Abstract
OBJECTIVE:
Test
the safety and efficacy of sequentially blocking angiogenesis by adding
oral cyclophosphamide to bevacizumab following cancer progression on
bevacizumab in patients with recurrent ovarian cancer.
METHODS:
Eligibility
included≤2 lines of treatment for recurrence and measurable cancer by
RECIST 1.0. Patients received bevacizumab (15mg/kg every 3weeks IV) and
upon RECIST progression, oral cyclophosphamide (50mg orally daily) was
added. Objectives included safety, toxicities, 3- and 6-month PFS rates,
response rate, PFS, and OS.
RESULTS:
20 patients were
enrolled. Overall response rate was 10%, and 65% of patients had
confirmed stable disease (SD). Thirteen of 20 patients received oral
cyclophosphamide added to bevacizumab upon bevacizumab progression. Of
these 13 patients, 1 patient subsequently achieved a PR (this patient
had SD as best response during bevacizumab) and 3 patients had a
confirmed SD. For all patients, median PFS was 8.41 months, 6 month PFS
rate was 65%, duration of response (DOR) 7.3 months, and median OS was
22.72 months. Median DOR for patients receiving both bevacizumab and
cyclophosphamide was 8.4months. Most toxicities were grade 1 and 2 and
manageable.
Grade 3 and grade 4 toxicities included 1 myocardial
infarction, 1 gastrointestinal perforation (GIP), and 12/20 patients
(60%) developed grade 3 HTN.
CONCLUSIONS:
Addition of
oral cyclophosphamide to bevacizumab at the time of cancer progression
on bevacizumab appears to have continued anti-cancer effects in a
subgroup of patients and appears to be safe. Randomized trials testing
combination versus sequential anti-angiogenic therapy for recurrent
ovarian cancer are warranted.