bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II trial of bevacizumab and pemetrexed for recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer.
Authors: Hagemann Andrea R. , Zighelboim Israel , Novetsky Akiva Pesach , Gao Feng , Massad L. Stewart , Thaker Premal H. , Powell Matthew A. , Mutch David Gardner , Wright Jason D. 
Published: March 2020

5013 Background: This phase II clinical trial evaluated the efficacy and safety of the combination of bevacizumab, a VEGF inhibitor, and pemetrexed, a multi-targeted antifolate agent inhibiting thymidylate synthase, for recurrent or persistent epithelial ovarian, fallopian tube (FT) or primary peritoneal (PP) cancer. Methods: Patients with measurable recurrent/persistent epithelial ovarian, FT or PP cancer after at least one prior platinum- and taxane-containing regimen were eligible. Patients might have received < 2 prior cytotoxic chemotherapy regimens but no prior bevacizumab. Pemetrexed 500 mg/m2 IV and bevacizumab 15 mg/kg IV were given every 3 weeks until progression, unacceptable adverse effects, or patient/physician choice. 32 patients were needed to have 90% power to detect the primary endpoint of 6-month PFS ≥ 40% with a two-sided 0.05 significance. Secondary endpoints included toxicity and response by RECIST and CA-125 criteria. Results: Thirty-four patients received a median of 7 treatment cycles (range, 2-26). Twenty-eight patients (82%, 95% CI: 66-92) were platinum-sensitive. Median follow-up was 17.1 months (range, 2.7-31.2). The 6-month PFS was 58.2% (95%CI: 40-73) for all patients and 50% (19-81) for platinum-resistant patients. Objective response rates by RECIST criteria included (%; 95%CI): 0 CR, 14 PR (41%; 25-59), 18 SD (53%; 35-70) and 2 PD (6%; 1-20). Of 27 patients evaluable by CA-125, levels declined ≥50% in 17 (62%; 44-79), and ≥75% in 8 (30%; 16-49). 12-month OS was 88% (95%CI: 71-95) and median PFS was 7.8 months (95%CI: 4.7-10.7). Of the 34 patients, grade 3-4 hematologic toxicities occurred in 53% (neutropenia 50%, leukopenia 26%, thrombocytopenia 12%, anemia 9%). Other grade 3-4 toxicities included metabolic (29%), constitutional (18%), pain (18%) and gastrointestinal (15%). No bowel perforations occurred. Conclusions: Combined bevacizumab/pemetrexed is well tolerated and highly active for the treatment of recurrent ovarian cancer. The dose and schedule tested here warrant further investigation in phase III trials.
Phase I/II study of weekly paclitaxel with or without MLN8237 (alisertib), an investigational aurora A kinase inhibitor, in patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer (OC), or breast cancer (BrC): Phase I results.
Authors: Falchook Gerald Steven , Goff Barbara Ann , Kurzrock Razelle , Gray Heidi J. , Martin Lainie P. , Coleman Robert L. , Liu Hua , Zhou Xiaofei , Benaim Ely , Schilder Russell 
Published: March 2020

5021 Background: Preclinical data indicate that inhibiting aurora A kinase (AAK), a key mitotic regulator, in OC can enhance the activity of taxane-based chemotherapy. This is the first clinical study to evaluate the AAK inhibitor MLN8237 (A) in combination with paclitaxel (P). Methods: Eligible women (aged ≥18 y) had previously treated, metastatic or locally recurrent OC or BrC. OC pts had previously received a platinum and taxane, and had disease recurrence within 12 mo of discontinuing platinum. Pts received IV P (D1, 8, 15) with oral A (enteric coated tablet, 3 d on, 4 d off, wkly for 3 wks) in 28-d cycles. Doses were escalated in a 3+3 schema. Phase I endpoints were safety, response by RECIST and CA125, and pharmacokinetics (PK). Results: 28 pts were treated at doses of P80 mg/m2 + A10 mg BID (n=5), P80+A20 (n=6), P60+A20 (n=4), P60+A30 (n=6), P60+A40 (n=4) and P60+A50 (n=3). 25 pts had OC (20 ovarian, 4 primary peritoneal, 1 mullerian) and 3 BrC. Median age was 59 y (range 37–72). Pts received a median of 2.5 (1–16) and 2.5 cycles (1–15) of A and P, respectively. 11 pts are ongoing. 3 pts had DLTs: Gr 4 diarrhea (P80+A20), Gr 3 stomatitis (P80+A20) and Gr 4 neutropenia for >7 d with fever (P60+A30). MTD has not yet been reached. 27 pts had ≥1 drug-related adverse event (AE); most common were neutropenia (n=18), anemia (n=13) and nausea (n=12). 21 pts had Gr ≥3 drug-related AEs; the most common was neutropenia (n=15). 5 pts had drug-related SAEs. No pts have died on study. Preliminary PK data (n=24) indicated fast absorption of A with a median Tmax of 3 hr. Geometric means of A AUC0–12hr on D3 were 3740 nM*hr (CV: 22%), 7180 nM*hr (31%), 11,900 nM*hr (49%) and 15,100 nM*hr (72%) at 10, 20, 30 and 40 mg BID, respectively. A exposures increased approximately dose proportionally. Partial responses by RECIST (n=5) and/or CA125 (n=7) in 8 pts (29%; 7 OC, 1 BrC); 3 pts had stable disease ≥6 mo. Conclusions: Emerging data from this first combination study suggest that P+A is generally well tolerated and has antitumor activity in pts with OC/BrC. Dose-escalation is ongoing to determine the recommended phase II dose.
A snapshot of potentially personalized care: Molecular diagnostics in gynecologic cancer.
Authors: Sales Elizabeth , Penson Richard T. , Sullivan Laura A , Borger Darrell R. , Krasner Carolyn N. , Goodman Annekathryn , del Carmen Marcela G , Growdon Whitfield Board , Schorge John O. , Boruta David M. , Birrer Michael J. 
Published: March 2020

5029 Background: Genetic abnormalities underlie the development of cancer. It has been proposed that tumors be recategorized by gene mutation such as BRAF in LG serous, TP53 in HG serous, and PIK3CA in clear cell and endometrioid tumors. These targets potentially represent an opportunity for personalizing cancer therapy. Methods: Gynecologic Oncology patients at the MGH Cancer Center can have their tumor genotyped for a panel of mutations by SNaPshot, a validated, CLIA approved assay developed by MGH that uses DNA from FFPE tissue to interrogate 160 site-specific mutations across 15 genes (AKT1, APC, BRAF, CTNNB1, EGFR, ERBB2, IDH1, KIT, KRAS, MAP2K1, NOTCH1, NRAS, PIK3CA, PTEN, TP53). At present SNaPshot has no validated endpoints in GYN Cancers but may help identify a useful clinical trial. Results: Between 5/17/10 and 10/17/11, 125 patients consented to SNaPshot genotyping. Patients had a median age of 59 (24-78) yrs. Tumors were ovarian 70(56%), uterine clear, UPSC, or MMMT 16(13%), uterine endometrioid 10(8%), fallopian tube 8(6%), PPC 7(6%), cervical 6(5%), uterine sarcomas (3), ACUP (2), vulvovaginal (2), metastatic (1). A mutation was identified in 41(33%), with 9 of these (23%) having 2 or 3 (n=2) mutations. In the 85 ovarian, FT, and PPC cancers 33% were +ve, but 50% were in TP53. The low mutation rate for TP53 is likely explained by copy number abnormalities (Amplification). 50% of the 10 uterine tumors were +ve, with 3 of those 5 having multiple mutations in the PIK3CA pathway, while 69% of the non-endometrioid uterine tumors had mutations. Only 20% of the vulvo-vaginal and Cx tumors had mutations, both PIK3CA. 19% of the purely serous tumors (n=58) had TP53 mutations, and 37% of the purely clear/endometrioid tumors (n=19) had mutations in PIK3CA, PTEN or AKT. Certain rare tumors did not have identifiable mutations: granulosa cell tumors (2), ovarian small cell (2). 5 pts with a PIK3CA mutation were enrolled on a clinical trial (2 phase II, 3 phase I, 3 uterine, 1 ovary, 1 cervix). Conclusions: SNaPshot can identify potentially important therapeutic targets. However, the incidence of "drugable" targets in ovarian cancer is low, and <5% subjects eventually were treated on a relevant clinical trial.
Carboplatin dosing in the treatment of epithelial ovarian cancer (EOC): A Gynecologic Oncology Group (GOG) study.
Authors: O'Cearbhaill Roisin Eilish , Miller Austin , Muggia Franco , Smith Judith A. , Bookman Michael A. , Sabbatini Paul ,   Gynecologic Oncology Group
Published: March 2020

5041 Background: Optimal carboplatin dosing (CPRx) for patients (pts) with renal dysfunction or low creatinine (Cr) values in the setting of malnutrition and ascites is unknown. Multiple methods have been utilized to estimate Cr clearance (CrCl) but these perform differently in pts with abnormal Cr values. We sought to determine 1) the relationship between adverse events (AE) and baseline CrCl used for CPRx; 2) the effect on CPRx of using Cockcroft-Gault (CG) +/- the NCI/CTEP recommended limits (CGL), Modification of diet in renal disease (MDRD) or Jelliffe Formula (J) renal function estimates. Methods: Retrospective data were drawn from pts treated on GOG 182, a phase III trial of carboplatin doublet vs triplet or sequential doublet combinations in stage III/IV EOC. For patient safety, the protocol was amended to assign the lower limit of Cr at 0.6mg/dl for CPRx. Area under the receiver operating characteristic curve (AUC) was used to describe associations between CrClJ and various AE. Sensitivity and positive predictive values (PPV) described the AE rate in pts with CrClJ <60ml/min. CPRx for each pt was calculated using J, CG, CGL and MDRD. Results: 3830 evaluable pts had a mean age 58.7yrs, mean BMI 26.8kg/m2 and mean baseline CrClJ 81.9ml/min (range 23.4-239). The AUC statistics (range 0.52-0.64) show that the log(CrClJ) was not a good predictor of grade ≥3 AE (anemia, thrombocytopenia, febrile neutropenia, auditory, renal, metabolic, neurologic). A cutoff value of CrClJ <60 ml/min would have deemed 15% of pts treated on GOG182 ineligible. The range of PPV for the above AEs in pts with CrClJ <60 ml/min was 1.8-15%. Using CG, CGL, MDRD instead of J for CPRx would have resulted in >10% decrease in CPRx in 21%, 32% and 12% of pts, respectively. Using CG, CGL, MDRD instead of J for CPRx would have resulted in >10% increase in CPRx in 45%, 9.6% and 5.2% of pts, respectively. Conclusions: Our data do not support excluding patients with CrClJ <60ml/min from clinical trials. The new GOG guidelines replacing J with CGL affect CPRx. The clinical significance of this change with regards to toxicity, particularly in pts with abnormally low Cr values, is yet to be determined.
What do 676 primary and recurrent ovarian cancer (OC) patients expect from their doctors and therapy management? Results of a German survey of the northeastern German Society of Gynecological Oncology (NOGGO).
Authors: Oskay-Özcelik Gülten , Chekerov Radoslav , Neubert Sylvia , Münstedt Karsten , Hindenburg Hans-Joachim , Liebrich Clemens , Hanker Lars Christian , Lorenz Ralf , Wimberger Pauline , Sehouli Jalid 
Published: March 2020

5044 Background: The primary aim of this study was to investigate information needs and preferences among patients with ovarian cancer, focusing especially on doctor-patient relationships and therapy management. Methods: A 42-item questionnaire was developed and validated in a mono-centre phase I study and was then provided to primary and recurrent ovarian cancer patients via internet (online) or as a print-version. In the first part basic data (age, tumour status, therapy) were requested. In the second part, most of the questions try to evaluate the expectations and needs concerning their therapy management and doctor-patients communication. Results: From January to November 2009, a total of 676 (201 online; 475 print version) patients with ovarian cancer from 44 German centres took part in the survey.The median age of the online group was 49 years (range 19-84), for the print group 62 years (26-92). Nearly all patients (98.7%) had a primary surgery and a primary chemotherapy (89%). Asked for side effects during therapy, the most frequent answers were alopecia, paraesthesia/dysaesthesia and fatigue. Most of the patients were content with the completeness and understandability of the explanations about the therapies from their doctors . The three most important aspects, which were proposed by patients to improve therapy against ovarian cancer were: “Doctors should have more time for explanations”, “The therapy should not lead to any loss of hair”, and “The therapy should be more effective”. Conclusions: This study underlines the high need of ovarian cancer patients to discuss all details concerning treatment options and clinical management. As matter of fact, the physician involved in the treatment is the most important source of information.
Longitudinal health-related quality of life assessment: Implications for prognosis in ovarian cancer.
Authors: Braun Donald Peter , Gupta Digant , Staren Edgar Donald , Markman Maurie 
Published: March 2020

5049 Background: Several studies in the oncology literature have demonstrated the prognostic value of baseline quality of life (QoL). However, there is little to no information on the prognostic effects of changes in QoL during treatment. We investigated whether changes in QoL could predict survival in ovarian cancer patients treated with an integrative model of care. Methods: We evaluated 137 ovarian cancer patients treated at our institution between Jan 2001 and Dec 2009 who were available for a minimum follow-up of 3 months. QoL was evaluated at baseline and after 3 months of treatment using EORTC-QLQ-C30. The QLQ-C30 incorporates a global scale, 5 function scales and 8 symptom scales. Patient survival was defined as the time between date of first patient visit and date of death from any cause/date of last contact. Cox regression was performed to evaluate the prognostic significance of baseline and changes in QoL scores after adjusting for age, treatment history and stage at diagnosis. Results: Mean age at diagnosis was 51.1 years. 28 patients were newly diagnosed while 109 were previously treated. Stage at diagnosis was I, 16; II, 15; III, 72; IV, 28; and 6 indeterminate. Median overall survival was 33.5 months (95% CI: 11.5-55.6 months). Baseline QoL scale predictive of survival upon multivariate analysis was nausea/vomiting (p=0.04). Associations between changes in QoL and survival were observed for global function, appetite loss and constipation. Every 10-point increase (improvement) in global function from baseline to 3 months was associated with a 10% decreased risk of death (HR=0.90; 95% CI=0.81 to 0.99, p=0.03). The corresponding HRs for 10-point increase (deterioration) in appetite loss and constipation scales were 1.20 (1.06 to 1.35; p=0.005) and 1.13 (1.02, 1.24; p=0.02) respectively. Conclusions: This exploratory study provides some preliminary evidence to indicate that ovarian cancer patients whose QoL improves within 3 months of treatment have a significantly increased survival time compared to those who fail to demonstrate improvement. These findings might be used in clinical practice to systematically address QoL-related problems of ovarian cancer patients throughout their treatment course.
Sexual function, sexual activity, and quality of life in women with ovarian and endometrial cancer.
Authors: Harter Philipp , Schrof Inga , Lehmann Karl M , Hils Rita , Kullmann Verena , Traut Alexander , Scheller Herbert , Du Bois Andreas 
Published: March 2020

5051 Background: Gynecological cancer (GC) is generally assumed to have an impact on sexual function and activity. Although there are several studies addressing the issue, case control studies are currently limited. Methods: We performed a cross-sectional investigation of sexual function and activity utilizing the sexual activity questionnaire, the female sexual function index, and parts of the EORTC QLQ C30. Patients with gynecological cancer (GC) like ovarian and endometrial cancer were compared with a control group (C) of non-cancer patients. Inclusion of GC was only allowed if treatment was completed ≥12 months previously and patients were disease-free. Results: The questionnaires were sent out to 727 women (335 x GC and 392 x C), 22.8% of which responded. Response rates in both groups were equivalent (79 pts with GC [23.6%] and 87 control subjects [22.2%]). Median age was 57 years (C) and 62 years (GC), respectively (p=0.237). 51.5% (C) and 59.5% (GC) were not sexually active, mainly owing to lack of a partner (37%) or lack of interest (21%) in controls and lack of interest (40%, p<0.05), self-reported physical problems (31.9%, p<0.05), and physical problems of the partner (21%, p<0.05). There were significant differences between both groups in the SAQ discomfort score (p<0.05). We did not observe significant differences in quality of life or other scores regarding sexuality. Conclusions: About half of the women in both groups were not sexually active. However, reasons for non-activity differ. Quality of sexuality tends to be impaired in GC patients, but this seems not to influence quality of life. A shift of priority caused by substantial anxiety regarding cancer specific survival might explain our findings.
The effect of the APPRISE mandate on use of erythropoiesis-stimulating agents and transfusion rates in ovarian cancer patients.
Authors: Boone Jonathan David , Walters Christy Lynn , Fauci Janelle M. , Whitworth Jenny M. , Bevis Kerri S. , Alvarez Ronald David 
Published: March 2020

5060 Background: Erythropoiesis-stimulating agents (ESAs) have long been used to support chemotherapy-induced anemia in patients with epithelial ovarian cancer (EOC). Recent studies have demonstrated that ESAs may lead to increased tumor growth and shorter survival. The FDA mandated new guidelines (APPRISE, for Assisting Providers and Cancer Patients with Risk Information for the Safe use of ESAs) for consenting patients before ESA administration. We sought to quantify the change in ESA use and RBC transfusion rates after the APPRISE mandate was instituted. Methods: A retrospective chart review identified patients with EOC undergoing chemotherapy after initiating the APPRISE mandate. A similar subset of patients treated prior to the APPRISE guidelines served as a control cohort. Abstracted data included patient demographics, primary or second line treatment status, chemotherapy regimen, number of patients requiring ESA or RBCs, or both, and a cost savings analysis. Results: 84 patients with EOC were identified as having undergone 367 cycles of first or second line chemotherapy after the APPRISE guidelines were instituted. A matched set of 88 patients receiving 613 cycles of chemotherapy within a year prior to institution of the APPRISE guidelines was analyzed for comparison. The two groups were statistically similar. Most patients in each group were initially diagnosed with advanced stage disease, were receiving primary chemotherapy, and were receiving taxane/platinum-based chemotherapy. 45 of 88 patients (51%) in the pre-APPRISE group received a total of 196 ESA injections compared to 0 of 84 patients (0%) in the post-APPRISE group. In spite of discontinuing the use of ESAs and no change in transfusion thresholds, RBC transfusion in the post-APPRISE group was similar to that in the pre-APPRRISE group (8.3% vs. 14.8%, p=.28). Omission of ESAs in the post-APPRISE group resulted in a cost-savings of an estimated $700,000 in billable charges. Conclusions: In our institution, the APPRISE guidelines resulted in complete cessation of ESA use in patients with EOC, resulting in considerable cost savings. Importantly, RBC transfusion rates did not increase after the guidelines were imposed.
A phase I, dose escalation trial to assess the safety and biological activity of recombinant human interleukin-18 (SB-485232) in combination with pegylated liposomal doxorubicin in platinum-resistant recurrent ovarian cancer.
Authors: Simpkins Fiona , Flores Aurea M. , Chu Christina , Lucci Joseph A. , Berek Jonathan S. , Coukos George , Bauman John W. , Murray Sharon Cornell , Struemper Herbert , Germaschewski Fiona , Jonak Zdenka , Gardner Olivia S. , Toso John F 
Published: March 2020

5065 Background: SB-485232, a recombinant human form of interleukin-18 (IL-18), is being studied as a novel cytokine for tumor immunotherapy. IL-18 has been shown to increase the anti-tumor activity of doxorubicin in other cancer mouse models. Methods: This multi-center study enrolled 16 patients (pts), and evaluated four cycles (28 days each) of standard pegylated liposomal doxorubicin (PLD) (40 mg/m2 day 1) in combination with increasing doses of IL-18 (1, 3, 10, 30, and 100 mg/kg) on days 2 and 9 of each cycle with a 1 yr follow-up to further evaluate safety and efficacy. Results: Of the 16 pts, 10 (63%) completed study treatment and 6 (37%) did not because of disease progression (5 pts) and PLD hypersensitivity (1 pt). Thirteen (82%) were platinum resistant/refractory having received a median of > 3 prior lines of therapy. SB-485232 up to 100 mg/kg in combination with PLD had an acceptable safety profile. All 16 pts experienced at least 1 AE including chills (81%), nausea (75%), anemia (63%), fatigue (56%), hyperglycemia, and pyrexia (50% each). Eight of 16 pts had Grade 3 AEs including anemia (19%), and 6% each for abdominal pain, asthenia, dehydration, PLD hypersensitivity, edema, fatigue, hyperglycemia, hyperkalemia, jaundice, pain, nausea, vomiting, and pyelonephritis. There were no grade 4/5 AEs. Four subjects experienced 10 non-fatal SAEs with 3 related to study drug: anemia, PLD hypersensitivity, and cytokine release syndrome. Maximal SB-485232 biological activity, assessed by peripheral blood NK and T cell markers, was observed at 10mg/kg-100mg/kg. This drug combination resulted in a 6% partial response rate (RR) and a 38% stable disease rate using RECIST 1.0. Median (95% CI) time of progression-free survival (PFS) was 4.50 (3.52,--) months. Conclusions: The SB-485232/PLD combination was tolerable with minimal toxicity. These preliminary efficacy data are comparable to the historical RR and PFS observed with PLD monotherapy in platinum-resistant ovarian cancer. However, given the small sample size, this combination warrants further investigation.
Secondary surgery with intraoperative chemohyperthermia in recurrent ovarian adenocarcinoma.
Authors: Bereder Jean Marc , Desantis Mariangella , Benizri Emmanuel , Abakar-mahamat Abakar , Bernard jean-Louis , Rahili Amine , Mounier Nicolas , Benchimol Daniel 
Published: March 2020

5075 Background: Optimal treatment of peritoneal recurrences in ovarian cancer is debating with second line chemotherapies. We proposed association of secondary surgery with heated intraperitoneal per operative chemotherapy (HIPEC). The aim of study is to determine prognostic factors in a single center cohort. Methods: Retrospective study of consecutive 169 patients with peritoneal recurrence from ovarian cancer were performed to evaluate HIPEC and to identify prognostic factors. Peritoneal Cancer Index (PCI) assess tumor load and completeness cytoreductive score (CCS) were used to give quality of resection CCS0 (no visible tumor), CCS1 (persistent diffuse lesions < 2.5mm), CCS2 (2.5mm <CC2< 25mm) and over CCS3 status. HIPEC is performed with platinum based regimen. Endpoint was survival. Cox's regression model was used for multivariate survival analysis and extending Cox model for modelling survival data. Results: We have operated on 197 procedures (HIPEC) in 169 patients from 2000 to 2011. Mean age was 58 years old range [28-75]. Median PCI was 10. After completion of resection, allocation of CCS was CCS0=120, CCS1=70, CCS2 & CCS3 =7. Procedure related mortality was 1% and morbidity 21%, mean length of hospital stay was 17 days range [7-51]. 3 and 5 years overall survival were respectively 64.7% and 37.4 %. Median survival was 47.6 months and the median disease free survival was 20 months. PCI >10 (even if complete resection performed) and CCS2&3 were worse prognostic factors (HR respectively = 2.64 IC 95% [1.29-5.36] and = 3.31 IC 95 % [1.55-7.08]). Modelling of these factors, is very strong to predict risk of death over the 2 first years after HIPEC. Conclusions: The chemo-hyperthermia is a standardized and reproducible feasible method. Less extensive disease and the quality of cytoreduction remain an independent factor of better outcome. To date HIPEC allows to reach the longest median time survival in peritoneal recurrent ovarian cancer. Modelling survival data is useful to know the risk of dying.