bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II randomized, double-blind, placebo-controlled trial of clinical activity and safety of Å6 in patients with asymptomatic CA 125 progression of epithelial ovarian, fallopian tube, or primary peritoneal cancer
Authors: Ghamande S. , Silverman M. , Gold M. , Huh W. , Behbakht K. , Ball G. , Cuasay L. , Brunner N. 
Published: March 2020

16014 Background: Patients (pts) with epithelial ovarian cancer (EOC) often relapse and rising CA 125 levels predate clinical or radiological appearance of tumor. High tumor and serum levels of urokinase plasminogen activator (uPA) in EOC correlate to adverse outcomes. Å6 is a novel peptide derived from human uPA that down-regulates the uPA system and has anti-angiogenic and anti-metastatic activity in animals. Methods: Pts with EOC, fallopian tube, or primary peritoneal cancer in clinical remission after first line chemotherapy had to have 2 consecutive rises of CA 125 levels above normal with no disease on physical examination or imaging studies. Pts were randomized to receive daily subcutaneous injections of placebo, 150 mg Å6, or 300 mg Å6 until disease progression. The primary objectives were to assess safety and clinical activity of Å6 by the effect on the onset of disease progression. Results: 48 pts were planned for the study. The trial ended early with 24 patients {12 pts (50%) placebo, 8 pts (33%) low dose Å6, 4 pts (17%) high dose Å6} randomized, treated and followed for up to 9 months. Despite early study termination and small sample size, A6 therapy was associated with a statistically significant progression free survival (PFS) (log rank p value=0.01) with a median PFS of 100 days (95% CI 64,168) compared to 49 days (95% CI 29,67) in pts who received the placebo. The treatments were well tolerated with one serious adverse event (transient nausea and dyspnea ) possibly related to study drug. Treatment was not associated with CA 125 response (Fisher exact test p value= 0.44). Conclusions: Å6 therapy increases PFS of patients with EOC and asymptomatic progression of CA 125. This therapy is novel, safe, feasible and deserves further investigation [Table: see text]
Prognostic value of change in CA 125 levels after the first cycle of induction chemotherapy for epithelial ovarian cancers: Results of a multicentric French study
Authors: Riedinger J. , Basuyau J. , Eche N. , Bonnetain F. , Pichon M. F. , Fargeot P. 
Published: March 2020

16017 Background: CA 125 assays enable treatment-response monitoring in ovarian cancer. Patients and Methods: This multicentric study was performed to assess the predictive value with regard to pathologic complete response at surgical second look and the prognostic value of the serum CA 125 change (=rease [D], 50%, 25%, < 25%ase) after one or two courses of induction chemotherapy (CT) with platinum salts and cyclophosphamide Of the 494 stage IIc - IV patients who were treated at the French Cancer Centres of Dijon, Bordeaux, Toulouse, Rouen, Reims, Nantes, Angers, Saint Cloud, 397 (80.4%d and 382 (77.3%om cancer. Median (range) follow up time was 34 months (3 - 215 months). Among them, 194 patients had a surgical second look. Results: The CA 125 change after the first, the second and the two first CT courses and CA 125 concentration (> or =-1) before the third CT cycle had an univariate prognostic value for overall survival (OS) (p < 0.0001 for both). In Cox models, CA 125 change after the first CT course (p < 0.0001), residual tumour (p = CA 125 concentration before the second CT course (p =and patients’ age (p =were independent prognostic factors for OS. A normal CA 125 before each of the two first CT courses or a CA 125 decrease higher than 50%e first CT course with a CA 125 =-1 before the second CT course identify patients with good prognosis. Both criteria retained a significant value in predicting second-look findings by univariate and multivariate analysis (p < 0.0001). Conclusion: Among well-established prognostic factors in ovarian cancers, the CA 125 change after the first CT course was independent prognostic factors for both achievement of pathological complete response and OS. No significant financial relationships to disclose.
Clinical outcome and risk factors for recurrence in borderline ovarian tumors
Authors: Yokoyama Y. , Mizunuma H. , Yaegashi N. , Tanaka T. , Kurachi H. , Sato A. , Tase T. , Sugiyama T. 
Published: March 2020

16020 Background: We investigated the long-term prognosis of borderline ovarian tumors and determined risk factors for recurrence. Methods: One hundred and twenty one borderline ovarian tumors treated between 1994 and 2003 at the participating institutions in the Tohoku Gynecologic Cancer Unit were retrospectively investigated for clinical stage, histopathological subtype, surgical technique, postoperative chemotherapy, the presence or absence of recurrence, and prognosis. Results: The median follow-up period was 57 months (1–126 months). One hundred and nine cases (90.6%) were at clinical stage I. The histopathological subtypes consisted of 91 cases of mucinous tumor (75.2%), 27 cases of serous tumor (22.3%), and 3 cases of endometrioid tumor. Conservative surgery was used in 53 cases (43.8%), radical surgery in 68 cases (56.2%), a staging laparotomy in 43 cases (35.5%), and postoperative adjuvant therapy in 30 cases (24.8%). Recurrence was found in 8 cases, but no tumor-related deaths were reported. Although no significant difference in disease free survival rate was seen between different clinical stages, the difference in disease free survival rate between serous and non-serous (mucinous and endometrioid) types was significant (p<0.05). The 10-year disease free survival rate was 89.1% for the radical surgery group, and 57.4% for the conservative surgery group- this difference was significant (p<0.05). In the conservative surgery group, cystectomy and serous tumor were independent risk factors for recurrence. Although recurrence was observed, the long-term prognosis of borderline ovarian tumor was favorable, without tumor-related deaths. Conclusion: Considering the favorable prognosis, conservative surgery can be chosen as far as the patient has a non-serous tumor and receive adnexectomy. However, in cases of serous type and/or receiving cystectomy special care should be given as relative risk rates of recurrence elevate by 2 to 4 folds. No significant financial relationships to disclose.
Pregancy after bilateral dysgerminoma treated with conservative surgery and BEP chemotherapy
Authors: Shami N. , Shaila A. , Shaharyar A. , Asif S. 
Published: March 2020

16039 Background: Pregnancy after treatment of germ cell tumours of ovary is common. However patients with bilateral dysgerminoma treated with unilateral oophorectomy, wedge biopsy of opposite ovary, and conservation of uterus face difficulty in conception. This study was conducted with the objective to evaluate the fertility status of ovarian dysgerminoma patients treated with conservative surgery and BEP chemotherapy. Methods: Patients of bilateral dysgerminoma who underwent conservative surgery and chemotherapy with cisplatin 20 mg / m2 and etoposide 100 mg / m2 day 1 to 5 and bleomycin 30 mg on day 1, 8 and 15 of three weekly cycles were eligible. A normal AFP and beta HCG at baseline was required. Post treatment CT scans of abdomen and pelvis were obtained. Patients were regularly followed on monthly basis. Pregnancy was allowed 2 years after completion of last cycle of chemotherapy. Results: From January 1998 to December 2003, 11 patients were enrolled. Medain age was 16 years (range 13–18). All patients had complete disappearance of disease after treatment. Treatment related amenorrhea did not last beyond one year. During a median follow up of 5 years, all patients conceived and a total of 14 pregnancies were completed successfully.Three patients required use of clomiphene citrate for ovulation induction. No patient was treated with gonadotrophins. Six patients underwent lower segment caesarean section for obstetric indications and seven delivered vaginally. All babies were healthy without the signs of birth abnormalities or retardation. Conclusions: With conservative surgery and BEP chemotherapy for treatment of bilateral dysgerminoma the fertility is retained with good pregnancy outcome, when conception occurs at least two years after the last dose of chemotherapy. No significant financial relationships to disclose.
Relation between vascular endothelial growth factor receptor (VEGFR) in tumor sample and response rate in patients with cervical cancer treated with chemo-radiotherapy
Authors: Richardet E. , Richardet M. , Mascheroni M. B. , Lingua A. , Gómez Storniolo P. , Celiz P. , Bella S. , Guidi A. , Ferraris G. , Kaen L. , De la Colina M. 
Published: March 2020

16040 Background: The vascular endothelial growth factor (VEGF) and their receptors play a fundamental role in the regulation of the angiogenesis and linfoangiogenesis. This study examined the relation between levels of expression of the VEGFR with the rate of response in patients (pts) with cervical cancer treated with chemo-radiotherapy-brachytherapy with cisplatinum. Methods: Clinical records of 30 women with their pathology were analyzed. The expression of the VEGFR was evaluated by inmunohistochemestry (IHQ-) by a pathologists committee and It was classified in 4 categories according percentage of tumor cells cytoplasm marked: 0 = 0% / 1=< 25% / 2=<26%-50% and 3 = > 50%. In order to correlate the VEGFR expression with response rate, patients were classified in 2 groups: lower level of expression (VEGFR 0–1), and high level of expression (VEGFR 2–3). In a second analysis we discriminated those with VEGFR expression 3 ant the rest of the group. The evaluation of the tumor response was made by clinical examination and magnetic nuclear resonance (RNM). We used Fisher exact test for statistical analysis Results: Median age: 47 years (r: 27 - 69). Pts with VEGFR 0 =2 (6.66%) pt with 1,2,3 VEGFR =28 (93.33%)(p:<0,001) . Objective respnse rate (OR) in pts with low expression of VEGFR was 90.9%, OR rate for pts with high levels of expression VEGFR was 56.97% (p: 0,52). The OR rate for pts with VEGFR 3 OR was 28.57% and for pats with VEGFR 0,1,2 was 69.56% (p:0,035) Conclusions: We observed that 93.33% of pts expresed VEGFR. OR rate was higher among pts. with lower expression compared with pts. of higher level of expression. These results, although in a small group of patients, stimulate investigation of anti angiogenic therapies in cervical cancer. [Table: see text]
Computer simulation of pharmacokinetic analysis of 161,051 drugs after intraperitoneal (IP) or intravenous (IV) administrations
Authors: Miyagi Y. , Fujiwara K. , Nagao S. , Kigawa J. , Miyake K. , Oda T. , Miyagi Y. 
Published: March 2020

16042 Background: Recent clinical studies for ovarian cancer have demonstrated the survival benefit of intraperitoneal (IP) administration of anti-cancer drugs, such as platinum agents, or paclitaxel. It is of great interest to investigate whether IP administration of other cytotoxic agents are more effective compared with intravenous (IV) administration. In this study we investigated the pharmacological advantage of IP administration using anti-cancer drugs, of which cytocidal effect is determined by the value of the area under the time concentration curve (AUC), by using computer simulation model. Methods: The 3-compartment pharmacokinetic computer model was used and 161,051 sets of the rate constants were substituted into the model. Because one set of the rate constants determines a pharmacokinetic behavior of one drug, it was considered to simulate over 160,000 drugs in this study. The constants were referred to ones of carboplatin. The simulations were made after 210 mg/body of the drugs were administered. The values of the AUC in the serum and in the IP cavity after IP or IV administration were calculated for each set, and then, these two administration methods were compared. Results: The values of the AUC in the serum by IP vs IV administration were 6.675 ± 21.603 (mean±SD); [0.08 - 106.155 (range)] vs 6.663 ± 21.541; [0.183 - 105.726]. The values of the AUC in the cavity after IP vs IV administration were 128.799 ± 344.491; [0.342 - 2288.48] vs 90.700 ± 283.946; [0.002 - 2259.32]. The ratios of AUC in the serum after IP or IV administrations were 0.995 ± 0.023; [0.401 - 1.020]. 147,201 sets (91.4%) were between 0.99 and 1.01. On the other hand, the ratios in the IP cavity were 25.327 ± 86.515; [1.003 - 548.976]. All the IP/IV ratios in the cavity were more than 1. Conclusions: The simulated probability clearly indicated that IP administration is not a local but a systemic chemotherapy for most drugs. All of the chemotherapeutic agents should be investigated for IP administration as well as conventional IV administration in clinical research protocol, especially in phase I/II study to clarify the effects and toxicities. No significant financial relationships to disclose.
Platinum and taxane intraperitoneal chemotherapy after secondary cytoreductive surgery for recurrent ovarian carcinoma
Authors: Seamon L. G. , Seward S. , Richardson D. , Fowler J. M. , Cohn D. E. 
Published: March 2020

16043 Background: Intraperitoneal chemotherapy (IP) after primary optimal debulking for advanced stage epithelial ovarian carcinoma improves survival. The objective of this research is to describe our experience with IP taxane and platinum chemotherapy after optimal secondary cytoreductive surgery in patients with platinum-sensitive recurrent ovarian cancer. Methods: We retrospectively reviewed charts from January 2006 to January 2007 and identified approximately 30 patients who received IP chemotherapy for optimally debulked advanced ovarian carcinoma. Of these patients, 8 were treated at first recurrence with cytoreductive surgery followed by second-line IP chemotherapy with intravenous docetaxel (70 mg/m2) and IP cisplatin (75–85 mg/m2) on day 1 and IP paclitaxel (60 mg/m2) on day 8, every 21 days. Results: The median disease free interval from completion of initial chemotherapy to recurrence was 19 months. All patients who underwent secondary cytoreductive surgery were considered optimally debulked (less than 1 cm residual disease), with 6 patients having no residual disease. One patient required rectal resection and another patient had ileocecal resection without a protective ostomy. All patients had insertion of an intraperitoneal venous access device for infusion of IP chemotherapy at the time of cytoreduction. While four patients have completed all 6 cycles of IP chemotherapy, one patient completed only 3 cycles due to catheter related toxicity requiring removal of the port (abdominal pain). This patient did not undergo concurrent bowel surgery. In addition, two patients have completed 3 cycles and two patients are currently scheduled to begin IP chemotherapy. Only two patients experienced grade 3 or 4 neutropenia. No other grade 3 or 4 toxicities were identified. A median of 5 cycles (range 2–5 cycles) was required to achieve a CA125 nadir. Complete clinical response was obtained in all patients at a median follow up of 9 months (range 4–10 months). Conclusions: In optimally debulked, platinum-sensitive patients following secondary cytoreductive surgery for recurrent ovarian cancer, intraperitoneal taxane and platinum chemotherapy is feasible with acceptable toxicity and provides another option for treatment. No significant financial relationships to disclose.
Activation of MMP-2 by endometrial cancer cells in vitro is enhanced by LPA
Authors: Boyd L. R. , Ariztia E. V. , Fishman D. A. 
Published: March 2020

16047 Background: Matrix metalloproteinases (MMPs) are responsible for the breakdown of extracellular matrix components, and are important in the metastatic phenotype. HEC-1A is an endometrial cancer cell line, derived from a moderately-differentiated tumor. These cells do not produce MMP-2, an important mediator of invasive behavior. We sought to: evaluate if HEC-1A cells have the capacity to activate proMMP-2 if given the proenzyme exogenously; and determine if the addition of lysophosphatidic acid (LPA), a known activator of MMPs in other cancers, would further enhance this conversion. Methods: HEC-1A cells were maintained per known protocols. Conditioned media from HT1080 chondrosarcoma cells, a source of proMMP-2, was added to HEC-1A cells. Cells were also treated with 0.1, 1.0 and 10uM LPA. Conditioned media from the cells was analyzed for the presence of MMP-2 and its proenzyme utilizing gelatin zymography. Cellular invasion through collagen matrix was quantified using a modified Boyden chamber assay. Migration was evaluated using a wound healing assay with quantification of wound closure at 48 hours. Proliferation was assessed following cell culture for 48 hours using an MTS tetrazolium salt/phenazine methosulfate assay. Results: HEC-1A cells activated exogenous proMMP-2 to MMP-2, as confirmed by gelatin zymography. This occurred in both the presence and absence of LPA. Invasion of HEC-1A cells treated with proMMP-2 was significantly increased as compared to controls (p < .001). LPA increased invasion in cells with and without exogenous proMMP-2, with the most invasive cells being those treated with both LPA and exogenous proMMP-2. The addition of both exogenous MMP-2 and LPA significantly increased cellular migration as quantified using the wound healing assay (p < .001). Cellular proliferation was significantly increased with LPA vs. controls. The addition of proMMP-2 did not lead to a significant difference in proliferation. Conclusions: HEC-1A cells can convert exogenous proMMP-2 to its active form, and in doing so exhibit a more invasive phenotype. LPA serves to further increase these behaviors. This may reflect the tumor microenvironment, with endometrial cancer cells responding to bioactive lipids and proenzymes secreted by the surrounding stroma. No significant financial relationships to disclose.
A phase I study combining high-dose (HD) topotecan (TPC) plus cyclophosphamide (CPM) with blood stem cells support in poor prognosis ovarian carcinoma (OC): The ITOV 01bis protocol
Authors: Lotz J. , Pautier P. , Selle F. , Fabbro M. , Viens P. , Ribrag V. , Lokiec F. , Gligorov J. , de Labareyre C. M. , Lhommé C. 
Published: March 2020

16061 Background: TPC and CPM-based CT may be proposed as 2nd-line chemotherapy (CT) after taxanes/platinum-compounds in refractory/relapsed OC. We have previously shown that the maximum tolerated dose (MTD) of TPC used as a single agent was 45 mg/m2 in a 5-d administration schema (ITOV 01 protocol - Lotz et al, BMT 2006, 37: 669). Method: We decided herein to combine TPC at a dose ranging from 8 to 10 mg/m2/d x 5d (30’ daily perfusion) to a fixed HD CPM (60 mg/kg/d x 2d) until the MTD of TPC was reached. Three pts were to be treated at each planned dose level (8.0, 8.5, 9.0, 9.5, 10 mg/m2/d). Limiting toxicity was defined as one toxic death (excluding sepsis) or grade (G) 4 non-hematological toxicity. In this event, a further 3 pts were to be recruited at the same dose level. Mobilization to collect 3x106 CD34+/kg BW (6x106 if a 2nd HD course using TPC alone was planned) was performed with CPM + filgrastim. Results: From 09/02 to 05/06, 26 pts (median age, 54, range: 21–64) were included (platinum-refractory/relapse - 15 pts, initial stage FIGO IV - 5 pts, residual disease at 2nd-look - 6 pts). Three pts failed to be collected, one progressed before and one progressed after mobilization, so that 21 pts were able to complete their 1st course. Six received a second cycle of HD TPC. One septicemia-related toxic death occurred at level 8 mg/m2/d. Median durations of G4 neutropenia & thrombocytopenia observed during the first course of HDCT were 10 & 9 d. No patients experienced G4 diarrhea. One pt experienced a G4 cutaneous toxicity at level 8.5 and 2/3 at level 9.5 mg/m2/d. MTD of TPC combined with CPM was consecutively set up at 9.0 mg/.m2/d x 5d. Pharmacokinetic data (Cmax, AUC) will be available. Conclusion: The MTD of TPC combined with CPM was set up at 9 mg/m2/d x 5d, i.e., 45 mg/m2. The forthcoming ITOV 04 protocol will combine HD TPC and Carboplatin (AUC 20) in patients whose relapse occurs between 6 and 12 months after platinum- based first-line CT. No significant financial relationships to disclose.
Risk factors for febrile neutropenia and the utilization of pegfilgrastim in patients receiving chemotherapy for gynecologic malignancies
Authors: Numnum T. M. , Bryant S. , Williams E. , Kilgore L. , Straughn J. M. 
Published: March 2020

16063 Background: Recently published gudelines for the use of granulocyte-colony stimulating factors define risk factors for the development of febrile neutropenia (FN) in patients receiveing chemotherapy. Our objective is to assess the risk factors associated with FN and the utilization of pegfilgrastim (G-CSF) for the prevention of FN in patients receiving chemotherapy for gynecologic malignancies. Methods: A computerized database identified all outpatient chemotherapy encounters over a 4 month period. Risk factors for FN (adapted from guidelines published by ASCO) were determined for each chemotherapy encounter and a risk factor score was calculated (1–17). Each chemotherapy encounter was analyzed to determine if G-CSF was administered and the reason for utilization. Dose delays/modifications were also determined. Statistical comparisons were performed using the χ2 test. Results: 692 chemotherapy encounters were identified in 209 patients. 77 % of patients had a diagnosis of ovarian cancer. The mean risk factor score was 3.9 (range 1–9). The most common risk factors were: female (100%), advanced cancer (81%), prior chemotherapy (54%), and age > 65 yo (46%). 276 of the 692 (40%) encounters utilized G-CSF. 135 patients (49%) received G-CSF as primary prophylaxis for the development of FN; 141 patients (51%) received G-CSF after an episode of Grade 3 or 4 neutropenia. The mean risk factor score was 4.3 in patients receiving primary prophylaxis. After primary prophylaxis, 1 dose delay/modification for neutropenia was experienced versus 14 dose delays/modifications without prophylaxis (p <0.01). There were 12 dose delays/modifications due to thrombocytopenia in patients receiving PP. There was only one episode of FN. 64% of patients receiving primary prophylaxis were treated with a docetaxel-containing regimen and 61% of patients were receiving primary chemotherapy. Conclusions: G-CSF is utilized in 40% of chemotherapy encounters and is commonly associated with docetaxel-containing regimens. Dose delays/modifications are uncommon after primary prophylaxis with G-CSF in patients receiving chemotherapy for gynecologic malignancies. No significant financial relationships to disclose.