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Microsatellite instability (MSI) and deficiency of mismatch repair (dMMR) are key markers for predicting the response of immune checkpoint inhibitors (ICIs) and screening for Lynch syndrome (LS). This study examined the incidences of and factors associated with the concordance of MSI and MMR in human cancers. A total of 518 formalin-fixed cancer tissues were analyzed for MSI and MMR immunohistochemistry (IHC). MSI was analyzed by a PCR-based method using Promega markers. Concordance with MMR expression and factors associated with concordance were analyzed. In 2 colorectal cancer samples, MMR IHC failed due to inadequate staining conditions. In the remaining 516 cancers, a high level of MSI (MSI-H) was identified in 113 cases, and dMMR was identified in 112. The concordance of MSI and MMR IHC was 98.3%. Only 9 cases (4 pancreatobiliary, 3 colorectal, and 2 endometrial cancers) were discordant. Of the 113 MSI-H cases, 4 (3.5%) were proficient MMR (pMMR); of the 403 microsatellite stability (MSS) cases, 5 (1.2%) were dMMR. The independent factors associated with MSI-H/dMMR included meeting Amsterdam II criteria, assay purpose, and sampling method. Multivariate analysis revealed that cancer type (gastrointestinal cancers or others) was associated with concordance of MSI and MMR IHC. Three LS cases with pancreatic or endometrial cancer demonstrated MSS and dMMR, and one biliary cancer showed MSI-H and pMMR. Discordance between MSI and MMR IHC occasionally occurs in pancreaticobiliary and endometrial cancers. When suspected, both MSI and MMR IHC should be done to judge the ICI indication and screen for LS.

In 2021, Japan's national health insurance made germline BRCA (g.BRCA) testing available to unresectable pancreatic cancer (PC) patients as a companion diagnostic (CD) of the PARP inhibitor. This study investigated the incidence of the g.BRCA variant (g.BRCAv.) and the status of the genetic medicine associated with its testing. A total of 110 PC patients underwent the testing, five of whom (4.5%) had a deleterious g.BRCA2v. (all truncations) but no g.BRCA1v. The turnaround time (TAT) to the doctors was 13 days, and to the patients, 17 days. A higher incidence of a BRCA-related family history and a shorter TAT were seen in the g.BRCAv. patients, but they were insignificant (p = 0.085 and p = 0.059, respectively). Genetic counseling was not performed for three g.BRCA2v. patients because two of them had no accessible relatives and one died of the cancer before the genetic report was completed. Two families underwent generic counseling and testing based on the patient's genetic data. g.BRCAv. is recognized in a small fraction of PC cases, and the following genetic counseling is done more for the relatives than for the patients. TAT was constant and did not affect much on the genetic counseling, but the earlier testing is expected for patients with a deadly cancer.

Background: Tumor mutation burden (TMB) is the total exonic mutation count per megabase of tumor DNA. Recent advances in precision medicine occasionally detect Lynch syndrome (LS) by germline sequencing for mismatch-repair (g.MMR) genes but not using TMB. The current study analyzes the utility of TMB in detecting LS. Methods: Whole-exome sequencing (ion-semiconductor sequencing) was performed for somatic and germline DNA from 2,501 various cancer patients to detect TMB and g.MMR sequencing. MMR IHC was conducted when high TMB (≥10) was detected in LS-related cancers with an additional condition of wild-type BRAF in colorectal cancers. Target sequencing and multiplex ligation-dependent probe amplification (MLPA) were further performed for g.MMR genes in MMR-deficient cancers (TMB-based g.MMR target sequencing). We compared universal sequencing and TMB-based target sequencing in their sensitivity for detecting LS. Results: LS was detected in 16 (0.6%) of the 2,501 patients: 1.1% (9/826) of colorectal cancer patients, 16.2% (6/37) of endometrial cancer patients, and 14.3% (1/7) of small intestine cancer patients. TMB-based g.MMR target sequencing (81.3%) showed superior sensitivity for detecting LS than universal g.MMR sequencing (56.3%; P = 0.127) but missed 3 LS patients (1 with a low-TMB cancer, 1 with a BRAF-mutant colorectal cancer, and 1 with an MMR-proficient cancer). Ion-semiconductor sequencing could detect single-nucleotide substitutions but not large deletions. POL-mutated cancers showed extremely high TMBs (48.4–749.2). Conclusions: g.MMR target sequencing, combined with TMB, somatic BRAF mutation, and MMR IHC is an effective strategy for detecting LS. Impact: TMB can be a biomarker for detecting LS in precision medicine.

Purpose The aim of this study was to investigate the efficacy and safety of prophylactic administration of 5 mg olanzapine (OLZ) combined with neurokinin 1 receptor antagonist (NK1RA), 5-hydroxytryptamine type-3 receptor antagonist (5-HT3RA), and dexamethasone (DEX) to prevent nausea and vomiting in carboplatin (CBDCA) combination therapy for patients with gynecological cancer. Methods We conducted a single-arm, multi-institution, phase II study. Gynecological cancer patients scheduled to receive AUC ≥4 mg/mL/min CBDCA were enrolled. All patients received 5 mg OLZ (once daily after supper on days 1–4) combined with NK1RA, 5-HT3RA, and DEX. The primary end point was complete response (CR; no emesis and rescue therapy) during overall phase (120 h after the start of carboplatin administration). Results Between May 2018 and June 2019, 60 patients were enrolled from 3 institutions in Japan. A total of 57 patients who met the criteria were included in the efficacy and safety analysis. The CR rate for the overall phase was 78.9%. Acute (0–24 h) and delayed phases (24–120 h) were 96.5% and 80.7%, respectively. Somnolence was observed in 73.7% patients. However, somnolence of grade 2 or higher was observed in only 3.5% of cases. There were no grade 3 or 4 toxicities associated with OLZ. Conclusions Preventive use of OLZ combined with standard triplet therapy had promising activity with manageable safety, suggesting that this combination could be an effective standard treatment option for patients with AUC ≥4 mg/mL/min CBDCA combination therapy.

Since the human papillomavirus (HPV) vaccination program for Japanese girls aged 12–16 years began in 2010, vaccination uptake has been low in women born before 1993 but high (approximately 70%) in those born during 1994–1999. We previously compared the prevalence of vaccine types HPV16 and HPV18 in cervical intraepithelial neoplasia grade 1–3 (CIN1–3) or adenocarcinoma in situ (AIS) between vaccinated and unvaccinated cohorts and found direct protection effects among vaccinated women in Japan. In this study, we focused on changes in HPV16/18 prevalence among “unvaccinated” cohorts with CIN/AIS. We analyzed HPV16/18 prevalence among 5051 unvaccinated women aged

Objective Since 2019, precision cancer medicine has been covered by national insurance in Japan; however, to date, germline findings have not been fully reported. The aim of this study was to evaluate the current status and raise a problem of germline finding analysis and disclosure in Japanese precision cancer medicine. Methods Germline findings of 52 genes were examined in 296 cases with advanced cancer by a case series study. Results Six (2.0%) cases were examined by the Oncoguide™ NCC Oncopanel with germline testing, but no germline findings were reported. The remaining 290 (98.0%) cases were analyzed by FoundationOne® CDx (tumor-only testing), which recognized 404 pathogenic variants; those of BRCA1/2 were recognized in 16 (5.5%) tumors. Our institutional algorithm suggested 39 candidate germline findings in 34 cases, while the public algorithm listed at least 91 candidate germline findings. Four germline findings had been previously identified (BRCA1: 3 and ATM: 1). Nine of 30 cases with candidate germline findings excluding these known germline findings refused or deferred germline testing. Only 4 of 16 cases that received counseling underwent germline testing, and those 4 revealed 3 germline findings (BRCA2, CDK4 and RAD51C); in total, 8 (2.7%) germline findings were revealed. Reasons for refusing genetic counseling and/or germline testing included extra hospital visits, added expense for germline testing due to limited national insurance coverage, poor patient physical condition and no known family members associated with the possible germline finding. Conclusions In current Japanese precision cancer medicine, only a small fraction of the patients undergoes germline testing and demonstrated germline finding. The current results suggested a need for earlier indications for precision cancer medicine, broader insurance coverage and more efficient germline finding prediction algorithms, to increase the number of germline testings and to improve the following managements.

The treatment for most patients with early-stage cervical cancer involves radical hysterectomy and pelvic lymph node dissection, and indications for postoperative adjuvant therapy have been determined by evaluating the prognostic risk factors for recurrence in each case. The aim of this review is to raise and discuss the various issues that have not yet been resolved regarding the prognostic risk factors and postoperative adjuvant therapy. Several clinicopathological factors, such as tumor size, lymphovascular space involvement, deep stromal invasion, parametrial involvement and lymph node metastasis, have been identified to have prognostic significance in early-stage cervical cancer. However, this remains controversial because there is suggested to be substantial heterogeneity among patients after radical hysterectomy and lymphadenectomy and it would be difficult to define the risk groups clearly. This indicates the need to develop more convenient and accurate criteria to define risk groups. According to the currently available evidence, patients in the high-risk group should receive adjuvant concurrent chemoradiotherapy (CCRT) with cisplatin (CDDP) and fluolouracil. However, CCRT with CDDP administered weekly (CCRT-P) has instead been applied in a clinical context worldwide. Whether CCRT-P has a survival benefit compared with radiotherapy (RT) alone is unknown because no randomized phase III trials have been performed for patients in the high-risk group after radical surgery. Patients with high-risk factors have a high incidence of distant metastasis, for whom systemic chemotherapy might be a key to improving overall survival. The pivotal study that investigated the role of RT alone for patients with intermediate-risk factors after hysterectomy is the GOG092 trial. This trial showed a 47% reduction in the risk of recurrence after RT compared with no further treatment (NFT). However, the improvement in overall survival with RT did not reach statistical significance, while patients allocated to the RT group did experience an increase in severe toxicities compared with the NFT group. This could be why many physicians are reluctant to treat patients with this approach, although guidelines recommend RT for patients with intermediate-risk factors. With regard to toxicities, postoperative RT would be problematic because the organs in the pelvis targeted by RT have already been damaged by radical surgery. To reduce the toxicities, intensity-modulated radiotherapy would best be used worldwide. Further improvement in adjuvant therapy will come from enhanced definition of prognostic risk factors, better patient selection, and refinements in both local and systematic therapies.

Background: To examine trends in the clinicopathological characteristics of vulvar cancer in Japan. Methods: This is a nationwide retrospective study examining consecutive women with vulvar cancer between 2001 and 2010 in Japan (n = 1061). Temporal trends in demographics, tumor characteristics, and survival were assessed by cohort-level analysis. The National Cancer Institute&rsquo, s Surveillance, Epidemiology, and End Result Program was used for external validation (n = 10,154). Results: The number of oldest-old women aged &ge, 80 years significantly increased (from 18.0% in 2001 to 30.6% in 2010, 70.5% relative increase) in the study period. A stage shift was observed, with stage I disease decreasing from 43.0% to 34.0% (21.0% relative decrease), and tumors with distant metastases increasing from 23.2% to 35.6% (53.3% relative increase, p &lt, 0.05). The number of women who underwent surgical treatment decreased from 84.0% to 69.7% (17.0% relative decrease), whereas utilization of radiotherapy increased from 34.4% to 43.2% (25.7% relative increase) over time (p &lt, 0.05). In the cohort-level analysis, the five-year survival rates significantly decreased from 2001 to 2010 (p &lt, 0.05), specifically, 66.9% to 51.0% for progression-free survival (23.7% relative decrease), 79.5% to 67.9% for cause-specific survival (14.6% relative decrease), and 74.9% to 62.3% for overall survival (16.9% relative decrease). In the patient-level analysis, oldest-old women were less likely to undergo surgical treatment and were independently associated with decreased survival (p &lt, 0.05). In the US cohort, the number of oldest-old women (25.2% to 27.8%) and the five-year cause-specific survival rate (81.8% to 79.9%) remained unchanged during the study period (p &gt, 0.05). Conclusion: Demographics and outcomes of vulvar cancer in Japan significantly changed during the study period. An increasing oldest-old population and a stage shift to more metastatic disease resulted in a cohort-level decrease in survival rates.

High-throughput sequencing has greatly contributed to precision medicine. However, challenges remain in reporting secondary findings (SFs) of germline pathogenic variants and managing the affected patients. The aim of this study was to examine the incidence of SFs in Japanese cancer patients using whole exome sequencing (WES) and to understand patient preferences regarding SF disclosure. WES was conducted for 2480 cancer patients. Genomic data were screened and classified for variants of 59 genes listed by the American College of Medical Genetics and Genomics SF v2.0 and for an additional 13 hereditary cancer-related genes. Majority of the participants (68.9%; 1709/2480) opted for disclosure of their SFs. Thirty-two pathogenic or likely pathogenic variants, including BRCA1 (7 patients), BRCA2 (4), CHEK2 (4), PTEN (3), MLH1 (3), SDHB (2), MSH6 (1), NF1 (1), EXT2 (1), NF1 (1), NTRK1 (1), MYH7 (3), MYL2 (1), TNNT2 (1), LDLR (2), FBN1 (1), and KCNH2 (1) were recognized in 36 patients (1.5%). Twenty-eight (77.8%) patients underwent genetic counseling and received their SF results. Eighteen (64.3%) patients underwent clinical management for SFs. Genetic validation tests were administered significantly more frequently to patients with than without a SF-related personal history (P = 0.025). This was a first attempt at a large-scale systematic exome analysis in Japan; nevertheless, many cancer patients opted for disclosure of SFs and accepted or considered clinical management.

Background Somatic PTEN mutation occurs in a proportion of ovarian endometrioid carcinomas. However, these cancers have seldom been reported in diseases associated with germline PTEN variants, such as Cowden syndrome (CS). Case presentation The present case was a 39-year-old woman with a left ovarian carcinoma who demonstrated a germline splice variant of PTEN (c.1026 + 1G > T) following genome-wide whole exome sequencing of her germline DNA. Histology of her resected tumor revealed endometrioid carcinoma of the same type as a right ovarian cancer resected eight years previously. These tumors showed null immunostaining for PTEN. She was genetically diagnosed with CS. Despite her clinical examinations had demonstrated several characteristic findings of CS, including mammary fibroma, esophageal and skin papilloma, colonic hamartoma, uterine myoma, and lipoma, the clinicians could not approach this diagnosis. Conclusion Ovarian endometrioid carcinoma is generally thought to develop from endometrial tissue menstruated from the uterus and implanted on the ovary. To date, ovarian cancers have not been listed as CS-related cancers; however, ovarian endometrioid cancer can have a potential association with CS in endometriosis cases.

Modified radical hysterectomy (MRH) is thought to be equivalent to class II (Piver classification) or type B (Querleu classification) radical hysterectomy (RH) and identical to the original method of the Wertheim operation. MRH is a method of hysterectomy defined as being intermediate between simple hysterectomy and RH and enabling almost full preservation of the pelvic splanchnic nerves and hypogastric plexus. This surgical procedure entails the cutting of the anterior leaf, not the posterior one, of the vesicouterine ligament of the uterus. The ureter is mobilized laterally, part of the parametrial tissue is transected at the level of the ureteral tunnel, and at least 10 mm of the vaginal wall from the uterine cervix is removed. The indication of MRH (with pelvic lymphadenectomy) in cervical cancer is International Federation of Gynecology and Obstetrics stage IA1 with lymphovascular space invasion or stage IA2. MRH is associated with a very low (≤1%) rate of significant postoperative complications, and compared with RH, it reduces the rate of adverse effects on the urinary tract, such as fistula formation and severe voiding dysfunction. The mortality rate for those undergoing this procedure is 0.4–0.5%. The possibility of MRH for low-risk FIGO stage IB1 patients has been considered, and clinical trials are ongoing.

Aim The aim of this retrospective study was to analyze data for patients with stage IB–IIB uterine cervical cancer who were treated with concurrent chemoradiotherapy with fluorouracil (5-FU) and cisplatin (CCRT-FP) as postoperative adjuvant therapy and to re-examine these issues and further treatment. Methods Patients with high risk for recurrence underwent CCRT-FP as postoperative adjuvant therapy. A total of 73 patients who met these criteria were included in this study. Data related to survival, toxicity, and treatment feasibility were analyzed, and the question of whether there were differences in survival and toxicity according to the number of dissected lymph nodes at surgery was evaluated. Results Median patient age was 45 years (range, 24–67 years). Two-thirds of patients had squamous cell histologic type, 41 patients (56.2%) had parametrial invasion, and 60 patients (82.2%) had lymph node metastases. Estimated 4-year progression-free survival, overall survival, and local control rates were 71.8%, 84.1%, and 88.5%, respectively. Sixteen patients (21.9%) had grade 3–4 neutropenia and one of them died of septic shock. Non-hematological toxicities were also common: 13 (17.8%) experienced grade 3–4 nausea, and nine (12.3%) experienced grade 3–4 diarrhea. Ileus occurred in 17 patients (23.3%), and seven of them (9.6%) were not yet cured. One patient experienced gastrointestinal perforation. Conclusions CCRT-FP in the postoperative setting resulted in good survival outcome but toxicity remained problematic. Development of appropriate treatment for patients with high-risk prognostic factors after radical hysterectomy and lymphadenectomy is required.

Introduction/BackgroundStandard therapy for recurrent endometrial cancer is chemotherapy. There is less conclusive evidence about surgical treatment of recurrent endometrial cancer. We investigated outcomes after surgical treatment for recurrent endometrial cancer at our hospital and verified its effectiveness.MethodWe reviewed the medical records retrospectively for patients who underwent surgical treatment for primary recurrent endometrial cancer between September 2002 and March 2016.We evaluated disease free interval(DFI), age at surgery, the site of recurrence, completion surgery of residual disease, adjuvant therapy, progression-free survival (PFS) and overall survival (OS). Results18 patients were evaluated. The median follow-up was 28.9 months (12.7-134.2).Median age was 65.5 (48-78) years old. The site of recurrence were lung 7, peritoneal dissemination 7, and lymph nodes 5. 14 of 18 patients had underwent macroscopic complete tumor resection. Median PFS was 18.1 months (95%CI: 40.1-NA) and median OS was 158.4 months (95%CI: 5.9-63.6). Prognostic factors for surgical treatment of PFS were lung metastases (HR 0.18 [95% CI: 0.042-0.77], P

The treatment for most patients with early-stage cervical cancer involves radical hysterectomy and pelvic lymph node dissection, and indications for postoperative adjuvant therapy have been determined by evaluating the prognostic risk factors for recurrence in each case. The aim of this review is to raise and discuss the various issues that have not yet been resolved regarding the prognostic risk factors and postoperative adjuvant therapy. Several clinicopathological factors, such as tumor size, lymphovascular space involvement, deep stromal invasion, parametrial involvement and lymph node metastasis, have been identified to have prognostic significance in early-stage cervical cancer. However, this remains controversial because there is suggested to be substantial heterogeneity among patients after radical hysterectomy and lymphadenectomy and it would be difficult to define the risk groups clearly. This indicates the need to develop more convenient and accurate criteria to define risk groups. According to the currently available evidence, patients in the high-risk group should receive adjuvant concurrent chemoradiotherapy (CCRT) with cisplatin (CDDP) and fluolouracil. However, CCRT with CDDP administered weekly (CCRT-P) has instead been applied in a clinical context worldwide. Whether CCRT-P has a survival benefit compared with radiotherapy (RT) alone is unknown because no randomized phase III trials have been performed for patients in the high-risk group after radical surgery. Patients with high-risk factors have a high incidence of distant metastasis, for whom systemic chemotherapy might be a key to improving overall survival. The pivotal study that investigated the role of RT alone for patients with intermediate-risk factors after hysterectomy is the GOG092 trial. This trial showed a 47% reduction in the risk of recurrence after RT compared with no further treatment (NFT). However, the improvement in overall survival with RT did not reach statistical significance, while patients allocated to the RT group did experience an increase in severe toxicities compared with the NFT group. This could be why many physicians are reluctant to treat patients with this approach, although guidelines recommend RT for patients with intermediate-risk factors. With regard to toxicities, postoperative RT would be problematic because the organs in the pelvis targeted by RT have already been damaged by radical surgery. To reduce the toxicities, intensity-modulated radiotherapy would best be used worldwide. Further improvement in adjuvant therapy will come from enhanced definition of prognostic risk factors, better patient selection, and refinements in both local and systematic therapies.

The aims of this study were to evaluate the efficacy and toxicity of chemotherapy (CT) compared with concurrent chemoradiotherapy (CCRT) after radical hysterectomy and lymphadenectomy in high-risk patients with early-stage cervical cancer and to evaluate whether the radicality of the lymphadenectomy would affect the outcome and toxicity of postoperative adjuvant therapy. The cases of all patients (n = 393) with FIGO IB1–IIB cervical cancer who were treated by radical surgery at Shizuoka Cancer Center between January 2002 and December 2013 were reviewed. Of these, 111 patients met the inclusion criteria for this retrospective study: (1) high risk for occurrence due to pathologically confirmed parametrial invasion and/or pelvic lymph node metastasis; (2) postoperative treatment with adjuvant CT or CCRT. The clinical data of these patients were reviewed. Of the 111 patients, 37 and 74 patients underwent CT and CCRT, respectively. The 4-year progression-free survival rate [PFS; 71.7 (CT) vs. 68.3 % (CCRT)] and overall survival rate [76.0 (CT) vs. 82.7 % (CCRT)] did not differ significantly between the two groups. The CT group contained significantly more patients with severe neutropenia than the CCRT group (66.7 vs. 23.0 %, respectively; p

Olanzapine is effective in chemotherapy-induced nausea and vomiting (CINV). In patients receiving highly emetogenic chemotherapy (HEC), its efficacy was reported as rescue therapy for breakthrough emesis refractory to triplet therapy (palonosetron, aprepitant, and dexamethasone). However, its preventive effects with triplet therapy for CINV are unknown. This study aimed to investigate efficacy and safety of preventive use of olanzapine with triplet therapy for CINV of HEC.This study is a prospective multicenter study conducted by Kansai Clinical Oncology Group. Forty chemo-naïve gynecological cancer patients receiving HEC with cisplatin (≥50 mg/m(2)) were enrolled. Oral olanzapine (5 mg) was administered with triplet therapy a day prior to cisplatin administration and on days 1-5. The primary endpoint was complete response (no vomiting and no rescue) rate for the overall phase (0-120 h post-chemotherapy). Secondary endpoints were complete response rate for acute phase (0-24 h post-chemotherapy) and delayed phase (24-120 h post-chemotherapy) and complete control (no vomiting, no rescue, and no significant nausea) rate and total control (no vomiting, no rescue, and no nausea) rate for each phase. These endpoints were evaluated during the first cycle of chemotherapy.Complete response rates for acute, delayed, and overall phases were 97.5, 95.0, and 92.5 %, respectively. Complete control rates were 92.5, 87.5, and 82.5 %, respectively. Total control rates were 87.5, 67.5, and 67.5 %, respectively. There were no grade 3 or 4 adverse events.Preventive use of olanzapine combined with triplet therapy gives better results than those from previously reported studies of triplet therapy.

The aim of this retrospective study was to analyze data for patients with stage IB-IIB uterine cervical cancer who were treated with concurrent chemoradiotherapy with fluorouracil (5-FU) and cisplatin (CCRT-FP) as postoperative adjuvant therapy and to re-examine these issues and further treatment.Patients with high risk for recurrence underwent CCRT-FP as postoperative adjuvant therapy. A total of 73 patients who met these criteria were included in this study. Data related to survival, toxicity, and treatment feasibility were analyzed, and the question of whether there were differences in survival and toxicity according to the number of dissected lymph nodes at surgery was evaluated.Median patient age was 45 years (range, 24-67 years). Two-thirds of patients had squamous cell histologic type, 41 patients (56.2%) had parametrial invasion, and 60 patients (82.2%) had lymph node metastases. Estimated 4-year progression-free survival, overall survival, and local control rates were 71.8%, 84.1%, and 88.5%, respectively. Sixteen patients (21.9%) had grade 3-4 neutropenia and one of them died of septic shock. Non-hematological toxicities were also common: 13 (17.8%) experienced grade 3-4 nausea, and nine (12.3%) experienced grade 3-4 diarrhea. Ileus occurred in 17 patients (23.3%), and seven of them (9.6%) were not yet cured. One patient experienced gastrointestinal perforation.CCRT-FP in the postoperative setting resulted in good survival outcome but toxicity remained problematic. Development of appropriate treatment for patients with high-risk prognostic factors after radical hysterectomy and lymphadenectomy is required.

Objective. Olanzapine is proved to be effective for chemotherapy induced nausea and vomiting (CINV). But its efficacy in combination with standard antiemetic therapy is unknown. The purpose of this study is to prove the preventive effect of olanzapine for the prevention of CINV caused by highly emetogenic chemotherapy when used with standard antiemetic therapy.Method. Gynecologic cancer patients receiving cisplatin-based chemotherapy who had grade 2 or 3 nausea in overall phase (0–120 h after chemotherapy) despite standard therapy were assigned to this study. From the next cycles to cycles in which patients developed grade 2 or 3 nausea, they received olanzapine with standard therapy. 5 mg oral olanzapine was administered for 7 days from the day before chemotherapy. The effectiveness of preventive administration of olanzapine was evaluated retrospectively. The primary endpoint was nausea control rate (grade 0 or 1) with olanzapine.Results. Fifty patients were evaluable. The nausea control rate with olanzapine was improved from 58% to 98% in acute phase (0–24 h after chemotherapy) and 2% to 94% in delayed phase (24–120 h after chemotherapy). In overall phase, the nausea control rate improved from 0% to 92%, and it was statistically significant (P<0.001).Conclusion. Preventive use of olanzapine combined with standard antiemetic therapy showed improvement in control of refractory nausea.

e17075 Background: This study aimed to investigate the efficacy and safety of Nedaplatin single therapy for patients with platinum-resistant ovarian, tubal and primary peritoneal cancer after completing standard chemotherapy. Methods: From September 2002 to August 2016, 30 patients who were diagnosed with platinum-resistant ovarian cancer, were treated with Nedaplatin single therapy after completing all standard chemotherapy at our institution. Nedaplatin (80-100mg/m2) was adiministered intravenously on day 1 of a 28 day cycle. We retrospectively investigated the response rate, toxicities, and survival based on the use of Nedaplatin single therapy. Results: The median age was 58.5 years (23-76). The median number of prior chemotherapy regimen was 3 (1-7). The median platinum-free interval between the final use of platinum analogues and starting Nedaplatin single therapy was 9.4 months (0.9-54.9). Among 22 patients who had measurable disease, 8 (36.4%) responded partially to Nedaplatin single therapy. Seven patients (23.3%) experienced hematological toxicities of Grade 3/4. Six patients (20.0%) experienced non-hematological toxicities Grade 2. No treatment-related death occurred. The median progression-free survival was 3.2 months (0-23.3), and over all survival was 9.2 months (1.1-56.4) after treatment with Nedaplatin single therapy. Age (