Eribulin Plus Gemcitabine (EG) vs Paclitaxel Plus Gemcitabine (PG) in HER2-Negative Metastatic Breast Cancer

A total of enrolled 118 patients in EG and PG groups, will be provided chemotherapy regimen:

Paclitaxel/Gemcitabine (PG) : every 3 weeks D1 Paclitaxel 175mg/m2 + D5W 500mL MIV over 3hrs before gemcitabine administration D1, D8 Gemcitabine 1,250 mg/m2 + NormalSaline 100ml MIV over 30mins

• Pre & Post medication (which can be changed according to institutions' policy) D1 Corticosteroid 100 mg i.v. 30 min. before Paclitaxel Pheniramine 1A + D5W 50mL MIV 30mins before Paclitaxel Ranitidine 50mg IV + D5W 50mL MIV 30mins before Paclitaxel HT3 antagonist 1A + D5W 50 mL MIV 30mins before Paclitaxel

Eribulin/Gemcitabine (EG): every 3weeks D1, D8 Eribulin 1.0 mg/m2, 2-5min iv before gemcitabine (or miv with NormalSaline 100ml in max.) D1, D8 Gemcitabine 1000 mg/m2 + NormalSaline100ml MIV over 30mins

<schedule of Assessment adn procedures (±3 days window period ) >

• screening /baseline

• obtaining Informed consent form
• collecting information
• demographic data
• breast cancer treatment history/ medical history
• general physical examination/ vital sign & Performance status
• Test: CBC/blood chemistry/ Tumor response(CT or MRI)/
• collecting QOL questionnaire using FACT-Taxane
• cycle 1 ~ prior to EOT

• general physical examination/ vital sign & Performance status
• Test: CBC/blood chemistry/ Tumor response(CT or MRI)
• collecting QOL questionnaire using FACT-Taxane
• administration PG or EG
• EOT(end of treatment)

• general physical examination/ vital sign & Performance status
• Test: CBC/blood chemistry/ Tumor response(CT or MRI)
• collecting QOL questionnaire using FACT-Taxane
• survival follow up(every 12weeks)

• survival
• anti neoplastic therapy after end of treatment
• The tumor response will be performed every 12 (±2) weeks until disease progression

<WITHDRAWAL OF SUBJECTS>

Subjects may be withdrawn from the study (i.e. from any further study medication or study procedure) for the following reasons:

• At their own request
• If, in the investigator's opinion, continuation in the study would be detrimental to the subject's well-being
• In case of disease progression
• In case of unacceptable toxicity

Inclusion criteria

• Histologically confirmed metastatic, or recurrent breast cancer
• HER2-negative breast cancer
• age > 18 years
• ECOG performance status 0 - 2
• Pre- or postmenopausal breast cancer patients with measurable or non-measurable lesions, who are candidates for chemotherapy
• Life expectancy ≥ 3 months
• No prior history of chemotherapy for metastatic, recurrent breast cancer
• Patients may have received prior neoadjuvant or adjuvant taxane regimen as long as it has been 12 months since completion of regimen.
• Patients either may or may not have a prior anthracycline containing regimen.
• Prior hormonal therapy as a treatment of metastatic disease is allowed. But antitumoral hormonal therapy must be terminated prior to enrollment(up to the date of randomization)
• Prior radiation therapy allowed as long as < 25% of the bone marrow has been treated, and the patients must have recovered from the acute toxic effects of the treatment prior to study enrollment. Prior radiation to the whole pelvis is not allowed. Prior radiotherapy must be completed 2 weeks before study entry.
• Bisphosphonates for the treatment of bone metastases should not be initiated following the first dose of randomized therapy. It must be initiated prior to day of treatment (cycle 1, day 1). Patients may continue on bisphosphonates who already established on bisphosphonate therapy for bone metastases
• Adequate bone marrow function (≥ ANC 1,500/ul, ≥ platelet 100,000/ul, ≥ Hemoglobin 9.0 g/dl)
• Adequate renal function (≤ serum creatinine 1.5 mg/dl or CCr ≥ 50 ml/min)
• Adequate liver function (≤ serum bilirubin 1.5 mg/dl, ≤ AST & ALTX3 upper normal limit or AST and ALT ≤ 5.0XULN if judged by the investigator to be related to liver metastases)
• Written informed consent

Exclusion criteria

• Serious uncontrolled intercurrent infections
• Serious intercurrent medical or psychiatric illness, including active cardiac disease
• Pregnancy or breast feeding
• Second primary malignancy(except in situ carcinoma of the cervix or adequately treated nonmelanomatous carcinoma of the skin or other malignancy treated at least 5 years previously with no evidence of recurrence)
• Documented parenchymal or leptomeningeal brain metastasis
• Peripheral neuropathy ≥ grade 2
• Prior treatment with gemcitabine will not be allowed.
• HER-2 overexpressing breast cancer and concomitant trastuzumab treatment is not allowed
• Women of childbearing potential, unwilling to use a medically acceptable method of contraception during the trial