tbuckley/cabot-search huggingface dataset:
Comparison of neoadjuvant 6 vs 8 cycles of docetaxel/doxorubicin/cyclophosphamide (TAC) in patients early responding to TACx2-the GEPARTRIO Study
Authors: G. Von Minckwitz, J. Blohmer, P. Vogel, C. Hanusch, H. Eidtmann, J. Hilfrich, B. Gerber, J. Huober, S. Costa, M. Kaufmann
Journal: Journal of Clinical Oncology (2006)

576 Background: Primary breast cancer (BC) patients (P) with early response to neoadjuvant TACx2 (75mg/m, 50 mg/m, 500 mg/m, day 1, q21, supported with (pegylated) G-CSF and epoetin) experience a high pathologic complete remission (pCR) rate after further TACx4 (von Minckwitz et al, Ann Oncol 2005) compared to patients without early response (SABCS 2005, Abst 38). We compared prolongation to 8 cycles of TAC with conventional 6 cycles TAC in the chemosensitive subgroup. Methods: P with operable (T 2 cm by palpation) or locally advanced (T4 or N3, M0) BC were treated with TACx2. If tumor reduction was exceeding 50% according to breast ultrasound, P were randomized to receive either 4 or 6 additional cycles. Endpoints were pCR-rate (no invasive and no non-invasive residuals) (primary), sonographic response before surgery, breast conservation rate, safety and compliance (secondary). To detect an increase in pCR-rate from 20 to 26%, 606 evaluable patients were requested for each arm (α=0.05, β=0.2, one-sided). Results: 2106 P were recruited into the multi-centre, prospective, open-label, randomized GEPARTRIO-trial within 36 months. 1400 P with an early response to TACx2 were randomized with the last patient having surgery in Dec 05. Median clinical tumor size was 4.0 (1.0 - 30.0) cm at study entry. A planned safety and blinded efficacy interim analysis was performed on the first 600 patients (306 TACx6, 294 TACx8). Main toxicities (grade I-IV %TACx6 vs %TACx8) were: anemia (91 vs 93), thrombopenia (39 vs 49), neutropenia (65 vs 75), febrile neutropenia (10 vs 16), infection (29 vs 30), vomiting (42 vs 44), diarrhea (59 vs 52), stomatitis (66 vs 67), conjunctivitis (51 vs 57), allergic reactions (20 vs 14), edema (40 vs 47), asthenia (90 vs 93), hand-foot-syndrome (25 vs 28), nail (43 vs 50), dyspnea (33 vs 37), sensory neuropathy (51 vs 61). Treatment was discontinued early in 165 P (31.0%), 53 (19.8%) P during TACx6 and 112 (42.3%) P during TACx8. Overall pCR was reported in 102 (17.0%) of these patients. Conclusions: TACx8 is associated with moderate increase in toxicity and treatment discontinuations compared to TACx6. Final results on the primary and secondary endpoints will be presented. [Table: see text]
Imatinib mesylate inhibits the growth of breast cancer cells mediated by PDGF-receptor-β and Akt inactivation
Authors: C. Mundhenke, M. Weigel, I. Meinhold-Heerlein, C. Schem, D. O. Bauerschlag, W. Jonat, N. Maass
Journal: Journal of Clinical Oncology (2006)

20040 Background: The prognosis of patients with progressed breast cancer remains poor after intensive chemotherapy. Therefore new treatment options such as targeted therapies are needed. Imatinib Mesylate is a tyrosin kinase inhibitor targeting growth receptors like PDGF-R α and β, c-kit. These receptors and their downstream effectors trigger a cascade that regulates multiple cellular processes such as proliferation, differentiation and survival. The activity of the important downstream effector Akt leads to cell survival through inhibition of pro-apoptotic signals. We therefore evaluated the effects of Imatinib on of PDGFR β and Akt activity in breast cancer cell lines in vitro. We previously detected that Imatinib inhibits the growth of the breast cancer cell lines MDA MB 231, MCF 7, ZR 75–1 and T 47-D in vitro. Furthermore Imatinib induces apoptosis in these cell lines. Methods: To investigate effects on receptor activation, cells were stimulated with PDGF BB, the physiological ligand of PDGFR β. Phosphorylation of PDGFR β and Akt was examined after incubation with increasing concentrations of Imatinib by immunohistochemical and western blot assays. Imatinib concentrations from 2 μM to 10 μM were applied. Results: Imatinib Mesylate shows a dose dependent inhibitory effect on PDGFR β phosphorylation, determined by immunohistochemistry and western blot analysis. No changes in the expression pattern occured. The phosphorylation of the tyrosine kinase Akt can also be inhibited by Imatinib in a dose dependent manner. The expression of Akt remains also unchanged. Conclusions: It can be suggested that the growth inhibitory effect of Imatinib Mesylate on breast cancer cell lines is caused by a dose dependent decrease of activation in PDGFR β and Akt. The inhibition of Akt phosphorylation by Imatinib explains the induction of apoptosis. These interesting effects should be further validated in vivo in clinical trials. [Table: see text]
Long term efficacy of peripheral androgen blockade on prostate cancer: CALGB 9782
Authors: J. Picus, S. Halabi, E. Small, A. Hussain, G. Philips, E. Kaplan, N. Vogelzang
Journal: Journal of Clinical Oncology (2006)

4573 Background: The treatment of patients with a rising PSA after definitive local therapy is controversial. Patients are reluctant to undergo androgen suppression due to side effects and interest focuses on the timing and intensity of additional therapy. The use of peripheral androgen blockade in this setting is appealing. Methods: Patients with a rising PSA after definitive local therapy were enrolled in a multi-institutional trial. Accrual of 101 patients lasted from Sept 30, 1998 to July 16, 2001. All patients had undergone previous definitive local therapy at least 1 year, and no more than 10 years prior to enrollment. All patients had a repeated rising PSA, above 1 ng/ml, with no detectable evidence of recurrent disease. CT and bone scans were negative. Patients received a combination of oral therapy consisting of Finasteride, at a dose of 5 mg/day, and Flutamide, at a dose of 250 mg TID. Results: The median age was 71, with a median baseline testosterone level of 322 ng/dl. A &gt;80% PSA decline was seen in 91/94, (97%) of the patients. Three other patients had PSA declines of 77%, 73% and 38%, all of which were maintained for at least 28 days. The median time to PSA nadir was 3.2 months. The current median follow-up is 59 months. To date, only 22 patients have progressed, with 47 patients still on peripheral androgen blockade. Eight patients have died without progression, and 22 patients went off therapy for other reasons not related to progression. Also noted were patients showing PSA responses to Flutamide withdrawal, and per protocol remaining on Finasteride. Toxicity to date remains very mild. Conclusions: Peripheral androgen blockade showed excellent activity produced durable PSA responses in this select group of patients. While the clinical significance of a decline in PSA alone is not fully understood_the durability of these PSA responses is encouraging. The median duration of progression free survival and overall survival has not been reached, and is likely to be longer than five years. Quality of life data is undergoing further analysis. This report supports further study of less aggressive treatments for patients who have only a rising PSA after definitive local therapy. No significant financial relationships to disclose.
Brain metastases in breast cancer patients: Differences in survival depending on biological subtype and RPA RTOG prognostic class
Authors: A. Niwinska, M. Murawska
Journal: Journal of Clinical Oncology (2008)

1056 Background: The aim of the study was to perform a comprehensive analysis of breast cancer patients with brain metastases and to compare survivals depending on biological subtype and RPA RTOG prognostic class. Methods: The group of 222 consecutive breast cancer pts with brain metastases treated in one institution in the year 2003–2006 was analyzed. Clinical characteristics and survivals were analyzed in the entire group, in 3 RPA RTOG prognostic classes and in 3 biological subgroups formed based on the level of estrogen (ER), progesterone (PR) and HER2 receptors as follow: triple-negative (ER-, PR-, HER2-), HER2-positive (HER2+++ in IHC or HER2 amplification) and ER and/or PR(+) HER2(-) breast cancer. The following factors were analyzed in a Cox model in order to identify factors influencing survival from brain metastases: initial TNM stage, histological type and grade, visceral metastases, RTOG prognostic class, biological subtype and systemic treatment after WBRT. Results: The proportion of pts with triple-negative, HER2-positive and ER/PR positive HER2-negative breast cancer pts was 57 (28%), 109 (53%) and 39 (19%), respectively. Median survival calculated from brain metastases in biological subgroups was as follows: triple-negative - 3.7 months, HER2-positive - 9 months and ER/PR positive HER2-negative - 15 months (p=0.015). Median overall survival in 3 subgroups was 2.8, 4.3 and 5.4 years, respectively (p=0.025). Median survival from brain metastases in RPA RTOG I, II and III prognostic class was 15, 11 and 3 months (p=0.0000) and in pts with and without systemic treatment after WBRT - 11 and 3 months, respectively (p=0.0001). Cox multivariate analysis revealed RPA RTOG prognostic class (HR=3.4), visceral metastases (HR 1.4) and systemic treatment after WBRT (HR =0.59) as the most important factors influencing survival calculated from brain metastases. Conclusions: Patients with brain metastases are a heterogenous group with a different outcome. In triple-negative breast cancer pts the shortest survival was observed. Poor performance status, visceral metastases and lack of systemic therapy after WBRT were the most important factors worsening survival. No significant financial relationships to disclose.
Endocrine maintenance therapy in luminal breast cancer.
Authors: Lorenzo Gerratana, Marta Bonotto, Marika Cinausero, Donatella Iacono, Gianpiero Fasola, Fabio Puglisi
Journal: Journal of Clinical Oncology (2015)

e11578 Background: Patients with hormone receptor-positive metastatic breast cancer (Luminal MBC) are appropriate candidates for endocrine therapy (ET). Anyway, it is not established when to use ET versus chemotherapy (CT) as initial treatment for these patients. CT is generally preferred for symptomatic patients with heavy tumor burden involving visceral organs. Maintenance therapy with ET (CT- > ET) is a strategy option after initial CT regimen. The optimal duration of CT and role of maintenance therapy for MBC are still matter of debate. The aim of this study is to explore differences between cohorts of patients treated at fist line with CT or CT- > ET in real world scenario. Methods: The study included 434 consecutive patients with Luminal MBC treated at University Hospital of Udine, Italy from 2004 to 2014. We estimated overall survival (OS), progression free survival (PFS) and post progression survival (PPS). Clinico-pathological data were analyzed to investigate the association with first-line treatment strategy (ET, CT, CT- > ET). Results: First-line CT was chosen for 40% (173) of the whole Luminal B patients. Among these, 42% (72/173) received ET maintenance therapy. Median OS in CT and CT- > ET cohorts was 26.4 and 51.5 months, respectively (log-rank test, p < 0.0001). Median PFS was 5.8 months for CT cohort and 18.3 months for CT- > ET cohort (log-rank test, p < 0.0001). Median PPS of CT and CT- > ET cohort was 16.3 and 26.0 months, respectively (log-rank test, p < 0.09). The following variables were tested for association with treatment strategy: BC immunophenotype, visceral metastases, bone-only localization, number of metastatic sites, body mass index, menopausal status, age, ECOG performance status. No statistically significant associations were identified. Nevertheless, having a de novo metastatic disease was associated with ET maintenance treatment (OR 2.32, 95%CI 1.20-4.47; p = 0.012). Conclusions: Patients that received ET maintenance showed a better prognosis in terms of PFS and OS. No differences in clinico-pathological characteristics were observed between therapy groups with the exception of having a de novo metastatic disease which seemed to be associated with ET maintenance.
Prognostic factors for glioblastoma (GBM) in individuals age 70 and older: A study of 446 patients from two tertiary centers.
Authors: J. G. Scott, S. T. Chao, J. H. Suh, A. Cooper, A. S. Reiner, L. Nayak, K. Panageas, L. E. Abrey, F. M. Iwamoto
Journal: Journal of Clinical Oncology (2010)

2034 Background: Incidence of GBM is highest in the elderly. However, this population is understudied and the commonly used prognostic stratification methods, such as the RTOG recursive partitioning analysis (RPA), did not include patients above 70 years of age. Methods: The Memorial Sloan-Kettering Cancer Center and Cleveland Clinic institutional databases were used to identify patients with histologically confirmed GBM who were 70 years or older at diagnosis. Demographic variables, performance status, clinical presentation, tumor characteristics/location and extent of resection were evaluated as potential prognostic factors. Multivariate analyses were performed using Cox model to identify variables independently predictive of survival outcomes in a stepwise fashion. RPA sequentially divided patients into homogenous groups in terms of prognosis in a stepwise fashion; standard tree pruning methods were then applied. Results: 446 GBM patients with a median age of 75 years (range, 70 to 99 years) were included. The median overall survival was 5.7 months (95% CI, 5.3 to 6.4) and 92% of patients had died at the time of analysis. 36% underwent biopsy only while 43% had partial resection and 21% gross total resection (GTR); 72% received RT and 34% upfront adjuvant chemotherapy. In multivariate analysis, older age (HR = 1.06 for each 1-year increase, 95% CI: 1.03-1.08, p < 0.0001), KPS ≤ 60 (HR = 1.71, 95% CI: 1.37-2.13, p < 0.0001), mental status changes at presentation (HR = 1.28, 95% CI:1.04-1.57, p = 0.02), multifocal disease (HR = 1.37, 95% CI:1.00-1.88, p = 0.05) and corpus callosum location (HR = 1.86, 95% CI:1.19-2.90, p = 0.006) were associated with increased death risk while partial resection (HR = 0.46, 95%CI:0.37-0.59, p < 0.0001), GTR (HR = 0.33, 95% CI:0.24-0.45, p < 0.0001) and radiation to 5,000 cGy or higher (n = 205, HR = 0.68, 95%CI:0.51-0.92, p = 0.01) were associated with improved survival. A RPA model for GBM patients 70 and older will be presented. Conclusions: Elderly patients are often left out of similar prognostic studies but advancing age, KPS and extent of therapy are important prognostic factors in this population. Our prognostic scheme needs validation by ongoing clinical trials. No significant financial relationships to disclose.
Statins and prostate cancer risk: A large case control study in veterans
Authors: R. Singal, V. Khurana, G. Caldito, C. Fort
Journal: Journal of Clinical Oncology (2005)

1004 Background: Hydroxymethylglutaryl-CoA reductase inhibitors (statins)are commonly used to control high cholesterol. These agents that have been shown to induce apoptosis and inhibiting tumour growth and metastasis in human cancer cell lines and animal tumour models. We studied the association of prostate cancer and statins in veterans. Methods: VISN 16 data warehouse, which contains clinical and demographic information about all veterans (>1.4 million patients) cared for at the 10 VA Medical Centers in 4 states comprising the South Central VA health Care Network in the mid-south region of the US, was queried from Oct 1998 to June 2004. Retrospective case control design was used. The primary variable of interest was prostate cancer (ICD-9 code 185) and the use of statins prior to the diagnosis of prostate cancer. Multivariate logistic regression analysis was done to adjust for covariates including age, body mass index, smoking, diabetes, and race. Statistical analysis was performed using SAS software version 9.0 (Chicago, IL). Results: A total of 443,805 patients were evaluated and of these, 159,874 were on statins. A total of 26,139 were diagnosed with prostate cancer. Statin use was associated with a significant protective effect for prostate cancer (Odds ratio 0.46, 95% CI 0.45 to 0.48). The risk factors associated with an increased risk of prostate cancer included age (OR 1.082, 95% CI 1.081 to 1.084), body mass index (OR 1.015, 95% CI 1.012 to 1.018), smoking (OR 1.13, 95% CI 1.07 to 1.120), diabetes (OR 1.09, 95% CI 1.06 to 1.13), and race - blacks vs whites (OR 1.57, 95% CI 1.50 to 1.63). Conclusions: Statins are protective against the development of prostate cancer after controlling for age, body mass index, smoking, diabetes, and race. An internal consistency of the database is reflected by an increased risk associated with other documented risk facors such as age, race etc. Our data should be evaluated with caution, given the limitations of the population, the database, and this being a case control study. Dose, duration, and particular statin used were not factored into the analysis. If these results are confirmed in a large prospective study they may provide necessary evidence to consider the use of statin drugs in prostate cancer prevention. No significant financial relationships to disclose.
Phase III study of intermitent monotherapy versus continuous combined androgen deprivation
Authors: F. E. Calais da silva, F. M. Calais da Silva, F. Gonçalves, A. Santos, J. Kliment, N. Antoniou, S. Pastidis
Journal: Journal of Clinical Oncology (2007)

5125 Background: The intermittent monotherapy vs continuous combined androgen deprivation using an LHRH analogue and ciproterone acetate and associated components of quality of life. Methods: 854 patients (aged 44–81, mean 72) have been randomised (419 to Continuous and 435 to Intermittent). 350 patients have been randomised in the last years and the study is close to the target sample size 900 patients. The median PSA at randomisation is 1.0 ng/ml ranging from 0.1 to 4. 48 % of patients have a PSA less than 1 ng/ml at randomisation. Results: 1,000 men with a median PSA of 15.9ng/ml were registered between October 1999 and October 2006. 24% of registered patients have a PSA less than 10ng/ml; 39.3% of registered patients have a PSA greater than 20 ng/ml. 90.1% have a T3 tumour and only 13.5% have metastatic prostate cancer. After randomisation, sexual activity increases in the intermittent group to 32% (6 months), 32% (12 months), 24% (24 months) while in the Continuous arm the corresponding percentages are 19%, 20%, 6%, respectively. Among the 435 Intermittent patients only 18% returned to therapy within one year of randomisation because of symptoms or an increase in PSA and 40% have yet to return to therapy within 4 years of randomisation. An estimated 82% (95% Confidence Interval 79%, 87%) of patients have remained free of therapy for at least one year and 60% (95% CI 53%, 68%) for at least 2 years. Patients whose PSA reduces to less than 1 ng/ml at randomisation are off therapy longer than those whose PSA is between 1 and 4 ng/ml (p&lt;0.05). 80% of patients with PSA &lt; 1 ng are off therapy for at least 1.5 years whereas 80% with PSA between 1 and 4 ng/ml are off therapy for at least 9 months. 60% of patients with PSA &lt; 1 ng/ml are off therapy for 2.5 years while 60 % of patients with PSA 1–4 ng/ml are off therapy for 1.5 years. Among the 142 Intermittent patients who returned to therapy because of an increase in PSA or symptoms the median time on therapy was 16.7 weeks (95% CI 15.0, 22.1). The time on therapy did not depend upon PSA at randomisation, p=0.17. The median follow up period is 2.8 years. Conclusions: The early results from this trial are promising and are in line with previous studies of intermittent therapy. It is too early for any progression data. No significant financial relationships to disclose.
Constitutive Expression of CD40L on Bone Marrow Mast Cells Supports the Growth of Lymphoplasmacytic Cells in Patients with Waldenstrom’s Macroglobulinemia.
Authors: Olivier Tournilhac, Daniel Ditzel Santos, Lian Xu, Jeffery Kutok, Yu Tsu Tai, Steven Le Gouill, Evdoxia Hatjiharissi, Laurie Catley, Zachary Hunter, Andrew Branagan, Kenneth C. Anderson, Steven P. Treon
Journal: Blood (2004)
Oral morphine versus oral midazolam as upfront therapy to relief dyspnea in ambulatory cancer patients while its underlying cause is sought or treated
Authors: L. C. Cerchietti, A. H. Navigante, M. A. Castro
Journal: Journal of Clinical Oncology (2008)

9585 Background: By analogy with the approach taken to treat cancer pain, we designed this study to assess the safety and efficacy of oral morphine (MO) vs oral midazolam (MDZ) to relief cancer-related dyspnea while its underlying cause is sought or treated. Methods: Sixty-one ambulatory pts with advanced cancer (not actively treated) and dyspnea (as sole symptom) were initially assessed by physical examination, symptom characterization and grading, oxymetry and chest X-ray, and then randomized to receive either MO or MDZ. A fast titration scheme was implemented with starting doses of 2 mg for MDZ and 3 mg for MO, with incremental steps of 25% every 30 min. Unless dyspnea intensity reduced at least 50%, they received the next step dose. If dyspnea was not reduced after 2 incremental steps or adverse events appeared, patients were excluded as failure. If dyspnea was reduced by at least 50%, patients were medicated with the effective dose q.i.d. plus rescues as needed. Pts were followed for 5 days while the underlying causes of dyspnea were sought or treated. Dyspnea intensity, episodes of breakthrough dyspnea (EBD), number of rescues and adverse events were recorded. Results: Thirty pts with dyspnea entered MO and 31 pts entered MDZ (median intensity: 9 for both). 59 pts completed the study; one pt from each group withdrew. 10/19 pts were medicated with baseline dose, 13/9 with step one and 6/2 with step-two in the MO/MDZ groups resp. Median dyspnea intensity were: 6/3 (day 2), 7/4 (day 3), 6/3 (day 4) and 6/2 (day 5), for MO and MDZ resp (p<0.005 for the all comparisons). Mean EBD were: 1.5/1 (day 2), 1.7/0.9 (day 3), 2/1 (day 4), and 3/0.7 (day 5), for MO and MDZ resp (p<0.002 for day 5). Pts presented a median of 2.5 concurrent causes of dyspnea in both groups (range: 1–7). Main causes were lymphangitis, lung tumor and pleural effusion, in both groups. Neither MDZ nor MO interfered with the dyspnea evaluation or specific treatment (SRx). During the evaluation week, 31% and 27% of pts in MO and MDZ groups received SRx, however all of them continued with their assigned symptomatic treatment. Conclusions: It was safe to symptomatically treat pts with dyspnea while its underlying cause was being sought and/or treated. In this setting, MDZ is more effective than MO. No significant financial relationships to disclose.