ELDA: Elderly Breast Cancer - Docetaxel in Adjuvant Treatment

Adjuvant Chemotherapy in Elderly Patients With Breast Cancer: Weekly Docetaxel vs. CMF

The purpose of this study is to compare disease free survival of elderly breast cancer patients treated with standard adjuvant chemotherapy (CMF) versus experimental adjuvant chemotherapy (weekly docetaxel).

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: cyclophosphamide; Drug: methotrexate; Drug: 5-fluorouracil; Drug: docetaxel

Detailed Description

Adjuvant combination chemotherapy, given after breast cancer surgery, has been established as the standard approach to reduce the risk of breast cancer recurrence in those patients at intermediate or high risk for recurrence. However, since elderly patients have been underrepresented in past clinical trials, the optimal adjuvant therapy for elderly patients at risk for recurrence has not yet been defined.

Docetaxel is one of the most active drugs for patients with metastatic breast cancer and several trials are evaluating its efficacy in the adjuvant setting. Administration of docetaxel on a weekly schedule is effective and well tolerated in women with metastatic breast cancer.

In this study, patients from ages 65 to 80 will be randomized to one of two treatment strategies:

• standard adjuvant chemotherapy with CMF (cyclophosphamide, methotrexate, and 5-fluorouracil given intravenously on days 1 and 8 of each cycle)
• experimental adjuvant chemotherapy with weekly docetaxel (given intravenously on days 1,8, and 15 of each cycle)

In both treatment strategies:

• 4 cycles of chemotherapy will administered for patients at least 10% positive for ER or PgR, and 6 cycles will administered for patients expressing < 10% ER or PgR
• patients with any positive expression of ER or PgR will receive adjuvant hormonal therapy with tamoxifen (20mg/day for 5 years) after concluding chemotherapy
• adjuvant radiation therapy will be given to patients who are candidates at the conclusion of chemotherapy and within 6 months of surgery.

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Napoli, Italy, 80131
    • Istituto Nazionale dei Tumori, Divisione di Oncologia Medica C
  • Napoli, Italy
    • Università Federico II, Cattedra di Oncologia Medica
  • Napoli, Italy, 80131
    • Azienda Ospedaliera Cardarelli
  • Treviglio, Italy
    • Az. Osp. Treviglio - Caravaggio
  • Vallo della Lucania, Italy
    • Ospedale S. Luca ASL SA 3
  • AV
    • Monteforte Irpino, AV, Italy
      • Azienda Sanitaria S. Giuseppe Moscati
  • BN
    • Benevento, BN, Italy
      • Azienda Ospedaliera G. Rummo
  • PG
    • Sant'Andrea delle Frate, PG, Italy
      • Policlinico Monteluce

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 80 years (OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologically confirmed invasive unilateral breast cancer
• Age > 65 and < 80 years
• Intermediate-high risk of recurrence according to St. Gallen criteria: ER negative and PgR negative, or axillary lymph node metastasis, or tumor size > 2 cm, or tumor grade 2 or 3 (intermediate or high)

Exclusion Criteria:

• Performance status >1
• Distant metastasis
• Concomitant malignancy or malignancy within previous 5 years (except basal cell or spinocellular skin cancer and in situ cervical cancer if they have been adequately treated
• Previous breast cancer treatment
• Neutrophils < 2000/mm3 or platelets < 100000/mm3 or haemoglobin < 10 g/dl
• Creatinine > 1.25 the upper normal limit
• GOT and-or GPT and/or bilirubin > 1.25 the upper normal limit
• Concomitant conditions that contraindicate the use of the drugs in the protocol
• Incapacity or refusal to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: A; Standard chemotherapy with CMF	Drug: cyclophosphamide; 600 mg/m2 intravenously days 1, 8 every 28 days; Drug: methotrexate; 40 mg/m2 intravenously days 1 and 8 every 28 days; Drug: 5-fluorouracil; 600 mg/m2 intravenously days 1 and 8 every 28 days
EXPERIMENTAL: B; Weekly docetaxel	Drug: docetaxel; 35 mg/m2 intravenously on days 1, 8, and 15 every 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
disease free survival	at 5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
toxicity	weekly
compliance	every 3 weeks
quality of life	baseline and every 3 weeks during therapy
overall survival	at 5 years

Collaborators and Investigators

• Sponsor: National Cancer Institute, Naples

Publications and helpful links

General Publications

• Nuzzo F, Morabito A, De Maio E, Di Rella F, Gravina A, Labonia V, Landi G, Pacilio C, Piccirillo MC, Rossi E, D'Aiuto G, Thomas R, Gori S, Colozza M, De Placido S, Lauria R, Signoriello G, Gallo C, Perrone F, de Matteis A. Weekly docetaxel versus CMF as adjuvant chemotherapy for elderly breast cancer patients: safety data from the multicentre phase 3 randomised ELDA trial. Crit Rev Oncol Hematol. 2008 May;66(2):171-80. doi: 10.1016/j.critrevonc.2007.10.006. Epub 2007 Dec 21.
• Perrone F, Nuzzo F, Di Rella F, Gravina A, Iodice G, Labonia V, Landi G, Pacilio C, Rossi E, De Laurentiis M, D'Aiuto M, Botti G, Forestieri V, Lauria R, De Placido S, Tinessa V, Daniele B, Gori S, Colantuoni G, Barni S, Riccardi F, De Maio E, Montanino A, Morabito A, Daniele G, Di Maio M, Piccirillo MC, Signoriello S, Gallo C, de Matteis A. Weekly docetaxel versus CMF as adjuvant chemotherapy for older women with early breast cancer: final results of the randomized phase III ELDA trial. Ann Oncol. 2015 Apr;26(4):675-682. doi: 10.1093/annonc/mdu564. Epub 2014 Dec 8.
• Di Maio M, Gallo C, Leighl NB, Piccirillo MC, Daniele G, Nuzzo F, Gridelli C, Gebbia V, Ciardiello F, De Placido S, Ceribelli A, Favaretto AG, de Matteis A, Feld R, Butts C, Bryce J, Signoriello S, Morabito A, Rocco G, Perrone F. Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting in three randomized trials. J Clin Oncol. 2015 Mar 10;33(8):910-5. doi: 10.1200/JCO.2014.57.9334. Epub 2015 Jan 26.

Study record dates

Study Major Dates

• Study Start: July 1, 2003
• Primary Completion (ACTUAL): May 1, 2014
• Study Completion (ACTUAL): November 1, 2014

Study Registration Dates

• First Submitted: May 26, 2006
• First Submitted That Met QC Criteria: May 26, 2006
• First Posted (ESTIMATE): May 29, 2006

Study Record Updates

• Last Update Posted (ACTUAL): March 28, 2017
• Last Update Submitted That Met QC Criteria: March 27, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: adjuvant therapy; elderly; high risk; intermediate risk
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Docetaxel; Cyclophosphamide; Fluorouracil; Methotrexate
• Other Study ID Numbers: ELDA