bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral uracil-tegafur (UFT) compared to classical cyclophosphamide/methotrexate/5-fluorouracil (CMF) as postoperative chemotherapy in patients with node-negative, high-risk breast cancer (BC): Results of the national surgical adjuvant study for breast cancer
Authors: Watanabe T. , Sano M. , Takashima S. , Kitaya T. , Tokuda Y. , Yoshimoto M. , Kono N. , Nakagami K. , Iwata H. , Ohashi Y. 
Published: March 2020

551 Background: Oral UFT and classical (c-) CMF provide similar response rates in patients (pts) with metastatic BC (CMF: 36.1%, UFT: 39.3%). In a postoperative setting, these regimens showed comparable effectiveness in terms of odds reductions in relapse-free survival (RFS) (CMF: 23.5%, UFT: 21.0%), but data fromrandomized controlled trials (RCT) is not sufficient. Methods: We conducted a RCT to study the efficacy and toxicity of 2-year oral UFT as compared with c-CMF in pts with Stage I - IIIA node-negative, pathologically high-risk BC in a postoperative setting. In the CMF arm, pts received 6 cycles of c-CMF (C: 100 mg po, days 1 to 14, M: 40 mg/m2 iv, days 1 and 8, F: 500 mg/m2 iv, days 1 and 8). In the UFT arm, pts received UFT at 300 mg/m2/day po for 2 years. Tamoxifen (20 mg/day) was administered for 5 years if ER or PgR was positive or unknown. The primary endpoint was RFS. Overall survival (OS), toxicity, and quality of life were secondary endpoints. The statistical hypothesis was non- inferiority of UFT in terms of RFS (95% CI of HR: <1.30). Results: From October 1996 through March 2001, a total of 733 pts were enrolled of whom 707 pts were analyzed. Patients’ characteristics were well balanced between the two arms. Median follow-up time was 6.1 years. At 5 years the RFS rate was 88.2% in the CMF arm and 87.7% in the UFT arm, and OS rates were 96.0% and 96.1%, respectively. Hazard ratios of the UFT arm to the CMF arm were 1.05 (95% CI: 0.69–1.57) for RFS and 0.88 (95% CI: 0.48–1.63) for OS. The toxicity profile differed between the groups. Major grade 3 or higher adverse events were as follows: leukopenia (CMF: 3.1%, UFT: 0.3%, p=0.006), neutropenia (CMF: 5.5%, UFT: 3.5%, p=0.27), elevation of total bilirubin (CMF: 0.3%, UFT: 5.5%, p=0.00001), elevation of GOT (CMF: 1.4%, UFT: 5.7%, p=0.004), elevation of GPT (CMF: 5.1%, UFT: 8.9%, p=0.08), nausea/vomiting (CMF: 2.8%, UFT: 1.1%, p=0.18) and diarrhea, (CMF: 0.3%, UFT: 2.0%, p=0.04). Conclusions: Our results suggest that UFT is a promising alternative to CMF as postoperative adjuvant chemotherapy in women with node-negative, high-risk breast cancer. No significant financial relationships to disclose.
A phase II trial of the mTOR inhibitor AP23573 as a single agent in advanced endometrial cancer
Authors: Colombo N. , McMeekin S. , Schwartz P. , Kostka J. , Sessa C. , Gehrig P. , Holloway R. , Braly P. , Matei D. , Einstein M. 
Published: March 2020

5516 Background: There are few effective therapies for women with advanced or recurrent endometrial cancer. Targeted therapies such as AP23573, a novel mTOR inhibitor, may result in clinical benefit with fewer side effects. Preliminary results of a trial of single agent AP23573 in patients with progressive endometrial cancer who may have had up to 2 prior regimens of cytotoxic chemotherapy are reported. Methods: The trial is an open-label, Simon 2-stage, single-arm study enrolling patients who have advanced endometrial cancer with documented progression in the 3 months prior to entry. Patients receive 12.5mg AP23573 QDx5 as a 30-min. intravenous infusion every other week for 28-day cycles. The primary efficacy endpoint is Clinical Benefit Response (CBR), defined as a complete or partial response or prolonged stable disease (= 16 weeks) by modified RECIST guidelines. Results: Seven of the first 19 patients achieved CBR, allowing expansion to the second stage. Enrollment is now complete (45 patients). Demographic data are available for 35 (median 66 yrs.; range 46–89) patients who received treatment: 23 adenocarcinomas, 5 carcinosarcomas, 6 papillary serous carcinomas (UPSC) and 1 clear cell carcinoma. Thirty-four patients had prior chemotherapy including doxorubicin, taxanes or platinum agents. Fourteen of the 26 patients with available history had prior pelvic radiotherapy. Nine of 27 (33%) patients evaluable for response had CBRs, including 2 partial responses (PRs). One CBR had UPSC, the remaining patients, including the PRs, had adenocarcinomas. Seven of the patients achieving CBR are still on treatment. Eighteen of the 27 patients discontinued treatment before 4 cycles because of progressive disease (14), consent withdrawal (1) or unrelated adverse events (3). Adverse event data are available for 27 patients. The most common adverse events are fatigue, anemia (33% each), mouth sores and nausea/vomiting (30% each). There have been 16 grade 3/ 4 treatment related adverse events (2 hyperglycemia, 14 separate events similar to those reported in other AP23573 trials). Conclusions: AP23573 shows encouraging single-agent activity in pretreated patients with advanced, progressive endometrial cancer and is well tolerated. No significant financial relationships to disclose.
CA-125 response as a marker of clinical benefit in patients with recurrent ovarian cancer treated with gemcitabine and sorafenib—A trial of the PMH Phase II Consortium
Authors: Welch S. , Hirte H. , Elit L. , Schilder R. J. , Pond G. , Kovacs J. , Wright J. , Oza A. M. 
Published: March 2020

5519 Background: Molecularly targeted agents are expected to have a cytostatic effect on cancers, thus traditional radiographic criteria for objective response may not be optimal in evaluating these agents. There is considerable preclinical rationale for the use of angiogenesis inhibitors in ovarian cancer (OC), and early phase trials of these agents have suggested activity. We have completed a phase II trial evaluating the efficacy of the combination of gemcitabine (GEM), a cytotoxic agent with activity in OC, and sorafenib (SOR), a novel mutitargeted kinase inhibitor with antiangiogenic activity, in patients (pts) with recurrent OC. Methods: Eligible pts had recurrent OC after platinum-based therapy and received up to 2 prior lines of chemotherapy for recurrence. All pts were gemcitabine-naive. GEM (1,000 mg/m2 i.v.) was given weekly for 7 weeks out of 8 weeks in the first cycle, then weekly for the first 3 weeks of each subsequent 4-week cycle. SOR (400 mg p.o. bid) was given continuously. The primary endpoint was objective response rate by RECIST criteria. Secondary endpoints included CA-125 response, time to progression (TTP), overall survival (OS) and toxicity. Results: 43 pts were accrued to this study. 137 (median 3; range: 1–19) cycles of treatment were given to 38 evaluable pts. 26 were evaluable for CA-125 response. Median age was 60 (range: 37–78). 44% of pts were ECOG PS 0 and 56% were PS 1. Using RECIST criteria, 2 pts (4.7%) had a confirmed partial response and 26 pts (60.4%) had a best response of stable disease. 9/26 pts (36.6%) with abnormal baseline CA-125 level achieved a CA-125 response using GCIG criteria. The median TTP was 5.4 months (95% CI: 3.5–9.5) and the median OS was 13.3 months (95% CI: 9.0-NR). The most frequent grade 3 or 4 adverse events were lymphopenia (32%), neutropenia (21%), thrombocytopenia (21%), hand-foot syndrome (21%), fatigue (16%), and hypokalemia (16%). Conclusions: The combination of GEM and SOR is well tolerated and associated with encouraging rates of disease stability. This trial illustrates the need for novel clinical trial design and response endpoints in order to more clearly identify the activity of targeted therapies in recurrent OC. No significant financial relationships to disclose.
Treatment of ovarian cancer patients with malignant ascites using the trifunctional antibody catumaxomab: Results of a phase II/III study
Authors: Parsons S. L. , Kutarska E. , Koralewski P. , Gore M. , Wimberger P. , Burges A. , Stroehlein M. A. , Lahr A. , Jaeger M. , Heiss M. M. 
Published: March 2020

5520 Background: Malignant ascites in ovarian carcinoma patients (pts.) is associated with a poor prognosis and reduced quality of life. Catumaxomab (anti-EpCAM × anti-CD3) is known to effectively eliminate tumor cells within ascites by simultaneously activating T cells and Fc gamma-receptor positive cells and redirecting them against the tumor. Methods: A total of 129 ovarian cancer pts. with recurrent symptomatic malignant ascites containing EpCAM+ tumor cells were enrolled in the study; 85 were randomized to treatment with catumaxomab (paracentesis plus intraperitoneal infusions of 10, 20, 50 and 150 μg for 11 days), and 44 to the control arm (paracentesis alone). The primary endpoint was puncture free survival (time to first need for paracentesis after treatment or time to death, which ever occurred first). Results: Pts. characteristics were well balanced in both arms. Median puncture free survival was 52 days for catumaxomab vs. 11 days for control (p<0.0001) whereas the median time to first need for paracentesis was 71 days vs. 11 days l (p<0.0001). There was a pronounced decrease of tumor cell load accompanied by a distinct increase of leukocyte count during catumaxomab treatment within the ascites fluid. Overall and progression free survival data suggest longer survival for catumaxomab-treated pts. compared to control. Follow-up data will be presented. The most frequent AEs were symptoms related to cytokine release (pyrexia, nausea, vomiting). These were generally mild to moderate in intensity, and fully reversible. Transient increases in liver enzymes and bilirubin, and transient WBC abnormalities such as leukocytosis, neutrophilia and a decrease in peripheral lymphocyte were regularly observed as abnormal laboratory values but rarely considered clinically significant. Conclusions: Intraperitoneal therapy with catumaxomab resulted in a significant and clinically relevant improvement of puncture-free survival time, tumor cell load, and time to first need for puncture compared to the control group of best available treatment. The safety profile reflects catumaxomabs mode of action and reveals a low and acceptable toxicity. No significant financial relationships to disclose.
Randomized trials of combination chemotherapy (combo) versus monotherapy (mono) in relapsed ovarian carcinoma (ROC): A meta-analysis of published data
Authors: Orlando M. , Costanzo M. V. , Chacon R. D. , Tajer C. D. 
Published: March 2020

5524 Background: Results of recent randomized clinical trials (RCTs) support the use of combination chemotherapy in the management of ROC, more specifically in the platinum-sensitive setting. We performed a literature-based meta-analysis of RCTs comparing combination versus monotherapy in previously treated ROC to validate or refute conclusions of individual trials. Methods: This was a systematic review of the available literature identified from multiple databases using the terms ‘combination chemotherapy‘, ‘advanced ovarian cancer‘ and ‘randomized trial‘. Data were pooled for Meta-analysis using the Mantel Hanzsel Peto model. Event-based relative odds ratios (OR) with 95% confidence intervals (CI) were derived. Heterogeneity test was applied. Results: We identified and included 8 RCTs trials fulfilling the selection criteria, 6 phase III and 2 Phase II. Seven published trials and one ASCO poster presentation. One study was conducted exclusively in patients with platinum-resistant disease, five in platinum-sensitive disease only, and 2 in a mixed population. A total of 2312 patients were included in those 8 trials. Relevant endpoints of interest for this meta-analysis were: Overall Response Rate (ORR), Progression-Free Survival (PFS) at 2 years and Overall Survival (OS) at 2 years. Results are summarized in the table : Conclusion: Acknowledging all the drawbacks related to literature-based meta-analyses, combination chemotherapy seems to improve ORR, PFS and OS when compared to monotherapy in the mangement of ROC. References: Bolis G et al Gynecol Oncol 1999, 72:60; Bolis G et al Gynecol Oncol 2001, 81:3; Cantu M et al J Clin Oncol 2002, 20:1232; ICON and AGO collaborators Lancet 2003, 361:2099; Buda et al Br J Cancer 2004, 90:2112; Gonzalez-Martin AJ et al Ann Oncol 2005, 16:749; Pfisterer J et al J Clin Oncol 2006, 24:4699; Sehouli et al Proceedings ASCO 2006, Abstract 5030 [Table: see text] No significant financial relationships to disclose.
Topotecan weekly versus routine 5-day schedule in patients with platinum-resistant ovarian cancer (TOWER): A randomized, two-stage phase-II study of the North-Eastern German Society of Gynaecological Oncology (NOGGO)
Authors: Sehouli J. , Oskay-Oezcelik G. , Stengel D. , du Bois A. , Markmann S. , Loibl S. , Wilke J. , Nugent A. , Belau A. , Lichtenegger W. 
Published: March 2020

5526 Background: Optimizing the therapeutic index (that is, maintaining drug effectiveness while reducing toxicity) is a major goal in chemotherapy for platinum-resistant ovarian cancer. Early phase-I/II studies suggest that weekly topotecan (T) might be effective and apparently better tolerated than the established 5-day regimen. As yet, no randomized comparison of both regimes was attempted. To prove the hypothesis of an improved therapeutic index with weekly T, we conducted a randomized, multicenter, two-stage phase-II trial, and herein present the data of the planned interim analysis. Methods: Pts with platinresistent ovarian and fallopian tube cancers or primary peritoneal carcinoma, measurable or assessable disease (GCIG-CA-125 response criteria), were eligible. Pts were randomized to receive either weekly T (d1,8,15/q28d, 4 mg/m2) or T from d1–5/q21d at a dose of 1.25 mg/m2. According to Gehan’s two-stage-design, both arms were handled as independent studies. Overall response rate (CR + PR) was defined as primary study endpoint, secondary endpoints of the interim analysis were toxicity and safety. Results: 28 pts in the weekly and 21 pts in the conventional group, enrolled at 38 centers form the basis of this report. 230 cycles of chemotherapy were evaluated for toxicity analyses. Median age was 61 years (range, 36 - 82 years). Demographic baseline characteristics, including tumor stage and grade were well balanced between treatment arms. There were 2/28 and 5/21 responses in weekly and the conventional arm, respectively (Risk Ratio [RR] 0.30, 95% confidence interval [CI] 0.06 - 1.40, p=0.122). The risk of early treatment termination due to tumor progression (RR 1.39, 95%CI 0.75 - 2.56), haematological (RR 0.20, 95% CI 0.01 - 3.97) or non- hematological toxicities (RR 1.96, 95% CI 0.18 - 20.83) did not differ significantly between groups. The only three events of neutropenic fever occurred in the conventional arm (RR 1.70, 95% CI 0.99 - 1.16). Conclusions: Weekly T is well tolerated and potentially active. The second stage of this study will require additional 46 patients each arm. Complete enrolment is expected to be accomplished in May 2007. No significant financial relationships to disclose.
Factors predictive of response to cisplatin-based chemotherapy in stage IVB persistent or recurrent cervical carcinoma: A multivariate analysis of three Gynecologic Oncology Group trials
Authors: Moore D. H. , Tian C. , Monk B. J. , Long H. J. , Omura G. 
Published: March 2020

5534 Purpose: A number of patients with advanced/recurrent cervical cancer do not respond to cisplatin-based chemotherapy. A pool analysis of three published phase III GOG studies was undertaken to identify the predictive factors and develop a model predictive of (non-) response to chemotherapy. Methods: The study population consisted of patients who received single-agent cisplatin or a cisplatin-containing combination in GOG protocols 110, 169 and 179. Prognostic variables (age, race, performance status, stage, histology, grade, disease site, prior chemotherapy—with primary radiation, time to recurrence, single-agent versus combination) were analyzed and multivariate analysis was conducted to identify factors independently predictive of response and survival. These analyses were used to establish a predictive model. Results: 816 patients were evaluable for response. In addition to single-agent treatment, multivariate analysis identified six factors (age, African-American, PS > 0, pelvic disease, prior radiosensitizer, recurrence ≤ one year) independently predictive of poor response. Those factors, but not age and African-American, were also independently associated with increased risk of death. 428 patients treated with a cisplatin- containing combination were classified into three risk groups based on the total number of risk factors (low risk: 0–1 factor; mid risk: 2–3 factors; high risk: 4–5 factors). Patients with 4–5 of risk factors were predicted to have a treatment response of only 13% (observed 10%), and median progression-free and overall survival of PFS of 2.8 months and 5.5 months, respectively. This subgroup of patients consist ∼14% of the target population in clinical practice. The predictive model was externally validated using GOG protocol 149 data that were not used for model development and further supported the predictive accuracy. Conclusions: High risk patients should be directed to non-cisplatin chemotherapy or investigational trials. No significant financial relationships to disclose.
The 50-month results of the four non-platinum concurrent chemoradiation regimens for locally advanced cervical cancer
Authors: Kamnerdsupaphon P. , Chitapanarux I. , Sukthomya V. , Lorvidhaya V. 
Published: March 2020

5540 Objectives: To determine the efficacy, disease free and overall survivals of radiation therapy in combination with four non-platinum chemotherapy regimens for locally advanced cervical cancer. Materials and Methods: Eligible patients were those with a diagnosis of locally advanced cervical cancer, under 70 years of age, and undergone the necessary prestudy investigations. All patients received external-beam pelvic irradiation to a minimum dose of 5,000 cGy, and brachytherapy delivered to bring the minimum total dose at point A to 7,500 cGy. Patients were randomized to receive one of four chemotherapy regimens: Arm1: oral 5FU 250 mg/m2/day, Arm2: mitomycin 12 mg/m2 on days 1 and 28 + oral 5FU 200 mg/m2/day, Arm3: mitomycin 12 mg/m2 on days 1 and 28 followed by 5FU 1,000 mg/m2/day on days 1 through 4 and 28 through 31, Arm4: oral hydroxyurea 25 mg/kg/day. Results: From September 1995 to October 2001, the study include 921 women; 226 in arm 1, 229 in arm 2, 234 in arm 3, and 232 in arm 4. The median follow-up time was 51.69 months. More than 89% of the patients achieved complete response. Disease free survival rates were 62.4% among arm 1, 63.8% among arm 2, 66.2% among arm 3, and 68.5% among arm 4. Overall survival rates were 77.4%, 79.5%, 80.8%, and 84.5% respectively. Conclusion: The efficacy of these regimens were not inferior to the standard platinum based regimen for locally advanced cervical cancer. This study demonstrates the results of large randomized clinical study of radiochemotherapy and requires the longer follow up time for the late complications. No significant financial relationships to disclose.
A phase I study of tirapazamine in combination with radiation and weekly cisplatin in patients with locally advanced cervical cancer
Authors: Rischin D. , Narayan K. , Oza A. , Mileshkin L. , Bernshaw D. , Hanlon K. , McClure B. , Fyles A. 
Published: March 2020

5543 Background and Purpose: Hypoxia is an adverse prognostic factor in locoregionally advanced cervical cancer treated with radiation. GOG are currently studying the hypoxic cytotoxin, tirapazamine (TPZ) in combination with biweekly intermediate dose cisplatin (CIS) and radiation in a large phase III trial. The aim of this phase I study was to develop a better tolerated regimen that added TPZ to the standard regimen of radiation and weekly low dose CIS. Methods: Eligible patients had previously untreated carcinoma of the cervix, Stages IB2 - IVA. The starting schedule was radiotherapy (45 to 50.4 Gy external beam radiation followed by brachytherapy), with concomitant weekly CIS 40 mg/m2 weeks 1–6 and weekly TPZ 290 mg/m2 (prior to CIS) in weeks 1–5. Results: Between 3/05 and 7/06 eleven patients were enrolled, median age (range) 52 (31–65), squamous cell carcinoma 10, adenocarcinoma 1, 1B2–5, IIA-1, IIB-3, IIIB- 1, IVA-1. The first 2 patients on dose level 1 experienced a dose limiting toxicity (DLT), one grade 3 ALT (SGPT) elevation and grade 4 pulmonary embolism and one grade 3 ototoxicity. Doses were decreased to dose level -1 CIS 30 mg/m2 and TPZ 260 mg/m2. Three patients were treated without any DLTs. Six patients were then treated on dose level -1a, CIS 35 mg/m2 and TPZ 260 mg/m2, with 2 DLTs: grade 3 neutropenia with dose omission and grade 4 pulmonary embolism with major hemodynamic compromise. The sixth patient on dose level -1a withdrew from the trial in week 2 after being advised about the DLTs observed on this dose level. 3 additional patients will be accrued on dose level -1 to confirm safety of this dose level. One patient has relapsed in pelvic nodes, all other patients remain disease-free with a median followup of 10 months (range 5 - 21) Conclusions: The combination of weekly TPZ and CIS with radiation for locally advanced cervical cancer was associated with more toxicity than anticipated with the recommended dose level being TPZ 260 mg/m2, CIS 30 mg/m2. No significant financial relationships to disclose.
Cervix cancer regression measured using weekly MR imaging during fractionated radiotherapy: Radiobiologic modeling and correlation with tumor hypoxia
Authors: Lim K. S. , Chan P. , Dinniwell R. , Fyles A. , Haider M. , Cho Y. , Jaffray D. , Manchul L. , Levin W. , Hill R. P. , Milosevic M. 
Published: March 2020

5547 Background: To utilize cervix cancer volumetry, as measured with MR imaging during definitive chemoirradiation (RT-CT), to derive radiobiological parameters using a mathematical model of tumor regression, and compare them to pre-treatment measurements of tumor hypoxia. Methods: Twenty-eight patients receiving RT-CT for cervix cancer underwent weekly magnetic resonance imaging (MRI) scans. Tumor volume was assessed on each of these scans and the rate of regression plotted. A mathematical model of tumor regression was formulated to simulate the relationship between three independent radiobiological parameters, 1) surviving fraction of cells after 2 Gy, SF2, 2) the cell clearance constant Tc, and 3) the cellular proliferation constant Tp. Non-linear regression analysis was applied to fit the MR-derived tumor volumes to the mathematical model and to derive SF2 and Tc values for each patient. These were compared to pre-treatment hypoxia measurements. Results: Initial tumor volume ranged between 8 and 209 cm3. Relative reduction in volume during treatment was 0.02 to 0.79. Simulations using representative values of the independent biologic variables derived from the literature showed SF2 and Tc to strongly influence the shape of the volume response curves. Non-linear regression analysis yielded a median SF2 of 0.71 and median Tc of 10 days. Radioresistant tumors (SF2 >0.71) were significantly more hypoxic at diagnosis (p=0.02). Conclusion: Based on serial MR imaging during treatment, a marked variation in cervix tumor regression is seen from patient to patient. Through our radiobiological model, tumors can be classified as radioresistant or radiosensitive, which correlates with hypoxia [Table: see text] No significant financial relationships to disclose.