Single-drug vs combination cytotoxic chemotherapy in advanced breast cancer: A randomized study

Carmo-Pereira, J.; Costa, Francisco; Henriques, E.

doi:10.1016/0014-2964(80)90037-7

Cited by 16 publications

(6 citation statements)

References 7 publications

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“…Thus, the outcome of this prospective randomized trial confirm the results found in retrospective analyses by Smalley [7], Hoogstraten [8], Rubens [9] and Ahmann [10]. However, Carmo-Pereira [11] using fluorouracil, Canellos [12] using phenylalanin mustard, and Mouridsen [13] using cyclophosphamide as monotherapy got better OAS in the combination treatment. Chlebowski et al [14,15] using a sequence of cyclophosphamide, then fluorouracil, then methotrexate, then prednisolone found increased survival times in patients with liver involvement when receiving combination chemotherapy up-front.…”

Section: Resultssupporting

confidence: 78%

First-Line Monochemotherapy with Mitoxantroneversus Combination with Fluorouracil, Epirubicin and Cyclophosphamide in High-Risk Metastatic Breast Cancer: A Prospective Randomized Multicenter Clinical Trial

Heidemann¹,

Souchon²,

Stöger³

et al. 2000

Oncol Res Treat

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Background: The dogma that patients with high-risk, advanced breast cancer urgently need combination chemotherapy has never been proven in a prospectively randomized study. Patients and Methods: 412 patients with metastatic breast cancer requiring chemotherapy were stratified into a low-risk and a high-risk group. They then were randomized to be treated with monotherapy mitoxantrone (N) or combination chemotherapy. The high-risk group (n = 260), which is reported here separately, got N 12 mg/m² or fluorouracil 500 mg/m² plus epirubicin 50 mg/m² plus cyclophosphamide 500 mg/m² (FEC) every 3 weeks. Results: There was no significant difference between the two groups in terms of response rates or overall survival. There was, however, a significantly better score for gain from treatment and quality of life (modified Brunner’s score) in the single-agent N group. Conclusion: There is no evidence that high-risk, advanced cancer patients need combination chemotherapy. In order to maintain their quality of life, it may be wise to treat them with a single agent such as N.

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Section: Resultssupporting

confidence: 78%

First-Line Monochemotherapy with Mitoxantroneversus Combination with Fluorouracil, Epirubicin and Cyclophosphamide in High-Risk Metastatic Breast Cancer: A Prospective Randomized Multicenter Clinical Trial

Heidemann¹,

Souchon²,

Stöger³

et al. 2000

Oncol Res Treat

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“…Four randomised studies were identi ed, three including survival analysis (100 -103). The studies compared Cyclo vs CMF-Vinbl (103); Melph vs CMF (100); Cyclo vs MFVP (102) and 5-FU vs CMFVP (101). The objective response rate was statistically signicantly better in three (100 -102) of the four studies for the combined regimens (pB 0.01 to pB 0.001).…”

Section: Non -Anthracycline Chemotherapy: Single -Agents ×S Polychemomentioning

confidence: 95%

A Systematic Overview of Chemotherapy Effects in Breast Cancer

Bergh¹,

Jönsson²,

Glimelius³

et al. 2001

Acta Oncologica

150

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A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scientific literature are described separately (Acta Oncol 2001; 40: 155-65). This synthesis of the literature on chemotherapy for breast cancer is based on 233 randomised studies, 9 meta-analysis of randomised studies, a population-based cohort study and 18 overviews/retrospective analyses including a total of 155,243 patients. The conclusions reached can be summarised into the following points: Adjuvant treatment-- There is solid scientific support from randomised studies that adjuvant polychemotherapy at 10 years will result in an absolute mortality reduction for patients younger than 50 years by 12% for node positive (34% relative mortality reduction corresponding to an estimated median survival prolongation of several years) and 6% for node negative patients. For women aged 50 to 69 years, the corresponding figures for node positive and node negative patients are 6% and 2%, respectively (approximately 11% relative mortality reduction). Anthracycline-containing combinations result in an absolute survival benefit at five years of 3%, compared with non-anthracycline based polychemotherapy. There are indications that the taxane paclitaxel may further improve the survival compared with anthracyclines. However, the limited data preclude conclusions for the routine care. The addition of tamoxifen to chemotherapy further enhances the survival benefit for receptor positive subgroups. The roles of more dose-intensive regimens, including high-dose therapy with stem cell support, are presently studied in randomised investigations. The data presented so far are conflicting but they do not in general support high-dose therapy. Quality of life, based on analyses of randomised studies, demonstrate that adjuvant polychemotherapy has an initial detrimental effect, but long-term follow-up of treated patients demonstrates no impairment of quality of life compared with untreated patients. Polychemotherapy in standard doses should be offered to premenopausal node positive patients, and the corresponding postmenopausal group with a receptor-negative breast cancer and to node negative patients with high risk factors. Polychemotherapy should be combined with tamoxifen to all patients with receptor-positive tumours. Due to a need of more knowledge in this field, patients should be included in investigational protocols. Locally advanced breast cancer-- Based on current knowledge, treatment of patients with locally advanced breast cancer should include neoadjuvant/preoperative polychemotherapy since there is evidence from controlled studies that such therapy will statistically significantly increase the number of patients who can be offered breast-conserving surgery. Indirect comparisons also demonstrate survival improvements, but the scientific support is equivocal. Metastatic breast cancer-- The median survival for patients with metastatic disea...

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“…In general, a paradigm has been established for cytotoxic combinations, in which an increased response rate is often observed along with increased toxicities. [1][2][3][4] Combining two different chemotherapeutic agents with distinct mechanisms of action is also used in an effort to minimize the evolution of the cancer and to attenuate development of drug resistance. 5 As a result, combinations of cytotoxic agents became the standard of care for many advanced solid tumors.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of anticancer drug combinations: a meta-analysis of randomized trials with a focus on immunotherapeutics and gene-targeted compounds

et al. 2020

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Hundreds of trials are being conducted to evaluate combination of newer targeted drugs as well as immunotherapy. Our aim was to compare efficacy and safety of combination versus single non-cytotoxic anticancer agents. We searched PubMed (01/01/2001 to 03/06/2018) (and, for immunotherapy, ASCO and ESMO abstracts (2016 through March 2018)) for randomized clinical trials that compared a single non-cytotoxic agent (targeted, hormonal, or immunotherapy) versus a combination with another noncytotoxic partner. Efficacy and safety endpoints were evaluated in a meta-analysis using a linear mixedeffects model (guidelines per PRISMA Report).We included 95 randomized comparisons (single vs. combination non-cytotoxic therapies) (59.4%, phase II; 41.6%, phase III trials) (29,175 patients (solid tumors)). Combinations most frequently included a hormonal agent and a targeted small molecule (23%). Compared to single non-cytotoxic agents, adding another non-cytotoxic drug increased response rate (odds ratio [OR]=1.61, 95%CI 1.40-1.84)and prolonged progression-free survival (hazard ratio [HR] =0.75, 95%CI 0.69-0.81)and overall survival (HR=0.87, 95%CI 0.81-0.94) (all p<0.001), which was most pronounced for the association between immunotherapy combinations and longer survival. Combinations also significantlyincreased the risk of high-grade toxicities (OR=2.42, 95%CI 1.98-2.97) (most notably for immunotherapy and small molecule inhibitors) and mortality at least possibly therapy related (OR: 1.33, 95%CI 1.15-1.53) (both p<0.001) (absolute mortality = 0.90% (single agent) versus 1.31% (combinations)) compared to single agents. In conclusion, combinations of non-cytotoxic drugs versus monotherapy in randomized cancer clinical trials attenuated safety, but increased efficacy, with the balance tilting in favor of combination therapy, based on the prolongation in survival.

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Single-drug vs combination cytotoxic chemotherapy in advanced breast cancer: A randomized study

Cited by 16 publications

References 7 publications

First-Line Monochemotherapy with Mitoxantroneversus Combination with Fluorouracil, Epirubicin and Cyclophosphamide in High-Risk Metastatic Breast Cancer: A Prospective Randomized Multicenter Clinical Trial

First-Line Monochemotherapy with Mitoxantroneversus Combination with Fluorouracil, Epirubicin and Cyclophosphamide in High-Risk Metastatic Breast Cancer: A Prospective Randomized Multicenter Clinical Trial

A Systematic Overview of Chemotherapy Effects in Breast Cancer

Efficacy and safety of anticancer drug combinations: a meta-analysis of randomized trials with a focus on immunotherapeutics and gene-targeted compounds

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