Bendamustine hydrochloride in patients with refractory soft tissue sarcoma: a noncomparative multicenter phase 2 study of the German sarcoma group (AIO-001).
BACKGROUND
For patients with advanced soft tissue sarcoma (STS), no standard treatment is established after previous chemotherapy with anthracyclines and ifosfamide. Bendamustine hydrochloride is a bifunctional alkylating agent that is not cross-resistant to other DNA-interacting substances including anthracyclines and oxazaphosphorines. It has shown single-agent activity in refractory lymphoma, myeloma, and some solid tumors. A phase 2 study was initiated to evaluate the efficacy of bendamustine in previously treated patients.


METHODS
Thirty-six of 44 screened patients were included and received a total of 101 cycles (median, 2 cycles; range, 1-8 cycles), 21 as second-line treatment and 15 as third-line treatment. The median age was 55 years (range, 18-79 years). Bendamustine was given as an intravenous infusion over 30 minutes at a dose of 100 mg/m(2) on 2 consecutive days and repeated every 28 days. Eighty-eight percent of cycles could be given without dose or schedule modification.


RESULTS
The toxicity profile was mild, consisting of National Cancer Institute Common Toxicity Criteria (CTC) grade 3 neutropenia in 11% and grade 3 anemia in 9% of patients. Nonhematologic toxicities were noticed with CTC grade 3 fever in 3% of patients. No other grade 3 toxicity and no treatment-related toxic deaths were observed. The best overall response according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria was 1 partial remission (3%) and disease stabilizations in 31% of patients. Six of 15 patients (40%) with leiomyosarcoma histology achieved stable disease. The estimated 3-month and 6-month progression-free survival rates were 35.3% and 23.5%, respectively, for all histologic subtypes included.


CONCLUSIONS
In patients with refractory STS, bendamustine is well tolerated and appears moderately effective, particularly in patients with leiomyosarcoma histology.
Hartmann
Joerg T
JT
Department of Medical Oncology, Hematology, Immunology, Rheumatology, and Pulmonology, Medical Center, Eberhard-Karls-University, Tuebingen, Germany. joerg.hartmann@med.uni-tuebingen.de
Mayer
Frank
F
Schleicher
Jan
J
Horger
Marius
M
Huober
Jens
J
Meisinger
Ines
I
Pintoffl
Jan
J
Käfer
Gabriele
G
Kanz
Lothar
L
Grünwald
Viktor
V
D000293:Adolescent; D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000069461:Bendamustine Hydrochloride; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds; D000069461:Bendamustine Hydrochloride