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Background: Platinum/taxane (TC) chemotherapy with debulking surgery stays the mainstay of the treatment in ovarian cancer patients with peritoneal metastasis, and recently its novel modality, intraperitoneal carboplatin with dose-dense paclitaxel (ddTCip), was shown to have greater therapeutic impact. Nevertheless, the response varies among patients and consequent recurrence, or relapse often occurs. Discovery of therapeutic response predictor to ddTCip and/or TC therapy is eagerly awaited to improve the treatment outcome., Methods: Using datasets in 76 participants in our ddTCip study and published databases on patients received TC therapy, we first validated a total of 75 previously suggested markers, sought out more active biomarkers through the association analyses of genome-wide transcriptome and genotyping data with progression-free survival (PFS) and adverse events, and then developed multiplex statistical prediction models for PFS and toxicity by mainly using multiple regression analysis and the classification and regression tree (CART) algorithm., Results: The association analyses revealed that SPINK1 could be a possible biomarker of ddTCip efficacy, while ABCB1 rs1045642 and ERCC1 rs11615 would be a predictor of hematologic toxicity and peripheral neuropathy, respectively. Multiple regression analyses and CART algorithm finally provided a potent efficacy prediction model using 5 gene expression data and robust multiplex toxicity prediction models-CART models using a total of 4 genotype combinations and multiple regression models using 15 polymorphisms on 12 genes., Conclusion: Biomarkers and multiplex models composed here could work well in the response prediction of ddTCip and/or TC therapy, which might contribute to realize optimal selection of the key therapy., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Purpose: This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer., Materials and Methods: Eligible patients had platinum-resistant epithelial ovarian cancer, received ≤ 1 regimen after diagnosis of resistance, and had an Eastern Cooperative Oncology Group performance score of ≤ 1. Patients were randomly assigned 1:1 to nivolumab (240 mg once every 2 weeks [as one cycle]) or chemotherapy (GEM 1000 mg/m 2 for 30 minutes [once on days 1, 8, and 15] followed by a week's rest [as one cycle], or PLD 50 mg/m 2 once every 4 weeks [as one cycle]). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate, duration of response, and safety., Results: Patients (n = 316) were randomly assigned to nivolumab (n = 157) or GEM or PLD (n = 159) between October 2015 and December 2017. Median OS was 10.1 (95% CI, 8.3 to 14.1) and 12.1 (95% CI, 9.3 to 15.3) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.0; 95% CI, 0.8 to 1.3; P = .808). Median PFS was 2.0 (95% CI, 1.9 to 2.2) and 3.8 (95% CI, 3.6 to 4.2) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.5; 95% CI, 1.2 to 1.9; P = .002). There was no statistical difference in overall response rate between groups (7.6% v 13.2%; odds ratio, 0.6; 95% CI, 0.2 to 1.3; P = .191). Median duration of response was numerically longer with nivolumab than GEM or PLD (18.7 v 7.4 months). Fewer treatment-related adverse events were observed with nivolumab versus GEM or PLD (61.5% v 98.1%), with no additional or new safety risks., Conclusion: Although well-tolerated, nivolumab did not improve OS and showed worse PFS compared with GEM or PLD in patients with platinum-resistant ovarian cancer., Competing Interests: Junzo HamanishiResearch Funding: MSD, Ono Pharmaceutical, Sumitomo Dainippon Pharma Noriyuki KatsumataConsulting or Advisory Role: Nippon Zoki Pharmaceutical Co, Ltd Kimio UshijimaHonoraria: AstraZeneca, Chugai Pharmaceutical, Takeda, Nippon Kayaku, MSD, Kaken Pharmaceutical, Kyowa Kirin InternationalResearch Funding: AstraZeneca, Chugai Pharmaceutical, Takeda, Kaken Pharmaceutical, Nippon Kayaku, Mochida Pharmaceutical Co, Ltd, Taiho Pharmaceutical, Eisai, Ono Pharmaceutical, AbbVie, MSD Tadashi KimuraHonoraria: Nobelpharma Co, Ltd, GE Healthcare Japan, Mochida Pharmaceutical Co, Ltd, Chugai Pharmaceutical Co, Ltd, Bayer Pharmaceuticals, Aska PharmaceuticalConsulting or Advisory Role: Fermata Pharma, Rohto PharmaceuticalResearch Funding: Fuji Pharma, Nippon Shinyaku, Takeda Yakuhin, Taihou Yakuhin, Mochida Pharmaceutical Co, Ltd, Nihon Seiyaku, Zeria Pharmaceutical Koji MatsumotoHonoraria: Chugai Pharmaceutical, AstraZeneca, Kyowa Hakko Kirin, Eisai, MSD K.K., Eli Lilly Japan K.K., Taiho Oncology, AbbVie, PfizerResearch Funding: Ono Pharmaceutical, MSD, AstraZeneca, Novartis, Chugai Pharmaceutical, Eisai Kimihiko ItoHonoraria: AstraZenecaConsulting or Advisory Role: AstraZeneca, AbbVie, Nippon Shinyaku, TerumoUncompensated Relationships: Kansai Clinical Oncology Group Hidemichi WatariHonoraria: MSD K.K., Tsumura & Co, AstraZeneca, Aska Pharmaceutical Co, Ltd, Terumo, Bayer Yakuhin, Kaken Pharmaceutical, Mochida Pharmaceutical Co, Ltd, Daiichi Sankyo/UCB Japan, Chugai Pharmaceutical, TakedaConsulting or Advisory Role: Decision Resources Group Japan, Kaken Pharmaceutical, Chugai PharmaceuticalResearch Funding: Hokkaido Welfare Federation of Agricultural Cooperatives, Kaken Pharmaceutical, Mochida Pharmaceutical Co, Ltd, Taiho Pharmaceutical, Chugai Pharmaceutical, Hokkaido Cancer Society, TakedaOther Relationship: T-PEC Nobutaka TakahashiHonoraria: Olympus, Ethicon/Johnson & Johnson, Intuitive Surgical, Kaken Pharmaceutical Kosei HasegawaHonoraria: MSD K.K., Daiichi Sankyo, Bayer Yakuhin, Bristol-Myers Squibb K.K., Chugai Pharmaceutical, AstraZeneca, EisaiConsulting or Advisory Role: MSD K.K., Kaken PharmaceuticalResearch Funding: Ono Pharmaceutical, Daiichi Sankyo, Takeda Kan YonemoriHonoraria: Eisai, Pfizer, AstraZeneca, Novartis, Taiho PharmaceuticalConsulting or Advisory Role: Chugai Pharmaceutical, Ono Pharmaceutical, Novartis, EisaiResearch Funding: Ono Pharmaceutical Kazuhiro TakeharaHonoraria: Takeda Pharmaceutical Company, AstraZeneca, Eisai, Chugai Pharmaceutical, MSD, Mochida Pharmaceutical Co, LtdResearch Funding: Chugai Pharmaceutical Hitoshi NiikuraHonoraria: Takeda Sari NakaoUncompensated Relationships: Japanese Gynecologic Oncology Group Toshiaki SaitoHonoraria: Nippon Kayaku, Kyowa Hakko Kirin, Eisai, Kaken Pharmaceutical CompanyResearch Funding: Chugai Pharmaceutical, Taiho Pharmaceutical Takayuki EnomotoHonoraria: AstraZeneca, MSD, Chugai Pharmaceutical Satoru NagaseHonoraria: Chugai Pharmaceutical, AstraZeneca Aikou OkamotoHonoraria: AstraZeneca K.K., MSD, Chugai Pharmaceutical, TakedaConsulting or Advisory Role: AstraZeneca K.K., Chugai PharmaceuticalSpeakers' Bureau: AstraZeneca K.K.Research Funding: Kissei Pharmaceutical, Meiji Holdings, Pfizer, Fuji Pharma, Taiho Pharmaceutical, Kaken Pharmaceutical, Chugai Pharmaceutical, Tsumura & Co, Daiichi Sankyo Company, Ltd, Shinnihonseiyaku, Mochida Pharmaceutical Co, Ltd, Aska Pharmaceutical Co, Ltd, Takeda, Terumo Yoshito TeraiResearch Funding: Ethicon/Johnson & Johnson, MSD, Covidien, Terumo, Daiichi Sankyo/UCB Japan, Chugai Pharmaceutical, Taiho Pharmaceutical Akira TakazawaEmployment: Ono Pharmaceutical Yusuke TakahashiEmployment: Ono PharmaceuticalStock and Other Ownership Interests: Ono Pharmaceutical Yoshinobu NambaEmployment: Ono PharmaceuticalHonoraria: Boehringer Ingelheim Daisuke AokiHonoraria: AstraZeneca K.K., MSD K.K., Takeda, Chugai Pharmaceutical, Myriad GeneticsConsulting or Advisory Role: Takeda, MSD K.K., AstraZeneca K.K.Speakers' Bureau: AstraZeneca K.K., Takeda Keiichi FujiwaraHonoraria: Kyowa Hakko Kirin, Zeria Pharmaceutical, Nippon Kayaku, Chugai Pharmaceutical, Eisai, Taiho Pharmaceutical, Daiichi Sankyo, Ono Pharmaceutical, TakedaConsulting or Advisory Role: AstraZeneca, MSD, Taiho Pharmaceutical, Eisai, Takeda, Genmab, AbbVie, Pfizer, NanoCarrierResearch Funding: Eisai, Kaken Pharmaceutical, Chugai Pharmaceutical, Shionogi, ImmunoGen, ONCOtherapeutics, AstraZeneca, Eli Lilly, Zeria Pharmaceutical, Ono Pharmaceutical, MSD, Genmab, Regeneron, Merck KGaA, Ono PharmaceuticalTravel, Accommodations, Expenses: Pfizer, AbbVie, MSDNo other potential conflicts of interest were reported.

We had conducted phase 1/2 studies of cancer vaccination therapy using neo-tumor antigens in patients with refractory/persistent cervical cancer (CC) and ovarian cancer (OC) to assess the feasibility and efficacy. Enrollees must be refractory/persistent disease for usual treatments with Human Leukocyte Antigen-A*0201 or A*2402. The targets were epitope peptides obtained from driver genes in surviving pathways as follows: for CC A*0201, peptides from Up Regulating Lung Cancer 10 gene (URLC10) and Hypoxia-inducible gene 2 (HIG-2) and for OC A*0201, HIG2, VEGFR (vascular epithelial growth factor receptor) 1 and 2 were used. For CC A*2402, Forkhead Box M1 (FOXM1), Maternal Embryonic Leucine zipper Kinase (MELK), and Holliday Junction Recognition Protein (HJURP) were used. For OC A*2402, cocktails of peptides from FOXM1, MELK, HJURP, VEGFR1, and VEGFR2 were used. Subcutaneous administration was performed with adjuvant weekly. The toxicity profiles and tumor-response were analyzed in eight-week interval. Sixty-six patients were accrued, and 64 were evaluable for adverse events (AEs), and 35 for response. AEs of G2/3 dermatologic reaction (DR) of injection site had been identified in 15.6% and no other severe AEs were detected. Response rate in OC and CC were 22.9% and 20%, respectively. Median overall survival showed longer in performance status (PS) 0 (versus PS1/2), in CRP negative (versus positive) and in DR positive (versus negative) such as 8.7 m versus 1.2 m ( p < .001), 8.8 m versus 3.0 m ( p < .05) and 10.2 m versus 1.2 m ( p < .001), respectively. In conclusion, our vaccination therapy was feasible and effective in this cohort of patients., (© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Background: We evaluated the efficacy of intraperitoneal (IP) carboplatin in combination with dose-dense paclitaxel (ddTCip) for suboptimal residual ovarian cancer., Methods: This was a phase 2 study to evaluate ddTCip. Patients with stage II-IV ovarian carcinoma, who underwent primary cytoreductive surgery and had radiologically evaluable disease after surgery, were eligible to participate in this study. IP carboplatin (AUC = 6) was administered on day 1, and intravenous paclitaxel (80 mg/m 2 ) was administered on days 1, 8 and 15. The primary endpoint was response rate. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. Interval- debulking surgery followed by the same regimen was allowed when indicated., Results: A total of 117 patients were considered eligible for this study prior to surgery and temporarily registered. Of the 117 patients, 76 patients met the inclusion criteria and were enrolled in this study. Fifty-nine (83.1%) patients had objective clinical responses. Median PFS and OS were 18.3 and 55.5 months, respectively. Sixty-four (84.2%) patients had grade 3/4 neutropenia, 43 (56.5%) patients had anaemia and 17 (22.4%) patients had thrombocytopenia. Port-related adverse events occurred in nine (11.8%) patients., Conclusions: Front-line chemotherapy with ddTCip therapy appears safe and effective, even for patients with suboptimal residual ovarian cancer., Trial Registration: UMIN Clinical Trials Registry (ID: UMIN000001713) on February 16th, 2009.

This phase 1, open-label, dose-escalation study was conducted to determine the safety, tolerability, pharmacokinetics and preliminary efficacy of veliparib with carboplatin and weekly paclitaxel in Japanese women with newly diagnosed, advanced ovarian cancer. Patients received veliparib at 100 or 150 mg b.i.d. on days 1-21 with carboplatin (area under the concentration-time curve 6 mg/mL•min) on day 1 and paclitaxel 80 mg/m 2 on days 1, 8 and 15 every 3 weeks for up to 6 21-day cycles. Dose escalation followed a 3 + 3 design to determine dose-limiting toxicities, maximum tolerated dose and the recommended phase 2 dose. Nine patients (median age 62 [range 27-72] years) received a median of 5 (range 3-6) cycles of treatment (3 at 100 mg, 6 at 150 mg). There were no dose-limiting toxicities. The most common adverse events of any grade were neutropenia (100%), alopecia (89%), peripheral sensory neuropathy (78%), and anemia, nausea and malaise (67% each). Grade 3 or 4 adverse events were associated with myelosuppression. Pharmacokinetics of carboplatin/paclitaxel were similar at both veliparib doses. Response, assessed in five patients, was partial in four and complete in one (objective response rate 100%). The response could not be assessed in four patients who had no measurable disease at baseline. The recommended phase 2 dose of veliparib, when combined with carboplatin/paclitaxel, is 150 mg b.i.d. Findings from this phase 1 trial demonstrate the tolerability and safety of veliparib with carboplatin/paclitaxel, a regimen with potential clinical benefit in Japanese women with ovarian cancer., (© 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Ovarian clear cell carcinoma (OCCC) is mostly resistant to standard chemotherapy that results in poor patient survival. To understand the genetic background of these tumours, we performed whole-genome sequencing of OCCC tumours., Methods: Tumour tissue samples and matched blood samples were obtained from 55 Japanese women diagnosed with OCCC. Whole-genome sequencing was performed using the Illumina HiSeq platform according to standard protocols., Results: Alterations to the switch/sucrose non-fermentable (SWI/SNF) subunit, the phosphatidylinositol-3-kinase (PI3K)/Akt signalling pathway, and the receptor tyrosine kinase (RTK)/Ras signalling pathway were found in 51%, 42%, and 29% of OCCC tumours, respectively. The 3-year overall survival (OS) rate for patients with an activated PI3K/Akt signalling pathway was significantly higher than that for those with inactive pathway (91 vs 40%, hazard ratio 0.24 (95% confidence interval (CI) 0.10-0.56), P=0.0010). Similarly, the OS was significantly higher in patients with the activated RTK/Ras signalling pathway than in those with the inactive pathway (91 vs 53%, hazard ratio 0.35 (95% CI 0.13-0.94), P=0.0373). Multivariable analysis revealed that activation of the PI3K/Akt and RTK/Ras signalling pathways was an independent prognostic factor for patients with OCCC., Conclusions: The PI3K/Akt and RTK/Ras signalling pathways may be potential prognostic biomarkers for OCCC patients. Furthermore, our whole-genome sequencing data highlight important pathways for molecular and biological characterisations and potential therapeutic targeting in OCCC.

Background: The aims of this report were to describe a case of ovarian adenosquamous carcinoma and to systematically review the pertinent literature., Methods: We describe a case in which a 57-year-old woman had stage IC ovarian cancer histologically diagnosed as adenosquamous carcinoma. We also systematically reviewed the literature using the PubMed database., Case Presentation: Preoperative computed tomography and magnetic resonance imaging showed a tumor measuring 14 cm in diameter and containing solid areas. Tumor marker levels were as follows: CA125, 42.6 U/mL; CA 19-9, 134.1 U/mL; CEA, 0.9 ng/mL; and SCC, 1.6 ng/mL. The patient underwent multiple surgeries including total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic lymph node dissection, para-aortic lymph node biopsy, and total omentectomy. Based on the cytological features of the ascitic fluid, the tumor was diagnosed as a squamous cell carcinoma. Histological examination of an excised specimen showed the transition of an endometrioid adenocarcinoma to a squamous cell carcinoma. There was no evidence of any teratomas or endometriosis-related features. We considered the tumor to be an adenosquamous carcinoma, with the squamous cell carcinoma component arising from the endometrioid adenocarcinoma component. After surgery, the patient underwent 6 cycles of paclitaxel and carboplatin chemotherapy. There has been no recurrence to date, 66 months after the initial treatment., Results: Histologically, the 8 adenosquamous carcinomas reported in the literature either arose from the mature cystic teratoma (4 cases) or endometriosis (3 cases) or were pure adenosquamous carcinomas (1 case). Our literature search uncovered no cases of ovarian adenosquamous carcinomas originating from endometrioid adenocarcinomas., Conclusions: This is the first reported case of an adenosquamous carcinoma arising from an endometrioid adenocarcinoma. Because such tumors are rare, their standard management is unclear.

However, in patients with epithelial ovarian cancer, the standard chemotherapy of paclitaxel/carboplatin (TC) therapy is very effective as the overall survival (OS) reached 70-80% in early stage (stage I/II ) patients, in advanced stage patients like stage III/IV the recurrence rate exceeds 80%and the 5-year-OS remains 55%at most. Longer survival remains so worse as well that the 10-year-OS fails to 5-7%. In order to push up the rate of longer survival, the strategies have been considered from the some points of view such as additional new anti-cancer agents, changing of drug delivery system (DDS) (i.e. intraperitoneal administration), additional radiotherapy or radioactive agents (in USA), the combination of molecular agents and specific classification in treatment using "Bio-markers (so-called tailor-made medicine)". Here we reviewed the up-coming treatments in maintenance fashion using anti-angiogenic agents or supposing effective and curable treatment by PARP inhibitors in the cohorts of epithelial ovarian cancers with BRCAness.

Objective: Ovarian low-grade serous carcinoma (LGSC) is a rare and indolent tumor. The utility of 18F-FDG PET/CT in monitoring patients with LGSC has not been established. We assessed the accuracy and clinical impact of 18F-FDG PET/CT in patients with ovarian LGSC after initial treatment., Methods: A retrospective analysis was performed on patients with ovarian LGSC who had undergone 18F-FDG PET/CT scans during follow-up after primary treatment. The impact of 18F-FDG PET/CT on the management plan was assessed. The sensitivity, specificity, and accuracy of 18F-FDG PET/CT findings in the detection of recurrence were calculated. Total lesion glycolysis (TLG) was determined to assess metabolic activity of tumors. Potential prognostic factors for disease-free and overall survival after recurrence were assessed., Results: Forty-eight patients were included in the analysis, 39 with recurrent disease and 9 without recurrence. A total of 91 18F-FDG PET/CT scans were performed, and 30% of these (27/91) had an impact on the management plan. Sensitivity, specificity, and accuracy in the detection of LGSC recurrence were 94%, 100%, and 97%, respectively, for 18F-FDG PET/CT; 89%, 95%, and 93%,respectively, for CT; and 68%, 89%, and 73%, respectively, for serum CA-125. There was no significant difference in sensitivity between PET/CT and CT. Survival after recurrence was poorer in patients with a TLG value greater than 67.7g., Conclusions: 18F-FDG PET/CT may provide useful information during the follow-up of patients with LGSC after initial treatment. TLG may be a predictor of survival after recurrence., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Angiogenesis is required for cancer growth. To promote vascular sprouting, an angiogenic switch is flipped that up-regulates factors such as vascular endothelial growth factor(VEGF), fibroblast growth factor(FGF), and angiopoietins, and downregulates antiangiogenic factors such as thrombospondin-1 and angiostatin. Accumulating evidence supports the concept that angiogenesis plays a central role in ovarian and cervical carcinogenesis and disease progression. Two phase III randomized trials have been published that evaluated the addition of bevacizumab to standard chemotherapy as the front-line treatment of advanced ovarian cancer. Additional trials have evaluated the combination of bevacizumab with chemotherapy in platinum-sensitive and platinum-resistant recurrent disease. All these trials showed a statistically significant improvement in progression-free survival(PFS), although no improvement in overall survival(OS)has been reported. Based on these data, bevacizumab was recently approved for the treatment of ovarian cancer in Japan and Europe. Bevacizumab plus chemotherapy significantly improves the OS in patients with stage IVB, recurrent or persistent cervical carcinoma. The improvement in OS with bevacizumab treatment was not accompanied by a decrease in the quality of life(QOL). Bevacizumab is the first targeted agent to improve OS in gynecologic cancer.

Double gynecologic cancer (primary cancers in two organs) is relatively rare. However, triple gynecologic cancer (primary cancers in three organs) is extremely rare. We experienced a case of triple cancer, with primary cervical, endometrial and ovarian cancers, each showing different histopathological features. A 50-year-old woman with a preoperative diagnosis of cervical cancer stage Ib1 with a pathological diagnosis of mucinous adenocarcinoma underwent radical hysterectomy. The pathological diagnoses of the extracted masses were endometrioid adenocarcinoma in the uterine corpus and serous adenocarcinoma in the left ovary. Consequently, triple cancer was diagnosed. After the operation, six cycles of a paclitaxel/carboplatin regimen were administered, and no relapse of the cancers has been observed to date. To our knowledge, this is only the second case report in the international literature of concurrent gynecologic triple cancers of epithelial origin; that is, invasive cervical, endometrial and ovarian cancers, each with different histopathological features., (© 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.)

Background: A multicenter phase II trial was conducted to evaluate the efficacy and toxicity of irinotecan plus carboplatin chemotherapy in patients with epithelial ovarian cancer (EOC)., Patients and Methods: Patients with either radiologically- or serologically-recurrent EOC were administered intravenous irinotecan (60 mg/m(2); days 1 and 8) and carboplatin area under the curve of 5 mg/ml/min (day 1), repeated every 21 days. The primary end-point was response rate (RR), while the secondary end-points were adverse events and progression-free survival (PFS)., Results: Between 2005 and 2009, 40 patients (median age=59 years) with EOC were enrolled. Intention-to-treat analysis showed an RR of 43% [95% confidence interval (CI)=27-58%]. For patients with a platinum-free interval (PFI) of <6 months, overall RR based on RECIST was 21% (95% CI=0-43%) and median PFS was 3.7 months (95% CI=2.5-7.7 months), while those in patients with PFI ≥6 months were 52% (95% CI=31-74%) and 9.1 months (95% CI=7.9-11.2 months), respectively. Grade 3/4 toxicity encountered during the first cycle included G3/G4 neutropenia in 65% of patients (12/14), G3/G4 thrombocytopenia in 48% (18/1), G3 febrile neutropenia in 5% (2), G3 nausea in 5% (2), G3 diarrhea in 5% (2), and G3 fatigue in 5% of patients (2)., Conclusion: This carboplatin plus irinotecan combination demonstrated a modest activity in recurrent EOC. However, considering its hematological toxicities, the regimen should be further investigated to establish the feasibility of the modified dose for platinum-sensitive disease.

Objective: Intraperitoneal chemotherapy (IP) is known to be effective after optimal primary debulking surgery (PDS) for ovarian cancer (OC). Here, we conducted a phase II study to investigate its effectiveness after interval debulking surgery (IDS)., Methods: Thirty-seven patients with FIGO stage IIIB-IV and suboptimal (≥1cm diameter) residual disease after PDS were enrolled. Carboplatin (AUC 4 IV, Day 1) and cisplatin (50mg/m(2) IV, Day 3) were given q21d for 3cycles. After IDS, paclitaxel (175mg/m(2) IV Day 1 or 60mg/m(2) IV Days 1, 8, and 15, since 2000) and cisplatin (75mg/m(2) IP Day 2) were given q21d for 4cycles. The primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS) and adverse events (CTCAE ver. 2.0). Clinical manifestations at first recurrence and subsequent treatment were also surveyed., Results: Of the 37 patients, high-grade, serous adenocarcinoma was found in 33. Stages IIIB, IIIC, and IV were found in 2, 24, and 11 patients, respectively. After IDS, 23 patients had no macroscopic residual tumor. No patients had permanent enterostomy, febrile neutropenia, or platelet transfusion. The treatment protocol was completed in 22 patients, and discontinued in 5 due to IP catheter-related complications. Median PFS and OS were 22 and 57months, respectively. Among the 28 patients with recurrence, 10 had no intraperitoneal disease at first recurrence. Among the 8 patients who underwent surgical cytoreduction, 6 had no residual tumor, while 2 had a <1-cm-diameter residual tumor., Conclusion: IP after IDS for patients with initially suboptimally debulked OC was effective., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Recently, the resistant-to-paclitaxel/carboplatin therapy(TC), the standard first-line chemo-regimen for epithelial ovarian cancer(EOC), has been reported in subtypes of EOC, such as clear cell carcinoma and mucinous adenocarcinoma. The response to the chemo-regimen is evaluated by tumor markers and imaging of CT/MRI. The timing of regimen change depends on the identification of progressive disease(PD), using Rustin's criteria for CA125 and RECIST v1.1 for imaging, or severe adverse events(AEs>=grade 3, 4)in non-hematologic toxicities. For patients with refractory or recurrent EOC, the aim of their treatment was changed to keeping their quality of life for as long as possible with/without curing them from the disease. Thus, the selection of regimens for recurrent EOC should be suitable for the patient-friendly regimens, such as those with fewer AEs, out-patient- setting and shorter administration. As for molecular-targeted agents, bevacizumab and olaparib with TC therapy were reported to give patients significantly longer progression-free survival than control arms. Further investigation of immune-therapy or new agents for aiming total cell kill of tumor cell is should be warranted to obtain longer overall survival in patients with advanced EOC.

Ovarian carcinoid is a rare tumor accounting for approximately 0.1% of all ovarian malignancies. We describe a case of peptide-YY-producing strumal carcinoid of the ovary associated with severe constipation. A 48-year-old woman was found to have a pelvic mass on ultrasonography when she visited her primary doctor for a health check-up. She was thus referred to our department. Magnetic resonance imaging revealed a solid right ovarian tumor 60 × 50 mm in size. The patient underwent a right adnexectomy and was histopathologically diagnosed as having strumal carcinoid of the ovary. On immunohistochemical examination, the tumor cells were positive for peptide YY. The patient's constipation resolved rapidly after surgery. Based on her clinical course, her constipation was considered to have been caused by the strumal carcinoid of the ovary. The clinical course of this case supports the previously recognized correlation between peptide-YY-producing ovarian carcinoid and constipation., (© 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.)

Pure-type clear cell carcinoma (CCC) has been recognized as a distinct subtype of ovarian cancer, showing resistance to conventional platinum-based chemotherapy and resulting in poor prognosis. The aim of the study was to evaluate the effects of complete surgical staging procedures for early-stage CCC patients in a retrospective multi-institutional analysis. During the period 1992 to 2002, a total of 199 patients with pT1 M0 CCC were identified. Survival analysis was estimated by Kaplan-Meier methods, and prognostic factors were evaluated using a Cox regression model. Among pT1 M0 tumors, retroperitoneal lymph node status was negative in 125 cases (pN0, 63%), positive in 10 cases (pN1, 5%), and unknown in 64 cases (pNx, 32%). Progression-free survival of pN1 was significantly worse than that of pN0 (P < 0.05), whereas there was no significant difference between pN1 and pNx. There was no significant difference of overall survival (OS) among the 3 groups. Multivariate analysis revealed that peritoneal cytology status was the only independent prognostic factor for progression-free survival (P = 0.04), but completion of surgical staging procedures was not a prognostic factor. There was no significant prognostic factor for OS. Our study implied that complete surgical staging enabled us to distinguish a high-risk group of recurrence in pT1 M0 CCC; however, the procedure could not improve OS. Although the study was a limited retrospective study, the impact of peritoneal cytology status was more important than complete surgical staging procedure in CCC patients. More effective treatment modality was warranted, especially for CCC cases positive for malignant peritoneal cytology.

Background: A phase I/II study of docetaxel (DOC) and gemcitabine (GEM) combination for treatment-resistant ovarian cancer (OC) was conducted., Materials and Methods: Eligible patients exhibited recurrent OC within 12 months after initial treatment, or after more than 2 chemotherapy regimens. Planned dose levels (DL) were as follows: DOC 70 mg/m(2), GEM 800 mg/m(2) (DL1); DOC 70 mg/m(2), GEM 1000 mg/m(2) (DL2). DOC was administered on day 1 combined with GEM on days 1 and 8 every 3 weeks. Adverse events were assessed by NCI-CTC2.0J. Response was evaluated by RECIST or Rustin's criteria., Results: The recommended dose was DL1. For all enrolled patients, the median interval from last chemotherapy was 2.5 (1-11) months and 32 patients were assessable for response. One complete response, 6 partial responses and 6 stable disease were noted. Median time to progression was 4.8 months. Toxicities were mainly hematological and manageable., Conclusion: This combination could be an acceptable treatment option before palliation.

Background: Irinotecan hydrochloride, a topoisomerase I inhibitor, has been preliminarily recognized as an effective agent against clear cell carcinoma of the ovary (CCC), but there are few clinical data. Our aim was to compare progression-free survival (PFS) between patients treated with irinotecan hydrochloride and cisplatin (CPT-P) and those with treated with paclitaxel and carboplatin (TC)., Methods: One hundred and seventeen patients at International Federation of Gynecology and Obstetrics (FIGO) stages Ic (ascites/malignant washing) - IV were identified by scanning the medical records of ten Japanese hospitals. After complete surgical staging procedures including lymphadenectomy, 35 patients received CPT-P and 82 patients received TC. The PFS and overall survival of the two groups were compared using the Kaplan-Meier method., Results: There was no significant difference in median age, performance status, FIGO stage, rate of optimal cytoreduction, or follow-up period between the CPT-P and TC groups. Two-year and 5-year PFS was 48% and 40%, respectively, in the TC group and 55% and 55%, respectively, in the CPT-P group (P = 0.31). Multiple regression analysis revealed that only residual tumor was an independent prognostic factor for PFS (P < 0.01)., Conclusion: CPT-P showed a potential therapeutic effect, at least no less than that of TC therapy. Although there was no significant survival benefit in the present retrospective analysis, we recommend that the CPT-P regimen be evaluated in a larger, prospective, clinical trial.

Clear cell carcinoma (CCC) of the ovary has distinct characteristics showing resistance to conventional platinum-based regimen. Our aim was to evaluate the effects of combination therapy with irinotecan hydrochloride and cisplatin (CPT-P), comparing to regimen with paclitaxel and platinum (TP). We retrospective reviewed 172 patients with complete surgical staging procedures including lymphadenenctomy. Forty-six patients received CPT-P and 126 patients were treated with TP. Survival of the two groups was compared. Between CPT-P group and TP group, there was no significant difference in median age, performance status, FIGO stage, rate of optimal cytoreduction, and follow-up period. There was no significant difference in progression-free survival of patients with stage I tumors (p=0.95) and suboptimally debulked stage II-IV tumors (p=0.92). Although there was no significant difference of overall survival, progression-free survival of CPT-P group was significantly better than that of TP group in optimally debulked stage II-IV (p=0.03). Multiple regression survival analysis revealed CPT-P regimen (p=0.02) and residual tumor diameter (p<0.01) were both independent prognostic factors in stage II-IV tumors. The combination of CPT-P was shown to have a potential therapeutic benefit for advanced CCC of the ovary, especially for cases with optimal debulking surgery. However, this is a limited retrospective study, therefore we recommend that the CPT-P regimen be evaluated in a larger prospective study.