Randomized phase III trial of pegylated liposomal doxorubicin versus vinorelbine or mitomycin C plus vinblastine in women with taxane-refractory advanced breast cancer

Alan M. Keller, Robert G. Mennel, Vassilis A. Georgoulias, Jean Marc Nabholtz, Aura Erazo, Anna Lluch, Charles Vogel, Manfred Kaufmann, Gunther von Minckwitz, I. Craig Henderson, Lillian Mellars, Leila Alland, Craig Tendler

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Abstract

Purpose: To compare the efficacy of pegylated liposomal doxorubicin (PLD) with that of a common salvage regimen (comparator) in patients with taxane-refractory advanced breast cancer. Patients and Methods: Following failure of a first- or second-line taxane-containing regimen for metastatic disease, 301 women were randomly assigned to receive PLD (50 mg/m2 every 28 days); or comparator-vinorelbine (30 mg/m2 weekly) or mitomycin C (10 mg/m2 day 1 and every 28 days) plus vinblastine (5 mg/m2 day 1, day 14, day 28, and day 42) every 6 to 8 weeks. Patients were stratified before random assignment based on number of previous chemotherapy regimens for metastatic disease and presence of bone metastases only. Results: Progression-free survival (PFS) and overall survival (OS) were similar for PLD and comparator (PFS: hazard ratio [HR], 1.26; 95% CI, 0.98 to 1.62; P = .11; median, 2.9 months [PLD] and 2.5 months [comparator]; OS: HR, 1.05; 95% CI, 0.82 to 1.33; P = .71; median, 11.0 months [PLD] and 9.0 months [comparator]). In anthracycline-naïve patients, PFS was somewhat longer with PLD, relative to the comparator (n = 44; median PFS, 5.8 v 2.1 months; HR, 2.40; 95% CI, 1.16 to 4.95; P = .01). Most frequently reported adverse events were nausea (23% to 31%), vomiting (17% to 20%), and fatigue (9% to 20%) and were similar among treatment groups. PLD-treated patients experienced more palmar-plantar erythrodysesthesia (37%; 18% grade 3, 1 patient grade 4) and stomatitis (22%; 5% grades 3/4). Neuropathy (11%), constipation (16%), and neutropenia (14%) were more common with vinorelbine. Alopecia was low in both the PLD and vinorelbine groups (3% and 5%). Conclusion: PLD has efficacy comparable to that of common salvage regimens in patients with taxane-refractory metastatic breast cancer, thereby representing a useful therapeutic option.

Original languageEnglish
Pages (from-to)3893-3901
Number of pages9
JournalJournal of Clinical Oncology
Volume22
Issue number19
DOIs
StatePublished - Dec 1 2004
Externally publishedYes

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Vinblastine
Mitomycin
Breast Neoplasms
Disease-Free Survival
taxane
liposomal doxorubicin
vinorelbine
Stomatitis
Survival
Bone Diseases
Anthracyclines
Alopecia
Constipation
Neutropenia
Nausea
Vomiting
Fatigue
Neoplasm Metastasis
Drug Therapy
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Randomized phase III trial of pegylated liposomal doxorubicin versus vinorelbine or mitomycin C plus vinblastine in women with taxane-refractory advanced breast cancer. / Keller, Alan M.; Mennel, Robert G.; Georgoulias, Vassilis A.; Nabholtz, Jean Marc; Erazo, Aura; Lluch, Anna; Vogel, Charles; Kaufmann, Manfred; von Minckwitz, Gunther; Henderson, I. Craig; Mellars, Lillian; Alland, Leila; Tendler, Craig.

In: Journal of Clinical Oncology, Vol. 22, No. 19, 01.12.2004, p. 3893-3901.

Research output: Contribution to journalArticle

Keller, AM, Mennel, RG, Georgoulias, VA, Nabholtz, JM, Erazo, A, Lluch, A, Vogel, C, Kaufmann, M, von Minckwitz, G, Henderson, IC, Mellars, L, Alland, L & Tendler, C 2004, 'Randomized phase III trial of pegylated liposomal doxorubicin versus vinorelbine or mitomycin C plus vinblastine in women with taxane-refractory advanced breast cancer', Journal of Clinical Oncology, vol. 22, no. 19, pp. 3893-3901. https://doi.org/10.1200/JCO.2004.08.157
Keller, Alan M. ; Mennel, Robert G. ; Georgoulias, Vassilis A. ; Nabholtz, Jean Marc ; Erazo, Aura ; Lluch, Anna ; Vogel, Charles ; Kaufmann, Manfred ; von Minckwitz, Gunther ; Henderson, I. Craig ; Mellars, Lillian ; Alland, Leila ; Tendler, Craig. / Randomized phase III trial of pegylated liposomal doxorubicin versus vinorelbine or mitomycin C plus vinblastine in women with taxane-refractory advanced breast cancer. In: Journal of Clinical Oncology. 2004 ; Vol. 22, No. 19. pp. 3893-3901.
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abstract = "Purpose: To compare the efficacy of pegylated liposomal doxorubicin (PLD) with that of a common salvage regimen (comparator) in patients with taxane-refractory advanced breast cancer. Patients and Methods: Following failure of a first- or second-line taxane-containing regimen for metastatic disease, 301 women were randomly assigned to receive PLD (50 mg/m2 every 28 days); or comparator-vinorelbine (30 mg/m2 weekly) or mitomycin C (10 mg/m2 day 1 and every 28 days) plus vinblastine (5 mg/m2 day 1, day 14, day 28, and day 42) every 6 to 8 weeks. Patients were stratified before random assignment based on number of previous chemotherapy regimens for metastatic disease and presence of bone metastases only. Results: Progression-free survival (PFS) and overall survival (OS) were similar for PLD and comparator (PFS: hazard ratio [HR], 1.26; 95{\%} CI, 0.98 to 1.62; P = .11; median, 2.9 months [PLD] and 2.5 months [comparator]; OS: HR, 1.05; 95{\%} CI, 0.82 to 1.33; P = .71; median, 11.0 months [PLD] and 9.0 months [comparator]). In anthracycline-na{\"i}ve patients, PFS was somewhat longer with PLD, relative to the comparator (n = 44; median PFS, 5.8 v 2.1 months; HR, 2.40; 95{\%} CI, 1.16 to 4.95; P = .01). Most frequently reported adverse events were nausea (23{\%} to 31{\%}), vomiting (17{\%} to 20{\%}), and fatigue (9{\%} to 20{\%}) and were similar among treatment groups. PLD-treated patients experienced more palmar-plantar erythrodysesthesia (37{\%}; 18{\%} grade 3, 1 patient grade 4) and stomatitis (22{\%}; 5{\%} grades 3/4). Neuropathy (11{\%}), constipation (16{\%}), and neutropenia (14{\%}) were more common with vinorelbine. Alopecia was low in both the PLD and vinorelbine groups (3{\%} and 5{\%}). Conclusion: PLD has efficacy comparable to that of common salvage regimens in patients with taxane-refractory metastatic breast cancer, thereby representing a useful therapeutic option.",
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T1 - Randomized phase III trial of pegylated liposomal doxorubicin versus vinorelbine or mitomycin C plus vinblastine in women with taxane-refractory advanced breast cancer

AU - Keller, Alan M.

AU - Mennel, Robert G.

AU - Georgoulias, Vassilis A.

AU - Nabholtz, Jean Marc

AU - Erazo, Aura

AU - Lluch, Anna

AU - Vogel, Charles

AU - Kaufmann, Manfred

AU - von Minckwitz, Gunther

AU - Henderson, I. Craig

AU - Mellars, Lillian

AU - Alland, Leila

AU - Tendler, Craig

PY - 2004/12/1

Y1 - 2004/12/1

N2 - Purpose: To compare the efficacy of pegylated liposomal doxorubicin (PLD) with that of a common salvage regimen (comparator) in patients with taxane-refractory advanced breast cancer. Patients and Methods: Following failure of a first- or second-line taxane-containing regimen for metastatic disease, 301 women were randomly assigned to receive PLD (50 mg/m2 every 28 days); or comparator-vinorelbine (30 mg/m2 weekly) or mitomycin C (10 mg/m2 day 1 and every 28 days) plus vinblastine (5 mg/m2 day 1, day 14, day 28, and day 42) every 6 to 8 weeks. Patients were stratified before random assignment based on number of previous chemotherapy regimens for metastatic disease and presence of bone metastases only. Results: Progression-free survival (PFS) and overall survival (OS) were similar for PLD and comparator (PFS: hazard ratio [HR], 1.26; 95% CI, 0.98 to 1.62; P = .11; median, 2.9 months [PLD] and 2.5 months [comparator]; OS: HR, 1.05; 95% CI, 0.82 to 1.33; P = .71; median, 11.0 months [PLD] and 9.0 months [comparator]). In anthracycline-naïve patients, PFS was somewhat longer with PLD, relative to the comparator (n = 44; median PFS, 5.8 v 2.1 months; HR, 2.40; 95% CI, 1.16 to 4.95; P = .01). Most frequently reported adverse events were nausea (23% to 31%), vomiting (17% to 20%), and fatigue (9% to 20%) and were similar among treatment groups. PLD-treated patients experienced more palmar-plantar erythrodysesthesia (37%; 18% grade 3, 1 patient grade 4) and stomatitis (22%; 5% grades 3/4). Neuropathy (11%), constipation (16%), and neutropenia (14%) were more common with vinorelbine. Alopecia was low in both the PLD and vinorelbine groups (3% and 5%). Conclusion: PLD has efficacy comparable to that of common salvage regimens in patients with taxane-refractory metastatic breast cancer, thereby representing a useful therapeutic option.

AB - Purpose: To compare the efficacy of pegylated liposomal doxorubicin (PLD) with that of a common salvage regimen (comparator) in patients with taxane-refractory advanced breast cancer. Patients and Methods: Following failure of a first- or second-line taxane-containing regimen for metastatic disease, 301 women were randomly assigned to receive PLD (50 mg/m2 every 28 days); or comparator-vinorelbine (30 mg/m2 weekly) or mitomycin C (10 mg/m2 day 1 and every 28 days) plus vinblastine (5 mg/m2 day 1, day 14, day 28, and day 42) every 6 to 8 weeks. Patients were stratified before random assignment based on number of previous chemotherapy regimens for metastatic disease and presence of bone metastases only. Results: Progression-free survival (PFS) and overall survival (OS) were similar for PLD and comparator (PFS: hazard ratio [HR], 1.26; 95% CI, 0.98 to 1.62; P = .11; median, 2.9 months [PLD] and 2.5 months [comparator]; OS: HR, 1.05; 95% CI, 0.82 to 1.33; P = .71; median, 11.0 months [PLD] and 9.0 months [comparator]). In anthracycline-naïve patients, PFS was somewhat longer with PLD, relative to the comparator (n = 44; median PFS, 5.8 v 2.1 months; HR, 2.40; 95% CI, 1.16 to 4.95; P = .01). Most frequently reported adverse events were nausea (23% to 31%), vomiting (17% to 20%), and fatigue (9% to 20%) and were similar among treatment groups. PLD-treated patients experienced more palmar-plantar erythrodysesthesia (37%; 18% grade 3, 1 patient grade 4) and stomatitis (22%; 5% grades 3/4). Neuropathy (11%), constipation (16%), and neutropenia (14%) were more common with vinorelbine. Alopecia was low in both the PLD and vinorelbine groups (3% and 5%). Conclusion: PLD has efficacy comparable to that of common salvage regimens in patients with taxane-refractory metastatic breast cancer, thereby representing a useful therapeutic option.

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