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Single Agent Versus Combination Chemotherapy For Metastatic Breast Cancer.

S. Carrick, Sharon Parker, C. Thornton, D. Ghersi, J. Simes, N. Wilcken
Published 2009 · Medicine

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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.
This paper references
10.1002/14651858.CD002747
Chemotherapy alone versus endocrine therapy alone for metastatic breast cancer.
N. Wilcken (2003)
Phase II clinical trial of isophosphamide (NSC-109724) in patients with advances breast cancer.
D. Ahmann (1974)
Toxic deaths - Nil reported
HT Mouridsen (1977)
10.1200/JCO.2004.22.14_SUPPL.621
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.
C. Moinpour (2004)
Cancer Incidence, Mortality and Prevalence Worldwide. GLOBOCAN, Version 2.0. IARC CancerBase No. 5
Ferlay 2002 J Ferlay (2002)
10.3816/CBC.2004.N.030
Survival benefit with capecitabine/docetaxel versus docetaxel alone: analysis of therapy in a randomized phase III trial.
D. Miles (2004)
10.1200/JCO.2007.12.6557
Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment.
E. Thomas (2007)
10.1002/MPO.2950160505
VP-16 + adriamycin vs. adriamycin alone in advanced adenocarcinoma of the breast, phase II, a randomized trial: a Southwest Oncology Group Study.
C. Vaughn (1988)
10.1002/1097-0142(197611)38:5<1882::AID-CNCR2820380503>3.0.CO;2-H
Combination chemotherapy for metastatic breast carcinoma. Prospective comparison of multiple drug therapy with L‐phenylalanine mustard
G. Canellos (1976)
10.1002/14651858.CD006165.pub3
Interventions for latent autoimmune diabetes (LADA) in adults.
S. Brophy (2011)
Listed in review (2005) in ongoing studies. Excluded due to allowance of participants to have up to 6 treatment
C Jackisch (1999)
Continued) OR (CR + PR
E Heidemann (2002)
10.1016/S0959-8049(99)00122-7
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.
J. Sjöström (1999)
Continued) Risk of bias Item
H Joensuu (1998)
Continued) Incomplete outcome data addressed? All outcomes
M Stockler (2006)
10.1200/JCO.1987.5.12.1928
The effect on survival of initial chemotherapy in advanced breast cancer: polychemotherapy versus single drug.
D. Ahmann (1987)
10.1179/JOC.1997.9.6.442
Refractory breast cancer: a comparison of two different chemotherapy regimens.
M. Erkişi (1997)
10.1016/0277-5379(86)90075-1
Weekly adriamycin versus VAC in advanced breast cancer. A randomized trial.
S. Gundersen (1986)
10.1200/JCO.1998.16.12.3720
Combination chemotherapy versus single-agent therapy as first- and second-line treatment in metastatic breast cancer: a prospective randomized trial.
H. Joensuu (1998)
10.1016/S1470-2045(07)70041-4
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.
M. Martín (2007)
Continued) Toxicity - NE Toxic death
D Nielson (1990)
Continued) OR (CR+PR
H Tashiro (1994)
10.1097/00000421-198508000-00001
Randomized clinical trial of doxorubicin alone or combined with mitolactol in women with advanced breast cancer and prior chemotherapy exposure
J. Ingle (1985)
10.1007/s101470200037
Evidence for the use of chemotherapy in breast cancer
J. Nabholtz (2002)
10.1038/bjc.1993.74
Combination or mild single agent chemotherapy for advanced breast cancer? CMF vs epirubicin measuring quality of life.
S. C. Fraser (1993)
10.1200/JCO.2002.09.002
Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results.
J. O'Shaughnessy (2002)
Toxic death
RT Eagan (1976)
10.1038/sj.bjc.6600645
Docetaxel vs 5-fluorouracil plus vinorelbine in metastatic breast cancer after anthracycline therapy failure
J. Bonneterre (2002)
Randomised numbers not reported by group. Phase I only considered in this review Risk of bias Item
Hoogstraten (1976)
A phase 2 evaluation of 1-(2-chloroethyl)-3-(4- methylcyclohexyl)-1-nitrosourea (NSC 95441) in patients with advanced breast cancer.
D. Ahmann (1974)
Continued) Leukopenia
Venturino (2000)
10.1200/JCO.2003.10.086
Sequential single-agent chemotherapy for metastatic breast cancer: therapeutic nihilism or realism?
A. Seidman (2003)
Doxorubicin versus mitomycin versus doxorubicin plus mitomycin in advanced breast cancer: a randomized study.
M. Andersson (1986)
10.1016/S0033-0620(85)80003-7
Beta blockade during and after myocardial infarction: an overview of the randomized trials.
S. Yusuf (1985)
10.1186/1745-6215-8-16
Practical methods for incorporating summary time-to-event data into meta-analysis
J. Tierney (2007)
Continued) OR (CR+PR
B Ejlertsen (2004)
10.1200/JCO.1998.16.10.3439
Cytotoxic and hormonal treatment for metastatic breast cancer: a systematic review of published randomized trials involving 31,510 women.
R. Fossati (1998)
10.1007/s002800000178
Epirubicin or epirubicin and cisplatin as first-line therapy in advanced breast cancer. A phase III study
D. Nielsen (2000)
Current management of advanced breast cancer.
G. Hortobagyi (1996)
Continued) Incomplete outcome data addressed? All outcomes
J Bonneterre (2002)
Doxorubicin 45mg/m2 IV every 3/52 + Mitomycin 10 mg/m2 IV every 6/52 Outcomes
M Andersson (1986)
10.1634/THEONCOLOGIST.7-SUPPL_6-4
Treatment for anthracycline-pretreated metastatic breast cancer.
J. O'Shaughnessy (2002)
10.1634/THEONCOLOGIST.10-90003-20
Extending survival with chemotherapy in metastatic breast cancer.
J. O'Shaughnessy (2005)
Continued) 2)n = 90 Assessable no: (176) 2 in arm 1 did not receive treatment leaving: 1) n = 86 (median age
J Bonneterre (2002)
10.1200/JCO.2003.10.085
Combination chemotherapy for metastatic breast cancer: reaching for the cure.
B. Overmoyer (2003)
10.1200/JCO.2004.11.503
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).
B. Ejlertsen (2004)
10.1002/(SICI)1097-0258(19981230)17:24<2815::AID-SIM110>3.0.CO;2-8
Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints.
M. K. Parmar (1998)
10.1093/OXFORDJOURNALS.ANNONC.A057748
Epirubicin or epirubicin and vindesine in advanced breast cancer. A phase III study.
D. Nielsen (1990)
Continued) Risk of bias Item
J O’Shaughnessy (2001)
Continued) Not ITT Risk of bias Item
J Ingle (1985)
10.1038/sj.bjc.6602388
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
F. Içli (2005)
Characteristics of included studies [ordered by study
(1974)
10.1200/JCO.2000.18.12.2385
Phase III comparative study of vinorelbine combined with doxorubicin versus doxorubicin alone in disseminated metastatic/recurrent breast cancer: National Cancer Institute of Canada Clinical Trials Group Study MA8.
B. Norris (2000)
Doxorubicin 60 mg/m2 day 1 every 3/52 2) Doxorubicin 40 mg/m2 day 1 + Vinorelbine 20 mg/m2 on days
B Norris (2000)
10.1053/CTRV.1999.0161
Systematic reviews of chemotherapy and endocrine therapy in metastatic breast cancer.
M. Stockler (2000)
10.1002/1097-0142(197607)38:1<13::AID-CNCR2820380104>3.0.CO;2-5
Combination chemotherapy and adriamycin in patients with advanced breast cancer. A Southwest Oncology Group study
B. Hoogstraten (1976)
Continued) Risk of bias Item
H Joensuu (1998)
Applications of dose intensity to problems in chemotherapy of breast and colorectal cancer.
W. Hryniuk (1987)
Dynamic hormonal chemotherapy in advanced metastatic breast carcinoma.
L. Tj (1986)
10.1634/THEONCOLOGIST.9-SUPPL_2-24
Docetaxel and paclitaxel in the treatment of breast cancer: a review of clinical experience.
J. Crown (2004)
10.1053/j.seminoncol.2005.07.030
Goals of Treatment for Patients With Metastatic Breast Cancer.
I. Smith (2006)
10.1097/00000421-198912000-00003
Randomized Trial of Doxorubicin Alone or Combined with Vincristine and Mitomycin C in Women with Metastatic Breast Cancer
J. Ingle (1989)
10.1038/bjc.1993.62
A daily diary for quality of life measurement in advanced breast cancer trials.
S. C. Fraser (1993)
10.1093/ANNONC/MDF101
Second and subsequent lines of chemotherapy for metastatic breast cancer: what did we learn in the last two decades?
F. Cardoso (2002)
10.1002/1097-0142(19901001)66:7<1621::AID-CNCR2820660729>3.0.CO;2-G
Survival of premenopausal women with metastatic breast cancer. Long‐term follow‐up of eastern cooperative group and cancer and leukemia group B studies
G. Falkson (1990)
Three pts with treatment deviations were excluded from toxicity tables but otherwise included in the arms they were randomised to. Nine and 8 patients respectively who discontinued treatment
CB Vaughn (1988)
Toxicity WHO 3-4 Nausea
J O’Shaughnessy (2002)
10.1093/ANNONC/MDF070
Is colorectal cancer screening by fecal occult blood feasible?
M. Crespi (2002)
Some information has been interpreted by a Japanese speaking person Abstract suggests 100% firstline but unclear in table of patient characteristics so excluded from firstline analysis
TB Takayama (2000)
10.1002/1097-0142(19850915)56:6<1320::AID-CNCR2820560617>3.0.CO;2-R
A comparative study of PALA, PALA plus 5‐FU, and 5‐FU in advanced breast cancer
G. Mann (1985)
Continued) QOL EORTC QLQ-C30
J Sjostrom (1999)
10.1634/THEONCOLOGIST.12-3-253
Achievements in systemic therapies in the pregenomic era in metastatic breast cancer.
M. Colozza (2007)
10.1023/A:1012281104865
Randomized, open-label, phase II trial of oral capecitabine (Xeloda) vs. a reference arm of intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) as first-line therapy for advanced/metastatic breast cancer.
J. Oshaughnessy (2001)
10.1016/0277-5379(83)90085-8
Adriamycin alone or combined with vincristine in the treatment of advanced breast cancer.
R. Steiner (1983)
A new search was conducted March 2008 and the review has undergone significant and accumulated change
This review was updated in August (2008)
10.1093/OXFORDJOURNALS.JJCO.A039708
A double blind comparative study of tegafur (FT) and UFT (a combination of Tegafur and uracil) in advanced breast cancer.
H. Tashiro (1994)
10.1200/JCO.2002.08.012
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.
A. Berruti (2002)
10.1200/JCO.2003.08.013
Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193).
G. Sledge (2003)
10.1200/JCO.2004.08.157
Randomized phase III trial of pegylated liposomal doxorubicin versus vinorelbine or mitomycin C plus vinblastine in women with taxane-refractory advanced breast cancer.
Alan M. Keller (2004)
Continued) 2) n = 89
E Heidemann (2004)
10.1016/S0140-6736(02)81227-2
CONTINUATION OF THE CASE OF CAROTID ANEURISM,: Successfully treated by tying the Artery above the Aneurismal Tumour
J. Lambert (1827)
10.1159/000225129
Evaluation of VP-16 and the combination of adriamycin and vincristine in advanced breast cancer.
R. Eagan (1976)
Doxorubicin 60 mg/m2 day 1 every 3/52 2) Doxorubicin 40 mg/m2 day 1 + Vinorelbine 20 mg/m2 on days
B Norris (2000)
10.1200/JCO.1999.17.8.2355
Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast cancer.
J. Bishop (1999)
10.1093/ANNONC/MDF306
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.
E. Heidemann (2002)
10.1002/14651858.cd003372.pub2
Single agent versus combination chemotherapy for metastatic breast cancer.
S. Carrick (2005)
10.1023/A:1006350602108
Is salvage chemotherapy for metastatic breast cancer always effective and well tolerated? A phase II randomized trial of vinorelbine versus 5-fluorouracil plus leucovorin versus combination of mitoxantrone, 5-fluorouracil plus leucovorin
A. Venturino (2004)
10.1016/S0960-9776(07)70236-9
P176 Cardiac safety guidelines for the adjuvant use of trastuzumab (Herceptin®) in HER2-positive early breast cancer
M. Ewer (2007)
10.1200/JCO.2007.25.18_SUPPL.1031
A randomized trial of capecitabine (C) given intermittently (IC) rather than continuously (CC) compared to classical CMF as first-line chemotherapy for advanced breast cancer (ABC)
M. Stockler (2007)
Continued) Randomised no: 1) n = 49 2) n = 50 Interventions
RD Rubens (1975)
10.1002/1097-0142(197906)43:6<2215::AID-CNCR2820430609>3.0.CO;2-3
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
G. Falkson (1979)
10.1016/0014-2964(80)90037-7
Single-drug vs combination cytotoxic chemotherapy in advanced breast cancer: a randomized study.
J. Carmo-Pereira (1980)
Controlled evaluation of adriamycin (NSC-123127) in patients with disseminated breast cancer.
D. Ahmann (1974)
10.1038/bjc.1975.284
Chemotherapy of advanced breast cancer: a controlled randomized trial of cyclophosphamide versus a four-drug combination.
R. Rubens (1975)
Continued) 2) 9 mths Median TTP 1) 2mths
A Venturino (2000)
10.1002/1097-0142(197806)41:6<2073::AID-CNCR2820410601>3.0.CO;2-7
Combination chemotherapy for metastatic breast cancer. Comparison of multiple drug therapy with 5‐fluorouracil, cytoxan and prednisone with adriamycin or adrenalectomy
T. Nemoto (1978)
Continued) Toxicity (3-4) Nausea and vomiting
KS Albain (2004)
Randomised numbers not available. Sequential. Toxicity and response data is provided for all sequences
T. violations Nemoto (1978)
10.1200/JCO.1999.17.5.1413
Prospective Randomized Trial of Docetaxel Versus Mitomycin Plus Vinblastine in Patients With Metastatic Breast Cancer Progressing Despite Previous Anthracycline-Containing Chemotherapy
J. M. Nabholtz (1999)



This paper is referenced by
10.18632/oncotarget.23426
Gemcitabine-based chemotherapy as a viable option for treatment of advanced breast cancer patients: a meta-analysis and literature review
Zhibo Xie (2018)
10.1007/s00280-010-1390-1
The efficacy and safety of gemcitabine plus paclitaxel combination first-line therapy for Japanese patients with metastatic breast cancer including triple-negative phenotype
K. Aogi (2010)
10.1007/s10549-017-4336-z
Antitumor activity and safety profile of weekly carboplatin plus paclitaxel in metastatic breast cancer: a ten-year, monocentric, retrospective study
C. Vernieri (2017)
10.3109/1061186X.2012.729215
Targeting combinations of liposomal drugs to both tumor vasculature cells and tumor cells for the treatment of HER2-positive breast cancer
J. I. Hare (2013)
10.1007/S13556-013-0004-8
Combination of Cytotoxic Drugs for Patients with HER2-Negative Metastatic Breast Cancer
C. Angelis (2013)
10.1016/j.addr.2015.10.022
Recent advances of cocktail chemotherapy by combination drug delivery systems.
Q. Hu (2016)
10.1093/jnci/djn433
Nonhormonal systemic therapy for advanced breast cancer: do the math!
P. Bedard (2008)
10.1016/j.molonc.2012.01.009
Moving molecular targeted drug therapy towards personalized medicine: Issues related to clinical trial design
J. Verweij (2012)
10.6004/jnccn.2020.0016
Breast Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology.
William J. Gradishar (2020)
Podozyten-spezifischer Murine Double Minute (MDM) 2 Knockout führt zu fokal segmentaler Glomerulosklerose
Hauke A. Bruns (2017)
10.1159/000262808
The Role of Combination Chemotherapy in the Treatment of Patients with Metastatic Breast Cancer
J. Huober (2009)
Comparative Study of Vinorelbine Monotherapy Versus Vinorelbine-Cisplatin in Metastatic Breast Cancer Patients Previously Treated with Anthracyclines and Taxanes
A. M. Adel (2013)
10.1007/s00280-009-1141-3
Usefulness of chemotherapy beyond the second line for metastatic breast cancer: a therapeutic challenge
E. Vauléon (2009)
10.1007/s00280-012-1983-y
Vinorelbine and capecitabine in anthracycline- and/or taxane-pretreated metastatic breast cancer: sequential or combinational?
J. Zhang (2012)
10.1016/j.jconrel.2019.04.020
Immunological consequences of chemotherapy: Single drugs, combination therapies and nanoparticle-based treatments.
A. Pusuluri (2019)
10.1053/J.SEMBD.2007.10.009
Challenges in the Management of Metastatic Breast Cancer
H. Sanati (2007)
10.1016/j.jconrel.2017.08.016
A hyaluronic acid conjugate engineered to synergistically and sequentially deliver gemcitabine and doxorubicin to treat triple negative breast cancer
Douglas R. Vogus (2017)
10.1016/j.breast.2013.07.040
The first two lines of chemotherapy for anthracycline-naive metastatic breast cancer: a comparative study of the efficacy of anthracyclines and non-anthracyclines.
Wei-wu Chen (2013)
10.1186/bcr3475
A genome-wide association study of chemotherapy-induced alopecia in breast cancer patients
Suyoun Chung (2013)
10.1007/978-1-4020-5867-7_19
Therapeutic aspect of metastatic breast cancer: chemotherapy
R. F. Leonard (2007)
10.1007/978-3-642-30189-6_33
Mammakarzinomrezidiv und metastasiertes Mammakarzinom
E. Kantelhardt (2013)
10.1016/J.BREAST.2006.12.005
Quantification of circulating tumour cells for the monitoring of adjuvant therapy in breast cancer: an increase in cell number at completion of therapy is a predictor of early relapse.
K. Lobodasch (2007)
10.1007/s13277-015-3221-9
Neoadjuvant chemotherapy of breast cancer with pirarubicin versus epirubicin in combination with cyclophosphamide and docetaxel
X. Gu (2015)
Breast Cancer Guidelines Expert Panel
H. Wildiers (2013)
10.1200/JCO.2007.15.8485
Phase III study of gemcitabine plus docetaxel compared with capecitabine plus docetaxel for anthracycline-pretreated patients with metastatic breast cancer.
S. Chan (2009)
10.1055/a-0646-4630
Interdisciplinary Screening, Diagnosis, Therapy and Follow-up of Breast Cancer. Guideline of the DGGG and the DKG (S3-Level, AWMF Registry Number 032/045OL, December 2017) – Part 2 with Recommendations for the Therapy of Primary, Recurrent and Advanced Breast Cancer
A. Woeckel (2018)
10.1007/978-2-8178-0076-9_20
Stratégies thérapeutiques des cancers du sein métastatiques : RH+ HER2−. Hormonothérapies, chimiothérapies (monochimiothérapies séquentielles ou polychimiothérapies concomitantes ?), antiangiogéniques
M. Debled (2010)
10.11606/ISSN.2176-7262.V40I2P213-222
CONCEITOS DE CINÉTICA TUMORAL APLICADOS À QUIMIOTERAPIA PARA O CÂNCER DE MAMA
A. H. Macchetti (2007)
10.1016/j.clbc.2017.05.006
RESILIENCE: Phase III Randomized, Double‐Blind Trial Comparing Sorafenib With Capecitabine Versus Placebo With Capecitabine in Locally Advanced or Metastatic HER2‐Negative Breast Cancer
J. Baselga (2017)
Synthesis and Processing of Nanocapsules of Single and Multiple Cancer Drugs for Targeted Cancer Therapy
M. Hasan (2019)
10.20381/RUOR-3562
A Meta-analytic Approach for Testing Evolutionary Hypotheses of Acquired Resistance in Metastatic Cancer
K. Bhardwaj (2014)
10.1016/S1548-5315(11)70005-5
First-line treatment of metastatic breast cancer: current strategies and emerging systemic therapies
A. Brufsky (2010)
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