A phase II clinical trial of pegylated liposomal doxorubicin and carboplatin plus bevacizumab in patients with platinum-sensitive recurrent ovarian, fallopian tube, or primary peritoneal cancer.
OBJECTIVE
To assess the safety and efficacy of pegylated liposomal doxorubicin (PLD), carboplatin, plus bevacizumab in patients with ovarian, fallopian tube, or primary peritoneal cancer.


METHODS
Patients with platinum-sensitive, recurrent disease received PLD 30 mg/m(2) and carboplatin area under the curve (AUC) 5 on Day 1 plus bevacizumab 10mg/kg on Days 1 and 15 of every 28-day cycle, for a maximum of 10 cycles. The primary endpoint was objective response rate (ORR) [complete+partial response]; additional endpoints were safety, duration of response, progression-free survival (PFS), and time to progression (TTP).


RESULTS
Of the 54 patients enrolled, 15 (27.8%) completed the study treatment as planned. Intent-to-treat (all enrolled patients) ORR was 72.2% (95% CI: 58.4, 83.5). Median duration of response was 11.9 months (95% CI: 9.3, not estimable) and median TTP was 13.9 months (95% CI: 11.4, 16.0). PFS was virtually the same as TTP. Three (5.6%) patients discontinued therapy due to disease progression, and another 3 (5.6%) patients discontinued therapy due to serious adverse events (Grade 4 thrombocytopenia, Grade 3 small/large intestinal obstruction/small intestinal perforation, and Grade 3 abdominal abscess). Fifty (92.6%) patients had ≥1 adverse event of interest, most commonly neutropenia (42.6%), hypertension (37.0%), stomatitis (37.0%), proteinuria (37.0%), and palmar-plantar erythrodysesthesia (27.8%). No appreciable decreases in left-ventricular ejection fraction were observed.


CONCLUSIONS
Most patients responded to PLD, carboplatin, and bevacizumab combination therapy. The safety profile was consistent with the known toxicities of these agents. These findings present a potential treatment option for women with ovarian, fallopian tube, or primary peritoneal cancer.
Division of Gynecologic Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Marcela G
MG
del Carmen
John
J
Micha
Laurie
L
Small
Daron G
DG
Street
Anil
A
Londhe
Tracy
T
McGowan
D018784:Abdominal Abscess / Q000209:etiology; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000209:etiology; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D019540:Area Under Curve; D000068258:Bevacizumab; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002277:Carcinoma / Q000188:drug therapy*; D000077216:Carcinoma, Ovarian Epithelial; D016001:Confidence Intervals; D018450:Disease Progression; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy*; D005260:Female; D060831:Hand-Foot Syndrome / Q000209:etiology; D006801:Humans; D006973:Hypertension / Q000209:etiology; D057194:Intention to Treat Analysis; D007415:Intestinal Obstruction / Q000209:etiology; D007416:Intestinal Perforation / Q000209:etiology; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy*; D009503:Neutropenia / Q000209:etiology; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010534:Peritoneal Neoplasms / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D011507:Proteinuria / Q000209:etiology; D013280:Stomatitis / Q000209:etiology; D013318:Stroke Volume / Q000187:drug effects; D013921:Thrombocytopenia / Q000209:etiology; D013997:Time Factors
D061067:Antibodies, Monoclonal, Humanized; C506643:liposomal doxorubicin; D000068258:Bevacizumab; D011092:Polyethylene Glycols; D004317:Doxorubicin; D016190:Carboplatin