Multicenter Phase II Study of Pegylated Liposomal Doxorubicin in Combination with Vinorelbine as First-Line Treatment in Elderly Patients with Metastatic Breast Cancer

Abstract

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/m² intravenously (i.v.) on day 1 and vinorelbine 30 mg/m² 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.

Bi-weekly liposomal doxorubicin for advanced breast cancer in elderly women (≥70years)

“…21 Two trials evaluated a first-line combination regimen of PLD plus vinorelbine in elderly patients, obtaining fairly good response rates of 36% 22 or 50%, 23 conflicting TTP of 4 months 22 or 8 months, 23 and higher rates of hematological toxicity (neutropenia 15% grade 3 and 11% grade 4) with 10% of febrile neutropenia, and gastro-intestinal toxicity. 23 The authors' conclusion that "the combination of PLD and vinorelbine is active and well tolerated in elderly patients" should be considered with caution since they applied an inferior age limit of 65 23 or even 60 years, 22 while 70 years is believed to be the real turning point for age related physiologic changes. 13 Since the start of this trial, also a non-pegylated version of liposomal doxorubicin has been registered for breast cancer in association with cyclophosphamide, but, to our knowledge, data on elderly patients are very limited.…”

A multicenter prospective phase II randomized trial of epirubicin/vinorelbine versus pegylated liposomal doxorubicin/vinorelbine as first-line treatment in advanced breast cancer. A GOIM study

“…In details, the PLD/VNB combination was recently employed in two phase II trials in heavily pretreated patients, yielding a response rate of 36% and 39%, without any cardiac toxicity [37,38]. Two more recent reports with PLD/VNB combination as first-line treatment in elderly patients confirmed the good overall clinical response rate (36% and 50%, respectively), and t he high tolerability of the regimen [39,40] suggesting, due to the safety profile of the combination, the employment also in such "frail" patient population.…”

A Review of Vinorelbine in the Treatment of Advanced Breast Cancer

“…A large number of phase II trials have been performed which have generally shown encouraging activity with an acceptable safety profile (Table 3). Examples include Paclitaxel 30–37 Docetaxel; 38–46 Doxorubicin; 47–51 Epirubicin 52–54 Mitoxantrone; 55–57 Pegylated Liposomal Doxorubicin; 14,58–61 Gemcitabine; 62–73 5-Fluorouracil; 74–79 platinum compounds; 80–83 and Capecitabine, 84–88 which will be separately discussed. Several triplets have also been investigated but increased toxicity should be expected.…”