ABSTRACT
Epithelial ovarian cancer (EOC) is among the top ten causes of cancer deaths worldwide, and is one of the most lethal gynecological malignancies in high income countries, with incidence and death rates expected to rise particularly in Asian countries where ovarian cancer is among the 5 most common cancers. Despite the plethora of randomised clinical trials investigating various systemic treatment options in EOC over the last few decades, both progression-free and overall survival have remained at approximately 16 and 40 months respectively. To date the greatest impact on treatment has been made by the use of poly (ADP-ribose) polymerase (PARP) inhibitors in women with advanced EOC and a BRCA1/2 mutation. Inhibition of PARP, the key enzyme in base excision repair, is based on synthetic lethality whereby alternative DNA repair pathways in tumor cells that are deficient in homologous recombination is blocked, rendering them unviable and leading to cell death. The Australia New Zealand Gynaecological Oncology Group (ANZGOG) is the national gynecological cancer clinical trials organization for Australia and New Zealand. ANZGOG's purpose is to improve outcomes and quality of life for women with gynecological cancer through cooperative clinical trials and undertaking multidisciplinary research into the causes, prevention and treatments of gynecological cancer. This review summarizes current ovarian cancer research and treatment approaches presented by Australian and New Zealand experts in the field at the 2020 ANZGOG webinar series entitled “Ovarian Cancer systems of Care”.
ABSTRACT
OBJECTIVE: Intraperitoneal (IP) chemotherapy in women with optimally debulked stage III ovarian cancer has been reported to prolong overall survival, but has not been widely adopted due to concerns about its toxicity, inconvenience and acceptability to patients. The purposes of this study were to determine the regimen's feasibility, adverse events, catheter-related complications, progression-free survival, health-related quality of life (HRQL), and patients' preferences for IP versus intravenous (IV) chemotherapy. METHODS: We conducted a single arm, multi-center study of IP chemotherapy with IV paclitaxel 135 mg/m2 (D1) over 3 hours, IP cisplatin 75 mg/m2 (D2), and IP paclitaxel 60 mg/m2 (D8) for 6 cycles in women with optimally debulked stage III ovarian or related cancers. RESULTS: Thirty-eight eligible patients were recruited from 12 sites between July 2007 and December 2009. Seventy-one percent (n=27) completed at least 4 cycles and 63% (n=24) completed all 6 cycles. Grade 3 or 4 adverse events included nausea (n=2), vomiting (n=2), abdominal pain (n=2), and diarrhea (n=1), but not febrile neutropenia, neurotoxicity, or nephropathy. There were no treatment-related deaths. Catheter-related complications were the most frequent cause of early discontinuation of treatment (16 patients, 21%). Apart from neurotoxicity HRQL which worsened over time, HRQL was stable or improved with time. Most patients (> or =50%) judged moderate benefits (e.g., an extra 6 months survival time or a 5% improvement in survival rates) necessary to make IP chemotherapy worthwhile. CONCLUSION: IP chemotherapy was feasible, tolerable, and most participants considered moderate survival benefits sufficient to warrant the adverse effects and inconvenience.