Maintenance Treatment With Liposomal Doxorubicin (Caelyx) in Metastatic Breast Cancer Patients

Phase IV.III Clinical Trial to Evaluate Maintenance Treatment With Caelyx vs. Observation After Administration of Induction Chemotherapy in Metastatic Breast Cancer Patients

This is a randomized, prospective and multicenter phase IV clinical trial, which has been designed as a phase III study. One hundred fifty-four women (77 per treatment arm) will be recruited in the study.

The main variable is time to disease progression. All patients must be treated with first line of induction chemotherapy, consisting of doxorubicin 75 mg/m2, day 1 every 3 weeks, and docetaxel, 100 mg/m2, day 1 every 3 weeks. Both drugs must be administered sequentially. Patients previously treated with anthracyclines must receive 2 courses of doxorubicin and 4 courses of docetaxel. Otherwise, patients will receive 3 courses of doxorubicin followed by 3 courses of docetaxel.

Patients with complete response, partial response or stable disease are eligible for 2001-01 study.

The investigators assume that maintenance treatment with Caelyx will increase mean time to progression from 10, 46 months (observation) to 17, 43 months. Expected difference in mean time to progression is 6, 97 months (Hazard ratio = 0.6). With an alpha error of 0.01 (unilateral) and power of 80%, 77 patients per arm are needed, 154 patients in total.

Inclusion Criteria:

• Written informed consent.
• Patients with metastatic breast cancer who have responded to a first line induction chemotherapy treatment.
• Age: at least 18 years old.
• Performance status Eastern Cooperative Oncology Group (ECOG) scale 0, 1, 2.
• Normal cardiac function, confirmed by left ventricular ejection fraction (LVEF).
• Hematology: leucocytes >= 4 x 10^9/l; neutrophils >= 2.0 x 10^9/l; platelets >= 100 x 10^9/l; hemoglobin <= 10 g/dl.
• Hepatic function: total bilirubin < 1 upper limit of normal (UNL); aspartate aminotransferase (ASAT) (SGOT) and alanine aminotransferase (ALAT) (SGPT) < 2.5 UNL; alkaline phosphatase < 5 UNL. Patients with ASAT (SGOT) and ALAT (SGPT) > 1.5 UNL and alkaline phosphatase > 2.5 UNL are not eligible.
• Renal function: creatinine < 175 mmol/l (2 mg/dl); creatinine clearance > 45 ml/min.

Exclusion Criteria:

• Pregnant or lactating patients.
• Previous cardiac dysfunction grade II or higher as per New York Heart Association, along with congestive cardiac failure.
• Hypersensitivity to anthracyclines or Cremophor®.
• Clinically significant hepatic dysfunction.
• Current uncontrolled infection.
• Mental confusion and lack of orientation.
• Any circumstance precluding an adequate follow-up.
• Radiotherapy in the previous 4 weeks.
• Any other concurrent neoplasm, except for basal cell carcinoma or in situ carcinoma.
• Symptomatic metastasis in the brain.
• Previous radiotherapy radiating a third of haematopoietic centres.
• Males.