title: Phase I clinical trial of bendamustine and bevacizumab for patients with advanced cancer.
abstract: Bendamustine, a cytotoxic alkylating agent, has shown promising results in solid tumors. An investigator-initiated phase I clinical trial of the anti-vascular endothelial growth factor agent bevacizumab and bendamustine was conducted in patients with advanced cancer, because the 2 drugs have different mechanisms of antitumor activity and nonoverlapping toxicity. Patients were treated with escalating doses of intravenous bendamustine (70, 80, 90, and 100 mg/m(2); days 1 and 2) and intravenous bevacizumab (10 mg/kg; days 1 and 15). A conventional "3 + 3" study design was used. Forty-two patients were treated: 23 women and 19 men. The median age was 60 years. Patients had received a median of 4 prior therapies (range, 1-10). The most common cancer types were colorectal (n=9), head and neck (n= 8), non-small cell lung (n=6), and breast (n=5). Overall, 117 cycles were administered (median per patient, 2; range, 1-8). No dose-limiting toxicities were noted during the escalation phase. Therefore, the highest dose (level 4) of bendamustine (100 mg/m(2)) was used in the expansion phase. The most common toxicities were fatigue (n=22), nausea (n=14), anorexia (n=9), and thrombocytopenia (n=7). Of 38 patients who were evaluable for response, 23 (61%) had stable disease, including 2 (5.2%) who had stable disease for 6 months or more (1 with adenoid cystic carcinoma and 1 with non-small cell lung cancer). This regimen of bendamustine (100 mg/m(2)) and bevacizumab (10 mg/kg) was well tolerated and yielded disease stabilization in selected heavily pretreated patients with advanced cancer.
authors.affiliation: From the aDepartment of Investigational Cancer Therapeutics, and bDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Apostolia M
authors.initials: AM
authors.lastname: Tsimberidou
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Adamopoulos
authors.forename: Yang
authors.initials: Y
authors.lastname: Ye
authors.forename: Sarina
authors.initials: S
authors.lastname: Piha-Paul
authors.forename: Filip
authors.initials: F
authors.lastname: Janku
authors.forename: Siqing
authors.initials: S
authors.lastname: Fu
authors.forename: David
authors.initials: D
authors.lastname: Hong
authors.forename: Gerald S
authors.initials: GS
authors.lastname: Falchook
authors.forename: Aung
authors.initials: A
authors.lastname: Naing
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wheler
authors.forename: Adoneca
authors.initials: A
authors.lastname: Fortier
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Hess
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069461:Bendamustine Hydrochloride; D000068258:Bevacizumab; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D009588:Nitrogen Mustard Compounds; D000068258:Bevacizumab; D000069461:Bendamustine Hydrochloride