PARAGON (ANZGOG-0903): a phase 2 study of anastrozole in asymptomatic patients with estrogen and progesterone receptor-positive recurrent ovarian cancer and CA125 progression / 부인종양

OBJECTIVE: A subset of patients with recurrent ovarian cancer (ROC) may benefit from antiestrogen therapy with higher response rates reported in tumors that are strongly estrogen receptor (ER)-positive (ER+). PARAGON is a basket trial that incorporates 7 phase 2 trials investigating the activity of anastrozole in patients with ER+ and/or progesterone receptor (PR)-positive (PR+) recurrent/metastatic gynecological cancers. METHODS: Postmenopausal women with ER+ and/or PR+ ROC, who were asymptomatic and had cancer antigen 125 (CA125) progression after response to first line chemotherapy, where chemotherapy was not clinically indicated. Patients received anastrozole 1 mg daily until progression or unacceptable toxicity. RESULTS: Fifty-four patients were enrolled (52 evaluable). Clinical benefit at three months (primary endpoint) was observed in 18 patients (34.6%; 95% confidence interval [CI]=23%–48%). Median progression-free survival (PFS) was 2.7 months (95% CI=2.1–3.1). The median duration of clinical benefit was 6.5 months (95% CI=2.8–11.7). Most patients progressed within 6 months of starting anastrozole but 12 (22%) continued treatment for longer than 6 months. Anastrozole was well tolerated. In the exploratory analysis, ER histoscores and the intensity of ER staining did not correlate with clinical benefit rate or PFS. CONCLUSION: A subset of asymptomatic patients with ER+ and/or PR+ ROC and CA125 progression had durable clinical benefit on anastrozole, with acceptable toxicity. Anastrozole may delay symptomatic progression and the time to subsequent chemotherapy. The future challenge is to identify the subset of patients most likely to benefit from an aromatase inhibitor and whether the clinical benefit could be increased by the addition of other agents.

A practical guide to understanding, using and including patient reported outcomes in clinical trials in ovarian cancer / 부인종양

Health related quality of life (HRQOL) is a key priority for patients with ovarian cancer as there is significant morbidity associated with the disease and the treatment. It is therefore essential to include measures of HRQOL and patient reported outcomes (PROs) in all clinical trials and ideally report them in the initial manuscript. The results of these analyses help interpret the primary trial endpoints which are typically progression free survival and overall survival from the perspective of the patients, but can also assist with regulatory approval of new drugs and inform future patients regarding the potential benefits and downsides of the treatment as well as help support clinical recommendations. Including PROs in clinical trials allows patient-defined clinical benefits to be assessed in parallel to traditional survival outcomes to provide a more holistic overview and aid in the interpretation of the trial results. Given the importance of these instruments in clinical trials, greater effort is required to improve the appropriate inclusion, quality of analyses and reporting of PROs. It is also essential that all clinicians understand the intricacies of the selection, implementation and interpretation of these measures of HRQOL and PRO's and how important their contribution is to clinical trials as well as clinical practice. This review is a practical guide for clinicians to gain a better understanding of PROs and how they can be incorporated into ovarian cancer trials.

Feasibility, acceptability and preferences for intraperitoneal chemotherapy with paclitaxel and cisplatin after optimal debulking surgery for ovarian and related cancers: an ANZGOG study / 부인종양

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.