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.

Combination therapy of oral cyclophosphamide and bevacizumab for patients with recurrent ovarian and peritoneal cancer.

Chemotherapy for patients with recurrent cancer aims to obtain survival benefits, relieve symptoms, and improve quality of life. We used oral cyclophosphamide and bevacizumab (BEV) combination therapy in recurrent ovarian and peritoneal cancer cases, where standard chemotherapy was infeasible. Subsequently, we evaluated the safety and efficacy of this treatment. Between August 2014 and June 2020, patients received the following regimen: oral cyclophosphamide 50 mg daily and intravenous cyclic BEV 15 mg/kg every 3 weeks. Data from 2 facilities were retrospectively analyzed. Twenty-two patients were enrolled (20 with ovarian cancer and two with peritoneal cancer). The median follow-up period and age were 18.9 months (range, 5.0-51.5) and 60 years (range 37-81), respectively. Sixteen patients had platinum resistance. The median number of previous chemotherapy regimens was 2.5 (range 0-5). The median implementation cycle was five (range 2-14). Eighteen patients discontinued treatment due to side effects (3 patient) and disease progression (15 patient). Grade 2 toxicities included neutropenia (1 patient), proteinuria (1 patient), hypertension (2 patient), and esophagitis (1 patient). Two patients had complete response and one had a partial response. Five patients had stable disease. The response rate in platinum-sensitive recurrence was 33.3%, and 7.1% in platinum-resistant recurrence, and a clinical benefit was found in 8 (36.3%) patients. The median PFS and overall survival from cyclophosphamide and BEV initiation was 5.3 months (range, 0.8-23.5) and 9.2 months (range, 4.8-51.5), respectively. The combination of oral cyclophosphamide and BEV does not have a high response rate, but is well-tolerated and can be used safely in patients who are difficult to treat after second-line chemotherapy. Data from 2 facilities were retrospectively analyzed.

Advanced ovarian cancer that resulted in death from intestinal perforation following tumor lysis syndrome: A case report.

INTRODUCTION AND IMPORTANCE: Tumor lysis syndrome (TLS) is an oncologic emergency, with 20 % cases occurring in solid tumors. Preventive measures are necessary depending on TLS risk. We report a case of TLS development after chemotherapy for advanced ovarian cancer which resulted in death by intestinal perforation. CASE PRESENTATION: A 76-year-old woman with multiple metastases had multi-cystic mass in the pelvic cavity. We diagnosed stage IVB ovarian cancer after exploratory laparoscopy and imaging test. Paclitaxel and carboplatin were started as neoadjuvant chemotherapy. Since day 4 of chemotherapy, vomiting, appetite loss, and diarrhea manifested; blood tests on day 9 showed electrolyte abnormality and decreased renal function. We diagnosed TLS and ileus. Her symptoms disappeared and blood chemistry improved after electrolyte correction in intensive care unit. However, vomiting and arrhythmia worsened on day 11, consciousness level lowered, and computed tomography showed intestinal perforation. She died on day 13. CLINICAL DISCUSSION: Advanced ovarian cancer is at high TLS risk due to large tumors, multiple metastases, and impaired renal function caused by urinary tract stenosis. TLS reported in ovarian cancer had large tumor volume; disease onset was often within 1 week after chemotherapy. After TLS improves, follow-up is necessary to detect serious complications. In ovarian cancer with intestinal adhesions, intestinal perforation risk should be considered, and intestinal wall invasion may be evaluated before treatment. CONCLUSION: TLS can be followed by fatal complications; many advanced ovarian cancers are at high TLS risk. Therefore, prophylactic measures and adequate information to patients and families before chemotherapy are necessary.

[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.

Multiple metastases after laparoscopic surgery for early-stage endometrial cancer: A case report.

INTRODUCTION: Laparoscopic surgery for early-stage endometrial cancer is associated with lower morbidity compared to open surgery and has comparable oncologic outcomes. We observed unexpected multiple metastases after laparoscopic surgery for endometrial cancer, the recurrence risk of which has previously been estimated to be low. Herein, we present this case and discuss the optimal management of endometrial cancer. PRESENTATION OF CASE: A 58-year-old woman complaining of atypical genital bleeding lasting for 5 months was diagnosed with stage IA endometrioid carcinoma grade 1. According to our primary strategy, she underwent a total laparoscopic hysterectomy and bilateral salpingo-oophorectomy. The post-operative diagnosis was consistent with the pre-operative diagnosis. Since the recurrence risk was post-operatively revised to an intermediate level, she was administered adjuvant chemotherapy. However, multiple metastases were observed 4 months post-operatively, and despite treatment for recurrent disease, she died 2 months later. The uterine specimen was re-examined after the diagnosis of recurrence, and the post-operative diagnosis was revised to endometrioid carcinoma grade 3, indicating that her recurrence risk might have been underestimated. DISCUSSION: The multiple metastases observed in this case, including those in the subcutaneous tissue, were presumably caused by pneumoperitoneum. Aspiration biopsy was used to confirm the histological diagnosis pre-operatively. However, dilation and curettage would have been preferable, considering aspiration biopsy provides limited diagnostic accuracy in some cases. Laparoscopic surgery is less invasive; however, it leads to a peculiar recurrence pattern, which is sometimes difficult to assess pre-operatively. CONCLUSION: Physicians should carefully consider indications for laparoscopic surgery for malignant diseases.

A case of retroperitoneal desmoid-type fibromatosis that involved the unilateral ureter after gynaecologic surgery.

INTRODUCTION: Desmoid-type fibromatosis represents a rare, benign, soft tissue tumour that is locally invasive with high recurrence potential. PRESENTATION OF CASE: We encountered a case of retroperitoneal desmoid-type fibromatosis in a 45-year-old woman who presented with chief complaints of stomach ache and vomiting. She underwent total abdominal hysterectomy and left salpingo-oophorectomy due to uterine myoma and a paroophoritic cyst at 42 years of age. Abdominal computed tomography showed a 5-cm left retroperitoneal tumour and severe hydronephrosis of the left kidney. Multiple imaging studies failed to provide a definitive diagnosis. Therefore, we performed tumour resection, right salpingo-oophorectomy, ureterectomy, and ureterocystostomy. The tumour surrounded the left ureter and adhered to the left internal/external iliac artery, rectum, bladder, and the edge of the vagina. Histopathologic examination yielded a diagnosis of retroperitoneal desmoid-type fibromatosis. One month after the operation, transvaginal sonography showed a 2-cm mass in the pelvis. We suspected tumour recurrence and commenced pharmacotherapy with tranilast (300mg/day, three times per day). Four months after the operation, the mass disappeared. DISCUSSION: There are minimal reports of postoperative intra-abdominal desmoid-type fibromatosis and preoperative diagnosis is difficult. To the best of our knowledge, there are no reported cases of desmoid-type fibromatosis that involved the ureter with severe hydronephrosis following a gynaecologic operation. CONCLUSION: We experienced a case of retroperitoneal desmoid-type fibromatosis that involved a unilateral ureter after gynaecologic surgery.

Endometrioid adenocarcinoma originating simultaneously from endometrium, sites of adenomyosis and ovarian endometriosis: A case report and review of our cancer database.

INTRODUCTION: Although adenomyosis is a common disease, it is a relatively rare site for cancer origin. On the other hand, chocolate cysts have the potential to develop into cancer. We report a case of endometrioid adenocarcinoma occurred at three sites simultaneously; uterine endometrium, adenomyosis and ovarian endometriosis. PRESENTATION OF CASE: A 51-year-old woman underwent total hysterectomy and bilateral salpingo-oophorectomy after a diagnosis of corpus cancer (endometrioid adenocarcinoma, G1) stage IA. However, cancer was also found independently at the site of adenomyosis and in endometrioid cysts after a detailed postoperative histological investigation. There has been no sign of recurrence at 12 months after six cycles of chemotherapy with paclitaxel and carboplatin. DISCUSSION: We reviewed cases of corpus cancer between January 2011 and December 2015 from our cancer database. Two hundred thirty-three patients with corpus cancer were identified. Ovarian malignancies were found in nine cases and six cases of them were histologically the same with the corpus cancer, but ovarian endometriosis was found in only two cases. On the other hand, adenomyosis was found histologically in 30 of these cases, but the case presented here was the only one diagnosed with cancer at a site of adenomyosis. CONCLUSION: The mechanism by which malignancy develops in the normal endometrial tissue is not clear, but if endometrial cancer is found in the uterus, it could also be present in ectopic endometrial tissues such as sites of adenomyosis or chocolate cysts.

[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.