Olaparib Addition to Maintenance Bevacizumab Therapy in Ovarian Carcinoma With BRCA-Like Genomic Aberrations.

Importance: Testing for homologous recombination deficiency is required for the optimal treatment of high-grade epithelial ovarian cancer. The search for accurate biomarkers is ongoing. Objective: To investigate whether progression-free survival (PFS) and overall survival (OS) of patients with high-grade epithelial ovarian cancer treated with maintenance olaparib or placebo differed between patients with a tumor BRCA-like genomic profile and patients without a tumor BRCA-like profile. Design, Setting, and Participants: This cohort study was a secondary analysis of the PAOLA-1 randomized clinical trial that compared olaparib plus bevacizumab with placebo plus bevacizumab as maintenance treatment in patients with advanced high-grade ovarian cancer after a good response to first-line platinum with taxane chemotherapy plus bevacizumab, irrespective of germline or tumor BRCA1/2 mutation status. All patients with available tumor DNA were included in the analysis. The current analysis tested for an interaction between BRCA-like status and olaparib treatment on survival outcomes. The original trial was conducted between July 2015 and September 2017; at the time of data extraction for analysis in March 2022, a median follow-up of 54.1 months (IQR, 28.5-62.2 months) and a total follow-up time of 21 711 months was available, with 336 PFS and 245 OS events. Exposures: Tumor homologous recombination deficiency was assessed using the BRCA-like copy number aberration profile classifier. Myriad MyChoice CDx was previously measured. The trial was randomized between the olaparib and bevacizumab and placebo plus bevacizumab groups. Main Outcomes and Measures: This secondary analysis assessed hazard ratios (HRs) of olaparib vs placebo among biomarker strata and tested for interaction between BRCA-like status and olaparib treatment on PFS and OS, using Cox proportional hazards regression. Results: A total of 469 patients (median age, 60 [range 26-80] years) were included in this study. The patient cohort consisted of women with International Federation of Gynaecology and Obstetrics stage III (76%) high-grade serous (95%) ovarian cancer who had no evaluable disease or complete remission at initial or interval debulking surgery (76%). Thirty-one percent of the tumor samples (n = 138) harbored a pathogenic BRCA mutation, and BRCA-like classification was performed for 442 patients. Patients with a BRCA-like tumor had a longer PFS after olaparib treatment than after placebo (36.4 vs 18.6 months; HR, 0.49; 95% CI, 0.37-0.65; P < .001). No association of olaparib with PFS was found in patients with a non-BRCA-like tumor (17.6 vs 16.6 months; HR, 1.02; 95% CI, 0.68-1.51; P = .93). The interaction was significant (P = .004), and HRs and P values (for interaction) were similar in the relevant subgroups, OS, and multivariable analyses. Conclusions and Relevance: In this secondary analysis of the PAOLA-1 randomized clinical trial, patients with a BRCA-like tumor, but not those with a non-BRCA-like tumor, had a significantly longer survival after olaparib plus bevacizumab treatment than placebo plus bevacizumab treatment. Thus, the BRCA1-like classifier could be used as a biomarker for olaparib plus bevacizumab as a maintenance treatment.

Not taking sick leave for gynecologic cancer treatment is negatively associated with returning to the same workplace.

BACKGROUND: Gynecologic cancers are one of the most common types of malignancies in working-age women. We aimed to determine the factors that impede women from returning to the same workplace after treatment for such cancers. METHODS: A questionnaire-based survey was conducted on 194 women who underwent treatment for gynecologic cancer at the Okayama University (≥1 year after cancer treatment and <65 years of age). We performed a logistic regression analysis to determine the relationship between returning to the same workplace and not taking sick leave. RESULTS: The median age at diagnosis was 49.0 years, and the median time from cancer treatment to questionnaire completion was 3.8 years. Not returning to the same workplace was positively associated with not being regularly employed (P = 0.018), short work time per day (P = 0.023), low personal income (P = 0.004), not taking sick leave (P < 0.001), advanced cancer stage (P = 0.018) and long treatment time (P = 0.032). Interestingly, not taking sick leave was strongly associated with not returning to the same workplace in the multivariable analysis (P < 0.001). CONCLUSIONS: Not taking sick leave likely was negatively associated with returning to the same workplace after the treatment for gynecologic cancer. Therefore, we suggest that steps be taken to formally introduce a sick leave system over and above the paid leave system in Japan.

Neoadjuvant chemotherapy followed by interval debulking surgery for advanced epithelial ovarian cancer: GOTIC-019 study.

INTRODUCTION: Three randomized controlled trials have resulted in extremely extensive application of the strategy of using neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) for patients with advanced epithelial ovarian cancer in Japan. This study aimed to evaluate the status and effectiveness of treatment strategies using NAC followed by IDS in Japanese clinical practice. PATIENTS AND METHODS: We conducted a multi-institutional observational study of 940 women with Federation of Gynecology and Obstetrics (FIGO) stages III-IV epithelial ovarian cancer treated at one of nine centers between 2010 and 2015. Progression-free survival (PFS) and overall survival (OS) were compared between 486 propensity-score matched participants who underwent NAC followed by IDS and primary debulking surgery (PDS) followed by adjuvant chemotherapy. RESULTS: Patients with FIGO stage IIIC receiving NAC had a shorter OS (median OS: 48.1 vs. 68.2 months, hazard ratio [HR]: 1.34; 95% confidence interval [CI] 0.99-1.82, p = 0.06) but not PFS (median PFS: 19.7 vs. 19.4 months, HR: 1.02; 95% CI: 0.80-1.31, p = 0.88). However, patients with FIGO stage IV receiving NAC and PDS had comparable PFS (median PFS: 16.6 vs. 14.7 months, HR: 1.07 95% CI: 0.74-1.53, p = 0.73) and OS (median PFS: 45.2 vs. 35.7 months, HR: 0.98; 95% CI: 0.65-1.47, p = 0.93). CONCLUSIONS: NAC followed by IDS did not improve survival. In patients with FIGO stage IIIC, NAC may be associated with a shorter OS.

Pure abscopal effect in a patient with advanced uterine carcinosarcoma.

The abscopal effect is a rare phenomenon, in which tumor shrinkage in the nonirradiated metastatic region is observed after radiotherapy. Certainly, this response is sometimes reported with the combined use of immune-checkpoint inhibitors, but a pure abscopal effect is extremely rare, especially in endometrial cancer. We present the case of a 79-year-old woman with an advanced endometrial carcinosarcoma. She was treated with surgical reduction of the primary lesion, followed by radiotherapy of the metastatic regional lymph nodes. Distant metastases were detected in radiological imaging test 2 months after the completion of radiotherapy, and we carefully followed up without any treatment considering the patient's tolerability for further procedures. Six months after recurrence, she experienced cytoreduction in the metastatic lesions confirmed through imaging findings, which was believed to be an abscopal effect, and maintained this shrinking state for 15 months. Herein, we describe this pure abscopal effect from the perspective of imaging, pathological and molecular findings, and therapeutic strategies.

Association between financial toxicity and health-related quality of life of patients with gynecologic cancer.

OBJECTIVES: Patients often struggle with their financial situation during cancer treatment due to treatment-related costs or loss of income. This resulting negative effect is called financial toxicity, which is a known as a side effect of cancer care. This study aimed to evaluate the association between financial toxicity and health-related quality of life among patients with gynecologic cancer using validated questionnaires. METHODS: In this multicenter study, patients with gynecologic cancer receiving anti-cancer drug treatment for > 2 months were recruited. Patients answered the COmprehensive Score for Financial Toxicity (COST) tool, EORTC-QLQ-C30, disease-specific tools (EORTC-QLQ-OV28/CX24/EN24), and EQ-5D-5L. Spearman's rank correlation coefficient was used to determine associations. RESULTS: Between April 2019 and July 2021, 109 cancer patients completed the COST questionnaire. The mean COST score was 19.82. Strong associations were observed between financial difficulty (r = - 0.616) in the EORTC-QLQ-C30 and body image (r = 0.738) in the EORTC-QLQ-CX24, while weak associations were noted between the global health status/quality of life (r = 0.207), EQ-5D-5L index score (r = 0.252), and several function and symptom scale scores with the COST score. CONCLUSIONS: Greater financial toxicity was associated with worse health-related quality of life scores, such as financial difficulty in gynecologic cancer patients and body image in cervical cancer patients as strong associations, and weakly associated with general health-related quality of life scores and several function/symptom scales.

Veliparib with frontline chemotherapy and as maintenance in Japanese women with ovarian cancer: a subanalysis of efficacy, safety, and antiemetic use in the phase 3 VELIA trial.

BACKGROUND: The phase 3 VELIA trial evaluated veliparib with carboplatin/paclitaxel and as maintenance in patients with high-grade serous ovarian carcinoma. METHODS: Patients with previously untreated stage III-IV high-grade serous ovarian carcinoma were randomized 1:1:1 to control (placebo with carboplatin/paclitaxel and placebo maintenance), veliparib-combination-only (veliparib with carboplatin/paclitaxel and placebo maintenance), or veliparib-throughout (veliparib with carboplatin/paclitaxel and veliparib maintenance). Randomization stratification factors included geographic region (Japan versus North America or rest of the world). Primary end point was investigator-assessed median progression-free survival. Efficacy, safety, and pharmacokinetics were evaluated in a subgroup of Japanese patients. RESULTS: Seventy-eight Japanese patients were randomized to control (n = 23), veliparib-combination-only (n = 30), and veliparib-throughout (n = 25) arms. In the Japanese subgroup, median progression-free survival for veliparib-throughout versus control was 27.4 and 19.1 months (hazard ratio, 0.46; 95% confidence interval, 0.18-1.16; p = 0.1 [not significant]). In the veliparib-throughout arm, grade 3/4 leukopenia, neutropenia, and thrombocytopenia rates were higher for Japanese (32%/88%/32%) versus non-Japanese (17%/56%/28%) patients. Grade 3/4 anemia rates were higher in non-Japanese (65%) versus Japanese (48%) patients. Early introduction of olanzapine during veliparib monotherapy maintenance phase may help prevent premature discontinuation of veliparib, via its potent antiemetic efficacy. CONCLUSIONS: Median progression-free survival was numerically longer in Japanese patients in the veliparib-throughout versus control arm, consistent with results in the overall study population. Pharmacokinetics were comparable between Japanese and non-Japanese patients. Data for the subgroup of Japanese patients were not powered to show statistical significance but to guide further investigation.

Intraperitoneal Carboplatin for Ovarian Cancer - A Phase 2/3 Trial.

Intraperitoneal Carboplatin for Ovarian CancerThis trial compared intravenous weekly paclitaxel administered with intraperitoneal or intravenous carboplatin. There was a statistically significant increase in progression-free survival in patients with ovarian cancer treated with intraperitoneal versus intravenous carboplatin and paclitaxel, with no difference in overall survival between groups.

Tumor size before image-guided brachytherapy is an important factor of local control after radiotherapy for cervical squamous cell carcinoma: analysis in cases using central shielding.

We analyzed the local control (LC) of cervical squamous cell carcinoma treated by computed tomography (CT)-based image-guided brachytherapy (IGBT) using central shielding (CS). We also examined the value of tumor diameter before brachytherapy (BT) as a factor of LC. In total, 97 patients were analyzed between April 2016 and March 2020. Whole-pelvic (WP) radiotherapy (RT) with CS was performed, and the total pelvic sidewall dose was 50 or 50.4 Gy; IGBT was delivered in 3-4 fractions. The total dose was calculated as the biologically equivalent dose in 2 Gy fractions, and distribution was modified manually by graphical optimization. The median follow-up period was 31.8 months (6.3-63.2 months). The 1- and 2-year LC rates were 89% and 87%, respectively. The hazard ratio was 10.11 (95% confidence interval: 1.48-68.99) for local recurrence in those with a horizontal tumor diameter ≥ 4 cm compared to those with < 4 cm before BT. In CT-based IGBT for squamous cell carcinoma, favorable LC can be obtained in patients with a tumor diameter < 4 cm before BT. However, if the tumor diameter is ≥ 4 cm, different treatment strategies such as employing interstitial-BT for dose escalation may be necessary.

Validity of the COmprehensive Score for financial Toxicity (COST) in patients with gynecologic cancer.

OBJECTIVE: Financial toxicity is a financial burden of cancer care itself, which leads to worse quality of life and higher mortality and is considered an adverse effect. The COmprehensive Score for financial Toxicity (COST) tool is a patient-reported outcome measurement used to evaluate financial toxicity. We aimed to validate the internal consistency and reproducibility of the COST tool in patients with gynecologic cancer. METHODS: In this multicenter study covering the period April 2019 to July 2021, using the COST tool in Japan, patients diagnosed with ovarian, cervical, or endometrial cancer receiving systemic anti-cancer drug therapy for more than 2 months were eligible. Patients with no out-of-pocket costs for direct medical costs were excluded. The patients answered the initial test and a retest, which was completed from 2 to 14 days after the initial test. Internal consistency and reproducibility were assessed using Cronbach's alpha and intraclass correlation coefficient (ICC), respectively. Cronbach's alpha ≥0.8 indicates good internal consistency, and ICC ≥0.8 is highly reliable. RESULTS: A total of 112 patients (ovarian: 50, cervical: 26, endometrial: 36) responded to the initial test, and 89 patients answered the retest from 2 to 14 days after the initial test. The median patient age was 58 (range, 28-78) years. The median COST score was 19. Cronbach's alpha showed good internal consistency at 0.83 (95% CI 0.78 to 0.87). The ICC at 0.850 (95% CI 0.777 to 0.900) showed high reliability. CONCLUSIONS: The COST tool has good internal consistency and reliable reproducibility in patients with gynecologic cancer in Japan. The COST tool quantifies financial toxicity in the insurance system, where patients have limited out-of-pocket direct medical costs. The results support the use of the COST tool in patients with gynecologic cancer.

Effect of prior olaparib maintenance therapy for platinum sensitive recurrent ovarian cancer on response to subsequent platinum-based chemotherapy.

AIM: Several years have passed since olaparib maintenance therapy was approved in patients with platinum sensitive recurrent ovarian cancer (PSROC). We speculated that the response to platinum-based chemotherapy (PBC) would be impaired at the time of recurrence after olaparib maintenance therapy. We conducted a noninterventional retrospective study to clarify this clinical question in a single institution. METHODS: We included all patients with PSROC who received olaparib after second or later line of PBC between April 18, 2018, and August 31, 2021. We evaluated the effect of olaparib maintenance therapy on PBC after progression. RESULTS: We identified 42 patients who received olaparib maintenance therapy after second or later line of PBC. Twenty-four patients relapsed after olaparib maintenance therapy, and 17 patients received PBC again. Four of 17 patients (complete response 2, partial response 2) responded to the PBC. The median progression-free survival was longer in patients with platinum-free interval ≥12 months than platinum-free interval of 6-12 months (9.7 vs 2.6 months, hazard ratio, 0.20: 95% confidence interval, 0.04-0.90; p = 0.04). CONCLUSIONS: In the patients with PSROC who experienced disease progression after olaparib maintenance therapy, especially in those with platinum-free interval of 6-12 months, the response to subsequent PBC was extremely poor. The efficiency of re-administration of PBC for PSROC patients with a short-term recurrence after olaparib treatment may need to be reconsidered.

Clinical practice guideline for the treatment of malignant ascites: section summary in Clinical Practice Guideline for peritoneal dissemination (2021).

Patients with peritoneal dissemination (PD) caused by abdominal malignancies are often associated with massive ascites, which shows extremely dismal prognosis because of the discontinuation of systemic chemotherapy mostly due to poor performance status. Many treatment methods, such as simple drainage, peritoneovenous shunting (PVS) and cell-free and concentrated reinfusion therapy (CART), have been used for symptom relief. However, the clinical efficacies of these methods have not been fully investigated yet. Recently, we developed the Clinical Practice Guideline for PD caused by various malignancies according to "Minds Clinical Practice Guideline Development Guide 2017". In this guideline, we systematically reviewed information on clinical diagnosis and treatments for PD using PubMed databases (2000 - 2020), and clarified the degree of recommendation for clinical questions (CQ). The evidence level was divided into groups by study design and quality. The literature level and a body of evidence were evaluated in reference to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Based on the results of systematic review, the strength of the recommendations was evaluated at a consensus meeting of the Guideline Committee. This is the English synopsis of the part of treatment of malignant ascites in Clinical Practice Guideline for PD, 2021 in Japanese. The guidelines summarize the general aspect of the treatment of malignant ascites and statements with recommendation strengths, evidence levels, agreement rates and future perspective for four raised clinical questions.

Olaparib plus bevacizumab as maintenance therapy in patients with newly diagnosed, advanced ovarian cancer: Japan subset from the PAOLA-1/ENGOT-ov25 trial.

OBJECTIVE: The addition of maintenance olaparib to bevacizumab demonstrated a significant progression-free survival (PFS) benefit in patients with newly diagnosed, advanced ovarian cancer in the PAOLA-1/ENGOT-ov25 trial (NCT02477644). We evaluated maintenance olaparib plus bevacizumab in the Japan subset of PAOLA-1. METHODS: PAOLA-1 was a randomized, double-blind, phase III trial. Patients received maintenance olaparib tablets 300 mg twice daily or placebo twice daily for up to 24 months, plus bevacizumab 15 mg/kg every 3 weeks for up to 15 months in total. This prespecified subgroup analysis evaluated investigator-assessed PFS (primary endpoint). RESULTS: Of 24 randomized Japanese patients, 15 were assigned to olaparib and 9 to placebo. After a median follow-up for PFS of 27.7 months for olaparib plus bevacizumab and 24.0 months for placebo plus bevacizumab, median PFS was 27.4 versus 19.4 months, respectively (hazard ratio [HR]=0.34; 95% confidence interval [CI]=0.11-1.00). In patients with tumors positive for homologous recombination deficiency, the HR for PFS was 0.57 (95% CI=0.16-2.09). Adverse events in the Japan subset were generally consistent with those of the PAOLA-1 overall population and with the established safety and tolerability profiles of olaparib and bevacizumab. CONCLUSION: Results in the Japan subset of PAOLA-1 support the overall conclusion of the PAOLA-1 trial demonstrating that the addition of maintenance olaparib to bevacizumab provides a PFS benefit in patients with newly diagnosed, advanced ovarian cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02477644.

Treatment strategy for locally advanced squamous cell cervical cancer with clinically positive pelvic lymph nodes metastasis.

AIM: To determine the optimal treatment for locally advanced squamous cell cervical cancer with clinical positive pelvic lymph nodes metastasis (cN1). METHODS: We enrolled patients with squamous cell cervical cancer with 2008 FIGO stages IB, IIA, or IIB diagnosed with cN1, who were treated at Hyogo Cancer Center between April 2010 and December 2016. Patients with para-aortic lymph nodes metastasis were excluded. RESULTS: Of the 69 eligible patients, 24 underwent concurrent chemoradiotherapy (CCRT), 11 underwent radical hysterectomy with pelvic lymphadenectomy (RH) with or without adjuvant RT, and 34 underwent neoadjuvant chemotherapy (NAC) followed by RH as initial treatment. The regimens of NAC included dose-dense TC (paclitaxel 80 mg/m2 , days 1, 8, 15; and carboplatin at an area under the curve = 6 on day 1, every 3 weeks) and dose-dense TP (paclitaxel 80 mg/m2 on days 1, 8, 15; and cisplatin 75 mg/m2 on day 1, every 3 weeks). The median observation period was 57 (12-107) months. The 5-year disease-free survival rates of the CCRT, RH, and NAC groups were 78.7%, 63.6%, and 88.2%, respectively (p = 0.14). The 5-year overall survival rates of the CCRT, RH, and NAC groups were 78.6%, 70.1%, and 94.1%, respectively (p = 0.11). CONCLUSIONS: We recommend avoiding RH as primary treatment for cN1 with locally advanced squamous cell cervical cancer. Although CCRT should be considered for cN1, further studies are required to determine if NAC followed by RH will serve as an effective option.

Successful Endoscopic Treatment for High-grade Cervical Intraepithelial Neoplasia with Gross Lesions of the Vagina.

We present a patient diagnosed with high-grade cervical intraepithelial neoplasia (CIN) combined with macroscopic lesions of the vaginal epithelium. There was no lesion in pelvic magnetic resonance imaging examination, and histopathological examination revealed CIN3 and vaginal intraepithelial neoplasia (VAIN) 3 without invasion. We chose minimally invasive surgery for her and total laparoscopic hysterectomy with partial resection of the vagina was carried out. To determine appropriate surgical margins, vaginal colpotomy was performed. No recurrence of VAIN has been observed to date that passed for 9 months either.

Validation of tissue factor pathway inhibitor 2 as a specific biomarker for preoperative prediction of clear cell carcinoma of the ovary.

BACKGROUND: Tissue factor pathway inhibitor 2 (TFPI2) is a novel serum biomarker that discriminates ovarian clear cell carcinoma (CCC) from borderline ovarian tumors (BOTs) and non-clear cell epithelial ovarian cancers (EOCs). Here, we examined the performance of TFPI2 for preoperative diagnosis of CCC. METHODS: Serum samples were obtained preoperatively from patients with ovarian masses, who needed surgical treatment at five hospitals in Japan. The diagnostic powers of TFPI2 and cancer antigen 125 (CA125) serum levels to discriminate CCC from BOTs, other EOCs, and benign lesions were compared. RESULTS: A total of 351 patients including 69 CCCs were analyzed. Serum TFPI2 levels were significantly higher in CCC patients (mean ± SD, 508.2 ± 812.0 pg/mL) than in patients with benign lesions (154.7 ± 46.5), BOTs (181 ± 95.5) and other EOCs (265.4 ± 289.1). TFPI2 had a high diagnostic specificity for CCC (79.5%). In patients with benign ovarian endometriosis, no patient was positive for TFPI2, but 71.4% (15/21) were CA125 positive. TFPI2 showed good performance in discriminating stage II-IV CCC from BOTs and other EOCs (AUC 0.815 for TFPI2 versus 0.505 for CA125) or endometriosis (AUC 0.957 for TFPI2 versus 0.748 for CA125). The diagnostic sensitivity of TFPI2 to discriminate CCC from BOTs and other EOCs was improved from 43.5 to 71.0% when combined with CA125. CONCLUSIONS: High specificity of TFPI2 for preoperative detection of CCC was verified with the defined cutoff level of TFPI2 in clinical practice. TFPI2 and CA125 may contribute substantially to precise prediction of intractable CCC.

Survival impact of adjuvant concurrent chemoradiotherapy after radical hysterectomy in FIGO stage IIIC1 cervical adenocarcinoma.

BACKGROUND: We evaluated the survival effect of adjuvant concurrent chemoradiotherapy after radical hysterectomy in patients with clinical pelvic node-positive cervical adenocarcinoma. METHODS: Patients with pelvic node-positive cervical adenocarcinoma diagnosed between 2000 and 2016 at our institution were identified. Survival was compared between patients who underwent radical hysterectomy alone and those who received concurrent chemoradiotherapy as an adjuvant treatment. Survival analysis using log-rank test and Cox proportional hazards model was performed. RESULTS: We identified 80 patients who underwent radical hysterectomy for clinical pelvic node-positive cervical adenocarcinoma; of these, four with pathological pelvic node-negative adenocarcinoma were excluded. Of the 76 patients, 27 underwent radical hysterectomy alone and 49 received radical hysterectomy followed by concurrent chemoradiotherapy. With a median follow-up of 53 months, the 5-year overall survival rate was 51.0% in patients who underwent radical hysterectomy alone versus 53.0% in patients who received additional concurrent chemoradiotherapy (log-rank p = 0.455). CONCLUSION: The addition of concurrent chemoradiotherapy after radical hysterectomy did not significantly improve survival among patients with pelvic node-positive cervical adenocarcinoma. More appropriate treatment strategies are needed to improve the survival outcomes of these patients.

Docetaxel and carboplatin chemotherapy for treating patients with stage IVB or recurrent non-squamous cell carcinoma of the uterine cervix: a phase II study.

BACKGROUND: This phase II study evaluated the efficacy and safety of docetaxel/carboplatin chemotherapy for treating patients with stage IVB or recurrent non-squamous cell carcinoma of the uterine cervix. METHODS: A total of 50 patients with International Federation of Gynecology and Obstetrics stage IVB or recurrent non-squamous cell carcinoma of the uterine cervix were enrolled and administered docetaxel at a dose of 60 mg/m2, followed by carboplatin at a dose based on the area under the receiver operating characteristic curve of 6. The treatments were repeated every 21 days until disease progression or unacceptable adverse events. Except for two patients, 48 were eligible for evaluation. Another patient withdrew consent before treatment; adverse events were evaluated in 47. RESULTS: The response rate was 47.9% with 5 patients achieving complete response, 18 partial response, 14 stable disease, and 6 progressive disease. The disease control rate was 77.1%. With a median follow-up duration of 368 days, the median progression-free survival and overall survival were 6.1 months (95% CI 5.5-8.6) and 15.8 months (95% CI 18.2-28.3), respectively. The most frequent grade 3 and grade 4 hematological toxicity was neutropenia, with 38 patients (81%) having grade 4 and 4 (9%) having grade 3 neutropenia. The non-hematological toxicities were mainly grade 1 or 2 in severity. CONCLUSION: Docetaxel/carboplatin chemotherapy was effective, with a higher disease control rate and well-tolerated chemotherapeutic regimen for patients with stage IVB or recurrent non-squamous cell carcinoma of the uterine cervix.

Quality of life assessment of cell-free and concentrated ascites reinfusion therapy during initial treatment for advanced ovarian cancer: A prospective cohort study.

AIM: Cell-free and concentrated ascites reinfusion therapy (CART) is applied to relieve symptoms in patients with malignant ascites. We performed a prospective cohort study to evaluate the efficacy and safety of CART performed on patients with advanced ovarian and peritoneal cancers with massive ascites during the initial treatment. METHODS: From April 2018 to July 2020, CART was performed during the initial treatment of 31 patients with advanced ovarian and peritoneal cancers with cancerous ascites. Patient characteristics and clinical information before and after CART were collected. We performed quality of life assessment using the Japanese version of the M.D. Anderson Symptom Inventory (MDASI-J) 24 h before and after CART. RESULTS: CART was performed 38 times in 24 patients before or during neoadjuvant chemotherapy and 11 times in 11 patients prior to surgery. Four patients underwent CART before primary surgery and before and/or during chemotherapy. Grade 1-2 fever was observed in 18 of 31 cases (58%), and all were controllable by nonsteroidal anti-inflammatory drugs. CART did not adversely affect the main treatment, chemotherapy, or surgery. CART significantly improved the MDASI-J symptom and interference scores within 24 h after the procedure. The symptom and interference scores decreased from 2.4 to 1.8 and from 4.8 to 3.0, respectively. CONCLUSIONS: CART can be safely performed and is useful for symptom relief and improvement of general condition prior to initial surgery and during initial chemotherapy in ovarian and peritoneal cancers. Performing CART at the time of initial treatment may facilitate initiation of the main treatment.

Phase 2 single-arm study on the safety of maintenance niraparib in Japanese patients with platinum-sensitive relapsed ovarian cancer.

OBJECTIVE: The primary objective of this study was to evaluate the safety of niraparib 300 mg/day in Japanese patients with platinum-sensitive, relapsed ovarian cancer in a maintenance setting. METHODS: Phase 2, multicenter, open-label, single-arm study enrolled Japanese patients with platinum-sensitive, relapsed ovarian cancer who had received ≥2 platinum-based regimens. The primary endpoint (incidence of grade 3 or 4 thrombocytopenia-related events within 30 days after initial niraparib administration) was justified by the incidences of a global pivotal phase 3 study and its post-hoc safety analysis on thrombocytopenia, the major hematological adverse event of niraparib. The overall safety analysis examined other treatment-emergent adverse events (TEAEs). RESULTS: Enrolled patients (n=19) had a median (min, max) body weight of 53.9 (40.8-79.1) kg; all but one patient weighed <77 kg. Most (94.7%) patients initially received niraparib 300 mg/day but this decreased in subsequent cycles (mean±standard deviation dose intensity, 191.6±65.7 mg/day). In total, 6/19 (31.6%) patients experienced grade 3 or 4 thrombocytopenia-related events within 30 days of initial niraparib administration. Other common TEAEs included nausea, and decreased platelet or neutrophil counts. No progression-free or overall survival events occurred; only 1 of 4 response-evaluable patients had a post-baseline tumor assessment (stable disease). CONCLUSION: The incidence of grade 3 or 4 thrombocytopenia-related events in Japanese ovarian cancer patients was similar to that in the corresponding non-Japanese study. Overall, the safety profile was acceptable and consistent with the known safety profile and previous experience with niraparib. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03759587.