. Joyce O'Shaughnessy. Extending survival with chemotherapy in metastatic breast cancer. Oncologist 2005;10:20-9. - PubMed
Overmoyer 2003
    1. Beth Overmoyer. Combination chemotherapy for metastatic breast cancer: reaching for the cure. Journal of Clinical Oncology 2003;21(4):580-2. - PubMed
Parmar 1998
    1. Parmar MKB, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Statistics in Medicine 1998;17:2815-2834. - PubMed
Seidman 2003
    1. Andrew D Seidman. Sequential single-agent chemotherapy for metastatic breast cancer: therapeutic nihilism or realism. Journal of Clinical Oncology 2003;21(4):577-9. - PubMed
Smith 2006
    1. Smith I. Goals of treatment for patients with metastatic breast cancer. Seminars in Oncology 2006;32(S2):S2-5. - PubMed
Stockler 2000
    1. Stockler M, Wilcken NRC, Ghersi D, Simes RJ. Systematic reviews of chemotherapy and endocrine therapy in metastatic breast cancer.. Cancer Treatment Reviews 2000;26:151-168. - PubMed
Tierney 2007
    1. Jayne F Tierney, Lesley A Stewart, Davina Ghersi, Sarah Burdett, Matthew R Sydes. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 2007;8(16):http://www.trialsjournal.com/content/8/1/16. - PMC - PubMed
Wilcken 2003
    1. Wilcken N, Hornbuckle J, Ghersi D. Chemotherapy alone versus endocrine therapy alone for metastatic breast cancer.. Cochrane Database of Systematic Reviews 2003, Issue 2.. Art. No: CD002747. [DOI: 10.1002/14651858.CD002747] - DOI - PMC - PubMed
Yusuf 1985
    1. Yusuf S, Peto R, Lewis J, Collins R, Sleight P. Beta blockade during and after myocardial infarction: an overview of the randomized trials. Progress in Carciovascular Diseases 1985;27:335-371. - PubMed

References to other published versions of this review

Carrick 2005
    1. Carrick S, Parker S, Wilcken N, Ghersi D, Marzo M, Simes J. Single agent versus combination chemotherapy for metastatic breast cancer. Cochrane Database of Systematic Reviews 2005, Issue 2. Art. No: CD003372. [DOI: 10.1002/14651858.CD003372.pub2] - DOI - PubMed

MeSH terms

Substances