Taxane containing regimens for the adjuvant treatment of early breast cancer
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
The objective of this review is to compare taxane containing adjuvant chemotherapy regimens with adjuvant regimens not containing a taxane in the management of women with operable breast cancer. Regimens include:
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Regimen A plus taxane vs Regimen A
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Regimen A plus taxane vs Regimen B
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Regimen A with taxane substituted for one or more drugs vs Regimen A
Background
Breast cancer is a major cause of morbidity and mortality in women worldwide. In 2000, there were over 1 million cases of breast cancer worldwide, and over 350,000 deaths, corresponding to an age adjusted incidence rate of 35.6 per 100,000 women annually, and an age‐adjusted mortality rate of 12.5 per 100,000 women annually (Globocan 2000). Approximately 30 percent of women diagnosed and treated for early breast cancer will go on to die of this disease.
Polychemotherapy improves survival in pre and post menopausal women with early breast cancer (EBCTCG 2001).
The taxanes are amongst the most active agents in metastatic breast cancer (Bishop 1999; Chan 1999) and are widely used (Crown 2002) . Their incorporation into adjuvant regimens for early breast cancer is increasing in regions where they are licensed and available for this indication. However, mature studies of taxanes for early breast cancer are few, and there is uncertainty the optimal role of these agents outside clinical trials. There is a need to review the results of trials of adjuvant taxanes in early breast cancer, to identify patient subgroups who may benefit from this treatment, and to identify important unanswered questions for future study.
Objectives
The objective of this review is to compare taxane containing adjuvant chemotherapy regimens with adjuvant regimens not containing a taxane in the management of women with operable breast cancer. Regimens include:
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Regimen A plus taxane vs Regimen A
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Regimen A plus taxane vs Regimen B
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Regimen A with taxane substituted for one or more drugs vs Regimen A
Methods
Criteria for considering studies for this review
Types of studies
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Properly randomised controlled trials as defined in the Cochrane Reviewer's Handbook, excluding quasi‐randomised trials.
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Studies published in abstract form only will be included.
Types of participants
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Women with operable (early) breast cancer receiving adjuvant chemotherapy
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Women receiving neo‐adjuvant chemotherapy will be excluded
Types of interventions
Intervention Group: Any chemotherapy regimen containing a taxane
Comparator: Any chemotherapy regimen not containing a taxane
i.e. a). Taxane containing regimen versus the same regimen without a taxane
b). Any taxane containing regimen versus any regimen without a taxane
c). Any taxane containing regimen versus the same regimen with another drug or drugs substituted for the taxane
Endocrine therapy may be used if the same treatment has been given to all groups
Taxanes include paclitaxel and docetaxel (see Table 1)
| Generic name | Other names |
| paclitaxel | anzatax, taxol |
| docetaxel | taxotere |
Types of outcome measures
Primary outcome measure:
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Overall survival
Secondary outcome measures:
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Progression free survival (time to disease progression and/or death)
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Toxicity (as defined by WHO/NCIC criteria)
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Quality of life (validated or trial‐specific instrumants)
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Treatment‐related death
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Pharmacoeconomics
For the purpose of this review the following outcome definitions apply:
1. Overall survival (OS): time from date randomised to date of death (any cause).
2. Progression‐free survival (PFS) [also referred to as time to progression (TTP)]: time from date randomised to date of progression or death (any cause). May also be referred to as progression‐free survival.
Search methods for identification of studies
The specialised register maintained by the Secretariat of the Cochrane Breast Cancer Group will be searched. Details of the search strategy applied by the Group to create the register, and the procedure used to code references, are described in the Group's module on the Cochrane Library. Studies coded as "early breast cancer" and "chemotherapy" on the specialised register will be extracted for consideration. In addition, the reference lists of other, related literature reviews and presentations will be searched.
Abstract authors will be contacted for updated information and information on anticipated publication dates. Researchers working in this area will be contacted for identification of additional trials.
A copy of the full article for each reference reporting a potentially eligible trial will be obtained.
Data collection and analysis
A. Assessing trials for eligibility
The Selection Criteria will be applied to each trial.
1. Any exclusions from a review of a potentially eligible trial will be justified in the final report.
2. Trial publications will be used to assess the trial's eligibility with the results section (and any other area where results may appear) masked.
3. If a trial has not been published, information will be obtained from the trial protocol or next best available resource.
4. Where necessary, and possible, additional information will be sought from the principal investigator of the trial concerned.
B. Quality Control and Peer Review
Two reviewers will independently assess each potentially eligible trial for:
1. Inclusion in the review (according to the eligibility criteria)
2. Quality
A third reviewer will resolve any discrepancies regarding eligibility or quality.
C. Analysis
The most complete dataset feasible will be assembled.
1. Results of eligible studies will be statistically synthesised (meta‐analysis) if appropriate and possible.
2. All analyses will be by intention to treat.
3. Time to event analyses will be conducted (if possible) for time to death (survival). They will be approximated by either:
‐ Analysing for different follow‐up periods.
‐ Calculating a weighted average of median survival duration across studies.
These analyses may only be possible with individual patient data and the actual analyses from summary data will depend on how each trial has defined the outcomes and reported the data. It may be necessary to extract data from published survival curves if it is not available in the main text or tables. Time to event data may be combined, if appropriate and data is available (Parmar 1998).
4. A decision regarding if and how to combine quality of life outcomes will be made depending on if and how this information is collected in each trial.
5. Whether a fixed or a random effects model is used will depend on the nature of the question under investigation. A fixed effects model will be used for the primary analyses whenever possible.
6. Heterogeneity between trial results will be tested where appropriate.
7. If there are a sufficient number of trials of adequate size it may be possible to conduct sub‐group analyses. Ability to conduct sub‐group analyses will also depend on whether or not the required information is recorded in the trial publications. Possible sub‐groups include:
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Status of nodal involvement (LN positive versus LN negative, four or more LN involved versus three or fewer LN involved).
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Menopausal status (pre / peri / post)
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Hormone receptor status (ER positive versus ER negative or unknown).
8. Sensitivity analyses (e.g. including trials of borderline quality) and subgroup analyses will be performed if appropriate and possible.
D. Assessing the Methodological Quality of the Included Studies
Each study will be reviewed according to its design and by how the study was conducted to assess any bias. The checklist for quality of randomised controlled trials will include:
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concealment of the allocation sequence
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generation of the allocation sequence
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comparability between groups at the baseline
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inclusion of all randomised participants in the analysis
Allocation concealment is regarded as particularly important in protecting against bias and will be graded using the Cochrane approach as follows:
Grade A ‐ Clearly adequate concealment
Grade B ‐ Possibly adequate
Grade C ‐ Clearly inadequate concealment
Where there is uncertainty authors will be contacted for clarification.
| Generic name | Other names |
| paclitaxel | anzatax, taxol |
| docetaxel | taxotere |
