Oxaliplatin + Doxorubicin in Recurrent Ovarian Cancer Shows Promise, Tolerability
CHICAGO—The combination of oxaliplatin and doxorubicin showed promising efficacy in either platinum-sensitive or platinum-resistant recurrent ovarian cancer, as reported by Ilya Pokateav, MD, from the Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, Moscow, and colleagues at the American Society of Clinical Oncology's 2011 Annual Meeting.
The primary endpoint was progression-free survival (PFS) in this multicenter, Phase 2 clinical trial in patients who had failed first-line chemotherapy. Secondary endpoints included overall survival (OS), objective response rate, and toxicity. There is no current standard of salvage chemotherapy in recurrent ovarian cancer. Oxaliplatin is an effective third-generation platinum compound that has no complete cross-resistance with carboplatin or cisplatin in ovarian cancer.
Eligible patients had histologically confirmed diagnosis of epithelial ovarian cancer (including primary peritoneal and fallopian tube cancer), disease progression following first-line platinum-based chemotherapy, peripheral sensory neuropathy grade ≤1, and no other malignancies. Bone marrow, liver, renal, and myocardial functions had to be within normal limits.
Patients who failed first-line chemotherapy received second-line chemotherapy with oxaliplatin 130mg/m2 IV administered over 2 hours on Day 1 and doxorubicin 50mg/m2 IV administered over 15 minutes on Day 1 every 3 weeks for 4–6 cycles. The median number of cycles was five (range: 2–6). A total of 29 patients were included in the study. Tumors were platinum-sensitive (PFI>12 m) in five (17.2%), partially platinum-sensitive (PFI>6 m) in 12 (41.4%), platinum-resistant (PFI<6 m) in 11 (38%) cases, in one (3.4%) case sensitivity of tumor to platinum was not known.
Objective response rate was 55.1% (24.1% complete remissions and 31% partial remissions). Stable disease was observed in 38% and progression in 2% of patients. The median PFS was 10.7 months with a median follow-up of 15.2 months. Because of this the median overall survival was not reached. The 1-year overall survival was 89%. A subanalysis showed that there were no statistically significant differences in response rate and PFS between platinum-sensitive (10.5 months) and platinum-resistant cancers (13.1 months; P>0.05).
Grade 3–4 adverse events reported per cycle included neutropenia (14.6%), febrile neutropenia (0.7%), and thrombocytopenia (5.1%). Sensory neuropathy Grade 1–2 and 3–4 was observed in eight (27.6%) and two (1.4%) cases respectively. There were five cases (17.2%) of oxaliplatin dose reductions and 10 cases (34.5%) of doxorubicin dose reductions and 10 cycles of chemotherapy were delayed due to toxicity.
Dr. Pokateav et al conclude that oxaliplatin and doxorubicin show promising efficacy in patients with either platinum-sensitive or platinum-resistant recurrent ovarian cancer.