bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multicenter randomized phase II study of nonpegylated liposomal doxorubicin plus vinorelbine versus nonpegylated liposomal doxorubicin plus cyclophosphamide as first line in locally advanced breast cancer (LABC) or metastatic breast cancer (MBC): Safety results
Authors: Lorusso V. , Leo S. , Ciccarese M. , Giotta F. , Bordonaro R. , Filippelli G. , Del Prete S. , Piano A. , Gebbia V. , Pisconti S. , Colucci G. 
Published: August 2020

1116 Background: We conducted a multicenter randomized phase II trial to assess activity and tolerability of the combination of nonpegylated liposomal doxorubicin plus vinorelbine versus standard nonpegylated liposomal doxorubicin plus cyclophosphamide. Methods: This multicenter randomized phase II study was planned to enrol 140 patients (pts). Elegibile pts must have LABC or MBC, PS (ECOG) ≤ 2, and measurable disease. Adjuvant or neoadjuvant chemotherapy with anthracyclines was allowed as well as prior endocrine therapy. Pts assigned to arm A received nonpegylated liposomal doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 on day 1 of a 21-day cycle. Pts assigned to arm B received nonpegylated liposomal doxorubicin 50 mg/m2 plus vinorelbine 25 mg/m2 iv on day 1, and 60 mg/m2 on day 8 po, every 3 weeks. The primary outcome measure was response rate (RR), whereas safety was one of the secondary endpoints. Results: Between July 2006 and July 2008 110 women were treated; for 80 of these, safety results are available. Patient characteristics: Arm A pts (N=41): median age, 59 (range 37–69); ER status ±/unk, 26/15/0; Her-2 status ±/unk, 5/34/2; PS 0/1/2, 26/14/1; prior adjuvant treatment with anthracyclines 10 pts (24%); dominant site of disease visceral 31 pts (76%). Arm B pts (N=39): median age, 61 (range 25–70); Er status ±/unk, 29/10/0; Her-2 status ±/unk, 3/35/1; prior adjuvant treatment with anthracyclines 14 pts (36%); dominant site of disease visceral in 28 pts (72%). There was no study discontinuation due to AE either in arm A or in arm B, nor study-related deaths. Conclusions: The combination regimen of nonpegylated liposomal doxorubicin plus vinorelbine appears to be associated with a slight increase of hematological and nonhematological toxicity when compared with nonpegylated liposomal doxorubicin plus cyclophosphamide. No increase in cardiotoxicity was seen. The trial is ongoing and we plan to give preliminary efficacy results at the time of the Meeting. [Table: see text] No significant financial relationships to disclose.
A phase I study of oral metronomic vinorelbine plus capecitabine in patients with metastatic breast cancer
Authors: Kalykaki A. , Agelaki S. , Kotsakis A. , Vamvakas L. , Bozionelou V. , Kalbakis K. , Androulakis N. , Georgoulias V. , Mavroudis D. 
Published: August 2020

1127 Background: The combination of capecitabine plus intravenous vinorelbine has shown substantial activity in anthracycline and/or taxane pretreated patients with metastatic breast cancer (MBC). The metronomic administration may be associated with reduced toxicity and enhanced efficacy. We conducted a phase I study to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of capecitabine plus oral vinorelbine administered metronomically in patients with MBC. Methods: Patients were treated with vinorelbine (30–60 mg total dose) p.o three times per week continuously and capecitabine (800–1250 mg/m2 twice a day) from day 1 to 14 in three week cycles. DLT was defined during the first cycle as grade (G) 4 neutropenia or thrombocytopenia, febrile neutropenia, any ≥ G 3 non-hematological toxicity, and any delay of treatment due to toxicity. Results: To date 27 patients have been enrolled on 7 different dose levels. Treatment was first line for 16 and second line for 11 patients. DLTs included G3 febrile neutropenia and treatment delay due to G2 neutropenia occurring in 1 patient each, at dose level 4 and G3 diarrhea and treatment delay due to G2 neutropenia in 1 patient each, at dose level 7. The MTD has not yet been reached. Hematologic and nonhematological toxicities were generally mild to moderate. Most common were myelosuppression, asthenia, nausea, and diarrhea. Nine objective responses were observed with 2 complete and 7 partial. Conclusions: Vinorelbine 60 mg three times a week in combination with capecitabine 1250mg/m2 twice a day, has been well tolerated. Enrollment is ongoing. Updated data will be presented at the meeting. No significant financial relationships to disclose.
Effect of simvastatin on the pharmacokinetics of anastrozole
Authors: Bao T. , Slater S. A. , Blackford A. , Jeter S. C. , Wright L. , Rudek M. A. , Desta Z. , Stearns V. 
Published: August 2020

1517 Background: When used in the adjuvant setting, aromatase inhibitors (AIs) reduce the incidence of contralateral breast cancer and are therefore under investigation for primary breast cancer prevention. Statins hold promise for chemoprevention based on preclinical and epidemiological data. Adding statin to AI has the potential to enhance breast cancer prevention and to protect women from AI-related side effects. Prior to initiating a chemoprevention trial of combination therapy, we evaluated the potential for pharmacokinetic drug-drug interaction between anastrozole and simvastatin in postmenopausal women taking adjuvant anastrozole to ensure that the combination will not influence anastrozole concentration or affect its ability to reduce estrogen. Methods: Postmenopausal women with hormone receptor-positive, stage 0-III breast cancer who had been on adjuvant anastrozole (1 mg/day) for at least 30 days were prescribed 14 days of simvastatin (40 mg/day). We collected serum at baseline (anastrozole alone) and after 14 days of simvastatin initiation (combination therapy). Anastrozole and hydroxyanastrozole, its hydroxylated metabolite, concentrations were determined using liquid chromatography-tandem mass spectrometry assay. Estrogen concentrations will be determined using radio-immunoassay. Significant change in anastrozole was predetermined to be greater than a 30% decrease in concentrations. Percent changes from baseline in anastrozole and hydroxyanastrozole were evaluated using Wilcoxon signed-rank tests. Results: From December 2006 to September 2008, 11 women (10 Caucasian, 1 Black, all reported non-Hispanic with a mean age of 60 yrs [range 51–69]) were enrolled in the study. Of these women, nine had evaluable anastrozole concentrations. After 14 days of simvastatin, there were nonsignificant changes in anastrozole (median percentage difference = 10.1% [-13.5%, 38.4%], p = 0.36) and hydroxyanastrozole (median percentage difference = -3.0% [-19.1%, 11.2%], p = 0.65). Estrogen data will be available for presentation. Conclusions: Simvastatin is unlikely to alter the pharmacokinetics of anastrozole in a clinically meaningful way. Combination studies to assess chemopreventive properties of the combination are planned. [Table: see text]
Randomized phase II trial of budesonide versus placebo in high-risk population with screening-detected lung nodules: Update on secondary endpoints
Authors: Bonanni B. , Guerrieri-Gonzaga A. , Radice D. , Serrano D. , Varricchio C. , Ferretti S. , Johansson H. , Szabo E. , Decensi A. , Veronesi G. 
Published: August 2020

1518 Background: Lung cancer phase II chemoprevention trials have not focused so far on the peripheral lung. CT discovers small, undetermined peripheral nodules, which may be preinvasive lesions. In a recent phase II trial the glucocorticoid Budesonide reduced peripheral nodules at spiral CT. Methods: We performed a randomized, double-blind, placebo-controlled, phase IIb clinical trial of inhaled budesonide in current (CS) or former smokers (FS) with CT-detected peripheral nodules. Primary endpoint: shrinkage effect on nodules. Secondary endpoints: decrease in size/number of the target lesions, modulation of tumor markers in sputum and plasma, toxicity, effect on pulmonary function. Two hundred and two subjects received 800μg budesonide (B) twice daily or placebo (P) for 1 year. CT scans at 0 and 12 months (mts), and clinical evaluation + serum/plasma collection at 0, 3, 6, and 12 months were performed. Subjects were stratified according to gender, smoking habits (CS vs. FS), and nodule characteristics (solid vs. non-solid). Results: Preliminary data had shown no shrinkage of the nodules in the B treated arm in a per subject analysis (primary objective). We present now results on serum markers (ultrasensitive C-reactive protein, CRP), emphysema and pulmonary function. As compared to baseline, CRP median levels show at 12 months a nonsignificant (p = 0.85) reduction: -0.25 ± 0.63 (B) vs. -1.16 ± 0.97 (P). 12-month values are significantly (p = 0.01) associated with baseline values and smoking status, with higher mean values at 12 months in FS (B 2.1 ± 2.0 vs. P 3.4 ± 1.9). Emphysema values at 12 months are significantly higher (p = 0.0022) in the B (+ 0.29 ± 0.06) versus P arm (+ 0.12 ± 0.07). This difference is not correlated to sex (p = 0.7062) and smoking status (p = 0.8044). As regards spirometry, no significant difference on FEV 1% and DLC/VA appears between arms at 12 months: median FEV 1% values 3.7 ± 1.0 for B versus 2.9 ± 1.0 for P (p = 0.6221); median DLC/VA increase of 0.3 ± 1.9 (B) versus decrease of -3.8 ± 1.6 (P) (p = 0.4191). Conclusions: A significant effect of B on ultrasensitive-CRP and pulmonary function has not been shown. CRP results may indicate the lack of systemic absorption of B. Emphysema appears slightly worse in the B arm, particularly in FS; this is worth further investigation. No significant financial relationships to disclose.
Efficacy of capecitabine in secondary prevention of skin cancer in solid organ-transplanted recipients (OTR)
Authors: Jirakulaporn T. , Mathew J. , Lindgren B. R. , Dudek A. Z. 
Published: August 2020

1519 Background: Skin cancers are the most common malignancies in OTR. Topical 5% 5-FU has been used to successfully treat squamous cell carcinoma (SCC) in situ and actinic keratosis (AK). Capecitabine, an orally-administered prodrug of 5-FU, in combination with interferon was shown to be effective in the treatment of advanced SCC of the skin. This study was to determine the efficacy of low-dose capecitabine in secondary prevention of the skin cancers in OTR. Methods: OTR who developed recurrent skin cancers, SCC, and/or basal cell carcinoma (BCC), were given low-dose capecitabine 1g/m2 divided in two daily doses, day 1–14 of 21-day treatment cycle. Skin surveillances were performed by dermatologists every 1 to 3 months. Cumulative incidence rates of SCC, BCC, and AK before and after treatment were scored and statistically compared for each patient with a non-parametric Wilcoxon signed-rank test. Age and number of transplants were assessed with the Spearman non-parametric correlation analysis for their impact on the outcome. Results: 14 patients (12 males and 2 females) were enrolled with median age of 55 (range 40–73). 11 patients received kidney, two lung and one liver, one heart and one pancreas transplant. Two patients received double organ transplants. Mean incidence rates of SCC, BCC, and AK before treatment were 0.45, 0.05, and 4.99 lesions per month, respectively. Mean incidence rates of SCC, BCC, and AK after treatment were 0.22, 0.04, and 2.80 lesions per month, respectively. The differences in incidence rates of SCC, BCC, and AK before and after treatment were 0.24, 0.02, and 2.08 lesions per month with p value of 0.048, 0.844, and 0.151, respectively. Age and the number of transplants were not significantly related to the change in incidence rates for all skin lesion types. Six of the total of 14 patients experienced grade 3/4 toxicities, including mucositis (2), hand-foot syndrome (3), fatigue (2), nausea (1), diarrhea (2), hyperuricemia (1), and anemia (1), and all six needed capecitabine dose reduction or stopping therapy. Conclusions: Oral capecitabine significantly decreases the incidence rates of recurrent SCC in OTR and has manageable toxicity. No significant financial relationships to disclose.
Chemoprevention with enzastaurin: First-year results
Authors: Gray J. E. , Altiok S. , Alexandrow M. , Walsh F. , Tockman M. , Bepler G. 
Published: August 2020

1520 Background: Chemoprevention is crucial for reducing lung cancer mortality. The implementation and conduct of such trials is complex. We evaluated accrual in an ongoing trial. Methods: We are conducting a study evaluating if enzastaurin, a protein kinase C beta inhibitor, decreases the Ki-67 labeling index in bronchial epithelium after 6 months of therapy compared to placebo. Eligibility includes age 45 or younger, smoking 30 or fewer packs per year, quit for less than one 1 year, and bronchial meta/dysplasia. Results: Two-thousand eight hundred and nine potential subjects were selected from our database. Between December 2007 and November 2009, 1,242 were invited to participate by an introductory letter and at least 3 attempted telephone contacts. Phone contact was established with 621 (50%) subjects. 245 (39%) declined, 238 (38%) were ineligible, and 138 (22%) were interested in trial participation. At the first face-to-face visit, 57 out of 138 (38%) were eligible, 71 (51%) had not quit smoking for less than 1 year, one (1%) was ineligible for other reasons, and nine (7%) visits are pending. All 57 eligible subjects had an induced sputum exam: 36 had atypia, 19 were normal, and two were inadequate. Bronchoscopies with white light and laser-induced fluorescence and three or fewer biopsies have been done on 22 subjects (4 pending, 4 withdrew, 6 ineligible for bronch). Three had normal histology at all sites, 16 had metaplasia, and two had dysplasia in at least one site (84% abnormal bronchial histology rate, 1 pending). No occult cancers were identified. Conclusions: Of 1,242 preselected potential participants, 11% presented for a first face-to-face visit, 4.6% were eligible after a sputum exam, and 2.4% were fully eligible for randomization. Thus, to reach the accrual goal of 186 patients, we estimate that we will need to contact 7,700 subjects. During our 12-month period, we accessed 1,242 patients with 2.0 FTE for study coordinators (not including the pathologist, bronchoscopist, and laboratory personnel). Our expectation had been to accomplish accrual over a period of 42 months from a pool of 2,809 existing putative patients. Unless our eligibility rate of 2.4% increases, further sources of patients must be identified to accomplish our accrual goal. No significant financial relationships to disclose.
Low bone density in premenopausal women at high risk for breast cancer
Authors: O'Dea A. P. , Thirunavu M. , Nydegger J. , Klemp J. R. , Kimler B. F. , Fabian C. J. 
Published: August 2020

1532 Background: Tamoxifen when used in the high estrogen milieu of premenopausal women may reduce bone density. However, the proportion of premenopausal women at increased risk for breast cancer who have low bone density and are likely to take tamoxifen is unknown. Methods: Premenopausal women attending a high-risk clinic were invited to take part in an ongoing prospective study assessing bone mineral density (BMD) loss. Women on bisphosphonates or those previously treated with selective estrogen receptor modulators were excluded. BMD was measured by DEXA, serum 25-hydroxyvitamin D (25OHD) by chemiluminescence, and information on risk factors for osteoporosis and breast cancer was obtained by questionnaire. Results: 106 premenopausal women were entered between April and October 2008. Median age was 42 (range 23–57), median body mass index (BMI) was 25 kg/m2 (range 15–44). All but two were Caucasian. 13% had a prior biopsy with atypical hyperplasia (AH) or in situ carcinoma, 36% had a family history of osteoporosis, 56% took calcium supplements, and 47% took vitamin D supplements. Median sun exposure was 480 minutes per month, the majority with sunscreen. Median serum 25OHD was 34 ng/ml. Five had deficiency (< 20 ng/mL), and 45 women deficiency or insufficiency (< 32 ng/mL). Seven subjects ages 31 to 48 had evidence of low BMD (T-score of less than -1.0 in the spine or hip.) One woman with low BMD by DEXA had a 25OHD level < 32 ng/ml. Women with low BMD had lower BMIs (median of 22 vs. 25 kg/m2, p = 0.020) than women with normal bone density. There was no difference in history of vitamin D and calcium supplement use, and low 25OHD levels did not explain the low T-scores. Information on vitamin D receptor polymorphisms associated with BMD loss is pending. Importantly, 21% of women with a prior biopsy demonstrating AH or in situ carcinoma had evidence of bone density loss compared to 4% of women without such a biopsy (p = 0.048). Conclusions: Premenopausal women with a history of AH or in situ carcinoma are most likely to take tamoxifen for primary prevention and in our ongoing study have a high enough incidence of low bone density to make baseline assessment by DEXA a consideration, particularly for those with predisposing factors such as low BMI and lack of sun exposure. No significant financial relationships to disclose.
Knowledge and beliefs about breast cancer in rural women and indigenous population of southern Mexico
Authors: Saldana-Tellez M. , Marcial-Toledo S. , Terrazas-Espitia S. , Vazquez-Luna J. , Guzman-Patraca C. , Venegas- Hernandez L. , Perez-Romero J. , Gutierrez-Delgado F. 
Published: August 2020

1533 Background: Rural and indigenous women are generally considered to be at lower risk of breast cancer than women living in urban environments. However, a rising breast cancer incidence rates among those women has been reported. Moreover, up to 90% of those women are diagnosed as having advanced disease. With the aim to improve preventive programs in that population, this study evaluated socio-demographic factors associated with breast cancer early detection and women's knowledge about this malignancy. Methods: Between March 2008 and November 2008, women attending cancer screening programs in our clinic were asked to answer a questionnaire focusing on socio-demographic issues, breast cancer risk factors, breast self examination (BSE), mammography, and perception of breast cancer risk. Results: 838 consecutive women (median age 40 years, range: 15–85) were evaluated. 443 (53%) of them were 40 years and older. The highest education level was 9 years in 408 (49%), 72 (9%) were illiterates and 721 (86%) have no medical insurance. 104 (12%) women practice BSE. The main source of breast cancer awareness was physicians and media in 270 (32%) and 214 (26%) women, respectively. 285 (34%) women knew about breast cancer risk factors, 255 (30%) identified symptoms and signs, and 460 (55)% of them identified lump as the most common sign. 441 (53%) women recognized mammography as the best diagnostic tool in detecting breast cancer, but only 79 (18%) out of 443 women 40 years and older, reported having had a mammogram. Mammograms were not done in 364 (82%) women because of financial issues and difficulty in accessing facilities that perform mammography. 311 (37%) women thought that they were at higher risk of developing breast cancer. Conclusions: Rural and indigenous women have a poor knowledge about breast cancer. Low level education, lack of medical insurance, financial issues, insufficient mammography facilities, and low perception of breast cancer risk are the most important barriers to increase women´s participation in early breast cancer detection. These factors should be considered to improve preventive breast cancer programs. No significant financial relationships to disclose.
Knowledge about cancer screening among medical students and residents
Authors: Villarreal-Garza C. , Villa A. R. , Perfecto-Arroyo M. , García-Aceituno L. , Rojas-Flores M. , León-Rodríguez E. 
Published: August 2020

1541 Background: Cancer is the second cause of death worldwide. In certain types of cancer, screening may detect the disease in its early stages, increasing survival. Therefore, it becomes extremely important that physicians are aware of its precise indications. We sought to explore the level of knowledge about cancer screening among Mexican medical students and residents. Methods: A questionnaire-based survey about screening in breast, cervical, colon, and prostate cancer was completed by medical students attending either public or private medical schools, and internal medicine residents from five training centers in Mexico City. The survey included 16 questions regarding tumor markers, beginning of screening, method of early detection, and frequency of screening. Knowledge scores were expressed as percentages. Statistical analysis was performed using two-tailed Fisher's exact test and Kruskal-Wallis test. Results: The survey was answered by 451 individuals, 49.22% male and 50.78% female, with a mean age of 24.3 ± 2.55 years (range 20–33). Medical students comprised 64.52% and residents 35.48%. Mean knowledge score was 63.97 ± 14.97 (range 18.75–100), increasing directly with level of training: medical students obtained a mean score of 60.46 ± 14.09 compared to residents with score of 70.35 ± 14.44 (p = 0.0001). Statistical differences were noted between third (50.00), fourth (62.62) and fifth year (60.19) (p = 0.0001) medical students; while there was no difference between sixth and seventh year students, neither between distinct years of residency. No difference was encountered between private and public schools. Comparing screening knowledge regarding tumor subgroups, residents scored higher than students in relation to tumor markers 65.24 versus 22.82, breast cancer 77.33 versus 69.19, and prostate cancer 75.00 versus 68.53 (p = 0.0001 for the three comparisons); whereas there was no difference in the education concerning cervical and colon cancer screening, 69.44 versus 70.83 (p = 0.518) and 50.61 versus 45.20 (p = 0.114), respectively. Conclusions: Knowledge of screening guidelines is suboptimal among medical students and residents, especially regarding cervical and colon cancer. Further educational efforts should be targeted to educational and training programs in this country. No significant financial relationships to disclose.
Age and gender-related peculiarities of multiple primary cancers (MPC) in the Altai Territory
Authors: Sekerzhinskaya E. L. , Petrova V. D. , Lazarev A. F. 
Published: August 2020

1552 Background: Itis known that the age-related differences in cancer incidence become distinct among males and females above 30 years of age. The share of elderly females in the general population is growing due to anomaly high non-oncological mortality of able-bodied males. Methods: The data of the Altai territory cancer registry (1995–2008 y.y.) on 3861 patients with MPC were analyzed. Results: Three thousand seven hundred forty four patients (96.97%) had 2 MPC; 114 patients (2.95 %), 3; and 3 patients (0.07 %), 4. Among all the patients with MPC there were 50.58% females and 49.42 % males. The average age of patients with double MPC was 63.1 (varied from 14.4 to 82.6). The average age of patients with triple MPC was 63.0 (varied from 39.0 to 81.0). In most of the patients. cancers were diagnosed at the ages of 60 to 69, which is considered elderly in accordance with World Health Organization gerontological classification. Females prevailed over males among the patients at the ages of 30 to 39 (71.43% to 28.57%, p < 0.05) as well as at the ages of 40 to 49 (69.34% to 30.66%, [p <0.01). However, among the patients at the ages of 60 to 69, males amounted 55.69% in comparison with 44.31% of females (p < 0.01). The was no significant difference between the number of females and males among the patients with MPC at the ages of 70 to 79. Conclusions: Thus, MPC were frequently registered in both males and females. Yet among the patients with MPC in elderly ages, there were more males than females. No significant financial relationships to disclose.