Multicenter phase II study of pegylated liposomal doxorubicin in combination with vinorelbine as first-line treatment in elderly patients with metastatic breast cancer.

BACKGROUND: This multicenter phase II trial was conducted to analyze the clinical activity and toxicity of the combination of pegylated liposomal doxorubicin and vinorelbine as first-line treatment in elderly patients with metastatic breast cancer. PATIENTS AND METHODS: From August 2002 to August 2004, 42 patients with metastatic breast cancer were recruited for treatment with pegylated liposomal doxorubicin 40 mg/m(2) intravenously (i.v.) on day 1 and vinorelbine 30 mg/m(2) i.v. on days 1 and 15 every 4 weeks. RESULTS: The median age of the patients in this trial was 68 years (range 60-82). 40% of patients had 2 or more sites of metastasis, 33 (78%) had predominantly visceral metastasis, and 7 (16%) mostly bone metastasis. Just 2 (5%) patients had only lymphogenous or soft tissue metastasis. All patients had an ECOG performance status of 0-1, but 70% of the patients had relevant comorbidities. In an intention-to-treat analysis, the overall clinical response rate was 36%, the complete response rate was 2%, and the rate of partial remissions was 34%; stable disease occurred in 30%, and progressive disease was observed in 36%. Median duration of response was 10 months. Median time to progression was 4 months, and median overall survival time was 24 months. CONCLUSION: The combination of pegylated liposomal doxorubicin and vinorelbine is an active and well tolerated regimen in elderly patients with metastatic breast cancer in first-line treatment.

Cardiotoxicity with rituximab, cyclophosphamide, non-pegylated liposomal doxorubicin, vincristine and prednisolone compared to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone in frontline treatment of patients with diffuse large B-cell lymphoma: A randomised phase-III study from the Austrian Cancer Drug Therapy Working Group [Arbeitsgemeinschaft Medikamentöse Tumortherapie AGMT](NHL-14).

BACKGROUND: Chemoimmunotherapy containing rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) is the standard treatment for diffuse large B-cell lymphoma (DLBCL). Doxorubicin may induce early and late cardiotoxicity. Non-pegylated liposomal (NPL) doxorubicin may reduce cardiotoxicity. PATIENTS AND METHODS: Patients with untreated CD20+ DLBCL were randomised to conventional R-CHOP chemoimmunotherapy or rituximab, cyclophosphamide, non-pegylated liposomal doxorubicin, vincristine and prednisolone (R-COMP) with doxorubicin substituted by NPL-doxorubicin. Left ventricular ejection fraction (LVEF) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels were measured before each treatment cycle and after the end of treatment. RESULTS: The mean LVEF of 178 and 158 measurements in the R-COMP and R-CHOP arms was 63.31% and 62.25%, respectively (P = 0.167). During treatment the LVEF measurements were below 50% in 10/218 (4.6%) in the R-COMP arm and 31/196 (15.8%) in the R-CHOP arm (P<0.001). Thirty-six of 40 (90%) patients in the R-COMP arm, but only 24/36 (66.7%) in the R-CHOP arm had all NT-proBNP levels below 400 pg/ml during and at the end of treatment (P = 0.013). There were more serious adverse events in the R-CHOP arm (26 versus 40, P = 0.029). Infections were more common (15 versus 28) in the R-CHOP arm. INTERPRETATION: In patients with normal cardiac function, six cycles of R-CHOP resulted in a low rate of early cardiotoxicity. NPL-doxorubicin did not reduce cardiotoxicity, although cardiac safety signals were elevated in R-CHOP compared to R-COMP. FUNDING: Cephalon provided the Arbeitsgemeinschaft Medikamentöse Tumortherapie with NPL-doxorubicin and an unrestricted grant, but was not involved in the study protocol, data acquisition, data analysis or the writing of the paper.

Lapatinib-plus-pegylated liposomal doxorubicin in advanced HER2-positive breast cancer following trastuzumab: a phase II trial.

BACKGROUND: Trastuzumab, one important treatment option for HER2-positive metastatic breast cancer (MBC) is limited by its cardiotoxic potential. Lapatinib and pegylated liposomal doxorubicin (PLD) represent a cardiosparing alternative that can cross the blood brain barrier. This is important, because one third of breast cancer patients develop brain metastases. PATIENTS AND METHODS: We included 24 patients with HER2-positive MBC progressing under trastuzumab. They received 1,250 mg lapatinib daily until progression plus PLD (40 mg/m(2)) every 4 weeks for maximal 6 cycles. The primary end-point was the overall response rate (ORR). Secondary end-points were progression-free survival (PFS), overall survival (OS), 1-year PFS and 1-year OS rates. RESULTS: ORR was 54%. Median PFS was 5.8 and median OS 23.3 months. The one-year PFS rate was 27% and 1-year OS rate 76%. CONCLUSION: Lapatinib-plus-PLD is active and safe in HER2-positive MBC, especially suitable for patients with cardiological risk or brain metastases.