Vinorelbine Versus Gemcitabine Plus Vinorelbine in Metastatic Breast Cancer Patients

Randomized Phase III Trial Comparing Vinorelbine vs. Gemcitabine Plus Vinorelbine in Patients With Advanced Breast Cancer, Previously Treated With Anthracyclines and Taxanes

This is a multicenter, randomized, prospective, Phase III study in which patients with advanced breast carcinoma previously treated with anthracyclines and taxanes will be randomly assigned to receive one of two treatment options: vinorelbine (Arm A) or gemcitabine plus vinorelbine (Arm B).

The investigators assume that progression-free survival mean time for patients treated with vinorelbine will be 3 months, and for patients treated with gemcitabine plus vinorelbine will be 5 months. That implies a reduction in risk ratio of 40% (Hazard ratio = 1,67). Assuming a bilateral alpha error of 0.05 and beta error of 10%, and the number of events needed if 60% of patients have progressed after 1 year, the number of patients needed per treatment arm is 114. Considering a 10% post-randomization drop-out, the final number of patients is 252 (126 per arm).

Inclusion Criteria:

• Histological or cytological diagnoses of breast cancer, with metastases.
• Metastatic lesions should not be curable with surgery or radiotherapy.
• Women of age > 18.
• To have received a previous treatment with anthracyclines and taxanes.
• A maximum of 2 previous chemotherapy treatment lines for metastatic disease.
• Previous radiotherapy is allowed, whenever the radiated area is not the only disease location.
• At least 4 weeks since the last previous antineoplastic treatment; patient must have recovered from all previous toxicities.
• Performance status < 2 in World Health Organization (WHO) scale.
• Clinically measurable, non measurable or really non measurable disease, as per Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
• Life expectancy of at least 12 weeks.
• Patients able to comply and to receive an adequate follow-up.
• Adequate bone marrow function: neutrophils ≥ 2 x 10^9/L; platelets ≥ 100 x 10^9/L; hemoglobin ≥ 100 g/L.
• Calcium within normal limits.
• Premenopausal women must adopt an adequate contraceptive method during the study and up to 3 months after treatment finalization.

Exclusion Criteria:

• Active infection or serious concomitant disease (investigator's criteria).
• Clinical evidence of metastases in the central nervous system (CNS).
• Blastic bone lesions as only disease.
• Previous neurological toxicity grade 3-4 National Cancer Institute (NCI) Common Toxicity Criteria (CTC) v.2.0.
• Previous treatment with gemcitabine and/or vinorelbine.
• More than 2 previous chemotherapy treatment lines for metastatic disease.
• Abnormal liver function (bilirubin > 2.0-fold upper normal limit (UNL); alanine transaminase (ALT) and aspartate transaminase (AST) >2.5-fold UNL). In patients with hepatic metastasis, a value of ALT and AST of up to 5-fold UNL is permitted.
• Unpaired renal function (creatinine > 2.0 mg/dL).
• Pregnancy or lactating.
• Treatment with any investigational agent in the previous 4 weeks.
• Second malignancy (except for cervix carcinoma in situ or skin carcinoma - no melanoma- with an adequate treatment). Previous malignancies are allowed if disease-free survival is superior to 5 years, except for renal carcinoma or melanoma.
• Males.