Combination of bevacizumab and 2-weekly pegylated liposomal doxorubicin as first-line therapy for locally recurrent or metastatic breast cancer. A multicenter, single-arm phase II trial (SAKK 24/06).
BACKGROUND
pegylated liposomal doxorubicin (PLD) and bevacizumab are active agents in the treatment of metastatic breast cancer (MBC). We carried out a multicenter, single-arm phase II trial to evaluate the toxicity and efficacy of PLD and bevacizumab as first-line treatment in MBC patients.


METHODS
bevacizumab (10 mg/kg) and PLD (20 mg/m(2)) were infused on days 1 and 15 of a 4-week cycle for a maximum of six cycles. Thereafter, bevacizumab monotherapy was continued at the same dose until progression or toxicity. The primary objective was safety and tolerability, and the secondary objective was to evaluate efficacy of the combination.


RESULTS
thirty-nine of 43 patients were assessable for the primary end point. Eighteen of 39 patients (46%, 95% confidence interval 30% to 63%) had a grade 3 toxicity. Sixteen (41%) had grade 3 palmar-plantar erythrodysesthesia, one had grade 3 mucositis, and one severe cardiotoxicity. Secondary end point of overall response rate among 43 assessable patients was 21%.


CONCLUSIONS
in this nonrandomized single-arm trial, the combination of bimonthly PLD and bevacizumab in locally recurrent and MBC patients demonstrated higher than anticipated toxicity while exhibiting only modest activity. Based on these results, we would not consider this combination for further investigation in this setting.
Rochlitz
C
C
Department of Oncology, University Hospital Basel, Basel. Electronic address: crochlitz@uhbs.ch.
Ruhstaller
T
T
Breast Center, Kantonsspital St Gallen, St Gallen.
Lerch
S
S
SAKK Coordinating Center, Bern.
Spirig
C
C
Breast Center, Kantonsspital St Gallen, St Gallen.
Huober
J
J
Breast Center, Kantonsspital St Gallen, St Gallen.
Suter
T
T
Department of Cardiology and Oncology, Inselspital Bern, Bern.
Bühlmann
M
M
Department of Cardiology and Oncology, Inselspital Bern, Bern.
Fehr
M
M
Department of Gynecology, University Hospital Zurich, Zurich.
Schönenberger
A
A
Department of Oncology, Kantonsspital Aarau, Aarau.
von Moos
R
R
Department of Oncology, Kantonsspital Graubünden, Graubünden.
Winterhalder
R
R
Department of Oncology, Kantonsspital Luzern, Luzern.
Rauch
D
D
Department of Oncology, Regionalspital Thun, Thun.
Müller
A
A
Department of Oncology, Kantonsspital Winterthur, Winterthur.
Mannhart-Harms
M
M
Department of Internal Medicine, Andreas Klinik Cham, Cham.
Herrmann
R
R
Department of Oncology, University Hospital Basel, Basel.
Cliffe
B
B
SAKK Coordinating Center, Bern.
Mayer
M
M
SAKK Coordinating Center, Bern.
Zaman
K
K
Department of Oncology, University Hospital Lausanne, Lausanne, Switzerland.
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy*; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C506643:liposomal doxorubicin; D000068258:Bevacizumab; D011092:Polyethylene Glycols; D004317:Doxorubicin