Oral Vinorelbine in Combination With Trastuzumab for Metastatic Breast Cancer

Inclusion criteria

• Woman ≥ 18 years of age.
• PS 0-2. Expected lifetime of more than 12 weeks.
• Histologically verified breast cancer(adenocarcinoma)
• Primary tumor or metastasis is HER2 positive with IHC3+ or FISH+ (ratio ≥ 2.2).
• Documented metastatic breast cancer with min. one lesion measureable according to the RECIST 1.1 criteria. All solitary lesions must be verified cytologically/histologically if representing the only evidence of malignancy.
• The patient may have received (neo-) adjuvant chemotherapy (taxanes, anthracyclines and trastuzumab) and 1st line chemotherapy in combination with trastuzumab for metastatic disease.
• The patient may have received previous adjuvant antihormonal treatment for metastatic breast cancer.
• The patient may receive radiation therapy, however, not against lesions used for response evaluation.
• Normal heart function, LVEF ≥ 50% measured by MUGA/EKKO.
• Normal bone marrow function: Hemoglobin ≥ 6 mmol/l, ANC ≥ 1.5x10^9/l. Thrombocytes ≥ 100x10^9/l.
• Normal liver function: Bilirubin ≤ 1.5 x upper normal level, ALAT ≤ 2.5 x upper normal level, BASP ≤ 2.5 x upper normal level (≤ 5 if presence of bone metastases).
• Normal renal function: Creatinine ≤ upper normal level. In case of raised creatinine the measured/calculated GFR must be ≥ 50 ml/min.
• Fertile women must present a negative pregnancy test and use contraceptives during and 3 months after treatment. An IUD without hormone is considered a safe contraceptive.
• Written and orally informed consent prior to any study related procedure.

Exclusion criteria

• Local recurrence or counter-lateral breast cancer without other dissemination.
• Pregnant or breastfeeding women.
• Clinical symptoms of CNS metastases, incl. meningeal carcinomatosis.
• Malabsorption syndrome or other disease affecting the gastrointestinal function. Resection of the ventriculus or the small intestine, which can affect absorption of oral vinorelbine.
• Dysphagia or other conditions preventing the patient from swallowing tablets.
• Mental or social conditions preventing treatment or follow-up.
• Serious concurrent medical condition, such as:

• AMI within 12 months or unstable angina.
• Heart incompensation NYHA III or IV or uncontrolled hypertension (systolic > 150 mm/hg and/or diastolic >100 mm/hg).
• Serious arrythmia requiring medication, excl. atrial fibrillation and paroxystic supraventricular tachycardia.
• Active infection, uncontrolled diabetes or hypercalcemia.
• Other concurrent experimental treatment.
• Concurrent antihormonal treatment of metastatic breast cancer.
• Known neuropathia ≥ grade 2.
• Other previous malignant disease within the past 5 years excl. non-melanoma skin cancer and carcinoma in situ cervicis uteri.
• Previous treatment with vinca alkaloid.
• Previous serious allergic or unexpected reactions to trastuzumab treatment.