tbuckley/cabot-search huggingface dataset:
Preoperative oxaliplatin (O), capecitabine (X), and external beam radiotherapy (RT) in patients (pts) with newly diagnosed, primary operable, locally advanced rectal cancer (LARC)
Authors: D. Öfner, A. de Vries, J. Thaler, W. Eisterer, R. Greil, P. Lukas, H. Rabl, H. Samonigg, K. Kapp, M. Gnant
Journal: Journal of Clinical Oncology (2007)

14527 Background: Local recurrence after surgery is a cause of treatment failure and relapse in pts with LARC. Preoperative RT decreases local recurrence but not distant spread. X and O are both highly active chemotherapies for advanced colorectal cancer, particularly in combination, and both are radiosensitizers. Therefore, the addition of X and O to preoperative RT should improve efficacy in terms of local control and prevention of metastases. Methods: This study investigated the efficacy (rate of downstaging) and safety of preoperative chemoradiation in pts with LARC (of lower and middle rectum), T3NxM0 staged by MRT. RT was administered for 5 weeks, 5 days/week, 1.8 Gy/fraction, total dose 45 Gy, 3D conformation technique, in combination with O 50 mg/m 2 intravenously on days 1, 8, 15, and 22, and oral X 825 mg/m 2 twice a day on RT-days during weeks 1–4. Surgery was performed 14–28 days after completion of RT. Results: 59 pts were enrolled (19 female, 40 male); median age 61 years (range 34–76), 100% of pts are evaluable for efficacy and toxicity. 41 patients had comorbidities: 16 cardiac, 3 hepatic, 6 diabetes, 1 neurological/psychological, 49 others. Tumor downstaging was observed in 53% of pts (23 T2, 2 T1, 6 T0). 5 pts withdrew because of adverse events. 28 pts (47%) experienced grade 1 neurotoxicity and 5 pts (8%) had grade 2 neurotoxicity. The most frequent grade 3/4 NCI-CTC adverse event was diarrhea: 5/59 pts (8%). Total O and X doses received were 90% and 93% of the planned doses, respectively. The main reason for chemotherapy dose reduction was diarrhea occurring during the 3rd-4th week of treatment. Per-protocol therapy was terminated for 8 pts due to interruption of RT for more than 3 days or adverse events such as diarrhea and nausea (total dose received 25.2–34.2 Gy). Conclusions: These results demonstrate that preoperative O and X in combination with RT is feasible in pts with LARC, and comparable with 5-FU. As expected, the only clinically relevant toxicity was diarrhea, and dose intensity of both chemotherapeutic agents and RT was high. [Table: see text]
New combinations of anthracyclines, cisplatin, and metronomic capecitabine as preoperative chemotherapy for operable and locally advanced breast cancer: First data of efficacy and tolerability.
Authors: L. Orlando, P. Fedele, P. Schiavone, E. Mazzoni, M. Cinefra, M. D'amico, S. Burlizzi, M. Portaluri, M. Criscuolo, S. Cinieri
Journal: Journal of Clinical Oncology (2010)

e11017 Background: The goal of preoperative therapy is the achievement of pathological complete remission (pCR). We report the data of activity and tolerability of two anthracycline-containing regimens ECX and MCX with the introduction of metronomic oral fluoropyrimidine capecitabine as preoperative therapy for large operable and locally advanced breast cancer. Methods: Pts with operable (T2-T3) or locally advanced breast cancer (T4, N2-N3) were sequentially treated with 2 multimodality regimens including day 1: Epirubicin 50 mg/m2, cisplatin 60 mg/m2 and capecitabine 1,500 mg die continuously (ECX) or day 1: non pegilated lyposomal anthracicline 50 mg/m2, cisplatin 60 mg/m2 and capecitabine 1,500 mg die continuously (MCX) for 6 courses followed by surgery and radiotherapy. In endocrine-responsive pts concurrent letrozole if post or triptorelin if premenopausal were given. All pts had a core biopsy and a basal surgical evaluation. Results: 11 and 13 (24) pts were treated with ECX and MCX regimen respectively. Median age was 51 yrs (range 29-71), premenopausal 44%. At the core biopsy: ER and/or PgR > 1% in 60%, Ki-67 expression ≥ 20% in 67%, c-erbB-2 3+ in 16% (all in ECX group). Greater clinical stage at diagnosis was more represented in MCX group (IIIA in 23%, IIIB in 30%, IIIC in 15%) than in ECX group (IIIA in 27%, IIIB in 18%). 23 pts underwent surgery and are evaluable for response.There were 4 pCR (33%), 9 partial remissions (PR) (75%) and 3 clinical complete remissions (CR) (25%) in the MCX group.There were 2 pCR (18%), 9 PR (81%) and 1 CR (9%) in the ECX group.6 pts in MCX group and 5 in ECX group received breast conserving surgery. In MCX group,the worst toxicity was non febrile G4 neutropenia in 2 pts (15%), G3 anemia in 1 (8%), nausea/emesis G2 in 6 (46%) and alopecia in 4 (30%). In ECX group worst toxicity was G3 neutropenia in 2 pts (18%), nausea/emesis G2 in 5 (72%), alopecia G2 in 10 (90%), renal toxicity in 1 (9%). Conclusions: These combinations of chemotherapy are effective.The possibility to combine oral fluoropyrimidine capecitabine in anthracyclines-containing regimens is promising in terms of clinical activity and safety. No significant financial relationships to disclose.
Prospective, randomized phase III study comparing two intensified regimens (methotrexate/vinblastine/doxorubicin hydrochloride/cisplatin [MVAC] versus gemcitabine/cisplatin) in patients with inoperable or recurrent urothelial cancer.
Authors: A. Bamias, A. Karadimou, S. Lampaki, G. Aravantinos, I. Xanthakis, C. Papandreou, G. Lainakis, F. Zagouri, N. Soupos, E. Kostouros, E. Samantas, C. Hatzimouratidis, C. Konstantinidis, C. Deliveliotis, D. G. Pectasides, G. Fountzilas, M. A. Dimopoulos
Journal: Journal of Clinical Oncology (2011)

4510 Background: The combinations of methotrexate, vinblastine, doxorubicin hydrochloride (Adriamycin), cisplatin (MVAC) and gemcitabine, cisplatin (GC) are standard regimens for advanced urothelial cancer. Dose-dense (DD) MVAC prolonged progression-free survival (PFS) compared to classic MVAC (Sternberg 2001). Recent data also suggested a benefit by increased gemcitabine dose density (Sternberg 2001). Methods: We initiated a phase III, randomized study of DD MVAC (M 30mg/m2, V 3mg/m2, A 30mg/m2, C 70mg/m2 q 2 wks) vs. DD GC (G 2500mg/m2, C 70mg/m2 q 2 wks) (with G-CSF). Patients with advanced transitional cell urothelial carcinoma, PS < 2 and CrCl > 50 were eligible. Accrual closed at 130 patients. This analysis also includes 61 patients who subsequently received DD MVAC, in order to increase the statistical power. Selection criteria, doses and follow-up were identical to that of the randomized study. Results: 174 eligible patients were analysed: DD MVAC (n=118) and DD GC (n=57). Groups were well balanced for baseline characteristics, although a non-significant higher frequency of PS 0 (64% vs. 46%, p=0.064) was noted in the MVAC arm. Median fup was 39 months. Efficacy results were similar (Table). Nevertheless, subgroup analysis suggested a superiority of DD GC among patients with PS 1 (Table). This interaction was significant (p=0.018 for OS and 0.083 for PFS). Grade 3/4 toxicities included myelosuppression (48% vs. 42%), neutropenic infections (12% vs. 8%), GI (15% vs. 6%), and constitutional symptoms (14% vs. 6%). Conclusions: DD GC was not superior to DD MVAC but a benefit in symptomatic patients by DD GC was suggested. DD GC is more convenient than the conventional weekly GC and could be an alternative to the existing standards for advanced urothelial cancer. Efficacy results per treatment arm overall and according to PS. DD MVAC DD GC P value Responses 47.4% 47.4% 0.9 OS (months) Median (95% CI) 18.4 (12.2-24.6) 20.7 (12.9-28.5) 0.7 HR (95% CI) PS 0 1 1.22 (0.68-2.18) 0.5 PS 1 1 0.47 (0.28-0.89) 0.018 PFS (months) Median (95% CI) 8.5 (6.6-10.4) 7.8 (6.1-9.5) 0.6 HR (95% CI) PS 0 1 1.11 (0.64-1.92) 0.7 PS 1 1 0.60 (0.35-1.03) 0.066
Ph IB study of LEE011 and BYL719 in combination with letrozole in ER+, HER2- breast cancer.
Authors: Pamela N. Munster, Erika Paige Hamilton, Laura G. Estevez, Richard H. De Boer, Ingrid A. Mayer, Mario Campone, Shizuka Asano, Suraj Bhansali, Vickie Zhang, Becker Hewes, Dejan Juric
Journal: Journal of Clinical Oncology (2014)

143 Background: Activation of the PI3K/AKT/mTOR and cyclin D–CDK4/6–INK4–Rb pathways has been implicated in endocrine therapy resistance in pts with advanced HR+ breast cancer (BC). BYL719 (BYL), an α-isoform selective PI3K inhibitor and LEE011 (LEE), a CDK4/6 inhibitor have demonstrated clinical activity in pts with advanced HR+ BC and advanced solid tumors, respectively. In preclinical HR+ BC models, the combination of LEE, BYL, and letrozole (LET) had enhanced antitumor activity vs either agent alone. Here we report results from Arm (A)1 (LEE + LET) and A2 (BYL + LET) of the Ph Ib part of a Ph Ib/II, 3-arm study of LEE, BYL, and LET in pts with advanced ER+ BC (CLEE011X2107/NCT01872260). Methods: Postmenopausal women with advanced ER+, HER2− BC receive daily oral doses of LEE (3-wks on/1-wk off; A1) or BYL (continuous; A2), plus fixed, daily LET (2.5 mg, continuous), as part of a 28-day cycle. Primary objective: determine the MTD and/or RP2D of A1 and A2. Dose escalation is guided by a Bayesian Logistic Regression Model using the escalation with overdose control principle and real-time PK. Safety and preliminary efficacy are also assessed. Results: As of March 28, 2014, 10 pts have been treated with 600 mg LEE + LET (A1), and 7 pts with 300 mg BYL + LET (A2). One DLT was observed (A1: Grade [G]4 neutropenia; data cut-off: May 15). Common (all grade &gt;30%) study drug-related AEs (all grade/G3–4) were: A1: neutropenia (90%/50%) and nausea (40%/0%); A2: hyperglycemia (57%/14%), decreased appetite, diarrhea, and nausea (43%/0% each). PK for LEE and BYL on Days 1 and 21, and LET on Day 1, are comparable to historic single-agent data. PK of LET at steady state is being evaluated. In A1, 6 pts had known responses: 1 PR, 2 SD, 1 NCRNPD, and 2 PD. In A2 5 pts had known responses: 2 SD, and 3 NCRNPD. Conclusions: LET plus LEE or BYL had an acceptable safety profile and preliminary signs of clinical activity have been observed. Upon determination of the MTD/RP2D in A1 and A2, enrollment into A3 (LEE + BYL + LET) will commence. The randomized Ph II part of the trial will compare LET + LEE or BYL with LET + LEE + BYL. MONALEESA-2 (CLEE011A2301/NCT01958021), a Ph III, randomized, double-blind, placebo-controlled study of LEE + LET in untreated advanced HR+ BC is currently recruiting pts. Clinical trial information: NCT01872260.
Improvement in DAS28 response through one-year of golimumab treatment in patients with active RA despite treatment with methotrexate: A phase II, randomized, double blind, placebo controlled, dose ranging trial
Authors: J. Kay, Patrick Durez, E. L. Matteson, B. Dasgupta, P. Nash, S. Hall, E. C. Hsia, P. Chiruvolu, J. Han, M. U. Rahman
Journal: Annals of the Rheumatic Diseases (2007)
Endometrial carcinoma (EC) in women 35 years of age or younger
Authors: R. Ali-Fehmi, M. Cote, M. H. Arabi, A. Munkarah, V. Schimp, C. Bryant, R. Morris
Journal: Journal of Clinical Oncology (2007)

16000 Background: Although the majority of women with EC are postmenopausal, 25% are under the age of 50 years at the time of diagnosis. The aim of this study is to describe the demographic and survival data for women presenting with EC at age 35 years or younger (YOY). Design: Patients with a diagnosis of EC were identified from the Surveillance, Epidemiology, and End Results (SEER) cancer database from 1988 to 2003. Demographic and pathologic data were collected. Chi-square and t-tests were used to examine differences between the younger and older women, and survival analyses were performed using Kaplan Meier and Cox regression models. Results: Of the 61,364 women diagnosed with EC in the study period, 931 patients 1.5% were 35 YOY. Compared to women 36 years of age or older at diagnosis, the young-onset women were more diverse in terms of race/ethnicity (p&lt;0.0001), with white women comprising 48% of the younger population, and 80.4% of the older population. Hispanic 23.7%, black 8.3%, and other race/ethnicities 18.4% were more common in the younger age group. The mean age in the young population was 31.5 years. Mean age at diagnosis was greater for the young whites compared to the other racial groups combined (32.0 years vs. 31.0 years, p&lt;&lt;zemphx&gt;0.0001). Younger women were more likely to be diagnosed in earlier stages and grades compared to their older counterparts (both p&lt;0.0001). The overall stage by AJCC in younger women was 75.4%, 6.6%, 4.1% and 5.2% (stages I-IV, respectively), with 8.7% unstaged. In the younger women, 54.6%, 26.3%, and 9.5% of grade 1, 2, and 3 tumors were reported, respectively. Type II tumors comprised 4% (N=36) of the study population. The overall mean survival was significantly better for younger (75.4 months, 95% CI 71.8–79.0) compared to older women (66.6 months, 95% CI 66.2–67.0). The survival difference was seen for every AJCC stage of disease. Conclusions: The changing race and ethnicity demographics in the US, coupled with the increase in obesity, suggest that EC incidence may be on the rise in younger women. Early stage, well-differentiated EC represents the most common type of EC in the younger patients. As treatment standards differ for younger women who hope to preserve their fertility, it is important to follow the long-term outcomes in this group. No significant financial relationships to disclose.
Primary orbital lymphoma -A review of 25 cases from India
Authors: G. Narayanan, K. Ratheesan, J. Madhavan, B. Rajan
Journal: Journal of Clinical Oncology (2004)

6721 Primary orbital Non Hodgkin's lymphoma (NHL) accounts for about .01% of all lymphomas and 10% of all orbital tumors. Aim: The purpose of this study is to review our Institutional experience with primary orbital lymphoma. Material and Methods: Between 1995–2000, twenty-five patients were treated for orbital lymphoma at our Institute. These patients' data was reviewed. All patients had biopsy proven NHL. Results: The median age at diagnosis was 48 years (range 19–83), there were 17 males and 8 females. The commonest presenting features were swelling and proptosis. The median duration of symptoms was 12 months. The sites of involvement were eye lid (7), lacrimal gland (3), conjunctiva (3) and the entire orbit was involved in 12. The right eye was affected in 13, left in 10 and both eyes in 2 patients. Five patients presented to us when the disease recurred. The histology was low grade in 9 patients, intermediate or high grade in 16 including 2 with mantle cell lymphoma and 1 with MALT lymphoma. Thirteen patients underwent either complete or subtotal excision. Fifteen patients received radiotherapy, the dose ranged from 20–50 Gy with a median of 40 Gy, 2/3 rd received a dose of 40–45Gy. The major complication was cataract. Chemotherapy was given to 7 patients (CHOP, COP, Leukeran). Four patients recurred either locally or in the opposite eye and received chemotherapy or radiotherapy. The median survival of the series is 48 months, eight patients are alive for more than 5 years. Conclusions: Orbital lymphoma is curable, and radiotherapy is a safe and effective local treatment in the management. No significant financial relationships to disclose.
Diagnostic accuracy of multi detector-row computed tomography (MDCT) and endoscopic ultrasound (EUS) for clinical N staging in early gastric cancer.
Authors: Eun Hyo Jin, Dong Ho Lee, Ji Yeon Seo, Hyuk Yoon, Cheol Min Shin, Nayoung Kim, Young Soo Park, Hyun Chae Jung
Journal: Journal of Clinical Oncology (2015)

17 Background: An accurate preoperative assessment of potential lymph node metastasis is useful in the decision for the treatment strategy of early gastric cancer. The aim of this study was to retrospectively evaluate the accuracy of preoperative assessment of lymph node status with multi detector-row computed tomography (MDCT) and endoscopic ultrasound (EUS). Methods: We had analyzed 1,104 patients with early gastric cancer who underwent gastrectomy with lymph-node dissection at Seoul National University Bundang Hospital from May 2003 to July 2011. Patients were underwent preoperative MDCT in 1,104 and EUS in 1,028. Lymph nodes were considered positive for metastasis if they were larger than 8mm in the short axis diameter of MDCT. The criteria of EUS for metastatic lymph nodes are rounded nodes larger than 8 mm diameter with hypoechogenicity. The clinical N staging of preoperative MDCT and EUS was compared to the postoperative pathological finding. Results: The overall diagnostic accuracy of MDCT and EUS for determining lymph node metastasis was 89.1% and 90.5%. In MDCT, the rate of overestimation of lymph node metastasis was 8.20% (91/1104) and underestimation was 8.7% (96/1104). Tumor size (&gt;2cm) was significant related with overestimation (p=0.007). Underestimation of clinical N staging was related with female (p=0.025, OR 2.025), lymphovascular invasion (p&lt;0.0001, OR 7.807), positive EGFR (p=0.015, OR 2.566) and tumor size (&gt;2cm) (p=0.009, OR 3.221). In EUS, overestimated lymph node metastasis was 5.40% (56/1028) and underestimation was 9.6% (99/1028). No factor was significantly related with overestimation. Underestimation of lymph node metastasis was related with female (p=0.020, OR 2.049), lymphovascular invasion (p&lt;0.0001, OR 11.716), positive EGFR (p=0.024, OR 2.489) and tumor size (&gt;2cm) (p=0.020, OR 2.774). Conclusions: For preoperative assessment of lymph node metastasis in early gastric cancer, MDCT and EUS showed high diagnostic accuracy. Both MDCT and EUS, female, lymphovascular invasion, positive EGFR, large tumor size (&gt;2cm) were related to underestimation of clinical N staging. We proposed that careful attention is required to choose treatment based on clinical N staging by MDCT and EUS.
Characterizing the risk of drug-drug interactions in patients receiving enzalutamide for castration-resistant prostate cancer.
Authors: Esther K. Lee, Rehana Jamani, Scott R. Berry, Carlo DeAngelis, Angie Giotis, Urban Emmenegger
Journal: Journal of Clinical Oncology (2015)

261 Background: Enzalutamide (E) is an androgen receptor antagonist used to treat castration-resistant prostate cancer (CRPC). It inhibits various cytochromes (e.g. CYP2C8), or induces others (e.g. CYP3A4). Since these CYPs are involved in the metabolism of other widely-used medications, E may expose a significant number of patients to drug-drug interactions (DDI). These DDI may diminish the efficacy of E or concurrent medications, or they may increase the risk of DDI-related adverse events (AE); but the scale of E-related DDI is not yet established. Methods: We retrospectively reviewed pharmacy records and electronic patient charts to retrieve individual drug histories, comorbidities, and on-treatment AE of CRPC patients starting E between Oct 2012 and Apr 2014. Baseline medications of individual patients were analyzed for potential DDI using two commercial databases, Lexicomp and Micromedex. Results: 69 informative patients were identified. Using Lexicomp, the most common DDI flagged as being of potential clinical significance (i.e. “avoid combination”, or “consider therapy modification”) were with amlodipine, atorvastatin, tamsulosin, ondansetron, and oxycodone administered to 12 (17%), 12 (17%), 10 (14%), 5 (7%), and 5 (7%) patients, respectively. Micromedex identified a moderate risk for amlodipine and oxycodone. At baseline, 38/69 patients (55%; Lexicomp) and 24/69 patients (35%; Micromedex) used ≥ 1 drug at risk for clinically significant DDI with E. The most common AE were fatigue in 36 patients (52%), decreased appetite in 15 (22%), peripheral oedema and weight loss each in 13 (19%), and back pain in 10 (14%). There was no conclusive evidence to link these AE to DDI. One patient had recurring episodes of hypertension, a possible result of a DDI between E and nifedipine (Lexicomp/Micromedex class “avoid”/”major”). Conclusions: The risk of clinically relevant E-related DDI in CRPC patients seems substantial, yet the selection of flagged drugs is database-dependent. Further investigations with larger populations are warranted to understand the clinical relevance of these DDI more clearly.
Preliminary results of a phase II study of continuous low dose metronomic (LDM) cyclophosphamide (CTX) and celecoxib (CEL) for asymptomatic hormone refractory prostate cancer (HRPC) with assessment of anti-angiogenic biomarkers
Authors: S. R. Berry, Y. Ko, U. Emmenegger, Y. Shaked, R. Choo, L. Klotz, L. Zhang, C. Lee, R. Kerbel
Journal: Journal of Clinical Oncology (2007)

14046 Background: LDM CTX is a minimally toxic anti-angiogenic therapy that has demonstrated activity in multiple tumour types including HRPC. Increased Cyclooxygenase 2 (COX 2, a prostaglandin synthase enzyme) expression appears to be a consistent feature of a variety of human tumours, including prostate cancer. COX 2 inhibitors like CEL exhibit anti-tumour activity in pre-clinical studies, at least in part due to their anti-angiogenic activity. Pre-clinical work supports the concept that the combination of selective angiogenesis inhibitors like CEL with metronomic chemotherapy can enhance the effects of these agents on tumour angiogenesis. Methods: Men with asymptomatic HRPC at a single Canadian centre received celecoxib 400 mg po BID and cyclophosphamide 50 mg po daily. The primary efficacy endpoint of this 2 stage phase II study is disease control rate (DCR): 50% PSA response, tumour response or prolonged (=6 mos) PSA or stable measurable disease. This study is also assessing the safety of LDM CTX and CEL as well as potential anti-angiogenic biomarkers in these patients including circulating endothelial cells and their precursors (CEC/P), plasma levels of thrombospondin-1 (TSP-1) and vascular endothelial growth factor (VEGF). Results: Enrollment for the first stage of this study (10 men) has been completed. There were 2 patients with disease control by the a priori criteria: one patient with a partial tumour response (PR) (PR duration 13 mos with PSA stabilization for 12 mos) and one patient that had both prolonged stable PSA (7 mos) and prolonged stable measurable disease (8 mos). In addition, another patient had an unconfirmed PR. The therapy was well tolerated. One patient had angina that responded well to medical therapy but there were no serious arterial-thromboembolic events. One patient developed grade 3 hypertension. All other toxicities were grade 1/2. Data on CEC/P, TSP-1 and VEGF levels will be presented at the meeting. Conclusions: LDM CTX + CEL is a well tolerated therapy in men with asymptomatic HRPC. 2/10 patients achieved disease control in the first stage of the trial, meeting the criteria to proceed to the second stage. [Table: see text]