bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of adjuvant chemotherapy with paclitaxel and nedaplatin for FIGO stage IB-IIA uterine cervical cancer with lymph node metastasis following radical hysterectomy: A Kansai Clinical Oncology Group study (KCOG-G1101).
Authors: Takekuma Munetaka , Kasamatsu Yuka , Nishio Shin , Omi Hideo , Tabata Tsutomu , Takei Yuji , Nasu Kaei , Takahashi Yoshiyuki , Toyoda Shinji , Ichikawa Yoshikazu , Arakawa Atsushi , Ito Fuminori , Tsubamoto Hiroshi , Mori Taisuke , Ito Kimihiko 
Published: September 2018

e17024 Background: A multicenter phase II trial was conducted to assess the efficacy and toxicity of paclitaxel and nedaplatin as the initial postoperative adjuvant chemotherapy for high-risk uterine cervical cancer. Methods: The patients with FIGO stages IB1-IIA2 squamous cell carcinoma of the uterine cervix were enrolled. Histologic confirmation of lymph node metastasis was mandatory. Intravenous paclitaxel 175 mg/m(2) over 3hours and nedaplatin 80 mg/m(2) over 1 hour were administered on day 1 of a every 28 day cycle, of which there were 5 cycles after radical hysterectomy. Results: 62 patients were enrolled into the study protocol from November 2011 to July 2015. The median age of patients was 48.5 years (range; 28-64). Median tumor diameter was 37 mm (0-34). 10 patients (16.1%) had parametrial invasion, 44 (71.0%) had deep stromal invasion, and 53 (85.5%) had lymph-vascular invasion. 30 patients (48.4%) had one metastatic lymph node, 11 (17.7%) had two, 3 (4.8%) had three, 5 (8.1%) had four and 13 (21.0%) had five or more. With a median follow-up of 36.9 months (range: 17.2-61.5), the 2-year progression-free survival rate and pelvic disease progression-free rate were 78.9% (95% CI, 68.5% to 89.3%) and 85.0% (95% CI, 75.8% to 94.3%), respectively. The 2-year overall survival rate was 93.3% (95% CI, 86.8% to 99.8%). Adverse events were almost acceptable. Grade 3-4 adverse events (NCI-CTC ver4.0) that occurred in 5% or more patients were neutropenia (60.7%) and infection (6.6%). The proportion of patients who completed 5 cycles of treatment was 90.3%. Conclusions: Adjuvant chemotherapy with paclitaxel and nedaplatin for patients with high-risk cervical cancer after radical hysterectomy was demonstrated to be an effective and feasible treatment. Phase III trial should compare this with concurrent chemoradiotherapy. Clinical trial information: 000005605.
Components of tissue fibrinolytic system as markers for processes in tumors of female reproductive organs.
Authors: Vereskunova Marina I. , Frantsiyants Elena Mikhaylovna , Kozlova Larisa , Bandovkina Valeria , Cheryarina Natalia D. , Chugunova Natalya , Saforian Natalya S. , Kit Oleg I. , Ezhova Maria 
Published: September 2018

e17032 Background: Components of tissue fibrinolytic system are now considered as important agents providing progressive tumor growth. The purpose of the study was to analyze fibrinolytic system components in uterine and breast tumors. Methods: We studied tumor samples in breast cancer (BC, n=24), nodular type of fibrocystic breast disease (FBD, n-15) and uterine myoma (UM, n=14) and in synchronous BC and UM (n=12). Intact breast tissues (IBT, n=16) and intact myometrium (IM, n=14) were used as the control. Activity of plasmin (P), total content and activity of uPA-Ag and uPA-act, tPA-Ag and tPA-act were determined by ELISA; plasminogen (PG) concentration was measured by spectrophotometry (ACTICHROME PLG, USA). Results: uPA-Ag in solitary BC was 6.5 times higher and uPA-act – 4.5 times higher than in IBT. Concentration of tPA-Ag in 75% of BC patients exceeded the value in IBT by 2.1 times, and tPA-act in 87.5% – by 1.5 times. tPA-Ag and tPA-act in FBD tissues were similar to IBT values, while uPA-Ag and uPA-act were increased by 2.2 times each. uPA-Ag in BC in BC+UM exceeded the norm by 10.6 times, uPA-act – by 5.5 times; tPA-Ag in 75% of samples was 3.8 times higher than in IBT, and tPA-act – 2.7 times higher. uPA-Ag and uPA-act levels in UM in BC+UM were similar to IM values, while tPA-Ag and tPA-act exceeded the norm by 1.8 and 1.5 times, respectively. Both uPA and tPA levels and activity in solitary UM did not differ significantly from IM. Conclusions: The results show an active conversion of plasminogen into plasmin in both solitary and synchronous BC and in synchronous UM. Components of tissue fibrinolytic system can be considered as reliable markers for processes in solitary and synchronous tumors of female reproductive organs.
Sonic hedgehog inhibitors: Potential targeted therapy for squamous cell carcinoma of the vulva.
Authors: Yap Jason , Ganesan Raji , Fox Richard , Dawson Christopher , Kehoe Sean 
Published: September 2018

e17035 Background: Vulval squamous cell carcinoma (VSCC) is predominantly a disease of the elderly; with three-quarters of cases occurring in those aged over 60 years. Currently, chemotherapy is only used as an adjunct to surgery in advanced disease or for palliation. Unfortunately, the treatment response of VSCC to chemotherapies is variable, and toxicity remains a major problem, rendering it unsuitable for most patients. Dysregulation of the Hedgehog (HH) pathway has been described in many cancers, and HH inhibitors are being employed for the treatment of many cancers displaying aberrant pathway activation. To this end, we set out to evaluate 1) whether the HH pathway is dysregulated in VSCC and 2) the therapeutic utility of using HH inhibitors in the treatment of VSCC. Methods: Immunohistochemical staining of HH pathway components was performed on formalin-fixed paraffin-embedded sections of a well-characterized cohort of 201 patients with primary VSCC. Expression of HH pathway proteins was then correlated with clinico-pathological data, disease recurrence and survival. A panel of VSCC-derived cell lines was examined for HH pathway activity using an HH-GLI luciferase reporter assay. The effects of HH inhibitors on the growth and viability of VSCC cell lines, alone and in combination with cisplatin, was examined by BrdU label incorporation and XTT viability assays. Results: The HH signaling pathway was found to be over-expressed in approximately 80% of VSCC cases. Moreover, patients whose tumours displayed Sonic HH (SHH) ligand overexpression were more likely to develop a local recurrence within 3 years. Two HH inhibitors, Itraconazole and LDE225, not only inhibited the growth of VSCC cell lines in a dose-dependent manner, but also sensitized cells to the genotoxic affects of Cisplatin. Conclusions: We have shown for the first time that HH pathway is overexpressed in VSCC and that SHH overexpression may serve as a useful biomarker to predict local disease recurrence. In addition, results from our laboratory studies have shown that HH inhibitors may be used as a neo-adjuvant therapy to augment the actions of chemotherapeutic agents in this disease.
Lipid peroxidation in tissues of ovarian tumors after neoadjuvant chemotherapy.
Authors: Kravtsova Oksana E. , Nerodo Galina Andreevna , Nikitina Vera P. , Verenikina Ekaterina V. , Nikitin Ivan , Pustovalova Alla V. 
Published: September 2018

e17036 Background: The purpose of the study was to analyze neoadjuvant chemotherapy (NACT) effect on parameters of monoaminergic, free radical and hydrolytic systems in tissues of malignant ovarian tumors. Methods: Activity of parameters of monoaminergic, free radical and hydrolytic systems was determined in ovarian tissue of 92 patients with ovarian cancer. Tissues of tumorous and contralateral (non-tumorous) ovaries were studied, and results were compared to the data in 30 patients with uterine fibroids and other benign tumors. Results: Tumorous ovaries showed the decrease in vitamins E and A by 2.6 and 4.1 times, respectively, compared to the norm. The levels in contralateral ovaries were 5 and 2.8 times lower than the norm, respectively. SOD in tumor tissue exceeded the norm by 46%. Content of copper-zinc-SOD amounted to 15.7% of the total activity in healthy ovaries, while in tumorous ones – 8.2%. Diene conjugates in tumors were increased by 42% compared to the healthy ovaries. Contralateral ovaries showed 2.1 times increase in SOD activity compared to the norm; catalase activity was decreased by 35% which was similar to the value in tumor tissue. Diene conjugates in contralateral ovaries were increased by 38% compared to the healthy ovaries and did not differ from the value in tumor. MDA level was decreased by 4.1 times and did not differ from the value in tumor. Tumorous ovaries after NACT showed an increase in vitamins A and E by 1.8 and 3.2 times, respectively, compared to the levels before treatment; copper-zinc-SOD activity increased by 40.3%. Lipid peroxidation changed as well: diene conjugates level increased by 24.7% and MDA decreased by 47.7% compared to the values before treatment. Levels of the main antioxidant enzymes – SOD and catalase – in contralateral ovaries after NACT were similar to the normal ones; diene conjugates were close to the norm, vitamin E decreased by 40%, vitamin A – by 30%, MDA content did not change. Conclusions: Morphologically healthy tissue of the contralateral ovary in the organism affected by malignant tumor demonstrates signs of imbalance in antioxidant factors similar to those in the tumorous ovary. NACT results in normalization of metabolism indices in both tumorous and contralateral ovaries.
Anti-LeY monoclonal antibody (mAb) hu3S193 as consolidation therapy for patients (pts) with relapsing platinum sensitive ovarian cancer (OC) after achieving a second complete response (2CR).
Authors: Smaletz Oren , Ismael Gustavo , Estevez-Diz Maria Del Pilar , Nascimento Ivana Lucia Oliveira , Wiermann Ana Luiza Gomes de Morais , Cunha Geraldo Felicio , Azevedo Sergio J , Alves Venâncio A , Moro Ana M , Yeda Fernanda Perez , dos Santos Mariana Lopes , Majumder Indrani , Hoffman Eric W. 
Published: September 2018

e17039 Background: Lewis-Y (LeY) antigen is a blood group related antigen expressed in 75% of OC. hu3S193 is a humanized anti-LeY IgG1 mAb with strong complement and antibody dependent cytotoxicity with clinical benefit shown in a phase II study in pts with platinum-resistant OC and small tumor burden. Improving progression free survival (PFS) in pts who achieve a 2CR is an unmet need. Methods: This phase II study accrued pts with relapsed OC, LeY expression by IHC, and a KPS ≥ 70% who had achieved a 2CR after 5-8 cycles of platinum doublet chemotherapy (chemoRx). Patients received intravenous infusions of hu3S193, 30mg/m2every 2 weeks starting ≤ 8 weeks after the last dose of chemoRx and continuing for 12 doses (24 weeks) or until disease progression or unacceptable toxicity. Primary endpoint was PFS with a sample size calculated to detect a 50% increase in PFS, compared to a historical value of 10.8 months. Secondary objectives were safety and pharmacokinetics (PK). Results: 29 pts were enrolled. Median age: 55 yrs (range 29-67); Median KPS: 90% (range 80-100); LeY expression by IHC (N): strong (20), weak (9); stage at initial diagnosis: I/II (2), III/IV (27); median CA-125 prior to 2CR chemoRx: 104 (range 9-514); chemoRx agents to achieve 2CR: paclitaxel/platin (21), liposomal doxo/carboplatin (8); median cycles of prior chemoRx to achieve a 2CR:6; median doses of hu3S193 delivered: 10 (range 10-12). Evaluable pts: 28 (1 pt did not have 2CR); median PFS: 11.8 months (95% CI: 10.6-13.9) while 3 pts achieved PFS of 25+ months. Grade 4 toxicities observed: none. Most frequent toxicities (any grade/grade 3): Nausea (16/2), Vomiting (15/3), Hypersensitivity (9/0). PK data will be presented. Conclusions: Despite the good tolerance and the longer PFS compared to historical control, this trial did not show a significant improvement with hu3S193 as a consolidative strategy in patients with 2CR in platinum-sensitive OC. Tumor molecular analysis of patients with long PFS may provide insight for future studies. Clinical trial information: NCT01137071.
DNA cytometric parameters as prognostic factors of chemoimmunotherapy for ovarian cancer.
Authors: Nerodo Galina Andreevna , Kit Oleg Ivanovich , Novikova Inna Arnoldovna , Ardzha Anna , Verenikina Ekaterina V. , Nikitina Vera P. , Kravtsova Oksana E. , Bondarenko Elena , Mezentsev Stanislav Stanislavovich 
Published: September 2018

e17041 Background: The aim of the study was to analyze chemoimmunotherapy influence on DNA cytometric parameters in patients with ovarian cancer. Methods: The study included stage IIIC-IV ovarian cancer patients divided into two groups in dependence on the treatment: group A – 21 patients who did not receive neoadjuvant chemotherapy before surgery; group B – 24 patients who received neoadjuvant chemoimmunotherapy with intraperitoneal administration of interferon-gamma (ingaron) and the following surgery. The groups were identical in terms of the disease stages, age and general condition of patients. DNAs were analyzed in fresh tumor tissues using CycleTEST Plus DNA Reagent Kit (Becton Dickinson, USA). The data were processed using the ModFit LT program allowing analysis of ploidy and distribution of tumor cells in phases of the cell cycle. The proportion of cells with different DNA content in the histogram was calculated as a percentage of the total number of studied cells. Proliferation index (PI) was calculated as the total amount of tumor cells in S and G2+М phases of the cell cycle. Results: Full-volume surgery (panhysterectomy+omentectomy) was performed in 52.4% in group A and in 92% in group B, adnexectomy only – in 38.1% and 8%, respectively; exploratory surgeries were performed in group A only – 9.5%. During 2 years of the observation, recurrence in group A was found in 38% of patients, in group B – in 12.5%. Analysis of DNA cytometric parameters showed the minimal proliferation rates (percentage of cells in S phase) in group B – 12.6±2.3%, compared with 20.7±3.4% in group A. PI was lowest in group B – 13±2.7%, compared with group A – 22.4±3.3% (p≤0.05). Significant decrease in the DNA index by 1.3 times was noted in patients in group B in comparison with group A (1.11±0.01% and 1.4±0.05%, respectively) (p≤ 0.05). Conclusions: Thus,DNA cytometric parameters reflect the effectiveness of chemoimmunotherapy and can be used as prognostic factors.
Survival outcomes in patients with platinum-resistant (PL-R) ovarian cancer (OC): The Princess Margaret Cancer Centre (PM) experience.
Authors: Ethier Josee-Lyne , Wang Lisa , Oza Amit M. , Lheureux Stephanie 
Published: September 2018

e17049 Background: PL-R OC is associated with poor prognosis, and clinical trials indicate that overall survival (OS) is less than 12 months. Here, we describe real-world outcomes in patients with PL-R OC. Methods: Patients treated for PL-R OC presenting to PM from 2011-2015 were identified through the Oncology Patient Information System (OPIS) following research ethics board approval. Treatment data were extracted from OPIS. Baseline characteristics and survival data were obtained through linkage with the PM Survival Registry. Data were supplemented through individual chart review. OS was defined as time from first treatment for PL-R OC to date of death or last contact. Univariable and multivariable analyses were performed to assess the effect of patient characteristics (time from diagnosis to platinum resistance, OC subtype, tumor grade, PL-R or platinum-refractory [PL-RF] status, optimal debulking, clinical trial enrolment, number of treatment lines, germline BRCA1/2 status) on OS using cox proportional hazard models. P-values of 0.05 were considered significant. Results: Data from 165 patients with PL-R OC were included. Most patients had high grade (86%) and serous (84%) tumours. BRCA was mutated in 13%, wild-type in 49%, and unknown in 35%. The median number of lines received was 2 (range 1-6). Weekly paclitaxel (41%) and pegylated liposomal doxorubicin (41%) were the most common first-line regimens. Clinical trial participation was 36%. Median OS was 342 days (95% Confidence Interval 285-440), and was longer in PL-R (366 days) compared to PL-RF OC (302 days). Tumor grade and clinical trial participation were significantly associated with OS on univariable but not multivariable analysis. The number of treatment lines received for PL-R OC was independently predictive of OS (hazard ratio 0.63; p < 0.001), but may reflect capacity for continued treatment in surviving patients (immortal time bias). Conclusions: Real-word outcomes in PL-R OC are similar to those observed in clinical trial populations, and are worse in PL-RF disease. Receipt of a greater number of treatments for PL-R disease is associated with longer OS, but may be due to immortal time bias.
Feasibility of bevacizumab combined with gemcitabine in treatment of platinum-resistant epithelial ovarian cancer.
Authors: Kogiku Ai , Nagao Shoji , Suzuki Kazuhiro , Yamamoto Kasumi , Senda Tokihiro , Kitai Miho , Shiozaki Takaya , Matsuoka Kazuko , Sudo Tamotsu , Yamaguchi Satoshi 
Published: September 2018

e17064 Background: We assessed the efficacy and safety of a combination chemotherapy comprising gemcitabine and bevacizumab for the treatment of platinum-resistant recurrent ovarian cancer. Here we report the results of the interim analysis. Methods: Eligible patients showed recurrent, measurable tumors that had progressed within 6 months after the completion of platinum-based chemotherapy. Patients received gemcitabine (1000 mg/m2) on days 1and 8 and bevacizumab (15 mg/kg) on day1 every 3 weeks until disease progression or unacceptable toxicity levels were observed. The primary end point was the proportion of patients who completed three cycles of scheduled chemotherapy. Results: Twelve patients were enrolled in this study and three patients are still undergoing chemotherapy. The proportion of patients who completed three cycles of chemotherapy was 77.8 % (7/9), and response rate was 66.7 % (6/9). Grade ≥ 3 neutropenia, thrombocytopenia, and hypertension were observed in five, one, and one patients, respectively. There was no GI perforation or death in our study. Conclusions: Combination chemotherapy of comprising gemcitabine and bevacizumab was safe and effective in patients with platinum-resistant recurrent ovarian cancer. Therefore, it is important to continue this study. Clinical trial information: 000016619.
The first-in-class anti-cancer agent ABTL0812 is effective in preclinical models of human endometrial cancer.
Authors: Colàs Eva Colàs , Eritja Nuria , Muñoz-Guardiola Pau , Sole-Sanchez Sonia , Moiola Cristian , Felip Isidre , Gil-Moreno Antonio , Perez-Montoyo Hector , Alfon Jose Alberto , Domenech Carles , Lizcano Jose M , Matias-Guiu Xavier 
Published: September 2018

e17070 Background: ABTL0812 is a first-in-class anti-cancer agent with a unique mechanism of action currently in Phase Ib/IIa clinical development for endometrial cancer and squamous NSCLC. ABTL0812 successfully culminated a Phase I clinical trial showing a high safety profile and long disease stabilizations, including 14-months stabilization in a patient with platinum-unresponsive Grade IIIC endometrial cancer with mutated PI3KCA and Akt. Methods: ABTL0812 synergy with paclitaxel and carboplatin was tested in vitro on Ishikawa cells by MTT assay. ABTL0812 in vivo anti-tumor activity was assessed in a PTEN-null inducible mouse model of endometrial adenocarcinoma development upon tamoxifen injection. In vivo synergy between ABTL0812 and paclitaxel was validated in a xenograft model orthotopically implanted with Ishikawa cells and between ABTL0812 and paclitaxel/carboplatin (P/C) in xenografts derived from a patient (PDX) with grade IIIC2 endometrial carcinoma with mutated PI3KCA. Results: ABTL0812 reduced paclitaxel and carboplatin IC50 by 1.5 and 2.1 times respectively in Ishikawa cells. Synergy with paclitaxel was found in Ishikawa orthoxenografts, showing a maximum Tumor Growth Inhibition (maxTGI) of 56,7±16,9% compared with 34.6±33.2% of paclitaxel group. ABTL0812 alone was effective reducing endometrial intraepithelial neoplasia formation in a mouse model of endometrial adenocarcinoma. Additionally, in an endometrial cancer PDX, ABTL0812 alone showed similar efficacy with reduced toxicity when compared with P/C and improved maxTGI when given in combination (ABTL0812: 45,2±17,5%; C/P*: 38,7±26,9%; ABTL0812+C/P*: 59.3±8.8%; *p=0.031). Conclusions: ABTL0812 has shown efficacy as a single agent and in combination with chemotherapy in preclinical models of endometrial cancer with mutations on PI3K/Akt pathway, which appears frequently over-activated in patients with these cancers. These results supported the application of ABTL0812 as a first line therapy in combination with chemotherapy for the Phase Ib/IIa clinical trial currently ongoing, positioning ABTL0812 as a potential therapeutic agent in the treatment of endometrial cancers bearing these genetic alterations.
Use of a multi-drug regimen gemcitabine, 5-fluorouracil, irinotecan, cisplatin bevacizumab, docetaxel and cyclophosphamide (GFIP/BDC) for heavily pretreated epithelial ovarian (EOC), Fallopian tube (FT) and primary peritoneal (PP) cancer.
Authors: Schwartz Melissa , Cohen Samantha , Dottino Peter Remsen , Beddoe Ann Marie 
Published: September 2018

e17073 Background: Despite initial response rates to standard platinum-based chemotherapy for EOC/FT/PP, the majority of patients relapse. The purpose of this study was to describe response and tolerability of GFIP/BDC, a modification of the G-FLIP regimen (Bruckner et al), in patients with persistent or recurrent EOC/FT/PP. Treatment consisted of a 2-day combination of gemcitabine 300mg, 5-fluorouracil 500mg/m2, irinotecan 20-30mg/m2, cisplatin 20mg/m2, bevacizumab 4mg/kg, docetaxel 20mg/m2, and cyclophosphamide 20mg/m2 administered every 14 days. Methods: A retrospective descriptive analysis of 20 patients from a single academic institution who received combination GFIP/BDC therapy from January 1, 2011 to August 31, 2016 for persistent or recurrent EOC/FT/PP. Toxicities were retrospectively graded using CTCAE v4.0. Results: Twenty patients were identified with a median age 57.5 years (range 32-71). 85% of patients were non-Hispanic white, 90% had cancer of high-grade serous histology, and all had a GOG performance status of 0-1. Patients had received a median of 3 prior regimens and 95% were platinum-resistant. Median number of cycles administered was 9 (range 3-48) and patients remained on treatment for a median of 5.1 months (range 1.5-24). Thirteen patients (65%) experienced a clinical response (1 complete, 12 partial) with a median duration of 5 months (range 1.5-20). Eight patients (45%) survived progression free for at least 6 months. Grade 3 adverse events were hematologic (5), constitutional (3), gastrointestinal (3), neurologic (2), and vascular (1). Grade 4 adverse events included severe neutropenia (1) and anaphylaxis (1). Thirteen patients (65%) experienced at least one grade 3/4 adverse event. Patients discontinued treatment due to disease progression 65% (13), toxicity 20% (4), patient preference 10% (2), and one patient (5%) is currently on treatment. Conclusions: Selected EOC/FT/PP patients who have failed multiple lines of conventional cytotoxic treatment may benefit from GFIP/BDC. Toxicity might be a limiting factor for administration.