tbuckley/cabot-search huggingface dataset:
Inhibition of triple-negative breast cancer (TNBC) and breast cancer stem cells (bCSC) by caffeic acid phenethyl ester (CAPE).
Authors: C. O. Omene, J. Wu, J. A. Smith, K. Frenkel
Journal: Journal of Clinical Oncology (2010)

e13587 Background: TNBC is a high mortality disease with a paucity of therapeutics. Our preclinical data used CAPE, a main component of propolis, a honeybee product credited with antiinflammatory, antioxidant, and antitumor properties. CAPE, which is innocuous to normal human mammary epithelial cells, inhibits growth of MDA-MB-231 (231) cells, MDR gene expression, NF-kB, EGFR and VEGF. We used 231 cells, a model of human TNBC, to show that CAPE can combat TNBC as a therapeutic, and/or adjuvant to chemotherapeutic drugs like Taxol. Cancer stem cells (CSC) are implicated in tumor metastasis and recurrence, thus, agents impairing their self-renewal, could be invaluable as novel cancer therapeutics. We show that CAPE could be such an agent, because it inhibits CSC growth and self renewal. We propose that the mechanism for this inhibition is due to the induction of CSC apoptosis. Methods: Nude mice bearing 231 xenografts were fed CAPE diets and/or treated topically with CAPE and tumors measured 2x/week. bCSC were isolated from 231 cells and xenografts and propagated as mammospheres. Cell growth was analyzed using MTT and cell cycle by flow cytometry. Apoptosis was determined by co-staining of bCSC with Annexin V and propidium iodide. Results: Dietary CAPE significantly inhibited growth of 231 xenografts. Subsequent topical CAPE treatment further decreased tumor volume. 231 cells contain bCSC thought to be responsible for metastasis and recurrence. CAPE decreased bCSC clonal growth and inhibited their self-renewal and progenitors as evidenced by decreased growth in soft agar after pretreatment with CAPE. Further, CAPE induced apoptosis of bCSC in a dose-dependent manner up to 20μM CAPE, but apoptosis was decreased at 40μM. Conclusions: Our results strongly suggest that low doses of CAPE reduce TNBC growth by oral and/or topical routes, most likely by suppressing bCSC self-renewal at least partly by inducing apoptosis. CAPE could be a powerful inhibitor of CSC-mediated recurrence of aggressive types of breast cancer including TNBC. Research is ongoing to delineate in detail the mechanism(s) contributing to CSC inhibition by CAPE as it relates to the changes in CSC characteristics and differentiation. No significant financial relationships to disclose.
Utility of PSA doubling time (PSADT) in the detection of prostate cancer in men with a serum PSA ≤ 10 ng/ml
Authors: S. Spurgeon, M. Garzotto, L. Collins, R. Priest, Y.-C. Hsieh, L. Peters, T. M. Beer, M. Mori
Journal: Journal of Clinical Oncology (2005)

4645 Background: PSADT is a strong predictor of adverse outcomes in men with recurrent prostate cancer. Its utility has not been examined, however, for the most common diagnostic challenge: a man referred for suspected prostate cancer and a modest PSA elevation (PSA <=10 ng/ml). The optimal diagnostic approach to such patients is not known and multivariable models have been constructed to facilitate the selection of patients who require a prostate biopsy. Diurnal variation of PSA is common in such patients (JAMA 289:2695, 2003) and may reduce the utility of PSADT. We sought to determine if PSADT is an independent predictor of the presence of prostate cancer in men with a PSA < 10 ng/ml. Methods: Data were collected on 1,699 veterans seen at the Portland VA with a serum PSA of ≤ 10 ng/ml who underwent an initial prostate biopsy. Variables analyzed included: age, race, family history, digital rectal exam (DRE), prostate-specific antigen (PSA), PSA density (PSAD), PSA doubling time (PSADT), prostate volume, and ultrasound (US) findings. Data were analyzed using both logistic regression (LR) and Classification and Regression Tree (CART) analysis. Model building was carried out on 70% of the data and study validation was done on the remaining 30% of the randomly selected dataset. Results: PSADT was < 2 yrs in 256 patients (15.2%), 2 to 5 yrs in 297 patients (17.7%) and ≥ 5 yrs in 1128 patients (67.1%). Prostate cancer was histologically detected in 448 (26.4%) patients. Prostate cancer diagnosis was associated with age, PSA > 2.9 ng/ml, PSAD > 0.12 ng/ml/cc, positive DRE, and an US-detected lesion by LR (p < .05). PSADT of 2 to 5 years was weakly associated with the diagnosis of prostate cancer (RR 1.6, 95% CI 1.1- 2.3) while a PSADT < 2 years or > 5 years were not predictive. The LR model predicted the presence of prostate cancer with an area under the ROC curve of 0.76 in the validation set. Similarly, CART failed to select PSADT in the formation of a decision tree. Using the validation set, CART sensitivity was 96.2% and specificity was 15.8%. Conclusion: While useful in several clinical settings once the diagnosis of prostate cancer is established, PSADT is of limited utility in the initial evaluation of a patient suspected of harboring prostate cancer. No significant financial relationships to disclose.
Second-line everolimus treatment is effective in RCC patients with poor progression-free survival (PFS) in first-line VEGF-targeted therapies.
Authors: V. Gruenwald, C. Seidel, J. Busch, M. Fenner, S. Weikert
Journal: Journal of Clinical Oncology (2011)

e15028 Background: Everolimus is a standard second line treatment after failure of a VEGF targeted agent in patients (pts.) with metastatic renal carcinoma (mRCC) and was associated with a median progression free survival (PFS) of 4.9 months (mo.) in the pivotal trial. It remains unknown whether everolimus efficacy is similar in pts. who failed to respond to tyrosine kinase inhibitors (TKIs) or had a PFS ≤6 mo. in first line therapy compared to others. Methods: Fifty-six pts. who received everolimus as second line therapy after failure of either sunitinib (n=45) or sorafenib (n=11) were identified retrospectively at 2 German academic centres. Everolimus was applied between April 2007 and January 2011. Nine pts. are still ongoing. MSKCC-Score was considered as high in 1 patient, intermediate in 29 and low in 12 patients, respectively. In 14 patients MSKCC could not be evaluated. Disease control was defined by the fraction of patients achieving either objective response or stable disease as best response. Results: First line therapy achieved a median PFS of 10.7 months and was associated with a median overall survival (OS) of 37.6 mo. in first line therapy. Disease control was achieved in 46 pts. (82%). Three patients did not have tumor evaluation and 8 patients showed PD as best response. A PFS ≤6 mo. was detected in 13 pts. (23%) and considered as unfavourable. The median PFS of everolimus treatment is 5.5 mo., with disease control in 33 pts. (60%) and progressive disease in 19 pts. (35%) as best response. 4 pts. were not evaluable for response. The median OS from start of first TKI treatment in pts. with PFS ≤6 or >6 mo. of first line TKI treatment was 16.9 and 40 mo., respectively (P=0.001). However, PFS of everolimus treatment remained similar in both groups and achieved 3.6 and 5.8 mo., respectively (P=0.968). Conclusions: PFS ≤6 mo. in first line TKI treatment is associated with a poor prognosis in mRCC. However, 2nd line antitumor activity of everolimus remains unaffected irrespective of the previous therapeutic activity.
Abraxane, temozolomide, and oblimersen (The ATG Trial): A final report of toxicity and clinical efficacy in metastatic melanoma patients with normal lactate dehydrogenase (LDH).
Authors: J. L. Chang, P. A. Ott, C. Sorlie, C. Escano, E. Yepes, S. Mendoza, A. Gandhi, L. Liebes, A. C. Pavlick
Journal: Journal of Clinical Oncology (2011)

8545 Background: The combination (combo) of oblimersen (OBL), a bcl-2 anti-sense agent, with dacarbazine showed promise in metastatic melanoma (MM) patients (pts) with normal (nl) LDH. OBL, temozolomide (TMZ), and abraxane (ABX) were synergistic in preclinical models of A375 MM cell lines. We conducted a phase I trial of this combo in MM pts with nl LDH and will present the final analysis of toxicity (tox) and clinical efficacy. Methods: Chemo-naïve MM pts (ECOG PS≤2, nl LDH, measurable disease per RECIST) were enrolled onto a phase I protocol with 3 cohorts (ct). Treatment regimen consisted of 56-day cycles of OBL 7 mg/kg/d continuous IV infusion (CIV), d 1-7 and 22-28 in ct 1-2; OBL 900 mg fixed dose over 1 hour, twice weekly in weeks 1-2, 4-5 [d 1,4,8,11,22,25,29,32] for ct 3; TMZ 75/m2/d in ct 1-3, d 1-42, and ABX 175 mg/m2 in ct 1 and 3, 260 mg/m2 in ct 2, d 7 and 28. IHC staining for Bcl-2, Bcl-XL, BAK and caspase 3 were performed in pre- and post-therapy tumor samples. ABX and OBL PK and shed serum cryptic epitopes (SSCE) were monitored. Results: 32 pts were treated (ct 1-14; ct 2- 4; ct 3-14). Median age= 58 years (range: 34-78). Stage M1a-4; M1b-2; M1c-26. Average cycles=3. Tox, all ct: Gr III leukopenia (1), neutropenia (neut) (2), thrombocytopenia (thrombo) (1), sensory neuropathy (sens neuro) (2), OBL hypersensitivity (2); Gr IV neut (1), thrombo (1), sens neuro (4). Responses, all ct: 2-CR (48+ and 14 mos), 10-PR, 13-SD, 7-PD for a disease control rate (CR+PR+SD) of 78.1%. Survival, all ct: OS 14.7 mos; 50% survived > 1y. Correlates: No impact of combo on ABX PK. SSCE appeared to correlate with clinical response or disease progression. Alteration of the tumor biology based on phenotypic changes in Bcl-2, Bcl-xL, BAK and caspase 3 correlated with response to treatment. Conclusions: The combo of OBL, TMZ, and ABX in MM pts with nl LDH is safe and well tolerated. The disease control rate of 78.1% and the survival data are encouraging. Biomarker studies support the rationale that Bcl-2 antisense therapy specifically impacts apoptotic signaling pathways in MM cells. The twice-weekly, fixed-dose OBL schedule appears to be similar in safety and efficacy as the 7-day CIV regimen.
Radiochemotherapy with daily concomitant and adjuvant one week on/one week off temozolomide plus indomethacin in newly diagnosed glioblastoma: A phase II trial
Authors: M. Weiler, C. Hartmann, D. Wiewrodt, U. Herrlinger, J. Schuth, M. Bamberg, A. von Deimling, M. Weller, W. Wick
Journal: Journal of Clinical Oncology (2008)

2044 Background: To evaluate toxicity and efficacy of an intensified schedule of temozolomide plus indomethacin in addition to standard radiotherapy plus concomitant temozolomide in patients (pts) with newly diagnosed glioblastoma. Methods: This trial (UKT-05) enrolled 41 pts treated with pre-irradiation temozolomide at 150 mg/m² (one week on/one week off), radiotherapy with concomitant temozolomide (50 mg/m²), maintenance temozolomide starting at 150 mg/m² according to an intensified one week on/one week off schedule, plus maintenance indomethacin (25 mg bid) treatment. The primary endpoint was median progression-free survival (PFS). O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation was assessed by methylation-specific PCR in 39 (95.1%) pts. Results: The median follow-up interval is 15.3 months (minimum, 9.4 months). Hematologic grade 3/4 toxicities according to the Common Terminology Criteria for Adverse Events (CTCAE; v3.0) were: anemia (3/41, 7%), leukopenia (9/41, 22%), lymphopenia (26/41, 63%), neutropenia (6/41, 15%), and thrombopenia (8/41, 20%). Treatment-related non-hematologic CTCAE grade 3 through 5 toxicities were reported for n=6/41 (15%) pts. Median PFS was 7.6 months [95% CI, 6.0–9.9 months]. PFS rate at 6 months (PFS-6) was 68.8% [95% CI, 56.3–79.0%]. The censored one year survival rate was estimated at 69.9% [95% CI, 56.8–80.5%]. Median PFS, PFS-6 and median survival time (MST) in 16 pts with MGMT gene promoter methylation were significantly larger than in 23 pts without epigenetic MGMT gene silencing (PFS: 15.8 vs. 6.2 months, p=0.001; PFS-6: 85.8% vs. 59.3%; MST: 24.1+ vs. 12.9+ months, p=0.027). Conclusions: The dose-dense regimen of temozolomide administered in a one week on/one week off schedule resulted in relevant but acceptable toxicity. Compared with data from the EORTC26981/22981/NCIC CE.3 trial, pts with an unmethylated MGMT gene promoter in the tumor did probably not benefit from intensifying the temozolomide schedule regarding median PFS or MST whereas the efficacy in the methylated cohort looks very promising. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Essex Pharma GmbH Schering-Plough Schering-Plough
Randomized, placebo-controlled, phase III trial of sunitinib in combination with prednisone (SU+P) versus prednisone (P) alone in men with progressive metastatic castration-resistant prostate cancer (mCRPC).
Authors: Y. Ou, M. D. Michaelson, L. Sengeløv, F. Saad, N. Houede, P. J. Ostler, A. Stenzl, G. Daugaard, R. J. Jones, F. Laestadius, A. Bahl, D. E. Castellano, J. Gschwend, T. Maurina, D. Ye, I. Chen, S. Wang, E. C. Maneval, S. Oudard
Journal: Journal of Clinical Oncology (2011)

4515 Background: Options for treatment of men with mCRPC after progression on docetaxel-based chemotherapy are limited. SU is a multitargeted inhibitor of VEGFR and PDGFR that showed antitumor activity in phase II trials in advanced mCRPC (Sonpavde; Michaelson; Zurita, 2009). Here, we report results of a phase III trial of SU+P in men with progressive mCRPC after docetaxel-based chemotherapy. Methods: In this multicenter, double-blind study, eligible men were stratified by ECOG performance status and progression type (PSA or radiographic) and randomized (2:1) to receive P 5 mg BID and either SU 37.5 mg or placebo (Pbo) on a continuous once-daily dosing schedule. Overall survival (OS) was the primary endpoint. Secondary endpoints included radiographic progression-free survival (PFS) and improvement in pain. Two interim analyses were planned. Results: Between Jul 2008 and Aug 2010, 873 men (median age 68 years; 49% Gleason score ≥8) were randomized to receive SU (n=584) or Pbo (n=289). The study was stopped for futility at the second interim analysis (Sep 2010) by the data monitoring committee. At the time of analysis, median treatment duration was 2.8 (range 0−17.5) and 2.8 (range 0−19.4) months (mo) in the SU+P and Pbo+P arms, respectively. Reasons for discontinuation included disease progression (28.1 vs. 47.3%), adverse events (AEs; 21.4 vs. 5.9%) and consent withdrawal (5.8 vs. 6.2%). The most common treatment-related Grades 3/4 AEs were fatigue (18.8 vs. 7.3%) and anemia (6.2 vs. 5.5%). Efficacy data are shown in the table. Conclusions: Despite an improvement in median PFS, treatment with SU+P did not improve OS compared with Pbo+P in the second-line therapy of mCRPC. No new or unexpected safety issues were identified. Further evaluation will determine whether select subpopulations may benefit from this treatment. Endpoint (95% CI) SU+P (n=584) Pbo+P (n=289) HR (95% CI) P value OS, mo 13.1 (11.7−15.5) 12.8 (11.3−15.8) 1.03 (0.80−1.32) 0.5813* PFS, mo 5.6 (4.5−5.7) 3.7 (3.6−5.6) 0.76 (0.61−0.95) 0.0077* ORR, % (n=310) 5.5 (3.2−8.6) (n=160) 1.9 (0.4−5.4) NA 0.0495** * Stratified log-rank. ** Fisher's exact.
Modified cisplatin, etoposide, and ifosfamide (PEI) salvage therapy for male germ-cell tumors (GCT): Long-term efficacy and safety outcomes.
Authors: Andrea Necchi, Luigi Mariani, Nicola Nicolai, Daniele Raggi, Elena Farè, Patrizia Giannatempo, Luigi Piva, Davide Biasoni, Mario Catanzaro, Tullio Torelli, Silvia Stagni, Giorgio Pizzocaro, Alessandro M. Gianni, Roberto Salvioni
Journal: Journal of Clinical Oncology (2013)

328 Background: Second-line chemotherapy (CT) of advanced GCT is vividly debated and no standard of care has been established. Since 1985 we introduced the modified PEI combination with the aim to reduce toxicity while maintaining efficacy over the original regimen. Methods: We retrieved data of pts who received ifosfamide at 2.5 gr/m 2 (with mesna) on days 1-2, etoposide and cisplatin at 100 mg/m 2 and 33 mg/m 2 , respectively, on days 3-5 every 21 days for a maximum of 4 cycles, followed by surgery of residuals. Multivariable analysis (MVA) was undertaken for pre-specified variables and IGCCCG-2 score was analysed as a continuous covariate. ITT analysis was applied. Results: From 02/85 to 01/12, 189 pts failing cisplatin, bleomycin, and vinblastine (PVB, N=25) or etoposide (PEB, N=164) were treated. 87% had a gonadal primary, 50.3% were MSKCC poor risk, 74.7% were IGCCCG-2 intermediate-to-very high risk, 21.8% had liver, bone or brain (LBB) mets, 16.7% were late relapses. 35 pts (18.5%) had a complete response (CR), 68 (35.9%) a marker normalization (PRm-) (major response-rate: 54.4%). 41/68 PRm- were rendered disease-free (total NED-rate: 40.2%). After a median follow-up of 122.1 mos (IQR 71.4-232), median (95%CI) PFS was 7.2 mos (6.2-9.5) and median OS was 21.7 mos (16.7-69.5). 2yr PFS was 34.3% (28.1-41.9) and 5yr OS was 42.1% (35.3-50.2). Mediastinal primary (HR 3.06, 95%CI, 1.68-5.58), LBB mets (HR 2.02, 95%CI, 1.30-3.16), and AFP&gt;1000 ng/mL (HR 2.78, 95%CI, 1.51-5.14) were negative prognostic factors for OS at MVA while no effect was seen according to IGCCCG-2 category. 70.3% of grade 3-4 neutropenia (25% febrile neutropenia), 48.1% thrombocytopenia, 21.1% anemia, 3% neurotoxicity, and no severe renal toxicity were recored. 81 pts (78% before 2000) had a dose reduction of ≥1 drug for ≥1 cycle. No discontinuations for toxicity occurred. Conclusions: Dose-modified Italian PEI showed activity comparable with the best ones achievable by conventional-dose CT (CDCT) in an unselected patient population, and a favorable toxicity profile. Results are among the most robust available for a CDCT, and should be considered as an appropriate benchmark to be compared with high-dose CT.
Clinical outcomes and toxicity of estramustine phosphate (EP) addition to docetaxel (D) as first-line therapy for castration-resistant prostate cancer (CRPC): A cumulative analysis on 243 patients (pts) from two randomized phase II trials.
Authors: Orazio Caffo, Teodoro Sava, Fable Zustovich, Michele Lodde, Cosimo Sacco, Giovanni Lo Re, Sebastiano Buti, Umberto Basso, Teresa Gamucci, Gaetano Facchini, Alessandra Perin, Romana Segati, Lucianna Russo, Antonello Veccia, Enzo Galligioni
Journal: Journal of Clinical Oncology (2013)

208 Background: Although EP exerts a synergism with D and a meta-analysis suggested a survival advantage in combining EP to chemotherapy, D+EP combination is usually discouraged due to a marginal improvement in disease control at cost of an enhanced toxicity compared to D alone. In order to assess the role of EP added to D we have analyzed data from pts enrolled in two randomized trials with D ± EP conducted by our group (BJU Int 2008 – ASCO GU 2012). Methods: All patients received D 70 mg/m 2 IV q 3 wks ± E 280 mg/TID PO for 5 days starting 1 day prior to D. Ninety-five pts of the first study (started in 2002) were treated until progression; 148 pts of the second study received 8 D courses in continuous or intermittent fashion. We evaluated PSA response, PFS according to PCWG2, OS and toxicity. Results: We shared the clinical data from all 243 pts (123 D, 120 D+EP): the median baseline PSA values were 53 and 60 respectively; 49.5% and 59.1% of the D and D+EP pts presented visceral metastases, respectively. Clinical outcomes and main toxicities are summarized in the Table. Conclusions: The addition of EP to D was tolerable with a mild toxicity profile; it was able to double the biochemical responses which did not translate in any PFS or OS advantage. From our data the addition of EP addition to D should not further role in first line of CRPC, while it may help to overcome D resistance in selected cases according to our previously published data (Urol Oncol 2010). However, this statement should be critically considered at the light of new drugs availabile and active after D failure. Clinical trial information: 2006-005728-17. [Table: see text]
Sleep quality among inpatients with acute myeloid leukemia.
Authors: Thomas William LeBlanc, Kelli Aibel, Ryan Meyerhoff, David Harpole, Amy Pickar Abernethy, Chi-Fu Jeffrey Yang
Journal: Journal of Clinical Oncology (2016)

82 Background: Anecdotally, sleep is thought to be a significant problem for inpatients receiving treatment for acute myeloid leukemia (AML), butsleep disturbances in this setting are not well-characterized. We aimed to assess the feasibility of measuring sleep in AML patients using a wearable actigraphy device. Methods: Using the Actigraph GT3X “watch,”we assessed the total sleep time, sleep onset latency, wake after sleep onset, number of awakenings after sleep onset, and sleep efficiency for inpatients with AML receiving induction chemotherapy during their hospitalization. We also assessed patient self-reported sleep quality using the Pittsburgh Sleep Questionnaire Index (PSQI). Results: Of the thirteen patients enrolled in the study, 11 completed actigraphy and PSQI assessments. Two patients who were transferred to the ICU were excluded from this analysis. Data collection was feasible; patients wore the Actigraph device for a mean (SD) of 120 (58) hours. Subjects’ mean age was 55.9 (15.7) years. Mean length of hospitalization was 34 (13) days. The mean PSQI global score was 8.10 (4.91) indicating generally poor sleep. Actigraphy measures also suggested poor sleep. Overall sleep quantity was insufficient, with a mean total sleep time in minutes of 366.5 (61.0). Patients’ sleep was often interrupted, with a mean number of awakenings after sleep onset of 4.9 (3.3), average awakening length in minutes of 7.8 (5.5), and mean wake after sleep onset in minutes of 37.2 (26.4). Mean sleep onset latency in minutes was 0.4 (0.5) and sleep efficiency was high (90.7% (0.1)), suggesting that patients did not have difficulty falling asleep but rather experienced poor sleep due to external factors. Conclusions: Actigraphy assessment of sleep in AML inpatients is feasible, and suggests significant impairments in both quantity and quality of sleep. While patients did not appear to have difficulty falling asleep, they experienced significant sleep disturbances, perhaps from external factors like interactions with staff and interruptions such as from administration of medications, lab draws and vital sign measurements. Supportive care interventions are needed to further improve sleep quantity and quality among inpatients with AML.
Factors correlated with HPV vaccination in the LGBT community.
Authors: Amber M. Anders, Anees B. Chagpar
Journal: Journal of Clinical Oncology (2014)

202 Background: Human papillomavirus (HPV) infections and related cancers including cervical and anogenital cancer disproportionately affect LGBT populations. Currently, little is known about HPV vaccination in this community. The purpose of this study was to determine what factors were correlated to HPV vaccine receipt in LGBT individuals. Methods: A prospective web-based survey was conducted with regards to cancer related risks in LGBT populations. The data set was restricted to individuals ≤26 years of age who identified as LGBT (n=206). All analyses were performed using SPSS software v.22. Results: Of the 206 individuals in this survey, 92.2% stated they had heard about the vaccine, and 53.4% had received it. Factors correlating with receipt of the vaccine on bivariate analysis are shown in the table below. On multivariate analysis, gender and having a usual site of care remained significant predictors of having received the vaccine. Women were 3.6 times more likely to receive the vaccine than men (95% CI: 1.97-6.71, p &lt;0.0001), and those that had a usual place for health care were 2.9 times more likely to be vaccinated than those who did not (95% CI: 1.26-6.50, p&lt; 0.012). (See Table.) Conclusions: In this survey, 53.4% of people reported having received the HPV vaccine. The only predictive factors of receipt of the vaccine were female gender and having a usual site of care. This reinforces the need for clinicians to be cognizant of vaccinating gay or bisexual men against HPV, and highlights the importance of having a usual site of care as a public health imperative in this population. [Table: see text]