bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized study of docetaxel (D) and dexamethasone (DX) with low or high dose estramustine (E) for patients with advanced hormone-refractory prostate cancer (HRPC)
Authors: Nelius T. , Klatte T. , Reiher F. , Filleur S. , Yap R. , Allhoff E. P. 
Published: March 2020

4653 Background: D-based chemotherapy is a burgeoning option for men with advanced HRPC. Alone or in combination with E, D has been shown to improve median survival. In this study we tested the combination of D with two different doses of E in patients (pts) with HRPC to improve response rates and to lower side effects. Methods: 72 metastatic HRPC pts were randomly assigned to receive D (70 mg/m2 IV, d2, q3w) and E (3 × 280 mg/d PO starting 1 day prior to D, for 5 consecutive days) for arm A or E (3 x 140 mg/d PO starting 1 day prior to D, for 3 consecutive days) for arm B. Premedication with oral DX at a total daily dose of 16 mg, in divided doses two times a day was administered in arm A on day 1 to 5 and in arm B on day 1 to 3. Initially, 6 cycles were administered and repeated after significant PSA rise. Pts were monitored for PSA response, time to progression (TTP), survival and toxicity. Results: PSA declines of ≥75%, ≥50% and ≤50% were 36.8%, 55.3% and 44.7% in arm A and 38.2%, 67.6% and 32.4% in arm B, respectively (P = .442). TTP in Arm A and Arm B were 11 months (95% CI, 7–14) versus 14 months (95% CI, 8–19), P = .6911) and overall survival 21 months (95% CI, 6–35) versus 22 months (95% CI, 18–27), respectively, (P = .4149). The primary treatment-related side effects observed in arm A and arm B were granulocytopenia (34% and 29%, P = .663) and thrombotic complications caused by E (four pts (11%) and one pt (3%), respectively, P = .206). Associated baseline factors with overall survival in univariate analysis were ECOG performance status (P < .001), hemoglobin level (P < .001), bone pain (P < .001), and PSA (P < .097) and in multivariate analysis ECOG performance status (95% CI, 2.9–13.9) and bone pain (95% CI, 3.2–20.1), (P < .001). Conclusions: In this randomized phase II study the combination of D and E had substantial activity in HRPC. We did not find a statistically significant difference of higher dose of E in combination with D compared to a lower dose of E and D regarding PSA response, TTP and survival. However, there was a tendency of higher toxicity in the high dose E group. These treatment-related toxicities were mainly hematologic and manageable. The results of this study support the assertion that estramustine is not necessary in docetaxel-based treatment regimens. No significant financial relationships to disclose.
A multicenter, randomized, phase III study comparing paclitaxel/carboplatin (PC) versus topotecan/paclitaxel/carboplatin (TPC) in patients with stage III (residual tumor > 1 cm after primary surgery) and IV ovarian cancer (OC)
Authors: Scarfone G. , Scambia G. , Raspagliesi F. , Mangili G. , Danese S. , Presti M. , Petruzzelli F. , Costa B. , Bolis G. 
Published: March 2020

5003 Background: Despite treatment with standard first-line PC, survival rates of patients with OC is disappointing, especially in patients suboptimally debulked. In this phase III, open-label, randomised, parallel-arm study topotecan, a non cross-resistant topoisomerase I inhibitor was added to the standard platinum-taxane doublet in order to improve survival and progression-free interval compared to PC alone. Methods: 326 ITT patients with FIGO stage III (residual tumor > 1 cm) and IV OC were randomly allocated to receive either carboplatin AUC 5 and paclitaxel 175 mg/sqm d1q21 (arm A; 170 pts) or topotecan 1 mg/sqm dd1–3q21 + carboplatin AUC 5 and paclitaxel 175 mg/sqm d3q21 (arm B, 156 pts) for 6 cycles. Primary endpoint was the 3-year survival rate with 350 patients originally planned to show an increase in 3-year survival from 20 in arm A to 35% in arm B with 80% power and alfa = 0.05. Results: 81.8% and 77.6% of patients in arm A and B respectively completed the 6 cycles planned. The 2 arms were well balanced for demography, tumor staging and histology except for an excess of serous histotype in the arm B (68.2% vs 75%). Best overall response was CR/PR in 51.5%/33.7% (ORR 85.2%) in arm A and 57.8%/36.3% (ORR 92.5%) in arm B (p = 0.586 with χ2 test, NS). Median time to progression (TTP) was 70.4 and 71.8 weeks in arm A and B respectively (p = 0.5058 with Wilcoxon test, NS). Most common G3/4 hematological toxicity was neutropenia (7.1% and 13.2% of courses and 23.5% and 39.7% of pts in arm A and B) and most common non-hematological toxicities were alopecia (78.2% and 72.4% in arm A and B) and nausea/vomiting (43.5% and 50.5% in arm A and B). 13.9% and 15.5% of courses were delayed and 2.1%/2.4% and 7.2%/6.2% of carboplatin/paclitaxel doses reduced for toxicity in arm A and B respectively. 9.4% and 23.3% of courses required transfusions in arm A and B respectively. Conclusions: The addition of topotecan to standard PC primary chemotherapy does not increase RR and TTP in stage III (residual tumor > 1 cm) or IV OC compared to PC alone. The TPC regimen was well tolerated with a minority of patients experiencing G3/4 hematological toxicity. Study funded by GlaxoSmithKline. No significant financial relationships to disclose.
Phase III randomized trial of neoadjuvant chemotherapy (NAC) followed by radical hysterectomy (RH) versus RH for bulky stage I/II cervical cancer (JCOG 0102)
Authors: Katsumata N. , Yoshikawa H. , Hirakawa T. , Saito T. , Kuzuya K. , Fujii T. , Hiura M. , Tsunematsu R. , Fukuda H. , Kamura T. 
Published: March 2020

5013 Background: NAC may represent an alternative to conventional RH for locally advanced cervical cancer. We compared NAC followed by RH with RH for bulky stage I/II cervical cancer. Methods: Patients (pts) with stage IB2, IIA (> 4 cm), or IIB squamous cell carcinoma of the uterine cervix were randomly assigned to receive either BOMP (bleomycin 7mg day 1–5, vincristine 0.7mg/m2 day 5, mitomycin 7mg/m2 day 5 and cisplatin 14 mg/m2 day 1–5,) q21 days, 2 to 4 cycles followed by radical hysterectomy (NAC arm) or undergo RH (RH arm). Pts with positive surgical margins, metastatic nodes, infiltration to parametrium, and/or deep myometrial invasion received postoperative irradiation. Eligibility included preserved organ function, aged 20–70, and Performance Status 0 or 1. Primary endpoint was overall survival (OS) to be compared by log-rank test. Assuming 100 eligible pts in each arm, the study had 80% power to detect a 15% increase in 5-year survival at 0.05 one-sided alpha. Results: 134 pts (67 NAC, 67 RH) were randomized between 12/01 and 08/05. The first planned interim analysis was performed in July 2005 using data from 108 pts registered as of 11/04. Data and Safety Monitoring Committee recommended to terminate the study because overall survival in NAC arm was inferior to that in RH arm (HR 2.11, multiplicity adjusted 99% CI 0.34 to 13.2) and the predictive probability of significant superiority using Spiegelhalter’s method of NAC arm was extremely low (6.4%). No increase of operability and no decrease of surgery-related morbidity were observed in NAC arm. Response Rate of NAC was 61% (33 of 54) using RECIST criteria. One-year progression-free survival and overall survival, updated as of 05/05, were 69.9% and 91.8% (95% CI 84.1–99.6) in NAC arm and 78.6% and 95.4% (95% CI 89.1–100) in RH arm respectively. Conclusions: Neoadjuvant chemotherapy with BOMP regimen followed by radical hysterectomy did not demonstrate clinical benefit, and conventional radical hysterectomy still remains to be a standard treatment option for bulky stage I/II cervical cancer. [Table: see text]
Angiogenesis pathway gene polymorphisms associated with clinical outcome in recurrent ovarian cancer treated with low dose cyclophosphamide and bevacizumab: A California Consortium Trial
Authors: Schultheis A. M. , Yang D. , Garcia A. A. , Morgan R. , Gandara D. , Scudder S. , Oza A. , Hirte H. , Fleming G. , Roman L. , Lenz H. 
Published: March 2020

5017 Background: Despite advances in chemotherapy, ovarian cancer remains a major cause of cancer mortality worldwide. It has therefore become essential to identify novel therapeutic targets, such as angiogenesis which is a complex process regulated by the delicate balance between various local proangiogenic and antiangiogenic proteins. Bevacizumab, a monoclonal antibody binding to VEGF, has shown significant activity in colon, breast, lung and ovarian cancer. There are no established molecular markers to predict response or time to tumor progression for Bevacizumab based chemotherapy. The key enzymes of the VEGF pathway are: Vascular Endothelial Growth Factor (VEGF), VEGF Receptor (VEGFR), Hypoxia Inducible Factor1 (HIF α and β-subunit), Neuropilin1 (NRP), Interleukin-8 (IL-8), Adrenomedullin (AM) and Leptin. Methods: Seventy patients with refractory ovarian cancer were enrolled in a Phase II clinical trial and treated with Cyclophoshamide 50 mg po/Bevacizumab 10 mg/kg IV every 14 days. From 52 patients blood samples were available for gDNA extraction and PCR-RFLP assays. Results: 13 patients had a PR (25%) and 39 were non responders. 31 pts had progressed. Median follow-up of 8.3 months with a median progression-free survival of 6.6 months. Patients who were homozygous A/A or heterozygous A/T genotype at the −251 locus in the IL-8 gene had a lower response rate than those who were T/T (P = 0.047 Fisher’s exact test). Patients with Vegf936 C/C had a median TTP of 6.5 months, pts with any T (T/T, C/T) had a median TTP of 17.2 months. Pts carrying both AM 3’end alleles <14 CA repeats had 3.4 months median TTP, patients with at least one allele >14 showed a median TTP of 6.6 months; for both alleles >14 patients showed 8.7 months of median TPP (P = 0.0006 Log-rank test) Conclusions: Our data suggest for the first time, that IL-8 may be a potential molecular predictor of response to Bevacizumab based chemotherapy. We also demonstrate that both VEGF 936 and the AM 3’ dinucleotide repeat polymorphisms are potential molecular markers for time to tumor progression. A larger prospective study is needed to validate and confirm our preliminary findings. This study was supported by NCI grant NO1 CM 17101. [Table: see text]
Bevacizumab (B) plus erlotinib (E) for patients (pts) with recurrent ovarian (OC) and fallopian tube (FT) cancer: Preliminary results of a multi-center phase II trial
Authors: Friberg G. , Oza A. M. , Morgan R. J. , Vokes E. E. , Gandara D. R. , Fleming G. F. 
Published: March 2020

5018 Background: The epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are commonly over-expressed in OC and correlate with poor prognosis. The anti-VEGF antibody B and the EGFR tyrosine kinase inhibitor E have each demonstrated activity in OC. Dual inhibition with BE may overcome mechanisms of resistance encountered with either agent alone. Methods: We are conducting a 2-stage phase II trial of BE in pts with recurrent OC, primary peritoneal, and FT cancer. Eligible pts had ≤ 2 prior chemo regimens for recurrent or refractory disease; no prior VEGF or EGFR inhibitors; ECOG performance status (PS) 0–2; measurable disease; normal organ function; no proteinuria (<1000 mg/24 hours). B 15 mg/kg was given IV on day 1 every 21 days and daily E 150 mg PO was given continuously. CT scans were obtained every 9 weeks. 2 responses are required in the first stage to justify accrual into a second stage. Results: 13 pts enrolled at 3 centers from 7/05 to 10/05. Median age: 56 (range 45–70). PS (N with 0/1/2): 6/4/3. Primary site (N): OC 11, FT 2. Primary platinum response (N): refractory 4, resistant (<12 mo PFS) 2, sensitive (≥12 mo) 7. Total prior chemo regimens (N with 1/2/3): 1/8/4. 55 cycles of BE have been delivered (median 4, range 1–8). 12 pts are evaluable for response (1 too early). There has been 1 major response (8%). 8 patients (67%) had stable disease (SD). 1 pt with SD met 75% CA-125 response criteria. 8 pts remain on study. Median PFS has not been reached (median f/u 2.2 months). Attributable toxicities (N with grade 1/2/3/4): rash 4/7/0/0, diarrhea 6/1/2/0, stomatitis 3/1/0/0, myalgias 4/0/0/0, proteinuria 3/0/0/0, bilirubin 0/2/0/0. There were 2 bowel perforations (grade 3/4): both had 2 prior regimens, peritoneal implants >1 cm, 3 doses of B (last was 10 and 42 days prior), and small bowel obstructions in the preceding 28 days. Conclusions: The first stage of accrual is complete and further enrollment is on hold pending continued efficacy evaluation. There appeared to be an increased rate of bowel perforation, and identification of potential risk factors for this event would be critical for further development of this combination. Updated results will be presented. Supported by NCI Grant N01-CM-17102. [Table: see text]
Phase II study of carboplatin, paclitaxel and bevacizumab as first line chemotherapy and consolidation for advanced müllerian tumors
Authors: Penson R. T. , Cannistra S. A. , Seiden M. V. , Krasner C. N. , Matulonis U. A. , Horowitz N. S. , Berlin S. , Dizon D. S. , Lee H. , Campos S. M. 
Published: March 2020

5020 Background: Vascular endothelial growth factor (VEGF) is a major promoter of tumor angiogenesis. Bevacizumab is a recombinant humanized monoclonal antibody that neutralizes VEGF and is active in several tumor types, including epithelial ovarian cancer. Methods: We are conducting a phase II trial of carboplatin, paclitaxel and bevacizumab (CPB) in newly diagnosed patients with chemotherapy naïve, stage ≥ IC, epithelial ovarian, fallopian, primary peritoneal, or uterine papillary serous (UPSC) tumors. Patients receive carboplatin AUC of 5 IV, paclitaxel 175 mg/m2 IV, and bevacizumab 15 mg/kg IV for 6–8 cycles on a 21-day cycle. Bevacizumab is omitted in the first cycle, and continued for one year’s consolidation. Principle endpoints include response rate and progression free survival. Results: Since 3/05, 35 patients have been enrolled. Of the 30 evaluable patients, 24 have ovarian, 4 peritoneal, 1 fallopian tube cancer, and 1 UPSC (1 stage IIB, 22 stage III, and 7 stage IV), and median age is 57 (range 18–77). 133 cycles of chemotherapy have been administered with acceptable toxicity. Grade IV neutropenia has been seen in 3 cycles with 1 episode of febrile neutropenia. Grade I, II, and III HTN was observed in 1, 3, and 4 cycles, and grade I (42% hematuria 45% epistaxis) and II bleeding observed in 36 and 1 cycle(s), respectively. There has been 1 nasal perforation, 2 delayed wound healing, and no bowel perforation. 1 woman withdrew consent (for PMH diverticulitis), and 3 women have been removed for toxicity (1 autonomic neurotoxicity, 1 HTN, and 1 PE). To date, 13 patients have completed the chemotherapy phase of treatment, and only one patient has come off study for progression on consolidation bevacizumab. Conclusion: First line CBP is a highly active regimen that has been well tolerated thus far. Updated toxicity and response data will be available in the spring of 2006. [Table: see text]
A novel multiple biomarker assay for the detection of ovarian carcinoma
Authors: Moore R. G. , Brown A. K. , Miller C. M. , Badgwell D. , Lu Z. , Verch T. , Lu K. H. , Allard J. W. , Granai C. O. , Bast R. 
Published: March 2020

5023 Background: Studies show that ovarian cancer patients operated on by gyn oncologists are more often adequately staged and debulked than those operated on by non-gyn oncologists. Many benign gynecologic conditions will elevate the CA125 tumor marker decreasing its specificity. An accurate test is needed to help triage patients with a pelvic mass to centers with expertise in treating ovarian cancer. This project examined several novel tumor markers to develop a multiple biomarker assay to predict the risk of ovarian cancer in patients with an ovarian cyst or pelvic mass. Methods: Data from two separate IRB approved prospective trials from two institutions were collected. After obtaining informed consent, serum samples were obtained preoperatively from women undergoing surgery for an adnexal mass and analyzed for levels of CA125, SMRP, HE4 and CA72–4. All pathology results were compared to the tumor markers. Sensitivities at set specificities of 90, 95 and 98% were determined using logistic regression for each marker individually and all combinations of 2, 3, & 4 markers. Results: 448 samples were analyzed. There were 267 benign cases and 181 ovarian cancers (27 stage I, 20 stage II, 115 stage III and 19 stage IV). Median values for HE4, SMRP, CA125 and CA72–4 all differed significantly between benign masses and cancer (p < 0.001). In the differentiation of benign masses and stage I malignancies, the addition of HE4 to CA125 increased the sensitivity by 22.2% at a specificity of 90%. The combination of HE4 and CA125 for all stages was superior to HE4 or CA125 alone (p ≤ 0.003). Conclusions: The improvement in sensitivity shown by the addition of HE4 to CA125 suggests that this biomarker combination can be used to provide an accurate risk assessment for the presence of ovarian cancer in patients with an ovarian cyst or mass. This multiple biomarker assay is now undergoing validation in a multicenter prospective study. [Table: see text] [Table: see text]
Tumor-specific correlation of tumor-type M2 pyruvate kinase (Tu M2-PK) in patients with cervical carcinoma
Authors: Kuemmel S. , Jeschke S. , Landt S. , Korlach S. , Schmid P. , Sehouli J. , Blohmer J. , Ulm K. , Lichtenegger W. , Thomas A. 
Published: March 2020

5044 Background: Pyruvate kinase is a key enzyme in glycosis. Proliferating cells express the tetrameric isoenzyme pyruvate kinase type M2 (M2-PK), which decomposes to the dimeric form during tumor development (Tu M2-PK). This suggests that Tu M2-PK can be used as a tumor marker. The goal of the present study was to investigate the diagnostic value of Tu M2-PK in patients with cervix carcinoma and in patients with preinvasive lesions (CIN I-III). Methods: Plasma samples were investigated from a total of 116 patients using the quantitative sandwich enzyme immunoassay for Tu M2-PK (ScheBo, Tech GmbH). The patients were divided up into 3 groups depending on the severity of their condition: Group 1 (n = 43): CIN I-III; Group2 (n = 49): cervix carcinoma FIGO stage I-IV; Group3 (n = 24): relapse of cervical cancer. Results: The differentiation into three groups depending on the severity of the condition gave significant results, with the group of patients with relapsed cervix carcinoma having the highest concentration of Tu M2-PK (p < 0.001) (mean rank: Group 1 - 33.67, Group 2 - 62.48, Group 3 - 94.85 U/ml). In addition, there was a significant differentiation with respect to the FIGO stage, with increasing concentration for increasing stages (p < 0.001). In contrast with this there was no significant differentiation in patients with preinvasive lesions (p < 0.99). In the evaluation of the correlation with prognosis factors of cervix carcinoma (lymph-node status: N(+), N(−); lymphangioinvasion: L1;L0; angioinvasion: V1, V0 and grading G1–3) there were significantly higher values with positive lymph nodes (N+) (p < 0.0001). No significant differences were determined in the analysis of different tumor sub-types (squamous cell carcinoma, adenocarcinoma, adeno-squamous cell carcinoma) (p = 0.076). Conclusions: These are first results which indicate that Tu M2-PK can be used as a marker to differentiate between malignant and premalignant lesions for patients with cervical cancer. In addition, the concentration correlates with the stage of the disease. No significant financial relationships to disclose.
Herpes simplex virus 2 (HSV-2) is not a co-factor of human papillomavirus (HPV) in adenocarcinoma of the uterine cervix (AUC)
Authors: Zereu M. , Zettler C. G. , Zelmanowicz A. M. , Canto M. E. , Cambruzzi E. 
Published: March 2020

5048 Background: Cervical cancer is an important public health problem worldwide. Following skin and breast carcinoma, cervical cancer is the third most common cancer among Brazilian women, ranking first in some developing countries. AUC occurs in 15–20% of primary cervical neoplasias. Although some etiologic factors for squamous cell carcinoma are well defined, and its relationship with sexually transmitted disease as HPV is established, we still don’t know about the causative factors of most of AUC. The objective of this abstract is to determine the presence of HSV-2 DNA in AUC specimens, and its correlation with HPV infection. Methods: From 1995 to 2003, 229 cases of AUC were diagnosed in a hospital from Brazil. Data was collected retrospectively from medical records. The local ethical committee approved the study. Paraffin embedded tissue was selected and DNA extraction was performed. Samples were first screened for betaglobin DNA sequences. To detect HSV-2 DNA using polymerase chain reaction, a pair of primers that bracket 391 base pair segment of DNA polymerase gene was used as described by Madhavan et al. (2003). The sequences are an upstream primer HSV-5’-ATG GTG AAC ATC GAC ATG TAC GG-3’ and one type specific downstream primer HSV-2–5’- CCT CCT TGT CGA GGC CCC GAA AC-3’ (Invitrogen Custom Primers, Sao Paulo, Brazil). The reaction conditions contained 1microlitre sample DNA. The thermal profile consisted of denaturation 94° for 2” followed by 40 cycles with 45’ of denaturation (94°), annealing (60°) and extension (72°). Analysis with agarose gel electrophoresis with ethidium bromide staining was performed. HSV-2 positive sample was used as control. Results: In our series, patient’s mean age was 53.2 years (from 21 to 94), most of them were multiparous (60.6%) and 42% never used any kind of anticontraception method. In 79.4% of specimes DNA of HPV was identified (51% HPV 18 and 34% HPV 16). All samples were negative for DNA of HVS-2. Conclusion: Although some epidemiologic studies reported an interaction between HPV and HSV-2 in increasing cervical cancer risk, in our series HSV-2 is not found integrated to human genome of adenocarcinoma of the uterine cervix and does not seems to be a co-factor of HPV on the etiology of this cancer subtype. No significant financial relationships to disclose.