Phase II study of gemcitabine, cisplatin, and bevacizumab for first recurrent and refractory ovarian clear cell carcinoma Kansai Clinical Oncology Group-G1601

Abstract

Patients with advanced ovarian clear cell carcinoma (CCC) have a poor prognosis in the absence of an effective standard treatment. Combination therapy with gemcitabine, cisplatin, and bevacizumab (GPBev) is promising for ovarian CCC. Thus, we conducted a multi-institutional, phase II trial in Japan to examine the efficacy and safety of GPBev for CCC. This is the first study on the use of GPBev for CCC. Eighteen patients (median age, 56.5 years) with pathologically confirmed first recurrent or refractory CCC and having evaluable regions, as assessed using RECIST, were recruited between January 2017 and May 2019. Gemcitabine (1000 mg/m2), cisplatin (40 mg/m2), and bevacizumab (10 mg/kg) were administered intravenously on days 1 and 15, every 28 days, for 6–10 cycles, until disease progression or intolerable toxicity. The primary endpoint was overall response rate (ORR). The secondary endpoints included disease control rate (DCR) and adverse events (AEs). Fifteen patients (83.3%) completed 6–10 cycles of treatment; three patients (two with AEs and one with progressive disease) did not. The ORR was 61.1% [complete response (CR) 3 and partial response (PR) 8] and DCR was 88.9% (CR 3, PR 8, and stable disease 5). Grade 3 and 4 hematological AEs were observed in 16.7 and 5.6% of the patients, respectively. Nonhematological AEs of grades 3 and 4 were observed in 27.8 and 5.6% of the patients, respectively. GPBev is a promising therapy for CCC owing to the high ORR and acceptable toxicity for the first recurrence and refractory CCC.

Metastatic Clear Cell Carcinoma of Unknown Primary Origin in an Elderly Female Patient With Paraneoplastic Hypercalcemia

“…Treatment strategies for CCC typically depend on the identified primary site and may involve a combination of surgical resection, chemotherapy, and targeted therapies. In ovarian clear cell carcinoma, platinum-based chemotherapy is the mainstay of treatment, but targeted therapies such as bevacizumab (a monoclonal antibody targeting vascular endothelial growth factor) are being investigated in clinical trials [5,6].…”

Nicotinamide N-methyltransferase enhances paclitaxel resistance in ovarian clear cell carcinoma

“…A retrospective analysis of a multicenter, Phase 3, randomized, controlled trial (JGOG3017/GCIG) comparing TC (carboplatin and paclitaxel) and CPT-P (irinotecan and cisplatin) therapy in patients with recurrent or persistent OCCA found that patients with platinum-resistant relapse had a signi cantly shorter median post-progression survival (PPS) compared to those with platinum-sensitive relapse [8]. Combination therapy with gemcitabine, cisplatin, and bevacizumab (GP + Bev) has also been reported to be promising for advanced OCCA [9]. The identi cation of molecules involved in paclitaxel resistance in OCCA may provide an opportunity to improve the e cacy of paclitaxel and carboplatin regimens in OCCA.…”