bluuebunny/crossref_metadata_2025_split huggingface dataset:
Docetaxel in combination with radiation in prostate cancer: A phase I dose-finding study
Authors: Berry W. R. , Fairbanks R. K. , Gersh R. H. , Mull S. M. , Ilegbodu D. , Asmar L. 
Published: March 2020

14649 Background: Docetaxel (D), one of the more active agents against prostate cancer, also enhances the effects of radiation therapy (XRT). However, there is little information on the tolerability of the addition of D to pelvic XRT. This Phase I multicenter study was conducted to determine the maximum tolerated dose (MTD) and toxicities of D when given in combination with pelvic XRT. Methods: Patients (pts) with PSA levels >4.0 and <8.0 ng/mL after radical prostatectomy who were referred for salvage XRT were treated at 3 dose levels of D: 10 mg/m2, 16 mg/m2, and 22 mg/m2. One treatment course consisted of D given on Day 1 of each 1-week cycle for 7 cycles with daily XRT administered at 180 cGy Monday–Friday. The 3+3 standard Phase I escalation rule was used to establish the MTD. Results: A total of 9 pts were treated, 3 in each cohort at 3 dose levels. Median doses in the 3 cohorts were 22 mg, 35 mg, and 46 mg. Of the 9 pts, 89% were white, 89% had ECOG PS of 0, and 56% had Stage III disease. The median age was 56 years (range, 48–71). Eight patients completed all 7 weeks of D and XRT; 1 pt went off study after Week 4 due to a fall and fractured arm; 3 other pts subsequently went off study due to PD. In the 3rd cohort, 1 pt had Grade 3 diarrhea (a predefined dose-limiting toxicity [DLT]). The cohort was not expanded by 3 additional pts, and the study was closed to enrollment. The MTD of D with concurrent XRT was not determined. The most frequent adverse events (AEs) were fatigue and diarrhea (67% each), nausea and proctitis (44% each), and anorexia and insomnia (22% each). Except for fatigue, the incidences of these AEs were as expected for treatment with D. Four patients (44%) had a CR (1 CRu). There were 4 PR (1 PRu; 44%) and 1 SD (11%). The median time to response was 1.88 mo. (range, 1.8–7); the overall survival was 27.5 mo.; and the median progression-free survival was 17.7 mo. (range, 1.8–27.5). All patients are currently alive. Conclusions: This Phase I study did not allow definition of the MTD of weekly D with XRT before the trial was terminated. The maximum dose tested was 22 mg/m2/week for 7 weeks. D with pelvic XRT to the prostate was well-tolerated and showed promising responses. It thus deserves further study in Phase II trials. Supported in part by sanofi-aventis, Bridgewater, NJ. [Table: see text]
Phase II study of topotecan and carboplatin in the treatment of platinum-sensitive recurrent ovarian and peritoneal cancer
Authors: Hanjani P. , Shahin M. S. 
Published: March 2020

15001 Background: The aim of this trial was to investigate the efficacy and toxicity of the combination of Topotecan (T) and Carboplatinum (C) in the management of recurrent platinum sensitive ovarian and peritoneal cancer. Methods: T (1 mg/m2) was given as a 30-minute infusion daily × 3 days and C (AUC 5) was given as a 30-minute infusion following T on day 3 on a 21-day cycle. Results: Thirty patients (pts) were enrolled and all pts were evaluable for response and toxicity. Mean age was 63.2 (range = 44–84). One hundred eighty five cycles (mean/pt = 6, range 2–10) were evaluable for toxicity. Dose escalation (T = 1.25 mg/m2) was possible in 25 (83.3%) pts. Hematologic toxicity grade 3 and 4 neutropenia was seen in 60 (32.4%) and 10 (5.4%) cycles, respectively. Grade 3 thrombocytopenia was encountered in 24 (13%) cycles. Grade 3 Hgb was observed in 4 (2.2%) cycles. No grade 4 thrombocytopenia/Hgb or neutropenic fever was encountered. Blood transfusions were required in 9 (4.9%) cycles. Bone marrow support with erythropoiten (40% pts), and filgrastim (43.3% pts) were utilized. No neuropathy > grade 1 was encountered. Fourteen pts (46.6%) pts had a hypersensitivity reaction to C and successful desensitization was carried out in 8 (57.1%). Mean follow-up interval was 16.9 months (mos) (Range 1.7–43). To date, 6 (20%) pts are alive without disease, 16 (53.3%) are alive with disease, and 8 (26.7) have died of disease. The overall response rate was 83.3% (5 CR and 20 PR). Five (16.6%) pts had SD. Median progression-free interval was 8.2 mos. Overall mean survival for the cohort was 31.2 mos (95% CI: 24.47–37.71). Conclusions: Given the ICON-4 data, supporting combination therapy in recurrent platinum-sensitive patients, this regimen provides an effective and tolerable alternative to Taxane-platinum combination with no significant neuropathy. This regimen is especially attractive in patients who have significant residual neuropathy after initial treatment. Carboplatinum desensitization was feasible in previously pre-treated patients. No significant financial relationships to disclose.
Novel method for predicting chemoresistance to paclitaxel in epithelial ovarian cancer patients
Authors: Silasi D. , Rutherford T. J. , Schwartz P. E. , Chen R. , Alvero A. , Visintin I. , Mor G. 
Published: March 2020

15007 Background: No available test exists to guide the selection of effective chemotherapeutic regimen in recurrent ovarian cancer. Preliminary studies in our lab have identified a protein, MyD88, a major component in the inflammatory pathway, to be highly expressed in epithelial ovarian cancer cells that exhibit primary or acquired Paclitaxel chemoresistance. The objective of this study was to develop a sensitive approach that can detect expression of MyD88 in ovarian cancer tissue. We report the development of a test based on Laser capture microdissection that allows detection of MyD88 in a 6000 cell sample. Methods: Tumor tissue was obtained at surgery from epithelial ovarian cancer patients and snap-frozen in liquid nitrogen. Eight micron sections were prepared on polyethylene covered glass slides and tumor cells were dissected with a Laser capture microdissection system. Protein expression was detected by Western blot analysis. Results: Protein expression was detected by Western blot analysis in 1000 microdissected cells. An inverse correlation was observed between MyD88 expression in tumor cells and clinical response to Paclitaxel. Furthermore, this method allows the isolation of CD-45 positive cells from the tumor and analysis of their protein expression. Conclusions: We describe for the first time a method that will allow us to predict chemoresistance. Laser capture microdissection is a powerful technique that can be used to study the protein profile of each of the cellular components present in the tumor microenvironment. This technique will facilitate our understanding of the proteins necessary for tumor growth and may help to identify novel markers or potential protein targets. No significant financial relationships to disclose.
Study design considerations for phase II trials of anaplastic gliomas and its impact on phase III survival studies
Authors: Levin V. A. , Hess K. R. 
Published: March 2020

1501 Background: Phase 2 trials for anaplastic gliomas (AG; WHO 3) such as anaplastic astrocytoma, oligoastrocytoma, and oligodendroglioma remain the most productive path for the development of new therapeutic strategies for the treatment of patients with these tumors. To better understand methodology for their conduct and impact of phase 2 trials on survival-based phase 3 studies, we reviewed a large patient database of patients treated by faculty from the UTMDACC. Methods: Combined data from contemporary (1999–2004) clinical trials and a UT MDACC patient database of AG patients treated on phase 2 studies were analyzed to determine progression-free survival (PFS) at 6, 9, and 12 months. Variables of age, KPS, number of prior chemotherapies, and response to treatment were also evaluated in an effort to define PFS with respect to treatment activity (durability). Results: A total of 547 patients in 17 phase 2 studies were analyzed. The major effecter of PFS outcome at 6, 9, and 12 months was the specific chemotherapy used. The covariates of age, KPS, treatment response rate, and number of prior chemotherapies did not significantly affect PFS to the same extent. Cluster analyses demonstrated the existence of four major therapeutic efficacy groups ranging from A to D. A-group PFS6 was 13% and D-group 40%; for PFS12 A-group was 15% and D-group 32%. Conclusions: The relative differences in PFS among the 4 groups was similar implying that using PFS6 for AG studies is a valid endpoint and extending studies to PFS12 is not cost- or time-effective (27 patients vs. 57 patients). In addition, given that 8 of the 17 studies achieved PFS12 of >25%, it raises the question whether phase 3 survival studies can or should be conducted at this time. Since there are many effective secondary and tertiary treatments for patients who fail chemotherapy, the objective of overall survival for phase 3 AG studies is a flawed objective. For phase 3 studies, PFS is a much more valuable and reliable number to reflect the true antitumor benefit of a form of chemotherapy. Since the median survival of AG patients can range from 4 to 6 years, focusing on PFS in phase 3 studies will also allow more rapid studies and, therefore, the potential to evaluate and discover more and better treatment options for our patients. No significant financial relationships to disclose.
Drug safety profiling for assessment of drug combinations in oncology
Authors: Voss S. N. , Czarnecki A. 
Published: March 2020

15037 Background: It is important to understand the safety profile (SP)/toxicity of new drug regimens in oncology. We compared SPs of gemcitabine (Gem) + carboplatin (Carbo) in NSCLC with Gem alone and in different combinations and also tested the methodology of drug safety profiling (DSP). Methods: Spontaneous cases for the period of 1995–2005 were reviewed on the Lilly Safety Database (LSD). DSP was used to evaluate differences in the SPs of several combinations: Gem+Carbo in NSCLC, Gem+Carbo in ovarian cancer, Gem+ cisplatin (Cis) in NSCLC, Gem+Carbo in all indications, and Gem regardless of treatment regimen, for all indications. Frequencies of adverse events (AEs) for all MedDRA System Organ Classes (SOCs) were used for each regimen. In addition, the MedDRA Preferred Terms (PTs) were reviewed to detect potential safety signals. The numbers of AEs in different SOCs were assessed as proportions of the total reports for the Gem combinations in the LSD. Results: With the exception of the Investigations SOC, the proportions of AEs for patients treated for NSCLC with Gem+Carbo were consistent with those for patients treated for NSCLC with Gem+Cis and with Gem for all indications. However, the frequency in the Investigations SOC was consistent with that reported for Gem+Carbo in all indications (14.2% v. 12.0%). A greater frequency of AEs was seen in the Gastrointestinal Disorders SOC for patients treated with Gem+Carbo for ovarian cancer compared to patients treated with Gem+Carbo for NSCLC. The review of individual PTs for Gem+Carbo did not reveal any safety signals. Conclusions: The SP of Gem+Carbo in NSCLC using DSP showed similar patterns to all other Gem combinations with only some differences due to the indication. DSP is a useful tool in assessing the new drug combination treatments in existing or new indications. [Table: see text]
Weekly topotecan for platinum resistant ovarian cancer
Authors: Abushahin F. , Grendys E. C. , Lurain J. R. , Singh D. K. , Rademaker A. W. , Schink J. C. , Schink J. C. 
Published: March 2020

15040 Background: Topotecan is currently used to treat recurrent ovarian cancer after failure of platinum-based therapy. The FDA-recommended regimen (1.5 mg/m2 for 5 consecutive days of a 21-day cycle) is associated with a high incidence of grade 3/4 myelosuppression. Alternate dosing and scheduling may increase patient convenience and reduce toxicity. The objective of this study is to evaluate toxicity, response and progression free survival of weekly topotecan therapy in women with primary and secondary platinum resistant ovarian cancer after failure of 1 or more regimens. Methods: A retrospective analysis of 59 patients that received weekly topotecan with a median dose of 3.75 on days 1, 8, and 15 of a 28-day cycle treated between November 2002 and May 2005. All patients had recurrent epithelial ovarian cancer with primary or secondary resistance to platinum. Disease response was evaluated by CA-125 levels, physical exam, and when appropriate by imaging studies. Toxicity was evaluated using the NCI Common Toxicity Criteria. Results: Response to therapy was noted in (22%) 13 of 59 patients (complete 6.75%, partial 15.25%). Stable disease was noted in 19 patients (32.2%) and progression in 25 patients (42.4%). Two patients (3.4%) had significant side effects that warranted the discontinuation of therapy. There was no significant difference in response to therapy between patients with primary and secondary platinum resistance. A total of 204 cycles were given with a median of 3 (1–12) cycles per patient. Grade 3 and 4 myelosuppression were rare with 1 cycle (0.5%) with grade 3 leukopenia, 15 cycles (6.4%) with grade 3 or 4 neutropenia, 1 cycle (0.5%) with grade 3 anemia, and 1 cycle (0.5%) with grade 3 thrombocytopenia. No patients were admitted with neutropenic fever. The Median Progression-free-survival for responders was 195 days (56–471). Conclusions: Weekly topotecan is a well tolerated and effective regimen for platinum resistant ovarian cancer with considerable less hematological toxicity when compared with historical data for the 5-day regimen. [Table: see text]
A phase II study of two induction schedules of high dose carboplatin (HDC) vs weekly paclitaxel/gemcitabine (WPG) followed by paclitaxel/carboplatin/gemcitabine (PCG) in advanced ovarian cancer (AOC)
Authors: Bolis G. , Polverino G. , Sciatta C. , Scarfone G. , Scambia G. 
Published: March 2020

15062 Background: Patients (pts) with newly diagnosed AOC generally receive platinum plus taxane therapy. G represents a new active agent to improve the standard regimen. To investigate the safety of two schedules of induction treatments both followed by triplet PCG we have drafted a phase II study. Methods: 14 pts, suboptimally debulked (FIGO stage IIIc) entered the study. HDC ( AUC 7,5) was administered for 2 courses every 21 days ( arm A) and P ( 80 mg/sqm, d 1,8,15,22) + G ( 2500 mg/sqm, d 1,15) (arm B). Both regimens have been followed by standard triplet P ( 175 mg/sqm, d1) + C ( AUC 5, d1) + G ( 800 mg/sqm, d1,8) every 21 days for a total of 6 courses. Antiemetics, corticoids, antihistaminics and ranitidine have been added. Results: The median age was 57 y (39–68). Histology was serous in 64.3%, mixed 14.3% and other 21.4%. All pts had Grade 3 tumor but one. Seven pts received arm A schedule and 7 arm B both followed by PCG regimen. Worst haematological toxicities ( in term of nadir) observed in all courses for all pts were neutropenia G4 ( 42.8% arm A vs 71.4% arm B), anemia G2 (71.4% arm A vs 57.1% arm B), thrombocytopenia G2 ( 57.1% arm A vs 42.8% arm B). Most common non haematological toxicities were alopecia and mild nausea/vomiting. Mild paresthesias in both regimens were observed. No sepsis or neutropenic fever nor unespected toxicity or treatment-related deaths were observed. 71.4% of pts completed foreseen schedules of treatments. 78.5% of pts received erytropoietin and 28.5% G-CSF support. Conclusions: HDC and weekly PG followed by triplet PCG are feasible and safety regimens in AOC pts ( residual disease > 1 cm). Further phase II-III setting study using these schedules will be conducted. No significant financial relationships to disclose.
Ovarian tumours associated with pregnancy
Authors: Bakhidze E. V. 
Published: March 2020

15063 Background: Ovarian cancer occurs in 1.5–5.6% of all combination of malignant tumours and pregnancy. The purpose of this study was to review patients with ovarian tumours in pregnancy, the efficiency of the available methods of treatment and their prognosis. Methods: A retrospective research of the data about 52 patients with ovarian tumours associated with pregnancy who were operated in The N.N.Petrov Research Institute of Oncology from 1960 to 2002. Results: From 52 patients with ovarian tumours associated with pregnancy there were 40 patients (76.9%) with benign tumours and 12 patients (23.1%) with malignant tumours. Middle age of patients was 24.9 ± 5.2 years. Among malignant tumours there were 4 epithelial tumours, 7 herm cell tumours (6 were dysgerminoma and 1 choriocarcinoma) and 1 sex cord-stromal tumour. 9 patients had I stage, 2 had II stage and 1 patient had III stage by FIGO. 14 patients with benign and 7 patients with malignant tumours was operated during the pregnancy: 13 patients (9 with benign, 4 with malignant tumours) were operated during I trimester, 4 patients (3 with benign, 1 with malignant tumours) were operated during II trimester and 4 patients (2 with benign, 2 with malignant tumours) were operated during III trimester of pregnancy. 26 patients with benign tumours and 7 patients with malignant tumours were operated after delivery or abortion. All patients with benign tumours were treated by unilateral salpingoophorectomy. 6 patients with malignant tumours were treated by organ-preserving operations. The 5-year free reccurance survival rate was 83.3% in patients operated during I trimester both for radical and organ preserving operations. The 5-year free reccurance survival rate was 50% in patients operated during II, and 33.3% in patients operated during III trimester. In 6 patients with Ia stage dysgerminoma associated with pregnancy the 5-year free reccurance survival rate was 100%. Conclusions: Benign ovarian tumours associated with pregnancy occur in much more cases (76.9%). Among malignant ovarian tumours the non-surface epithelial tumours occur more often (66.6%). The majority of patients with malignant ovarian tumours who were operated during pregnancy had I stage by FIGO (75%). Prognosis depended not on but on stage and hystotype of tumour and trimester of pregnancy in which patients were operated. No significant financial relationships to disclose.
Analysis of serum phospholipid-fatty acid and antioxidant system in patients with cervical intraepithelial neoplasia and cervical cancer
Authors: Kim H. Y. , Kim J. W. , Kim Y. T. , Kim E. S. , Kim S. Y. , Shim Y. J. , Ko Y. S. , Yoon B. S. , Lee Y. J. 
Published: March 2020

15068 Background: The membrane compositions, especially phospholipid-fatty acid (PL-FA) and antioxidant system have been focused on carcinogenesis. Therefore, the objective was to examine the patterns of PL-FA and antioxidant status in patients with cervical intraepithelial neoplasia (CIN) and invasive cervical cancer. Methods: Blood samples were obtained from 23 patients diagnosed as invasive cervical cancer, 32 with CIN and 41 with other benign gynecologic diseases as the control group. Compositions of serum PL-FAs, total antioxidant performance (TAP), and lipid peroxidation were assessed and compared between these 3 groups. Serum levels of PL-FAs were analyzed by the GC system, after extracting phospholipids using Folch and TLC methods. Fluorometer were used to measure lipid-soluble radical for assessment of TAP and serum malondialdehyde (MDA) was quantified to evaluate the degree of lipid peroxidation. Results: With the highest proportion of saturated fatty acids (SFAs), polyunsaturated fatty acids (PUFAs)/SFAs ratio was lowest in the invasive cervical cancer group. While the EPA (eicosapentaenoic acid, C20:5ω3) + DHA (docosapentaenoic acid, C22:6ω3)/linolenic acid (C18:3ω3) ratio (ω3 product/ω3 precursor) was significantly lower in the CIN group (p < 0.0001), arachidonic acid (C20:4ω6)/linoleic acid (C18:2ω6) ratio (ω6 product/ω6 precursor) tended to be higher in patients with CIN and cervical cancer (p = 0.0682). In w6 series fatty acids, consistent trends of higher desaturation indices and lower enlongation indices were observed in CIN and invasive cervical cancer groups. The level of MDA was significantly higher in cervical cancer group than in CIN and control groups. The value of TAP was significantly lower in CIN. Conclusions: In patients with cervical neoplasia, the endogenous production of DHA and EPA, as well as ω3 derivatives seems to be decreased. Since cervical cancer patients displayed higher MDA levels and lower TAP, antioxidant status also tends to be lower in this group. These significant changes in patterns of PL-FAs and antioxidant status in cervical cancer patients suggest their possible involvements in carcinogenesis, but further studies are mandatory to define the exact causal relationship. No significant financial relationships to disclose.
Phase I/II trial of twice-daily temozolomide and celecoxib for treatment of relapsed malignant glioma: Final data
Authors: Pannullo S. C. , Burton J. , Serventi J. , Stieg P. , Subramanian H. , Elsoueidi R. , El-Jassous I. , Balmaceda C. 
Published: March 2020

1519 Background: Anaplastic astrocytoma (AA) and Glioblastoma multiforme (GBM) overexpress COX-2 enzyme. COX-2 inhibitors demonstrate preclinical efficacy in glioma models and have non-overlapping toxicity with chemotherapy, prompting a phase I/II trial for patients with recurrent/progressive AA or GBM utilizing a regimen of combined temozolomide (TMZ) and celecoxib (CEL). Final survival data is presented. Methods: For phase I, TMZ was given as a fixed loading dose of 200 mg/m2 followed by 9 doses of 90 mg/m2 BID for 5 days. CEL was given in 5 dose levels starting at 60 mg/m2 BID, escalating to 240 mg/m2 BID (maximum 400 mg BID) for 10 days. Cycles were repeated every 28 days until disease progression or toxicity occurred. Results: 46 patients (28 M, 18 F) received 247 cycles of therapy. 37 patients had GBM, 9 AA. Prior treatment was radiation (N=46) and chemotherapy (N=12). No patient received prior TMZ. Median age was 54 years (range 34–74). No dose-limiting toxicity was observed. Hematologic toxicity was mild with Grade 3/4 neutropenia occurring in 3/235 cycles and Grade 3 thrombocytopenia in 3/235 and did not recur following TMZ dose reduction. Grade 1/2 constipation was common, occurring in 28% of patients. No thrombotic events occurred. Overall response rate after 6 cycles was 72%, with 1/18 (5.6%) CR, 7/18 (38.9%) PR, 5/18 (27.8%) SD, and 5/18 (27.8%) PD. Average duration of response was 6 months (range 2–15). Median survival (MS) from time of trial entry for recurrent disease was 8 months (8 months for GBM, 10 months for AA). MS from initial tumor diagnosis was 15 months (15 months GBM, 23 months AA). Conclusion: A regimen of twice-daily TMZ and CEL is safe and potentially effective for the treatment of recurrent/progressive GBM and AA. This combination warrants further study, especially in patients newly diagnosed, given the current use of TMZ in newly diagnosed GBM and the possible value of COX-2 inhibitors in the upfront setting. [Table: see text]