Phase II Study of Pegylated Liposomal Doxorubicin in Combination With Gemcitabine in Patients With Metastatic Breast Cancer

2003 ◽  
Vol 21 (17) ◽  
pp. 3249-3254 ◽  
Author(s):  
Edgardo Rivera ◽  
Vicente Valero ◽  
Banu Arun ◽  
Melanie Royce ◽  
Rosni Adinin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Liposomal Doxorubicin ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Median Response

Purpose: We conducted a phase II clinical trial to determine the clinical efficacy and safety of pegylated liposomal doxorubicin in combination with gemcitabine in patients with metastatic breast cancer. Patients and Methods: Patients were eligible if they had measurable disease, no prior chemotherapy for metastatic disease, and a performance status ≤ 2 on the Zubrod scale. Patients received pegylated liposomal doxorubicin 24 mg/m2 intravenously on day 1, plus gemcitabine 800 mg/m2 intravenously on days 1 and 8 of each 21-day cycle. Results: Of 49 patients enrolled, 27 had received prior adjuvant chemotherapy (19 with an anthracycline). Prior median cumulative anthracycline dose was 240 mg/m2. In total, three complete responses and 21 partial responses were achieved in 46 assessable patients, for an overall response rate of 52% (95% confidence interval, 37% to 67%). Responses were observed in 11 (58%) of 19 patients with previous anthracycline exposure. Median response duration was 5.6 months, time to progression was 4.5 months, and overall survival was 16.1 months. Although the most common grade 3 to 4 toxicities were hematologic, few neutropenic complications resulted. The most frequent nonhematologic toxicities were nausea and vomiting, fatigue, stomatitis, and hand-foot syndrome. One patient previously treated with an anthracycline developed a transient decrease (21%) in the left ventricular ejection fraction, with cardiac function recovering within 2 months. Conclusion: Pegylated liposomal doxorubicin in combination with gemcitabine is active and well tolerated in patients with metastatic breast cancer. Median overall survival was 16.1 months, and approximately 78% of patients derived clinical benefit from treatment. This regimen represents a therapeutic option for patients receiving front-line therapy for their metastatic breast cancer.

Pegylated Liposomal Doxorubicin and Trastuzumab in HER-2 Overexpressing Metastatic Breast Cancer: A Multicenter Phase II Trial

2006 ◽  
Vol 24 (18) ◽  
pp. 2773-2778 ◽  
Author(s):  
Stephen Chia ◽  
Mark Clemons ◽  
Lee-Ann Martin ◽  
Angela Rodgers ◽  
Karen Gelmon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Liposomal Doxorubicin ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Her 2 ◽  
Grade 3

Purpose Cardiotoxicity precludes the concurrent use of doxorubicin and trastuzumab. Because pegylated liposomal doxorubicin (PLD) has equal efficacy but significantly less cardiotoxicity than conventional doxorubicin, this phase II study assessed the rate of cardiotoxicity and efficacy of first-line PLD plus trastuzumab in HER-2–positive metastatic breast cancer (MBC). Patients and Methods Women with HER-2–positive, measurable MBC, and a baseline left ventricular ejection fraction (LVEF) ≥ 55% were treated with PLD 50 mg/m2 every 4 weeks for six cycles and weekly trastuzumab (4 mg/kg loading dose then 2 mg/kg thereafter). Cardiotoxicity was defined as symptomatic congestive heart failure (CHF) with ≥ 10% decline in LVEF to below lower limits of normal, ≥ 15% decline in LVEF without symptomatic CHF, or less than 10% LVEF decline to less than 45%. Results Thirty women were enrolled, 13 had received prior adjuvant anthracyclines. A median 5.5 cycles of PLD were administered. Mean baseline LVEF was 62.8%, 59.5% after cycle four, and 58.3% after cycle six. Three patients (10%) developed protocol-defined cardiotoxicity. No patients developed symptomatic CHF. Response rate was 52%, with an additional 38% stable disease rate. At a median follow-up of 13.9 months, the median progression-free survival was 12.0 months; median overall survival has not yet been reached. The most common adverse events were grade 3 hand-foot syndrome (30%) and grade 3/4 neutropenia (27%). Conclusion The combination of PLD and trastuzumab is a well tolerated and active regimen in HER-2-positive MBC. Cardiotoxicity was observed, but limited to asymptomatic declines in LVEF. Further evaluation of this combination is warranted.

Phase II study of pegylated liposomal doxorubicin plus vinorelbine in metastatic breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10718-10718 ◽  
Author(s):  
S. Del Prete ◽  
L. Montella ◽  
V. Faiola ◽  
R. Guarrasi ◽  
G. Busto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Disease Progression ◽  
Phase Ii ◽  
Liposomal Doxorubicin ◽  
Phase Ii Study ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
Left Ventricular ◽  
Left Ventricular Ejection

10718 Background: Pegylated liposomal doxorubicin and vinorelbine are active single agents in metastatic breast cancer (MBC) and lack overlapping toxicity. The possibility of combining these two drugs therefore seems attractive. Methods: Twenty-five patients with MBC entered a phase II study of pegylated liposomal doxorubicin 40 mg/m2 intravenously (i.v.) on day 1 plus vinorelbine 25 mg/m2 i.v. on day 1 and vinorelbine 60 mg/m2 oral on day 14, every 4 weeks. A two-staged Simon accrual design was adopted for this phase II trial. Patients were required to have measurable disease, previous chemotherapy with or without an anthracycline-containing regimen, and a normal left ventricular ejection fraction (LVEF). Results: Twenty-one patients with MBC were eligible, assessable for response and toxicity. The overall response rate (on an intent-to-treat basis) was 36% (9 of 25; 95% CI, 20%-54%). One complete response and 8 partial responses were noted. In addition, 11 patients (44%) had stable disease of > 4 months duration, and 5 patients (20 %) had disease progression. Median time to disease progression was 10 months (range, 3–38 months) and median overall survival was 15 months (range, 4 to > 62 months). Neutropenia was the most frequent toxicity (grade 4 in 30% of patients and 19% of cycles), but neutropenic fever was seen in only 3 cases. No septic deaths occurred. Nonhematologic grade 3 side effects included skin toxicity (palmar-plantar erythrodysesthesia syndrome, 8%) and mucositis (14%). Late alopecia was seen in 51% of patients (grade 1 in 39%, and grade 2 in 12%). The median LVEFs were 64% (range, 50%-81%) at baseline and 62% (range, 37%-70%) after treatment. Only one patient presented an LVEF decrease to < 50%; however, no clinical heart failure was noted, and this patient recovered normal values after cessation of therapy. Conclusions: The combination of pegylated liposomal doxorubicin and vinorelbine can be safely administered to patients with anthracycline-pretreated MBC and is active in this population. Final data analysis will be presented. No significant financial relationships to disclose.

scholarly journals Pegylated liposomal doxorubicin plus carboplatin in patients with metastatic breast cancer: a phase II study

2012 ◽  
Vol 23 (10) ◽  
pp. 2599-2605 ◽  
Author(s):  
R.P. Collea ◽  
F.W. Kruter ◽  
J.E. Cantrell ◽  
T.K. George ◽  
S. Kruger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Liposomal Doxorubicin ◽  
Phase Ii Study ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin

Phase II Trial of Liposome-Encapsulated Doxorubicin, Cyclophosphamide, and Fluorouracil as First-Line Therapy in Patients With Metastatic Breast Cancer

1999 ◽  
Vol 17 (5) ◽  
pp. 1425-1425 ◽  
Author(s):  
Vicente Valero ◽  
Aman U. Buzdar ◽  
Richard L. Theriault ◽  
Nozar Azarnia ◽  
Gustavo A. Fonseca ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Cardiac Toxicity ◽  
Metastatic Breast ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Survival Duration ◽  
First Line ◽  
Ventricular Ejection Fraction

PURPOSE: To determine the efficacy and safety profile, including the risk for cardiac toxicity, of liposome-encapsulated doxorubicin (TLC D-99), fluorouracil (5-FU), and cyclophosphamide as first-line chemotherapy in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Forty-one women were registered in this phase II study. All patients had measurable disease and no previous chemotherapy for MBC. Treatment consisted of TLC D-99 60 mg/m2 and cyclophosphamide 500 mg/m2 on day 1 and 5-FU 500 mg/m2 on days 1 and 8 every 3 weeks. Serial cardiac monitoring, including endomyocardial biopsies, was performed. RESULTS: The overall response rate was 73% (95% confidence interval, 57% to 86%). The median duration of response was 11.2 months, the median time to treatment failure was 8.1 months, and the median overall survival duration was 19.4 months. The median number of cycles per patient was 10. The median cumulative dose of TLC D-99 was 528 mg/m2. Ten patients required hospitalization for febrile neutropenia. Nausea/vomiting, stomatitis, and fatigue higher than grade 2 occurred in 12%, 15%, and 41% of patients, respectively. Twenty-one patients reached a cumulative doxorubicin dose greater than 500 mg/m2. Three patients (7%) were withdrawn from the study due to protocol-defined cardiac toxicity, two because of a decrease in left ventricular ejection fraction to ≤ 40%, and one because her endomyocardial biopsy result was grade 1.5. One patient had congestive heart failure that was probably nonanthracycline related. CONCLUSION: This chemotherapy regimen, including TLC D-99, was highly active against MBC and associated with low cardiac toxicity despite high cumulative doses of doxorubicin.

Cardiac safety of pegylated liposomal doxorubicin (PLD) in combination with trastuzumab (T) in patients with metastatic breast cancer (MBC): Results from a multicenter phase II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1106-1106 ◽  
Author(s):  
E. Stickeler ◽  
D. O. Watermann ◽  
J. Woll ◽  
M. Foeldi ◽  
G. Gitsch
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Metastatic Breast ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Cardiac Safety ◽  
Ventricular Ejection Fraction ◽  
Cardiac Side Effects

1106 Background: Combination therapy of doxorubicin and trastuzumab is highly effective for Her2 positive MBC but characterized by frequent cardiac toxicity (CT). PLD can significantly reduce CT compared to conventional doxorubicin. Patients and Methods: 15 patients were enrolled in a phase II trial to evaluate cardiac safety of T (4 mg/Kg loading dose day 2, followed by weekly 2 mg/Kg) in combination with PLD (40 mg/m2 IV bolus day 1, q 28 d). 75% of pts. presented with more than 1 metastatic site and 40% for second line treatment. PLD was administered for 6 or 9 cycles, respectively, T until disease progression. To assess CT, all pts were evaluated with electrocardiogram (ECG) and echocardiograms (E) for Left Ventricular Ejection Fraction (LVEF) at baseline, every cycle during PLD and T, and every three months during T therapy alone. CT was defined as appearance of signs/ symptoms of congestive heart failure and/or an absolute decrease in LVEF > 10 units (below 50%) or decrease in LVEF > 15 units (above 50%). Results: Four pts. received 6 cycles, 4 pts. received 9 cycles of PLD, 4 pts discontinued treatment due to PD, 3 pts. due to toxicity. After a median follow up time of 15.4 months, 6 pts. (42.9%) demonstrated a clinical benefit and median OS was 16.2 months. Non cardiac side effects were mild with only 3 CTC Grade 3 events of 247 treatment cycles (1.2%). Three pts. developed minor ECG changes without pathological significance and 5 pts. had minor changes in their E with slight diastolic (n=3) or systolic (n=2) dysfunction. During follow-up, 3 pts. were diagnosed with pathological E findings, including 1 slight decrease of LVEF, one diffuse hypokinesia and one strong decrease in LVEF.The median LVEF in the study cohort was 66.1% at baseline, 62.7% after 6 cycles of therapy, 64.4% at the first follow up and did not change significantly until the 5 th examination. Conclusions: This study supports the combination of PLD and H in pts. with HER2 overexpressing metastatic breast cancer as a safe and feasible therapy. Due to the promising clinical response rates in this prognostically unfavorable group, this combination should be evaluated in larger studies as a potential regimen for adjuvant treatment of breast cancer. No significant financial relationships to disclose.

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