vinorelbine versus gemcitabine plus vinorelbine in metastatic breast cancer patients

Conditions: Breast Cancer; Neoplasm Metastasis

Summary: 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).

Eligibility criteria:
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.

Keywords: drug-resistant metastatic breast cancer