• Breast Cancer Disease Site Group. Trudeau M, Sinclair S, Clemons M, Shelley W. The role of taxanes in neoadjuvant chemotherapy for women with non-metastatic breast cancer [full report]. Toronto (ON): Cancer Care Ontario (CCO); 2004 Dec 10. 32 p. (Practice guideline report; no. 1-20). [53 references]

Non-metastatic breast cancer

Assessment of Therapeutic Effectiveness
Management
Treatment

Oncology

Physicians

• To evaluate the effect of neoadjuvant taxane-containing regimens on clinically meaningful outcomes (clinical response, pathologic response, breast conservation, disease-free survival, or overall survival) relative to other neoadjuvant regimens
• To evaluate the effect of neoadjuvant taxane-containing regimens on clinically meaningful outcomes relative to adjuvant taxane-containing regimens
• To evaluate the preferred dose and schedule for neoadjuvant taxane administration
• To evaluate the harms associated with neoadjuvant taxane-containing regimens

Women with non-metastatic breast cancer who are candidates for neoadjuvant chemotherapy

1. Neoadjuvant paclitaxel-containing regimens versus other neoadjuvant regimens
2. Neoadjuvant paclitaxel-containing regimens versus paclitaxel-containing adjuvant regimen
3. Neoadjuvant paclitaxel dose and/or schedule
4. Neoadjuvant docetaxel-containing regimens versus other neoadjuvant regimens
5. Neoadjuvant docetaxel dose and/or schedule
6. Neoadjuvant anthracycline-based chemotherapy

• Clinical response
• Pathologic response
• Node response
• Breast conservation
• Disease-free survival
• Overall survival
• Toxicity

Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases

Eighteen randomized trials and one practice guideline were reviewed

Expert Consensus (Committee)

Not applicable

Systematic Review with Evidence Tables

The trials of neoadjuvant taxane therapy were too clinically heterogeneous to pool.

Expert Consensus

In the context of current clinical practice, the Breast Cancer Disease Site Group (DSG) discussed the evidence for neoadjuvant taxanes in the treatment of women with non-metastatic breast cancer. The DSG agreed that the primary goal for treatment in this population is to achieve the longest survival with the best quality of life, using a treatment with acceptable toxicity. Refer to the original guideline document for a summary of the Breast Cancer DSG's interpretation of the evidence and consensus.

Not applicable

A formal cost analysis was not performed and published cost analyses were not reviewed.

External Peer Review
Internal Peer Review

Practitioner feedback was obtained through a mailed survey of 113 practitioners in Ontario (57 medical oncologists, 20 surgical oncologists, 35 surgeons, and one medical resident). The survey consisted of items evaluating the methods, results, and interpretive summary used to inform the draft recommendations and whether the draft recommendations above should be approved as a practice guideline. Written comments were invited. The practitioner feedback survey was mailed out on June 30, 2004. Follow-up reminders were sent at two weeks (post card) and four weeks (complete package mailed again). The Breast Cancer Disease Site Group (DSG) reviewed the results of the survey.

Sixty-three responses were received out of the 113 surveys sent (56% response rate).

Final approval of the practice guideline report was obtained from the Practice Guidelines Coordinating Committee and the Breast Cancer Disease Site Group.

• When neoadjuvant 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) or doxorubicin and cyclophosphamide (AC) chemotherapy regimen is planned for a woman with non-metastatic breast cancer, a neoadjuvant taxane (paclitaxel or docetaxel) should also be offered. Based on evidence from clinical trials, the following regimens are recommended:
  • Paclitaxel (80 mg/m²), administered weekly for 12 weeks prior to the anthracycline-based regimen
  • Docetaxel (100 mg/m²), administered every three weeks for four cycles following the anthracycline-based regimen
• There is no evidence at this time to suggest that one taxane is superior to the other in the neoadjuvant setting.

None provided

The recommendations are supported by randomized controlled trials.

Appropriate use of taxanes in neoadjuvant chemotherapy for women with non-metastatic breast cancer

• The following are toxicities associated with taxanes:
  • Paclitaxel: hematologic toxicity (neutropenia/febrile neutropenia, anemia), cardiotoxicity, neurotoxicity, gastrointestinal toxicity, and other toxicities (infection)
  • Docetaxel: hematologic toxicity (neutropenia/febrile neutropenia, leukopenia), neurotoxicity, cardiotoxicity, gastrointestinal toxicity, and other toxicities (hand-foot syndrome, death)

• Since disease-free and overall survival data are limited, the recommendations for neoadjuvant taxane chemotherapy are often based on pathologic and clinical complete-response data.
• Neoadjuvant therapy is not the standard of care for operable breast cancer but is usually given to improve the likelihood of breast conservation for large operable breast cancer or to increase the possibility of operability for locally advanced or inflammatory breast cancer.
• There is no evidence in the neoadjuvant setting for the use of taxanes after optimally dosed anthracycline-based regimens, such as 5-fluorouracil, epirubicin, and cyclophosphamide (FEC-100 or CEF).
• The recommended schedule for paclitaxel therapy (i.e., weekly) is based on two trials of weekly versus three-weekly regimens. There were no direct comparisons available for docetaxel; therefore, the recommended schedule (i.e., three-weekly) is based on that which showed improved efficacy in trials comparing a docetaxel-containing regimen with a non-docetaxel regimen. The suggested doses for paclitaxel and docetaxel are those associated with the recommended schedule.
• While neoadjuvant paclitaxel and docetaxel are recommended in sequence with a standard anthracycline-based regimen, it may be appropriate to switch to an anthracycline-based regimen from paclitaxel or to docetaxel from an anthracycline-based regimen earlier if the patient's disease progresses while on the initial regimen.
• Tumours that fail to respond to two cycles of neoadjuvant therapy are likely resistant (in terms of subsequent pathologic complete response rates) to chemotherapy, including taxane-anthracycline combinations, vinorelbine, and capecitabine. For these patients, a novel therapy may be considered.
• The data supporting neoadjuvant taxane therapy are maturing. While results to date do not support an increase in adverse events relative to other settings, physicians should monitor patients carefully for toxicity, especially hematologic toxicity, neurologic toxicity (with paclitaxel), and hand-foot syndrome (with docetaxel).
• There is at present no literature to support the use of adjuvant taxane-based therapy for residual tumour found after neoadjuvant anthracycline-based therapy.
• This practice guideline report is based upon the reported neoadjuvant literature and cannot be extrapolated to endorse the use of adjuvant docetaxel after adjuvant anthracyclines. Studies exploring that sequence of treatments are underway.
• Care has been taken in the preparation of the information contained in this document. Nonetheless, any person seeking to apply or consult the practice guideline is expected to use independent medical judgment in the context of individual clinical circumstances or seek out the supervision of a qualified clinician. Cancer Care Ontario makes no representation or warranties of any kind whatsoever regarding their content or use or application and disclaims any responsibility for their application or use in any way.

An implementation strategy was not provided.

Living with Illness

Effectiveness

• Breast Cancer Disease Site Group. Trudeau M, Sinclair S, Clemons M, Shelley W. The role of taxanes in neoadjuvant chemotherapy for women with non-metastatic breast cancer [full report]. Toronto (ON): Cancer Care Ontario (CCO); 2004 Dec 10. 32 p. (Practice guideline report; no. 1-20). [53 references]

Not applicable: The guideline was not adapted from another source.

2004 Dec 10

Program in Evidence-based Care - State/Local Government Agency [Non-U.S.]

The Practice Guidelines Initiative (PGI) is the main project of the Program in Evidence-based Care (PEBC), a Province of Ontario initiative sponsored by Cancer Care Ontario and the Ontario Ministry of Health and Long-Term Care.

Cancer Care Ontario
Ontario Ministry of Health and Long-Term Care

Provincial Breast Cancer Disease Site Group

Members of the Breast Cancer Disease Site Group (DSG) disclosed potential conflict of interest information.

None available

This summary was completed by ECRI on January 18, 2005. The information was verified by the guideline developer on February 10, 2005.