- 静脈血栓塞栓症（venous thromboembolism: VTE）の合併頻度が高く、治療前の評価を考慮する。
- 進行癌では腫瘍の拡がりあるいは癌の進行に伴うperformance status（PS）の悪化などにより術前化学療法から治療が開始される場合がある。
|1:||Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial.|
著者: Eric Pujade-Lauraine, Jonathan A Ledermann, Frédéric Selle, Val Gebski, Richard T Penson, Amit M Oza, Jacob Korach, Tomasz Huzarski, Andrés Poveda, Sandro Pignata, Michael Friedlander, Nicoletta Colombo, Philipp Harter, Keiichi Fujiwara, Isabelle Ray-Coquard, Susana Banerjee, Joyce Liu, Elizabeth S Lowe, Ralph Bloomfield, Patricia Pautier, SOLO2/ENGOT-Ov21 investigatorsLancet Oncol. 2017 Sep;18(9):1274-1284. doi: 10.1016/S1･･･
雑誌名: Lancet Oncol. 2017 Sep;18(9):1274-1284. doi: 10.1016/S1470-2045(17)30469-2. Epub 2017 Jul 25.
Abstract/Text BACKGROUND: Olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, has previously shown efficacy in a phase 2 study when given in capsule formulation to all-comer patients with platinum-sensitive, relapsed high-grade serous ovarian cancer. We aimed to confirm these findings in patients with a BRCA1 or BRCA2 (BRCA1/2) mutation using a tablet formulation of olaparib.
METHODS: This international, multicentre, double-blind, randomised, placebo-controlled, phase 3 trial evaluated olaparib tablet maintenance treatment in platinum-sensitive, relapsed ovarian cancer patients with a BRCA1/2 mutation who had received at least two lines of previous chemotherapy. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status at baseline of 0-1 and histologically confirmed, relapsed, high-grade serous ovarian cancer or high-grade endometrioid cancer, including primary peritoneal or fallopian tube cancer. Patients were randomly assigned 2:1 to olaparib (300 mg in two 150 mg tablets, twice daily) or matching placebo tablets using an interactive voice and web response system. Randomisation was stratified by response to previous platinum chemotherapy (complete vs partial) and length of platinum-free interval (6-12 months vs ≥12 months) and treatment assignment was masked for patients, those giving the interventions, data collectors, and data analysers. The primary endpoint was investigator-assessed progression-free survival and we report the primary analysis from this ongoing study. The efficacy analyses were done on the intention-to-treat population; safety analyses included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01874353, and is ongoing and no longer recruiting patients.
FINDINGS: Between Sept 3, 2013, and Nov 21, 2014, we enrolled 295 eligible patients who were randomly assigned to receive olaparib (n=196) or placebo (n=99). One patient in the olaparib group was randomised in error and did not receive study treatment. Investigator-assessed median progression-free survival was significantly longer with olaparib (19·1 months [95% CI 16·3-25·7]) than with placebo (5·5 months [5·2-5·8]; hazard ratio [HR] 0·30 [95% CI 0·22-0·41], p<0·0001). The most common adverse events of grade 3 or worse severity were anaemia (38 [19%] of 195 patients in the olaparib group vs two [2%] of 99 patients in the placebo group), fatigue or asthenia (eight [4%] vs two [2%]), and neutropenia (ten [5%] vs four [4%]). Serious adverse events were experienced by 35 (18%) patients in the olaparib group and eight (8%) patients in the placebo group. The most common in the olaparib group were anaemia (seven [4%] patients), abdominal pain (three [2%] patients), and intestinal obstruction (three [2%] patients). The most common in the placebo group were constipation (two [2%] patients) and intestinal obstruction (two [2%] patients). One (1%) patient in the olaparib group had a treatment-related adverse event (acute myeloid leukaemia) with an outcome of death.
INTERPRETATION: Olaparib tablet maintenance treatment provided a significant progression-free survival improvement with no detrimental effect on quality of life in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation. Apart from anaemia, toxicities with olaparib were low grade and manageable.
Copyright © 2017 Elsevier Ltd. All rights reserved.
|2:||Reproductive and sexual function after platinum-based chemotherapy in long-term ovarian germ cell tumor survivors: a Gynecologic Oncology Group Study.|
著者: David M Gershenson, Anna M Miller, Victoria L Champion, Patrick O Monahan, Qianqian Zhao, David Cella, Stephen D Williams, Gynecologic Oncology GroupJ Clin Oncol. 2007 Jul 1;25(19):2792-7. doi: 10.1200/JC･･･
雑誌名: J Clin Oncol. 2007 Jul 1;25(19):2792-7. doi: 10.1200/JCO.2006.08.4590.
Abstract/Text PURPOSE: To compare malignant ovarian germ cell tumor survivors with a matched control group of females on menstrual and reproductive outcomes, sexual functioning, and dyadic adjustment.
PATIENTS AND METHODS: Eligible patients met the following criteria: (1) history of malignant ovarian germ cell tumor; (2) treatment with surgery plus platinum-based chemotherapy; (3) age at least 18 years and continuously disease-free with minimum follow-up of 2 years; (4) capability of completing questionnaire and telephone interview; and (5) completion of written informed consent. The control group was drawn from acquaintances recommended by survivors and matched for age, race, and education. Scales with established reliability and validity were used to measure quality-of-life concepts of sexual functioning and social networks.
RESULTS: One hundred thirty-two survivors and 137 controls completed the study. Of 132 survivors, 71 (53.8%) had fertility-sparing surgery. Of fertile survivors, 62 (87.3%) reported still having menstrual periods. Twenty-four survivors reported 37 offspring after cancer treatment. Compared with controls, survivors had significantly greater reproductive concerns (P < .0001), less sexual pleasure (P = .003), and lower scores on the total Sexual Activity Scale Score (P = .001). However, survivors had better dyadic consensus (P = .004), dyadic satisfaction (P = .005), and dyadic cohesion (P = .014).
CONCLUSION: Women who had fertility-sparing surgery were very likely to retain menstrual function and fertility after chemotherapy. Although there is some increase in gynecologic symptoms and diminution in sexual pleasure, survivors tended to have stronger, more positive relationships with significant others.
|3:||High incidence of silent venous thromboembolism before treatment in ovarian cancer.|
著者: T Satoh, A Oki, K Uno, M Sakurai, H Ochi, S Okada, R Minami, K Matsumoto, Y O Tanaka, H Tsunoda, S Homma, H YoshikawaBr J Cancer. 2007 Oct 22;97(8):1053-7. doi: 10.1038/sj.･･･
雑誌名: Br J Cancer. 2007 Oct 22;97(8):1053-7. doi: 10.1038/sj.bjc.6603989. Epub 2007 Sep 25.
Abstract/Text Venous thromboembolism (VTE) such as deep-vein thrombosis (DVT) and pulmonary thromboembolism (PTE) often occurs after surgery and rarely occurs even before surgery in patients with ovarian cancer. It is well known that levels of plasma D-dimer (DD) before treatment in most ovarian cancer patients are increased. This study therefore examined whether increased levels of DD are associated with presence of VTE before treatment of ovarian cancer. Between November 2004 and March 2007, DD levels prior to initial treatment were measured in 72 consecutive patients with presumed epithelial ovarian cancer (final diagnosis: epithelial ovarian cancer, n=60; and epithelial ovarian borderline malignancy, n=12). Venous ultrasound imaging (VUI) of the lower extremity was conducted for all patients except for two patients in whom DVT was detected by pelvic computed tomography (CT). When DVT was found, pulmonary scintigraphy was subsequently performed to ascertain presence of PTE. D-dimer levels were above the cut-off value (0.5 microg ml(-1)) in 65 of 72 patients (90.2%). Venous ultrasound imaging or CT revealed DVT in 18 of 72 patients (25.0%) and pulmonary scintigraphy found PTE in 8 patients (11.1%). All patients with VTE were asymptomatic when VTE was found. D-dimer levels were associated with incidence of VTE (0-1.4 microg ml(-1); 0 of 26 (0%), 1.5-7.4 microg ml(-1); 9 of 30 (30%) and > or =7.5 microg ml(-1); 9 of 16 (56.3%), P for trend=0.0003). However, even if 1.5 microg ml(-1) was used as a cut-off value, this had low specificity and positive predictive value (47.2, 38.3%), though it had high sensitivity and negative predictive value (100, 100%). Therefore, ovarian cancer patients with DD level > or =1.5 microg ml(-1) should be examined using VUI to detect silent DVT. Patients with VTE underwent preventive managements including anticoagulant therapy before initial treatment, chemotherapy or surgery, and after surgery. There was no clinical onset of postoperative VTE in all 72 patients. Measurement of DD levels and subsequent ultrasonography revealed that silent or subclinical VTE frequently occurs before surgery in ovarian cancer. The usefulness of preoperative assessment of VTE needs further confirmation in randomised controlled trials.
|4:||Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis.|
著者: Robert E Bristow, Rafael S Tomacruz, Deborah K Armstrong, Edward L Trimble, F J MontzJ Clin Oncol. 2002 Mar 1;20(5):1248-59. doi: 10.1200/JC･･･
雑誌名: J Clin Oncol. 2002 Mar 1;20(5):1248-59. doi: 10.1200/JCO.2002.20.5.1248.
Abstract/Text PURPOSE: To evaluate the relative effect of percent maximal cytoreductive surgery and other prognostic variables on survival among cohorts of patients with advanced-stage ovarian carcinoma treated with platinum-based chemotherapy.
MATERIALS AND METHODS: Eighty-one cohorts of patients with stage III or IV ovarian carcinoma (6,885 patients) were identified from articles in MEDLINE (1989 through 1998). Linear regression models, with weighted correlation calculations, were used to assess the effects on log median survival time of the proportion of each cohort undergoing maximal cytoreduction, dose-intensity of the platinum compound administered, proportion of patients with stage IV disease, median age, and year of publication.
RESULTS: There was a statistically significant positive correlation between percent maximal cytoreduction and log median survival time, and this correlation remained significant after controlling for all other variables (P <.001). Each 10% increase in maximal cytoreduction was associated with a 5.5% increase in median survival time. When actuarial survival was estimated, cohorts with < or = 25% maximal cytoreduction had a mean weighted median survival time of 22.7 months, whereas cohorts with more than 75% maximal cytoreduction had a mean weighted median survival time of 33.9 months--an increase of 50%. The relationship between platinum dose-intensity and log median survival time was not statistically significant.
CONCLUSION: During the platinum era, maximal cytoreduction was one of the most powerful determinants of cohort survival among patients with stage III or IV ovarian carcinoma. Consistent referral of patients with apparent advanced ovarian cancer to expert centers for primary surgery may be the best means currently available for improving overall survival.