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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.
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Objective@#The standard dose for pegylated liposomal doxorubicin (PLD) is 50 mg/m2 every 4 weeks. While 40 mg/m2 has recently been used in clinical practice, evidence supporting this use remains lacking. @*Methods@#This phase III randomized, non-inferiority study compared progressionfree survival (PFS) for patients with platinum-resistant ovarian carcinoma between an experimental arm (40 mg/m2 PLD) and a standard arm (50 mg/m2 PLD) until 10 courses, disease progression or unacceptable toxicity. Eligible patients had received ≤2 prior lines.Stratification was by performance status and PFS of prior chemotherapy (<3 months versus ≥3 months). The primary endpoint was PFS and secondary endpoints were overall survival (OS), toxicity profile, clinical response and tolerability. The total number of patients was 470. @*Results@#The trial was prematurely closed due to slow recruitment, with 272 patients randomized to the experimental arm (n=137) and standard arm (n=135). Final analysis was performed with 234 deaths and 269 events for PFS. In the experimental arm vs. standard arm, median PFS was 4.0 months vs. 4.0 months (hazard ratio [HR]=1.065; 95% confidence interval [CI]=0.830–1.366) and median OS was 14.0 months vs. 14.0 months (HR=1.078; 95% CI=0.831–1.397). Hematologic toxicity and oral cavity mucositis (≥grade 2) were more frequent in the standard arm than in the experimental arm, but no difference was seen in ≥grade 2 hand-foot skin reaction. @*Conclusion@#Non-inferiority of 2 PLD dosing schedule was not confirmed because the trial was closed prematurely. However, recommendation of dose reduction of PLD should be based both on efficacy and safety.
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To determine the body constituents patterns comprised of “qi, blood, fluid” factors associated with oral health-related QOL (OHRQOL) of patients with Sjögren's syndrome (SS), 41 SS patients and 32 RA patients in remission were enrolled. The body constituents patterns were measured by using Terasawa's “qi, blood, fluid” score, and the simple version of yin deficiency questionnaire (yin-deficiency score). OHRQOL were evaluated using the oral health impact profile (OHIP-14). In the first study, the body constituents pattern scores were compared between SS group and RA (in remission) group, using the univariate and multivariate analysis. In the second study, the association between OHIP14 and the body constituents pattern scores was analyzed. In the first study, all the scores were significantly higher in SS group, and the multivariable logistic regression identified yin deficiency (p = 0.02) and blood stasis (p = 0.01) as the significantly associated factors with SS group. In the second study, all the scores, except for the blood stasis pattern, showed positive correlation with OHIP-14. The multiple regression analysis identified qi stagnation (p = 0.003) as the significantly associated factors with OHIP-14. This study revealed that yin deficiency and blood stasis are the significant body constituent patterns in SS patients. In the low OHRQOL cases, qi stagnation should be taken into consideration.
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The Fourth Edition of the Guidelines for Treatment of Uterine Body Neoplasm was published in 2018. These guidelines include 9 chapters: 1. Overview of the guidelines, 2. Initial treatment for endometrial cancer, 3. Postoperative adjuvant therapy for endometrial cancer, 4. Post-treatment surveillance for endometrial cancer, 5. Treatment for advanced or recurrent endometrial cancer, 6. Fertility-sparing therapy, 7. Treatment of uterine carcinosarcoma and uterine sarcoma, 8. Treatment of trophoblastic disease, 9. Document collection; and nine algorithms: 1-3. Initial treatment of endometrial cancer, 4. Postoperative adjuvant treatment for endometrial cancer, 5. Treatment of recurrent endometrial cancer, 6. Fertility-sparing therapy, 7. Treatment for uterine carcinosarcoma, 8. Treatment for uterine sarcoma, 9. Treatment for choriocarcinoma. Each chapter includes overviews and clinical questions, and recommendations, objectives, explanation, and references are provided for each clinical question. This revision has no major changes compared to the 3rd edition, but does have some differences: 1) an explanation of the recommendation decision process and conflict of interest considerations have been added in the overview, 2) nurses, pharmacists and patients participated in creation of the guidelines, in addition to physicians, 3) the approach to evidence collection is listed at the end of the guidelines, and 4) for clinical questions that lack evidence or clinical validation, the opinion of the Guidelines Committee is given as a “Recommendations for tomorrowâ€.
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Female , Humans , Pregnancy , Carcinosarcoma , Choriocarcinoma , Conflict of Interest , Endometrial Neoplasms , Gestational Trophoblastic Disease , Japan , Pharmacists , Sarcoma , TrophoblastsABSTRACT
OBJECTIVE: To investigate the relationship between the precursors of high grade serous ovarian cancer (HGSOC) and the characteristics of patients with a low HGSOC risk in terms of the effects of pregnancy. METHODS: We prospectively examined consecutive cases in which the bilateral fallopian tubes were removed during benign gynecological or obstetric surgery and assessed the relationship between the patient characteristics, including parity and pregnancy, and the incidence of HGSOC precursors. All the fallopian tubes were examined by applying the Sectioning and Extensively Examining the Fimbriated End (SEE-FIM) Protocol. RESULTS: Of the 113 patients enrolled, 67 were gynecological and 46 were obstetric. The p53 signature was identified in 21 patients. No other precursors were identified. In a comparison of the p53 signature-positive and negative groups, parous women and pregnant women were significantly fewer in the p53 signature-positive group (53% vs. 86%, p=0.002, 10% vs. 47%, p=0.001, respectively). Current pregnancy was also associated with a significantly lower incidence of the p53 signature after multivariate adjustment (odds ratio [OR]=0.112; 95% confidence interval [95% CI]=0.017–0.731; p=0.022). Among gynecological patients, parous women were fewer in the p53 signature-positive group on univariate (47% vs. 73%, p=0.047) and multivariate analysis (OR=0.252; 95% CI=0.069–0.911; p=0.036). No other characteristics were associated with p53 signature positivity. CONCLUSIONS: The incidence of the p53 signature was significantly lower in parous women and pregnant women. This decreased incidence of early phase serous carcinogenesis may be one of the possible mechanisms underlying HGSOC risk reduction among parous women.