Neoadjuvant Epirubicin, Cyclophosphamide, and Paclitaxel With or Without Gemcitabine in Treating Women Who Are Undergoing Surgery for Early Breast Cancer.

Research summary

The incidence of breast cancer continues to rise in the US and Western Europe and breast cancer remains a major health problem despite considerable improvements in the treatment of the disease both in the adjuvant and in the metastatic setting, and latterly some reduction in mortality. Although much of this progress has been made through large adjuvant randomised treatment trials, progress at times seems slow. By contrast, clinical trials in the neoadjuvant setting promise faster answers, but wider acceptance of their validity awaits formal comparison with data acquired from parallel-designed conventional adjuvant studies. tAnGo and Neo-tAnGo are designed to provide this cross reference, both comparing EC ->T with EC ->TG. In addition, Neo-tAnGo will address the quality of whether taxanes are better used prior to EC.

Neo-tAnGo is a phase III, randomised trial with two-by-two factorial design addressing both the role of gemcitabine (G) in a sequential neoadjuvant chemotherapy regimen of epirubicin/cyclophosphamide (EC) and paclitaxel (T) and the role of the sequencing of these treatment components in terms of short-term and long-term outcome in women presenting with high-risk early breast cancer. The trial employs a 20-week neoadjuvant chemotherapy regimen unless there is evidence of disease progression, in which case patients will proceed either to the second phase of chemotherapy or to surgery,
according to the circumstance and opinion of the responsible clinician.

Combining the power of the neoadjuvant, randomised phase III trials with randomised translational research will allow us to answer a number of clinical research questions concerning the addition of gemcitabine, and define a number of predictive and prognostic markers by molecular profiling and genomic analyses. In the immediate term, this study will answer important questions about which women benefit from the addition of gemcitabine, and in the longer term, this trial design could provide a template for testing newer therapies in combination with chemotherapy in the future.

Main inclusion criteria

  1. Women with histological diagnosis of invasive breast cancer

  2. Unifocal tumour :

    1. T2 or T3 tumours (radiological size > 20 mm; see Appendix 5)

    2. T4 tumour of any size with direct extension to (a) chest wall or (b) skin

    3. Inflammatory carcinoma with tumour of any size

  3. OR
  4. Other Locally Advanced disease:

    1. Involvement of axillary lymph node (radiological diameter> 20 mm) and primary breast tumour of any diameter

      1. Where no primary breast tumour was found, the presence of breast cancer in a Lymph Node must be histopathological confirmed by LN biopsy (trucut or whole LN)

  5. OR
  6. Multifocal tumour :

    1. The sum of the tumour diameters must be > 20mm (radiological size > 20mm)

  7. Patients with bilateral disease are eligible to enter the trial

  8. Any hormone receptor status

  9. Patient fit to receive any of the trial chemotherapy regimens:

    1. Patient must not have clinically significant cardiac abnormalities and must not have had a previous myocardial infarction during the 6 months prior to recruitment. Cardiac function should be assessed by physical examination

    2. Patient must have adequate bone marrow, hepatic, and renal function

  10. ECOG performance status of 0, 1, or 2 (see Appendix 4)

  11. No previous chemotherapy or radiotherapy

  12. No previous routine neo-adjuvant endocrine therapy. If the patient has already been commenced on hormone therapy, this requires discussion with the Neo-tAnGo trial office prior to randomisation

  13. No previous diagnosis of malignancy unless:

    1. managed by surgical treatment only, and disease-free for 10 years

    2. previous basal cell carcinoma, cervical carcinoma in situ or ductal carcinoma in situ of the breast treated by surgery only

  14. Non-pregnant and non-lactating, with no intention of pregnancy during chemotherapy, and prepared to adopt adequate contraceptive measures if pre-menopausal and sexually active

  15. No concomitant medical or psychiatric problems that might prevent completion of treatment or follow-up

  16. 18 years or older

  17. Written informed consent for the study

  18. Randomisation must take place within 4 weeks of biopsy

  19. Chemotherapy should start as soon as possible within 4 weeks of biopsy

  20. Availability of an embedded paraffin tumour block, tissue taken pre-chemotherapy, for research purposes only

Main exclusion criteria

  1. T0 and T1 tumours in absence of axillary node > 20mm.

  2. Not suitable for neoadjuvant chemotherapy in the opinion of the responsible clinician

  3. Evidence of metastatic disease

    1. History of atrio-ventricular arrhythmias and/or congestive heart failure, even where it is under medical control, or active second or third-degree cardiac block. History of myocardial infarct during the 6 months prior to recruitment. Non-controlled or malignant arterial high-pressure.

  4. Males 

Chief investigator

Dr Helena Earl

Contact details

Cancer Theme Email: [email protected]