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

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/m 2 ), cisplatin (40 mg/m 2 ), 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.

[Clinical Application of Gemcitabine plus Cisplatin plus Bevacizumab Combination Chemotherapy for Ovarian Clear Cell Carcinoma].

Ovarian clear cell carcinoma(OCCC)shows a poor response to standard chemotherapy, and it is often difficult to choose a regimen for patients with recurrent OCCC. Several reports have suggested a synergistic effect between gemcitabine and cisplatin; another report suggested that gemcitabine, platinum, and bevacizumab are efficacious against recurrent ovarian cancer. We treated patients with OCCC using a combination chemotherapy regimen consisting of gemcitabine(1,000 mg/ m2)and cisplatin(40 mg/m2)on days 1 and 15, and bevacizumab(15 mg/kg)on day 1, with the cycle repeated every 4 weeks. Six patients received this therapy after informed consent, and 2 evaluable patients showed a partial response. Adverse events were mild, with Grade 3 anemia, leukopenia, and neutropenia occurring in 67%, 33%, and 17% of cases, respectively. No Grade 4 events were observed, including hematological or non-hematological toxicities. This suggests that a regimen of combined gemcitabine, platinum, and bevacizumab can be efficacious and feasible for the treatment of OCCC.

[Comparison between Primary Debulking Surgery and Neo-Adjuvant Chemotherapy Followed by Interval Debulking Surgery for Patients with Stage III-IV Ovarian Cancer].

The current standard treatment for advanced ovarian cancer is primary debulking surgery(PDS). We may expect a good prognosis if complete debulking(no visible residual tumor)is possible. However, if complete surgery is not possible owing to the location of the tumor or poor performance status, neo-adjuvant chemotherapy(NAC)could be an alternative option. Interval debulking surgery(IDS)can be planned after NAC to try and achieve complete debulking surgery. We reviewed stage III and IV epithelial ovarian cancers treated at Kansai Rosai Hospital between January 2012 and January 2016. Fifty-one cases (PDS: 22 cases, NAC-IDS: 29 cases)were enrolled in our analysis. Progression-free survival(PFS), overall survival(OS), the successful complete surgery rate, and the contents and complications of the surgery were compared between the PDS and NAC-IDS groups. There was no significant difference in PFS and OS between the 2 groups(PFS: p=0.467, OS: p=0.685). Blood loss was larger in the PDS group(p=0.013). Patients in the NAC-IDS group were likely to be able to eventually achieve complete surgery(p=0.016). NAC followed by IDS is one of the effective treatment options for advanced ovarian cancers.

[A Retrospective Analysis of Systematic Lymphadenectomy for Loco-Regional(pT1)Epithelial Ovarian Cancer].

BACKGROUND: The incidence of lymph node metastasis in pT1 epithelial ovarian cancer is between 5% and 21%. Most cases with lymph node metastasis are those of serous carcinoma; it is relatively rare in mucinous carcinoma. Therefore, there is a recent trend to omit systematic lymphadenectomy in early stage mucinous carcinoma. The purpose of this study was to verify whether the omission of systematic lymphadenectomy in mucinous carcinoma is oncologically safe. METHODS: We reviewed all pT1 epithelial ovarian cancer cases that were treated in our hospital between January 2002 and December 2015. RESULTS: Fiftynine cases of pT1 epithelial ovarian cancer were included. The overall rate of lymph node metastasis was 6.8%(4 in 59). It was 6.5%(2 in 31)in clear cell carcinoma and 22.2%(2 in 9)in mucinous carcinoma. CONCLUSION: According to our study, lymph node metastasis in pT1 mucinous carcinoma has a rate of 22.2% and some affected cases were not detected by presurgery imaging studies. Therefore, we need to be careful about the omission of systematic lymphadenectomy in mucinous carcinoma.

[A Retrospective Case Study of Combination Chemotherapy with Bevacizumab for Recurrent Ovarian Cancer].

OBJECTIVES: Treatment for ovarian cancer with bevacizumab(Bmab)has been covered by public medical insurance in Japan since November 2013. It is recommended that the use of Bmab is limited to the first treatment for FIGO stage III or IV ovarian cancer. The OCEAN trial for platinum sensitivity in relapsed patients and the AURELIA trial for platinum-resistance in relapsed patients were performed, and both significantly improved progression-free survival. METHOD: We retrospectively studied patients receiving Bmab with an anticancer agent for recurrent ovarian cancer. Written informed consent was obtained from all patients. RESULTS: Between November 2013 and September 2015, Bmab at 15mg/kg/3-4 week was administered to 20 patients with recurrent ovarian cancer. The median age was 58 years(range 32-81)and the median performance status was 0-2. Platinum-sensitive recurrence occurred in 6 patients. The response rate and disease control rate of combination chemotherapy with Bmab was 50.0% and 57.1%. However, 11 patients stopped treatment with Bmab due to serious adverse events. CONCLUSION: Combination chemotherapy with Bmab for recurrent ovarian cancer may be feasible.

[A Case of Bilateral Pneumothorax after Chemotherapy for Uterine Leiomyosarcoma with Multiple Lung Metastases].

We encountered a case of uterine leiomyosarcoma with multiple lung metastases. The patient was a 52-year-old woman who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy followed by chemotherapy with gemcitabine and docetaxel. After 1 cycle of chemotherapy, the lung metastasis was reduced, but at the same time, she developed bilateral pneumothorax. Chemical pleurodesis using talc was performed. The lungs were expanded and stabilized in 7 days. After 5 cycles of chemotherapy were administered, no recurrence of pneumothorax and adverse effects were observed.

[A Case of Pneumocystis Pneumonia during Chemotherapy for Recurrent Ovarian Cancer].

A 53-year-old patient with recurrent ovarian clear cell adenocarcinoma developed fever (39°C) and cough on day 28 of liposomal doxorubicin chemotherapy, the 4th cycle of the 4th regimen since initial treatment. Drug-induced interstitial pneumonia was suspected from a chest CT image showing diffuse ground-glass opacities; however, we deduced pneumocystis pneumonia from the elevated serum beta-D-glucan levels. After effective treatment with sulfamethoxazole and amphotericin B, the patient's symptoms and radiological findings improved. Pneumocystis pneumonia is an opportunistic infection that poses a risk not only for patients undergoing aggressive immunosuppressive therapy, those infected with HIV, and those with transplants, but also for patients undergoing chemotherapy. When pneumonia is diagnosed during chemotherapy, it is essential to consider the possibility of pneumocystis pneumonia.

[A case of stage IV rectal cancer with whom EPA oral nutritional supplements could resolve cachectic condition and promote patient compliance with cancer chemotherapy].

We report a case of a Stage IV rectal cancer patient for whom EPA oral nutritional supplements promoted treatment compliance with cancer chemotherapy by resolving a refractory cachectic condition. A 76-year-old male who developed a local re-growth of residual disease and multiple lung metastases after abdomino-perineal resection for lower rectal cancer was referred to our clinic for chemotherapy. On admission, he suffered from a loss of appetite as well as a 30% loss of usual body weight, caused by a cachectic condition with systemic inflammatory response. On starting chemotherapy, his daily diet was supplemented with EPA containing oral nutritional supplements (EPA ONS). Within 2 weeks after initiating EPA ONS treatment, the systemic inflammatory response resolved, and at the same time, body weight and the serum level of albumin increased, which allowed treatment compliance with aggressive multidrug chemotherapy. The patient gained 10 kg in body weight even after 12 months of aggressive chemotherapy, and has attained a longstanding partial remission from the disease. Although cancer cachexia is generally regarded as an end-stage irreversible pathological condition, EPA ONS may promote patient compliance with cancer chemotherapy by resolving cachectic condition, and thus may improve survival.

A case in which laparoscopic right salpingo-oophorectomy was performed in a patient with a lumboperitoneal shunt.

INTRODUCTION: Ventriculoperitoneal (VP shunts) and lumboperitoneal shunts (LP shunts) are used to treat hydrocephalus. The effectiveness of LP shunts has recently been demonstrated. Due to population aging, the number of patients with LP shunts is expected to increase. PRESENTATION OF CASE: A 51-year-old female, in whom an LP shunt had been inserted to treat hydrocephalus after a subarachnoid hemorrhage, underwent laparoscopic right salpingo-oophorectomy for a right endometriotic cyst. We consulted a neurosurgeon and confirmed the route of the shunt. We started a normal laparoscopic procedure. The head of the shunt tube was located in Douglas' pouch and was an obstacle to the procedure. We moved the head of the shunt tube to the vesicouterine pouch and successfully conducted the standard operation. We report the case together with a literature review. DISCUSSION: There have been several reports about gynecological laparoscopic surgery being performed in patients with VP shunts. On the other hand, we did not find any English literature about gynecological laparoscopic surgery being conducted in patients with LP shunts during a PubMed search. CONCLUSION: This is the first report about gynecological laparoscopic surgery being performed in a patient with an LP shunt.