Biweekly Pegylated Liposomal Doxorubicin (Caelyx) in Heavily Pretreated Metastatic Breast Cancer: A Phase 2 Study

• Published in: Clinical breast cancer 2016-12, Vol.16 (6), p.514-519
• Main Authors: Jehn, Christian F., Hemmati, Philipp, Lehenbauer-Dehm, Silvia, Kümmel, Sherko, Flath, Bernd, Schmid, Peter
• Format: Article
• Language: English
• Subjects: Adult; Advanced breast cancer; Aged; Anthracyclines; Anthracyclines - therapeutic use; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - adverse effects; Antibiotics, Antineoplastic - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Breast Neoplasms - drug therapy; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Capecitabine - therapeutic use; Cardiotoxicity - epidemiology; Disease-Free Survival; Doxorubicin - administration & dosage; Doxorubicin - adverse effects; Doxorubicin - analogs & derivatives; Doxorubicin - therapeutic use; Drug Administration Schedule; Female; Hand-Foot Syndrome - epidemiology; Hand-Foot Syndrome - etiology; Humans; Middle Aged; Neutropenia - chemically induced; Neutropenia - epidemiology; Pegylated liposomal doxorubicin (PLD); Phase II Trial; Polyethylene Glycols - administration & dosage; Polyethylene Glycols - adverse effects; Polyethylene Glycols - therapeutic use; Taxoids - therapeutic use; Thrombocytopenia - chemically induced; Thrombocytopenia - epidemiology; Treatment Outcome; Vinblastine - analogs & derivatives; Vinblastine - therapeutic use
• ISSN: 1526-8209; 1938-0666
• DOI: 10.1016/j.clbc.2016.06.001

Limited information exists regarding the efficacy and toxicity of an anthracycline rechallenge in heavily pretreated patients with metastatic breast cancer. This prospective phase 2 trial with 25 patients demonstrated a clinical benefit in 23% of the patients for a median duration of 12.5 months. The toxicity profile is reasonable for such advanced disease. Pegylated liposomal doxorubicin (PLD) has shown to be as effective as conventional doxorubicin in the treatment of metastatic breast cancer but provides a lower risk of cardiotoxicity. This phase 2 study in heavily pretreated patients with metastatic breast cancer was initiated to evaluate a biweekly instead of a 4-week schedule of PLD in order to obtain a more flexible and tolerable regimen. A total of 25 patients with 2 or more prior lines of chemotherapy for metastatic disease were treated with PLD (25 mg/m2) at 2-week intervals for a maximum of 12 courses. Pretreatment with anthracyclines was allowed as long as the cumulative doxorubicin dose at study entry was below 400 mg/m2. Most patients were pretreated with anthracyclines, taxanes, vinorelbine, alkylating agents, and capecitabine. The clinical benefit rate, ie, objective response or stable disease, for at least 6 months was 22.7% for all patients and 22.2% in anthracycline- and taxane-pretreated patients, respectively. Median duration of clinical benefit and median time to progression were 12.5 months (95% confidence interval [CI], 10.1-32.3) and 7 weeks (95% CI, 5.4-8.6), respectively. Median overall survival was 9.6 months (95% CI, 5.4-13.9). One- and 2-year survival rates were 38% and 4%, respectively. Myelosuppression was low, with no grade 3 or 4 neutropenia or thrombocytopenia. Most common nonhematologic toxicities were nausea, alopecia, asthenia, and hand–foot syndrome. The low rate of hematologic toxicity and hand–foot syndrome is clinically noteworthy. Biweekly PLD is an easily manageable schedule with a favorable toxicity profile. Efficacy was moderate in heavily pretreated patients.