Vinorelbine Versus Gemcitabine Plus Vinorelbine in Metastatic Breast Cancer Patients
Vinorelbine Versus Gemcitabine Plus Vinorelbine in Metastatic Breast Cancer Patients
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.