bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pazopanib (GW786034) is active in women with advanced epithelial ovarian, fallopian tube and peritoneal cancers: Initial results of a phase II study
Authors: Friedlander M. , Hancock K. C. , Benigno B. , Rischin D. , Messing M. , Stringer C. A. , Tay E. H. , Kathman S. , Matthys G. , Lager J. J. 
Published: March 2020

5561 Background: Pazopanib is a potent and selective multi-targeted receptor tyrosine kinase inhibitor of VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-a/β, and c-kit that blocks tumor growth & inhibits angiogenesis. Clinical studies have demonstrated activity of anti-angiogenesis agents in ovarian carcinoma. Methods: Pts with epithelial ovarian, fallopian tube or primary peritoneal carcinoma; ECOG PS 0–1 with complete CA-125 response to initial platinum-based chemotherapy with subsequent rise to = 42 U/mL; no disease on CT; or non-bulky disease (masses ≤ 4 cm) were eligible. All pts must have received 1–2 prior regimens. Treatment consisted of pazopanib 800mg QD until PD, withdrawal due to AEs, or withdrawal of consent. Two-stage Green-Dahlberg design was employed requiring 2 CA-125 responses in Stage I (20 pts) to proceed to Stage II (15 pts). Primary endpoint was CA-125 response (= 50% decrease from 2 baseline samples, confirmed ≥ 21 d after initial response sample). Results: Data were available from 15/17 pts enrolled. Median age was 60 yrs (46–79). Majority of pts had platinum-sensitive disease to first line therapy (74%) and had 1 prior line of therapy (60%). 40% of pts relapsed < 6 mos, 27% relapsed 6–12 mos; 27% relapsed > 12 mos. CA-125 responses were seen in 7 pts (47%) with a median time to response of 29 d (5 pts have continuing response of 56–140 d and 2 pts had response duration of 56 & 112 d). SD was observed in 4 pts (27%) and PD in 4 pts (27%). Most common AEs were fatigue, diarrhea, nausea, vomiting, and headache. Most common Gr 3/4 AEs were diarrhea (n=2) and ALT elevation (n=2). Five pts (33%) withdrew due to an AE; 1pt (7%) withdrew due to a potentially disease-related AE (Gr 3 ascites) and 4 pts (26%) withdrew due to toxicity (Gr 3 fatigue, Gr 2 vomiting, Gr 3 double vision, Gr 3 AST/ALT elevations). Conclusions: Preliminary review of Stage I suggests that pazopanib monotherapy demonstrates biologic activity in pts with ovarian cancer with biochemical relapse following prior platinum chemotherapy. The study has met the response criteria to proceed to stage II of enrollment. No significant financial relationships to disclose.
Gefitinib in combination with paclitaxel (P) and carboplatin (C) as second-line therapy for ovarian, tubal or peritoneal adenocarcinoma: Final results of a phase II study
Authors: Pautier P. , Joly F. , Kerbrat P. , Bougnoux P. , Fumoleau P. , Petit T. , Rixe O. , Ringeisen F. , Lhommé C. 
Published: March 2020

5566 Background: High EGFR expression occurs in 35–70% of primary ovarian tumors and is often associated with poor prognosis. This Phase II, open-label, non-comparative multicenter study investigated the efficacy and tolerability of gefitinib (Iressa) in combination with paclitaxel (P) and carboplatin (C) for second-line treatment of patients (pts) with ovarian, tubal or peritoneal adenocarcinoma. Methods: Women (>18 years) with platinum-resistant/refractory (relapsed <6 months after first-line platinum-based and P chemotherapy), or platinum-sensitive (relapsed >6 months) disease were enrolled. Pts received gefitinib (500 mg/day), P (175 mg/m2) and C (AUC 5) every 3 weeks for 6–8 cycles, after which pts could continue to receive gefitinib. The primary endpoint was objective response rate (ORR) assessed using RECIST or Rustin criteria. Results: Sixty-eight pts (26 resistant/refractory and 42 sensitive) were enrolled (median age [range]: 57 [34–72] years; ECOG performance status 0/1/2: 41/26/1). ORR and disease control rates were 19.2% and 69.2%, respectively, for resistant/refractory; and 61.9% and 81.0%, respectively, for sensitive pts (see table ). Grade 3/4 toxicities (in =10% pts) were neutropenia (59%), diarrhea (25%), leukopenia (22%), anemia (13%), and acne (13%). Two myelodysplastic syndromes (MDS) and one acute biphenotypic leukemia were observed during treatment. Another pt developed MDS 34 months after study treatment discontinuation. Conclusions: Gefitinib (Iressa) in combination with P and C has promising activity as second-line treatment for ovarian, tubal or peritoneal adenocarcinoma and is generally well tolerated. The hemopathies are under further investigation. [Table: see text] No significant financial relationships to disclose.
A clinical pathway for patients undergoing primary cytoreductive surgery with rectosigmoid colectomy for advanced ovarian or primary peritoneal cancer
Authors: Gerardi M. A. , Santillan A. , Meisner B. , Diaz-Montes T. P. , Gardner G. J. , Giuntoli R. L. , Bristow R. E. 
Published: March 2020

5569 Background: To evaluate the safety, feasibility, and economic impact of a clinical pathway including rapid diet advancement for patients undergoing rectosigmoid colectomy as part of cytoreductive surgery for advanced ovarian or primary peritoneal cancer. Methods: Post-operative management was dictated by surgeon preference in 45 consecutive patients (Group 1) and according to the prescribed clinical pathway in 19 consecutive patients (Group 2). Critical elements of the clinical pathway included: rapid diet advancement, early discontinuance of nasogastric suction, criteria-based utilization of parenteral nutrition, selective laboratory testing, and deferring initiation of chemotherapy until after discharge. Results: The median age was 58 years for Group 1 patients and 67 years for Group 2 patients. Median time to flatus was 6 days for both groups; however, the median time to tolerating diet was 6 days for Group 1, and 4 days for Group 2. Patients in Group 1 had a median length of hospital stay of 12 days (range=5–30 days), a median total 30-day post-operative hospital charge of $42,868 (range=$19,960-$130,252), and a 30-day readmission rate of 33%, compared to 8 days (range=4–28 days) (p=0.020), $32,840 (range=$18,353-$140,283) (p=0.016), and 21% (p=0.379) for Group 2, respectively. Clinical pathway-directed management was associated with a median reduction in hospital charges of $10,027 per patient. Conclusions: A critical pathway incorporating rapid diet advancement for patients undergoing primary cytoreductive surgery with rectosigmoid colectomy for ovarian or primary peritoneal cancer is feasible, safe, and associated with a significant reduction in length of hospital stay and hospital-related charges and did not increase morbidity. No significant financial relationships to disclose.
Protein expression and clinical features of ovarian cancer in the elderly
Authors: Liu J. , Hirsch M. S. , Lee H. , Matulonis U. A. 
Published: March 2020

5574 Background: Ovarian carcinoma is the leading cause of death due to gynecologic malignancies, and age at the time of diagnosis has been suggested to predict for a poorer prognosis. However, few studies have determined if specific biomarkers can predict a difference in prognosis between younger and older patients. We have constructed a tissue microarray (TMA) with correlative clinical data comprised of cases of advanced papillary serous (PS) ovarian cancer to evaluate the features of ovarian cancer in the elderly. Methods: Two cohorts (patient’s age =65 and =55 at diagnosis) were identified by retrospective review of PS ovarian carcinoma pathology cases seen between 1999 and 2005. Patients with stage III or IV were included; those with BRCA mutations were excluded. A high density TMA (with 4 cores per primary tumor) was constructed, and sections were immunostained with ER, PR, and ErbB2. Clinical data were obtained by chart and database review; age, stage, and protein expression were then correlated with overall survival. Correlation of protein expression and age was also examined. Results: 154 cases were examined, with 74 cases in the =55 group and 80 cases in =65 group. There was no difference in survival between the 2 cohorts (p=0.42), but overall survival differed significantly between those patients diagnosed at =70 and >70 years of age (p=0.004). Tumors from the =65 cohort were more likely to express ER (66.7% ≥65, 44.1% ≤55; p=0.009) and less likely to express PR (34.7% ≥65, 57.1% ≤55; p=0.009). Only 3 cases in the older cohort, and none in the younger cohort, expressed ErbB2; these findings were not significant. Protein expression did not correlate with overall survival. However, multivariate analysis revealed that stage IIIc or IV disease (HR 2.38, p=0.04) and age>70 (HR 1.93, p=0.008) were independent risk factors for poorer outcome. Conclusions: This study suggests that patients with advanced PS ovarian carcinoma diagnosed at age >70 have poorer overall survival. PS ovarian cancer in older patients is more likely to express ER and less likely to express PR, but this does not correlate statistically with clinical outcome. Other characteristics of ovarian cancer in the elderly may account for their poorer prognosis, and this TMA will be a valuable tool to assess additional biomarkers. No significant financial relationships to disclose.
A phase II study of the feasibility of sequential carboplatin (C) followed by paclitaxel (P) and gemcitabine (G) as first-line chemotherapy for stage Ic-IV ovarian (OC), fallopian tube (FTC), and primary peritoneal carcinoma (PPC)
Authors: Agarwal R. , Paul J. , Carty K. , Perren T. , Reed N. , Gourley C. , Parkin D. , Gore M. , Kaye S. 
Published: March 2020

5578 Background: We previously explored the feasibility of adding G to C + P in a phase II study, in which 4 cycles of C followed by 4 cycles of concurrent weekly P and G were given (BJC (2004) 91:627–32). Although highly active (med PFS 19.5m), the feasibility of this 1st-line regimen was limited by dyspnea during the weekly P+G phase. The current trial assessed whether the dyspnoea could be ameliorated by altering the schedule. Methods: Untreated FIGO stage Ic-IV OC, FTC and PPC patients (pts) were eligible. Chemotherapy (CTX) consisted of 4 cycles of C (AUC 7) q21 days, followed by 4 cycles of concurrent P (175 mg/m2) d1 and G (1,000 mg/m2) d1 and d8 q21 days. The primary endpoint of the study was the percentage of pts completing the planned 8 cycles of CTX. The planned sample size was 54 pts, based on a one stage single arm study design with 95% power to reject the null hypothesis (completion rate less than 60%), assuming a true completion rate of 80% using one-sided alpha=0.05. Results: All 54 pts were recruited between June 05 and June 06. Details for 44 pts are currently available for the C phase. 38% of these pts had one or more dose reduction (DR), and 68% had dose delays (DD). The commonest reason for DR and DD was neutropenia. Details for 33 pts are currently available for the P+G phase. 27% of these pts had a DR of P and 51% had a DR of G. 71% of pts omitted G on D8, and 64% had a DD. The commonest reasons for DR and DD were neutropenia and thrombocytopenia. Overall, the KM estimate of the percentage completing 8 cycles is 75% (95% CI 61%-89%) based on the current data. Dyspnoea (Grade 2 only) was observed in 4.5% and 3% pts during the C and P+G phases respectively. No significant treatment related CXR changes were observed. The overall response rate was 68% (95% CI 45–86%; 36% CR, 32%PR, 14% SD, 5%PD, 14% NE; n=22). The median follow-up is 7.5 months and the PFS at 8 months is 92% (95% CI 77–97%). Conclusion: This schedule appears to ameliorate the previously observed dyspnoea, while retaining comparable efficacy. The feasibility of this regimen is limited by myelosuppression which could potentially be overcome by: a) reducing the dose of gemcitabine to 750 mg/m2, or b) using prophylactic Peg-GCSF. [Table: see text]
The relationship between tumor size and stage in early versus advanced ovarian cancer: A retrospective chart review
Authors: Horvath L. E. , Werner T. , Jones K. 
Published: March 2020

5580 Background: Ovarian cancer has a different prognosis between early (I and II) and advanced stage (III and IV). The mechanism of disease progression is unknown, but patients with advanced disease may have a higher propensity for seeding of the abdominal cavity early in the disease process than those with early stage. Theoretically if this is so, then patients with advanced stage should have smaller sized tumors than patients with early stage. Methods: This was a retrospective chart review of patients in the tumor registry in 2003 to 2006. Patients had epithelial ovarian cancer, other cell types were excluded. Only cases with documentation of surgical and pathologic staging and measured dimensions on pathologic specimen were included. Patient stage and all available dimensions measured on diseased ovaries were recorded. The dimensions for each patient were averaged into a single dimension for that patient, and then these measurements were totaled and averaged. Results: There were 110 patients analyzed: 85 with advanced disease, 25 with early stage. The average measurement was 4.8 cm in advanced disease, and was 10.7 cm in early stage disease. This difference was statistically significant (p < 0.001). Conclusions: Overall, patients with early stage ovarian cancer have diseased ovaries that are more than twice as large as those found in advanced disease. This finding supports the fact that early versus advanced ovarian cancer are 2 separate disease processes. Early stage grows locally and does not disseminate, and advanced stage disseminates while the tumor is still relatively small. Theoretically there may be a factor that separates these 2 into different diseases, where advanced disease patients have a substance produced by their tumor that allows for early dissemination, and early stage lacks this substance and only grows locally. Basic science research comparing the tissue microarrays of early versus advanced stage disease may be able to identify this difference. If the difference is found, perhaps therapy can be targeted against this difference. No significant financial relationships to disclose.
The significance of radiotherapy for adenocarcinoma of uterine cervix
Authors: Shimada M. , Kigawa J. , Terakawa N. , Nishimura R. , Takano T. , Yaegashi N. , Takehara K. , Suzuki M. , Yokoyama Y. , Hiura M. 
Published: March 2020

5590 Background: We conducted the present study to determine the significance of radiotherapy for cervical adenocarcinoma. Methods: A total of 1,133 patients with cervical cancer, who underwent radiotherapy in 7 institutes between 1996 and 2005, were enrolled in this study. There were 966 squamous cell carcinoma (SCC) and 167 adenocarcinoma (AC). The mean age of patients with AC was 53.6 (range: 28–81) and 55.9 (range: 22–92) for SCC. Patients were distributed as follows: 370 in stage 1b, 116 in stage IIa, 344 in stage IIb, 16 in stage IIIa, 240 in stage IIIb, and 47 in stage IVa. All patients were identified with the medical records. Of 1,133 patients, 544 received radiotherapy as primary treatment, and 589 underwent adjuvant radiotherapy. Results: Regarding primary treatment, the 5-year survival rate for AC was 41.8% and that for SCC was 62.5% (p=0.0172). The rate of refractory or recurrence for patients with AC was significantly higher than that for SCC (53.3% vs. 33.3%, p=0.0068). Patients with AC more commonly showed recurrence inside irradiated field compared with SCC (83.3% vs. 58.2%, p=0.0240). The outcome for patients with AC was significantly worse compared with SCC in adjuvant treatment (5-year survival rate: 27.5% vs. 45.4%, p=0.0434). Recurrence for AC were significantly higher observed than that for SCC (40.0% vs. 24.7%, p=0.0008). The incidence of recurrence inside irradiated field and lymph node involvement did not differ between AC and SCC (30.1% vs. 43.8%, 46.7% vs. 44.0%). Conclusions: Cervical adenocarcinoma had poorer prognosis because of its low radiosensitivity compared with SCC. New strategy for cervical adenocarcinoma should be necessary. No significant financial relationships to disclose.
Phase II trial of mifepristone (RU-486) in advanced or recurrent endometrioid adenocarcinoma or low-grade endometrial stromal sarcoma (LGESS)
Authors: Burke T. W. , Navo M. A. , Smith J. A. , Jung M. S. , Broaddus R. , Iyer R. B. , Lu K. H. , Sun C. C. , Atkinson E. N. , Ramondetta L. M. 
Published: March 2020

5595 Background: Endometrial cancer is the most common cancer of the female genital tract. It affected 41,200 women in the year 2006 and caused 7,350 deaths. Therapy options for recurrent/advanced endometrial cancer are limited. Treatment with radiation and chemotherapy has shown only limited success. Methods: In a phase II IRB approved trial, Mifepristone was given to patients with progesterone receptor positive advanced or recurrent endometrioid adenocarcinoma or low-grade endometrial stromal sarcoma at a dose of 200mg/day orally. Patients were evaluated every 4 weeks to assess treatment-related toxicities and response. Imaging was obtained initially at 8 weeks then every 12 weeks for evaluation of response. Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 was used to assess toxicity. Results: Twelve of 13 enrolled patients were evaluable for response in the first phase of accrual. Stable disease was noted in 3/12 (16, 20, and 44+ weeks). Two were endometrioid endometrial cancer and one with LGESS. No complete responses were seen, one patient remains in treatment. The most frequently reported grade 1–2 tumor related toxicities were anorexia, mood alterations, and fatigue (55%). Twenty-seven percent had asymptomatic elevations of ACTH. The most common Grade 3 toxicities were fatigue and dyspnea (27% and 18%). Only one patient experienced a Grade 4 dyspnea. No serious treatment-related adverse events occurred. Conclusions: Single agent mifepristone in patients with recurrent endometrioid adenocarcinoma or low-grade endometrial stromal sarcoma showed no complete responses. Stable disease was reported 25%, one patient remains stable at 44 weeks. Recent reports suggests that mifepristone may also work via non hormonal targets while single agent mifepristone has minimal activity in this setting. Further evaluation in combination therapy in endometrial cancer should be considered. No significant financial relationships to disclose.
Endometrial cancer survivorship in obese patients: A lifestyle intervention program
Authors: Von Gruenigen V. E. , Waggoner S. , Gibbons H. , Kavanagh M. , Courneya K. , Lerner E. 
Published: March 2020

5596 Background: The majority of early stage endometrial cancer (EC) survivors are obese, have cardiovascular disease and are at significant risk of death from causes other than cancer. The purpose of this study was to examine outcomes at 6 and 12 months in obese EC survivors enrolled in a randomized trial of a nutrition and exercise counseling program. Methods: Patients (pts) with early stage (I or II) EC with a body mass index ≥ 25 diagnosed from 1999–2005 were invited to participate. The intervention (I) group received 6 months of nutritional and exercise counseling while the control (C) group received an informational brochure only. Primary outcome variable was weight loss. Quality of life (QoL) was measured by the Functional Assessment of Cancer Therapy-General (FACT-G) and Medical Outcomes Short-form (SF-36) survey. Exercise [leisure score index (LSI)] and eating patterns (quantitative food records) were assessed at baseline, 3, 6 and 12 mos. Repeated measures ANOVA and independent samples t-test were used for analysis. A sample size of 50 pts with a type1=0.05 and type 2=0.20 error rate was used to test the hypothesis that pts in the I group would lose weight as compared to the C group. Results: 45 pts were enrolled and 23 were randomized to I and 22 to the C group, stratified by BMI. Baseline QoL was decreased in morbidly obese pts (BMI ≥ 40) as compared to pts with a BMI < 40 (FACT-G: 78.0 vs. 83.7; p=0.140; physical SF-36: 40.6 vs. 49.1 p=0.008). Women in the I group lost weight and increased exercise over the 12 mos as compared to controls ( Table ). Repeated measures ANOVA demonstrated a borderline significant interaction effect for weight (F=2.7, p=.074) and a significant interaction effect for exercise (F=5.0; p=.005) over time. The I group had lower intake of calories and total fat during the intervention. Conclusions: Obese EC survivors can undergo and maintain positive lifestyle changes. Future studies will examine long-term changes in co-morbidities and mortality. [Table: see text] No significant financial relationships to disclose.
Neuropsychological sequelae of tamoxifen and exemestane after AC-chemotherapy in postmenopausal women with early breast cancer
Authors: Schilder C. M. , Eggens P. C. , Boogerd W. , van Dam F. S. , Schagen S. B. 
Published: March 2020

566 Background: Cognitive deficits and cognitive complaints in daily life have been associated with adjuvant chemotherapy in breast cancer survivors. The role of endocrine treatments with respect to these cognitive problems is unclear. Because estrogen deficiency may have adverse effects on certain cognitive functions, it is plausible that endocrine treatments affect cognitive functioning in addition to chemotherapy. The current aim was to investigate whether cognitive functioning of breast cancer patients treated with AC-chemotherapy and endocrine therapy differs from healthy controls and to examine possible distinctive effects between tamoxifen and exemestane. Methods: Postmenopausal breast cancer patients from the TEAM-trial, randomized to receive tamoxifen (n=30) or exemestane (n=51), underwent neuropsychological testing and were interviewed regarding cognitive complaints in daily life 1.5–4 years post AC- chemotherapy. At the time of testing, all patients still received their assigned endocrine treatment. Depression was measured with the Hopkins Symptom Checklist (HSCL), fatigue with the Multidimensional Fatigue Inventory (MFI). Healthy controls (n=48) underwent the same assessment. Results: After controlling for age and IQ, both tamoxifen and exemestane users scored significantly lower on ‘information processing speed’ than healthy controls (Reaction times; p = .023 and p = .008). Tamoxifen users scored significantly lower on ‘mental flexibility’ (Stroop Card 3; p = .007) and ‘category fluency’ (p = .<0001) than healthy controls. A significant higher proportion of both tamoxifen and exemestane users reported memory problems in daily life compared to healthy controls (27.6 and 25.5% versus 6.3%, p = .02). Reported cognitive complaints did not correlate with test scores but with fatigue and depression. Conclusions: These results suggest that endocrine treatments combined with AC-chemotherapy have an effect on certain cognitive functions and provide indications for distinctive cognitive effects of different types of endocrine therapy. No significant financial relationships to disclose.