Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Infective Agents

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Docetaxel

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Tubulin Modulators

Antimitotic Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Patients received doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2), both in a short intravenous infusion, every three weeks for four cycles. Later, docetaxel (36 mg/m2) was administered an intravenous infusion, weekly for six weeks followed by a 2-week resting period (8-week cycle).

Study Director

Treatment consists of 4 AC cycles followed by 2 weekly docetaxel cycles (12 infusions).

The pathological complete response rate obtained in previous studies is around 12%. The expected pathological complete response rate in this study is 25%. With an alpha error of 0.05 and a beta error of 0.2, and following Simon´s 2 phase test, 19 patients are needed initially. With 2 pathological complete responses, patient recruitment will continue until approximately 61 patients are recruited. Twelve pathological complete responses are needed to confirm the study hypothesis.

Patients received doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2), both in a short intravenous infusion, every three weeks for four cycles (days 1, 22, 43 and 64). Three weeks later, docetaxel (36 mg/m2) was administered as a 30-min intravenous infusion, weekly for six weeks (days 85, 92, 99, 106, 113 and 120) followed by a 2-week resting period (8-week cycle). After that, patients received a second docetaxel cycle (infusions on days 141, 148, 155, 162, 169 and 176). Adjuvant chemotherapy and radiotherapy were delivered according to the protocol of each participating center. Hormonal treatment was started after the last chemotherapy infusion in all patients with positive estrogen and/or progesterone receptor tumors and was continued for five years.

Semiquantitative determination of three molecular markers was carried out by immunocytochemical methods. Tissue samples were taken prior to initiation of chemotherapy from the core of the primary tumors. Specimens were sent to a central laboratory for analysis of Topo II, survivin and p27.

Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Docetaxel as Neoadjuvant Treatment of Breast Cancer Patients

Multicenter Phase II Trial of Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Docetaxel (T) as Neoadjuvant Treatment for Operable Stage II and IIIA Breast Cancer Patients

Pathological complete response was defined by the Miller \& Payne criteria. pCR was defined as no invasive cells identifiable in breast sections at surgery. Response was measured by physical exam and breast imaging before surgery and was evaluated according to the World Health Organization (WHO) criteria. Pathological response after surgery, was based on the proportion of remaining tumor and postchemotherapy changes, evaluating separately the response in the breast and in the axilla lymph nodes.

CRR measured according to the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions, where:

* Complete Response (CR): disappearance of all target lesions
* Partial Response (PR): \>=30% decrease in the sum of the longest diameter of target lesions
* Progresive Disease (PD): \>=20% increase from smallest sum of longest diameter recorded since treatment started (best response).
* Stable Disease (SD): Neither PD nor PR

Paraffin-embedded tumors were processed with standard immunocytochemical techniques. Over-expression of Topo II was defined as \>10% cells with nuclear staining.

Paraffin-embedded tumors were processed with standard immunocytochemical techniques. Tumors with more than 1% of cells with nuclear staining were considered to be over-expressing this protein.

Paraffin-embedded tumors were processed with standard immunocytochemical techniques. Sections were rated according to the percentage of tumor cells nuclei with positive staining (1 = \< 25%; 2 = between 25-75% and 3 = \> 75%).

Sanofi

Spanish Breast Cancer Research Group

Patients received doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2), both in a short intravenous infusion, every three weeks for four cycles (days 1, 22, 43 and 64). Three weeks later, docetaxel (36 mg/m2) was administered as a 30-min intravenous infusion, weekly for six weeks (days 85, 92, 99, 106, 113 and 120) followed by a 2-week resting period (8-week cycle). After that, patients received a second docetaxel cycle (infusions on days 141, 148, 155, 162, 169 and 176).

Doxorubicin + Cyclophosphamide Followed Docetaxel

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Spain

Region of Enrollment

Premenopausal

Postmenopausal

Menopausal status

Median Tumor size, cm

Stage was classified following the TNM system of the American Joint Committee on Cancer (AJCC).

Stage 0. Cancer in situ ("in place"). Still located in the place they started and have not spread to nearby tissues. This stage is highly curable, by removing the entire tumor with surgery.

Stage I. Small cancer that has not grown into nearby tissues. Also has not spread.

Stage II and Stage III. Larger cancers that have grown deeply into nearby tissue. They may have also spread to lymph nodes but not to other parts of the body.

Stage IV. Cancer has spread to other organs or parts of the body.

Disease stage (I, IIA, IIB y IIIA)

ER+/PR+

ER+/PR-

ER-/PR+

ER-/PR-

Hormonal receptors (Estrogen Receptor [ER]+/ Progesterone Receptor [PR]+, ER+/PR-, ER-/PR+, ER-/PR-)

Scientific Director / Medical Lead / Project Manager

2 patients did not received surgery, 1 because of disease progression, and 1 due to inacceptable toxicity.

Pathological Complete Response (pCR) Rate

Clinical Response Rate (CRR)

20 patient tumor sample could not be evaluated

Number of Participants With Over-expression of Topo II (>10% Cells With Nuclear Staining)

> 1 %

< 1%

17 patient tumor sample could not be evaluated

Number of Participants With Over-expression of Survivin (>1% Cells With Nuclear Staining)

< 75%

> 75%

Number of Participants With Over-expression of p27 (>75% Cells With Nuclear Staining)

Overall Study

Spots Global Cancer Trial Database for weekly docetaxel.