A final report of a phase I study of veliparib (ABT-888) in combination with low-dose fractionated whole abdominal radiation therapy (LDFWAR) in patients with advanced solid malignancies and peritoneal carcinomatosis with a dose escalation in ovarian and fallopian tube cancers.
Gynecol Oncol
; 144(3): 486-490, 2017 03.
Article
in En
| MEDLINE
| ID: mdl-28109627
ABSTRACT
BACKGROUND:
The combination of low-dose radiation therapy with PARP inhibition enhances anti-tumor efficacy through potentiating DNA damage. We combined low-dose fractionated whole abdominal radiation (LDFWAR) with ABT-888 in patients with peritoneal carcinomatosis with a dose escalation in ovarian and fallopian cancer patients (OV).METHODS:
Patients were treated with veliparib, 40-400mg orally BID on days 1-21 of 3 28-day cycles on 6 dose levels. Dose levels 5 and 6 included only OV patients. LDFWAR consisted of 21.6Gy in 36 fractions, 0.6Gy twice daily on days 1 and 5 for weeks 1-3 of each cycle. Circulating tumor material and quality of life were serially assessed.RESULTS:
32pts were treated. Median follow-up was 45months (10-50). The most common treatment-related grade 3 and 4 toxicities were lymphopenia (59%), anemia (9%), thrombocytopenia (12%), neutropenia (6%), leukopenia (6%), nausea (6%), diarrhea (6%), anorexia (6%), vomiting (6%) and fatigue (6%). The maximum tolerated dose was determined to be 250mg PO BID. Median PFS was 3.6months and median OS was 9.1months. In OV patients, OS was longer for platinum-sensitive patients (10.9mo) compared to platinum-resistant patients (5.8mo). QoL decreased for all groups during treatment. Germline BRCA status was known for 14/18 patients with OV cancers, 5 of whom were BRCA mutation carriers. One objective response (3%) was observed.CONCLUSION:
ABT-888 plus LDFWAR is tolerable with gastrointestinal symptoms, fatigue and myelosuppression as the most common toxicities. The single observed objective response was in a germline BRCA mutated, platinum-sensitive patient.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ovarian Neoplasms
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Peritoneal Neoplasms
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Benzimidazoles
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Fallopian Tube Neoplasms
/
Poly(ADP-ribose) Polymerase Inhibitors
Aspects:
Patient_preference
Limits:
Aged
/
Female
/
Humans
/
Middle aged
Language:
En
Journal:
Gynecol Oncol
Year:
2017
Document type:
Article
Affiliation country:
United States