A phase I/II study of bortezomib and capecitabine in patients with metastatic breast cancer previously treated with taxanes and/or anthracyclines.

BACKGROUND: Proteasome inhibitors are a novel class of compounds entering clinical trials as a method to increase tumour sensitivity to standard chemotherapy. This phase I/II trial was carried out to evaluate the combination of capecitabine and the proteasome inhibitor bortezomib in anthracycline and/or taxane-pretreated patients with metastatic breast cancer. PATIENTS AND METHODS: A total of 35 patients were treated with bortezomib (1.0-1.3 mg/m(2) on days 1, 4, 8 and 11) and capecitabine (1500-2500 mg/m(2) on days 1-14) in 3-week intervals for up to eight cycles. RESULTS: The maximum tolerated doses (MTDs) were bortezomib 1.3 mg/m(2) and capecitabine 2500 mg/m(2). The treatment was generally well tolerated and associated with toxic effects that were consistent with the known side-effects of the individual agents. The intent-to-treat overall response rate was 15% and an additional 27% of patients had stable disease (SD). In the 20 patients treated at the MTD, the response rate was 15% and 40% had SD. Median time to progression and overall survival were 3.5 months [95% confidence interval (CI) 1.9-4.4] and 7.5 months (95% CI 5.6-14.6), respectively. Median duration of response was 4.4 months. CONCLUSION: The combination of bortezomib and capecitabine is well tolerated and has moderate antitumour activity in heavily pretreated patients.

Primary chemotherapy with gemcitabine as prolonged infusion, non-pegylated liposomal doxorubicin and docetaxel in patients with early breast cancer: final results of a phase II trial.

BACKGROUND: Combinations of anthracyclines, taxanes and gemcitabine have shown high activity in breast cancer. This trial was designed to evaluate a modified combination regimen as primary chemotherapy. Non-pegylated liposomal doxorubicin (NPLD) was used instead of conventional doxorubicin to improve cardiac safety. Gemcitabine was given 72 h after NPLD and docetaxel as a prolonged infusion over 4 h in order to optimize synergistic effects and accumulation of active metabolites. PATIENTS AND METHODS: Forty-four patients with histologically confirmed stage II or III breast cancer were treated with NPLD (60 mg/m(2)) and docetaxel (75 mg/m(2)) on day 1 and gemcitabine as 4-h infusion (350 mg/m(2)) on day 4. Treatment was repeated every 3 weeks for a maximum of six cycles. All patients received prophylactically recombinant granulocyte colony-stimulating factor. Patients with axillary lymph node involvement after primary chemotherapy received adjuvant treatment with cyclophosphamide, methotrexate and fluorouracil. RESULTS: The clinical response rate was 80%, and complete remissions of the primary tumor occurred in 10 patients (25%). Breast conservation surgery was performed in 19 out of 20 patients (95%) with an initial tumor size of less than 3 cm and in 14 patients (70%) with a tumor size

Orbital metastases in breast cancer: report of two cases and review of the literature.

PURPOSE: Intraorbital metastases of solid tumors are a rarely diagnosed clinical condition, even though pathological reports suggest an incidence of up to 30% in cancer patients. We report two cases of intraorbital, extraocular metastases in breast cancer. The first patient was a 45-year-old man who presented with diplopia, upward divergence of the left bulb, and local pain. METHODS: In the standard cerebral magnetic resonance imaging (MRI) no cerebral or ocular tumor was detectable. A subsequent T1-weighted, contrast-enhanced orbital MRI with fat suppression revealed an infrabulbar mass of 18 x 13 mm in size. The second patient, a 59-year-old woman, complained of slight diplopia when looking to the left. Cerebral MRI with fat suppression showed a retrobulbar mass with 17x13 mm. In both patients metastatic breast cancer was known for several years, and both had been in a stable disease situation. Both patients were treated with stereotactic radiation, applying a cumulative dose of 35 and 45 Gy, respectively, which resulted in marked improvement of local symptoms. Most eye metastases of breast cancer are located in the choroidea, while an extrabulbar localization within the orbit is rare, with only 3-10% of all ocular metastases. Autopsy reports reveal that an estimated 10-30% of breast cancer patients develop this form of metastasis. This is in strong contrast to rare clinical case reports, suggesting frequently absent to mild clinical signs and difficult diagnosis. CONCLUSION: If breast cancer patients complain of ophthalmological symptoms such as local pain, impaired vision, or diplopia, it is important to consider ocular or orbital metastatic disease.