tbuckley/cabot-search huggingface dataset:
Phase I study of oral S-1 in combination with oxaliplatin (oxali) and bevacizumab (bev) in patients with advanced solid tumors
Authors: J. Zhang, K. Chung, C. Zergebel, P. Urrea, M. Quinones, L. Saltz
Journal: Journal of Clinical Oncology (2007)

4091 Background: S-1 is a novel oral fluoropyrimidine (tegafur, CDHP and potassium oxonate) designed for enhanced DPD inhibition and reduced GI toxicity. Bev and oxali have demonstrated safety and synergistic anti-tumor activity with oral and IV fluoropyrimidines. The primary objective is to investigate the safety and maximum tolerated dose (MTD) of S-1 combined with bevacizumab and oxaliplatin in patients with advanced solid tumors. Secondary objective is to investigate the clinical pharmacokinetics (PK) of the components of S-1 (FT, CDHP, Oxo), 5-FU, a-fluoro-β-alanine, cyanuric acid, uracil, and oxali and to document any antitumor activity. Methods: ECOG 0/1 patients with advanced or metastatic solid tumors received oral S-1 starting at 20 mg/m 2 /dose BID x 14 days (classic 3+3 cohort dose escalation by 5mg/m 2 /dose until MTD), plus fixed doses of bev 7.5 mg/kg IV day 1, and Oxali 130 mg/m 2 IV day 1 of every 3 week cycle, with discontinuation of oxali after 4 cycles. Reintroduction of oxali was allowed upon progression of disease. Toxicity, antitumor activity and PKs were assessed. The MTD was defined as the highest dose level at which &lt; 33% of the patients experience a dose- limiting toxicity (DLT) during the first 2 cycles. Results: Of 22 evaluable patients, 3 patients were treated at 20mg/m 2 S1 and 13 patients were treated at 25mg/m 2 S1 without a DLT. At 30mg/m 2 , two patients experienced a DLT(Grade 3 diarrhea, Grade 4 mucositis). The MTD and recommended phase II dose of S-1 is 25mg/m 2 in combination with oxali and bev. A median of 8 cycles of S-1 were initiated at the 25 mg/m 2 dose level. Common MTD level toxicities included fatigue (62%), nausea (62%) and diarrhea (46%), with no grade 4 toxicities observed. Best responses (RECIST): stable disease(16 patients), partial response (2 patients), non-measurable disease (3 patients). The Day 8 AUC (0–8) of 5-FU at 20/25/30 mg/m 2 dose level were 230±115 hr*ng/ml, 470±172 hr*ng/ml and 502±169 hr*ng/ml, respectively. Conclusions: The MTD combination of 25mg/m 2 S-1, oxali and bev can be given safely. The study will be expanded to test S-1 one week on, one week off schedule in combination with oxali/bev every two weeks. No significant financial relationships to disclose.
BK viral infections in patients treated with alemtuzumab
Authors: K. Sharma, W. H. Wilson, K. Dunleavy, P. M. Shovlin, H. X. Chen, J. E. Janik, J. Gea-Banacloche
Journal: Journal of Clinical Oncology (2007)

3033 Background: Alemtuzumab is a humanized monoclonal antibody against CD52 resulting in profound, prolonged T-cell depletion that may be associated with opportunistic infections and reactivation of latent viruses (e.g., CMV). BK virus is a polyomavirus that infects most humans during childhood and remains latent in the urinary tract. Reactivation of BK virus is an important cause of tubular nephropathy following renal transplantation and hemorrhagic cystitis after allogeneic stem cell transplant. Methods: A single institution pilot trial of alemtuzumab and Dose-Adjusted (D-A) Etoposide, Prednisone, Doxorubicin, Vincristine, and Cyclophosphamide (EPOCH) investigating efficacy and toxicity in chemotherapy naïve aggressive T- and NK-cell lymphomas was undertaken. BK virus was detected in urine by polymerase chain reaction (PCR) methods to quantify genomic copies in pts with dysuria and hemorrhagic cystitis. Results: Four of 20 pts treated with alemtuzumab and DA-EPOCH developed five episodes of hemorrhagic cystitis. One had grade 1 and 2 cystitis, two had grade 2 cystitis and one had grade 3 cystitis. In contrast, only one of over 200 pts treated with EPOCH alone or in combination with rituximab developed hemorrhagic cystitis. Hemorrhagic cystitis occurred at a median of 88 days after initiation of therapy and lasted a median of 22 days. Even if considered an unlikely cause, steps to minimize cyclophosphamide toxicity were taken; in one, mesna was given during the fifth cycle and cyclophosphamide was withheld from the final cycle of therapy. Another received a reduced dose of cyclophosphamide during the final cycle of therapy and the third did not receive the final cycle of therapy altogether. The fourth pt developed hemorrhagic cystitis after completion of therapy. PCR for BK virus showed a median of 8.87 x 10 8 (range 2.3 x 10 5 -8.7 x 10 9 ) genomic copies per ml. Conclusions: Hemorrhagic cystitis secondary to BK virus reactivation may occur following Alemtuzumab therapy. Symptoms tend to abate after 1 to 7 weeks with conservative measures alone. [Table: see text] No significant financial relationships to disclose.
Estrogens and Cancer
Authors: J Rogers
Journal: New England Journal of Medicine (1969)

In the article by Dr. Joseph Rogers Estrogens in the Menopause and Postmenopause publish in the February 13 issue of the Journal he summarily dismisses the problem of estrogens and carcinoma with one sentence and a reference to a 15 year  old paper (Obst. & Gynec.  3:551-572 1954) dealing with the problem of estrogen and its possible carcinogenicity toward the endometrium.  Surely he must be aware of the concern since then on the part of several investigators about the potential effect of estrogen on the acceleration of growth of early or quiescent breast carcinoma.  Moore (New Eng. J. Med 277: 293-296 1967) has called attention to the fact that both progestins and estrogens will stimulate growth of dormant breast metastases.  Emerson and Jessiman (New Eng. J. Med. 254: 252=258 1956) stated that breast cancer in patient under 65 is readily stimulated by estrogens.  Pearson et al. (J.  Clin. Endocrinol. & Metab. 12:926. 1952) showed that cyclic estrogenic stimulation of the lst 1/2 of a normal menstrual cycle is associated with a clearly demonstrable stimulation of the growth of breast carcinoma.  Dr. Rogers has admirably surveyed the literature concerning the equivocal value of estrogenic therapy in osteoporosis and in the prevention and treatment of atherosclerosis.  He has also justly concluded that estrogens supply no Fountain of Youth.  It seems contradictory at least to recognize on the one hand that breast cancer is the leading cause of death in the middle aged female possibly curable only in its early stages and on the other hand to propose for control of hot  flushes the widespread use of a substance widely believed to accelerate its growth.(FULL TEXT)
Biochemical recurrence after capsular violation during robotic assisted radical prostatectomy
Authors: D. B. Samadi, A. Akhavan, D. S. Berkman, S. L. Rusnack, E. Goluboff, A. W. Levinson
Journal: Journal of Clinical Oncology (2008)

16081 Background: A positive surgical margin after radical prostatectomy (RP) in organ confined prostate cancer (pT2) is considered a surgical error. The mechanism and significance of capsular violation may be different between open RP and Robotic Assisted Laparoscopic Prostatectomy (RALP). We compared biochemical disease free survival (BDFS) for RALP patients stratified by margin status. Methods: We reviewed an IRB database of consecutive RALP s. We then compared the BDFS outcomes between those patients who suffered a positive margin (PM) and those who did not, focusing on pT2. To permit adequate follow up we excluded RALPs performed during the last year. BDFS was strictly defined as no PSA≥0.2ng/ml. No pt received adjuvant therapy without a biochemical recurrence. For the purposes of analysis, patients with positive nodes were excluded. Results: 322 patients met inclusion criteria. Mean/median follow-up for the entire cohort was 11.1/10.7mo (range 3.0–41.6). Mean age, BMI and PSA were 60, 26.8, and 6.33 respectively. Gleason distribution was 5 (<1%), 6 (22%), 7 (67%), 8 (6%), and 9 (5%). Pathologic distribution was pT2 248 (77.0%), pT3a 48 (14.9%), pT3b 15 (4.7%), and pT4 11 (3.4%). Overall, 7.8% (25/322) experienced biochemical failure (BF) at a mean/median of 4.1/1.5 months (0.2 - 15.3). BDFS rates by across pathologic stage were pT2 94.8% (235/248), pT3a 87.5% (42/48), pT3b 73.3% (11/15), and pT4 80.0% (8/10). Pathologic stage T2 pts with negative margins (NM) had the same rate of BF, as T2 pts with a PM, [4.4% (9/204) v. 4.5% (2/44) p=0.97] at mean/median 13.0/12.4mo. In multiple linear regression analysis, preoperative PSA >10ng/ml was the most predictive variable of biochemical failure even after adjusting for Gleason sum, pathologic stage, and surgical margin status. Conclusions: There may be a different mechanism between a PM in organ confined open RP pts and RALP pts. In our series of RALPs, only one of 44 pts who were pT2 with a PM suffered BF during followup. At a mean of 13.0mo, BDFS for these pts was 95.5%, and was not significantly different than pT2 pts with a NM. A larger series with longer follow-up will determine whether the oncologic significance of a PM in pT2 RALP patients is different from that of open RP patients. No significant financial relationships to disclose.
Continuous low-dose intravenous lidocaine is effective for visceral pain secondary to peritoneal carcinomatosis in terminal cancer patients
Authors: T. Tanaka, S. Okano, R. Tsukui, M. Tomaru, M. Ueno, M. Tsuchiya, K. Obokata, S. Saigo, T. Ogawa, T. Abe, T. Ikeya
Journal: Journal of Clinical Oncology (2006)

8533 Background: Lidocaine, a local anesthetic, is often used as an anti-arrhythmic and as an analgesic of best support care (BSC) for patients with neuropathic pain. However, little is known about the effect of low-dose lidocaine on the abdominal pain of terminally-ill patients with peritoneal carcinomatosis. Aim: To evaluate whether visceral pain is controlled and activities of daily life (ADL) are improved during continuous lidocaine infusion. Methods: 28 terminally ill patients with peritoneal carcinomatosis due to the gastrointestinal (26) and gynecologic (2) cancers were studied. Despite aggressive pain management with opiates, non-steroidal anti-inflammatory drugs and other adjuvants, debilitating pain persisted. After a test dose of 2mg/kg intravenously, lidocaine was administered at low-doses (0.4 and/or 0.8mg/kg-h) through a vein and continued for more than 24 hours. Pain was quantitated on a faces rating scale from the level 0 (no pain) to 5 (severe pain); doses of opiates, amounts of oral intake, side effects, and ADL were measured before and after lidocaine. Results: Age (mean±SE) was 62±2, and percentage of males was 54%. Patients were not hypercalcemia but were slightly malnutrished (albumin 2.9±0.1g/dl) and anemic (hemoglobin 10.3±0.4g/dl). The duration of lidocaine administration in hospital was 18±3days. Abdominal symptoms improved within 1.2±0.1days after beginning lidocaine, and pain scale decreased from 2.7±0.2 to 0.6±0.2; p&lt;0.001. In 68% of patients, the pain level became zero. Blood concentration of lidocaine at 0.8mg/kg-h was 3.0±0.4μg/ml 1 week later. 68% of patients needed no increase in opiate dosage during lidocaine administration. Waist size did not decrease, however, oral intake increased (p=0.002) during lidocaine administration. No obvious side effects, such as perioral numbness, were seen except for emotional lability noted in 4 patients. 43% patients were able to be discharged for continued end-of-life comfort care with home parenteral nutrition and continuation of lidocaine administration. Conclusions: We suggest that continuous, low-dose intravenous lidocaine is BSC and is a very effective approach for analgesia and improvement of ADL in patients with peritoneal carcinomatosis. No significant financial relationships to disclose.
Abstract P326: Impact of Cardiac Rehabilitation on Depressive Symptomatology in Female Cardiac Patients
Authors: Bharathi Reddy, Kiseok Lee, Nancy Rullo, Donna Cheslik Candy, John P Nicholson
Journal: Circulation (2012)

BACKGROUND: Coronary artery disease (CAD) is the leading cause of mortality in women and is responsible for more than 500,000 lives each year in the United States. Depression and depressive symptomatology in healthy subjects increases cardiovascular mortality in both men and women and its prevalence is exponentially rising in women. Research suggests that participation in a cardiac rehabilitation (CR) program reduces depression. Unfortunately studies have shown that CR is widely underutilized, particularly with significantly lower CR enrollment rates among women. HYPOTHESIS: The aim of this study was to demonstrate the effect of CR in the improvement of depressive symptoms in female cardiac patients after a cardiovascular event enrolled at the Cardiac Health Center (CHC) New York Hospital Queens (NYHQ). METHODS: The study sample comprised of 295 patients who completed 36 visits of CR at CHC NYHQ from 2007-2009. Out of 295 patients (age 66.85 ±10.64), 214 are males (71%) and 81 are females (29%). Mood scores were assessed using the PHQ-9 at the initial visit and again upon completion of the CR program. Of the 81 female patients enrolled, 31 female patients had documented pre and post CR-PHQ scores and of the 214 male patients enrolled, 81male patients had documented pre and post CR-PHQ scores. Using paired t test average mean difference in mood scores was tested. RESULTS: There was a significant decrease in mood scores in female patients (7.57 ± 5.18 to 3.11 ± 4.00, Δ 4.45 p= 0.00) compared to male patients (5.72 ± 5.19 to 2.37 ± 3.95 Δ 3.34 p = 0.00) after the completion of CR. CONCLUSION: The result of this study confirms that both male and female cardiac patients demonstrated significant reduction in depressive symptoms upon completion of CR. Female cardiac patients reported higher levels of depressive symptoms than male cardiac patients at the beginning of CR and exhibited a significant decrease in mood scores at the end of CR. This evidence supports that CR is an effective treatment in the reduction of depressive symptoms among female cardiac patients. Future studies are needed to establish the relationship among gender, CR, and depression. Clearly this is a complex issue and further efforts are needed to institute strategies to increase participation rates among female cardiac patients.
Abstract 10784: Blockade of the Late Na Current Accelerates Electrical Recovery and Restore Diastolic Function in the Aging Heart
Authors: Andrea Sorrentino, Christian Arranto, Sergio Signore, Kazuya Isobe, Ramaswamy Kannappan, Fabio del Ben, Mehrdad Shafaie, Joao Ferreira-Martins, Fumihiro Sanada, Matteo Valle, Barbara Ogorek, Annarosa Leri, Jan Kajstura, Piero Anversa, Marcello Rota
Journal: Circulation (2012)

Cardiovascular disorders in the elderly are partly associated with impaired diastolic function, a condition characterized by elevated filling pressures to maintain left ventricular (LV) volumes and...
Chronic Nicotine Exposure Mediates Resistance to Egfr-Tki in Egfr-Mutated Lung Cancer Via Egfr Signal
Authors: Hidetoshi Hayashi, Yosuke Togashi, Kunio Okamoto, Soichi Fumita, Masato Terashima, Kazuko Sakai, Yoshihiko Fujita, Shuta Tomida, Kazuhiko Nakagawa, Kazuto Nishio
Journal: Annals of Oncology (2014)
The acute-phase protein alpha 1-antitrypsin inhibits growth and proliferation of human early erythroid progenitor cells (burst-forming units-erythroid) and of human erythroleukemic cells (K562) in vitro by interfering with transferrin iron uptake
Authors: I Graziadei, S Gaggl, R Kaserbacher, H Braunsteiner, W Vogel
Journal: Blood (1994)
Gonadal steroid–dependent effects on bone turnover and bone mineral density in men
Authors: Joel S. Finkelstein, Hang Lee, Benjamin Z. Leder, Sherri-Ann M. Burnett-Bowie, David W. Goldstein, Christopher W. Hahn, Sarah C. Hirsch, Alex Linker, Nicholas Perros, Andrew B. Servais, Alexander P. Taylor, Matthew L. Webb, Jonathan M. Youngner, Elaine W. Yu
Journal: Journal of Clinical Investigation (2016)

Severe gonadal steroid deficiency induces bone loss in adult men; however, the specific roles of androgen and estrogen deficiency in hypogonadal bone loss are unclear. Additionally, the threshold levels of testosterone and estradiol that initiate bone loss are uncertain.One hundred ninety-eight healthy men, ages 20-50, received goserelin acetate, which suppresses endogenous gonadal steroid production, and were randomized to treatment with 0, 1.25, 2.5, 5, or 10 grams of testosterone gel daily for 16 weeks. An additional cohort of 202 men was randomized to receive these treatments plus anastrozole, which suppresses conversion of androgens to estrogens. Thirty-seven men served as controls and received placebos for goserelin and testosterone. Changes in bone turnover markers, bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA), and BMD by quantitative computed tomography (QCT) were assessed in all men. Bone microarchitecture was assessed in 100 men.As testosterone dosage decreased, the percent change in C-telopeptide increased. These increases were considerably greater when aromatization of testosterone to estradiol was also suppressed, suggesting effects of both testosterone and estradiol deficiency. Decreases in DXA BMD were observed when aromatization was suppressed but were modest in most groups. QCT spine BMD fell substantially in all testosterone-dose groups in which aromatization was also suppressed, and this decline was independent of testosterone dose. Estradiol deficiency disrupted cortical microarchitecture at peripheral sites. Estradiol levels above 10 pg/ml and testosterone levels above 200 ng/dl were generally sufficient to prevent increases in bone resorption and decreases in BMD in men.Estrogens primarily regulate bone homeostasis in adult men, and testosterone and estradiol levels must decline substantially to impact the skeleton.ClinicalTrials.gov, NCT00114114.AbbVie Inc., AstraZeneca Pharmaceuticals LP, NIH.
Prevalence of secondary causes of bone loss in patients with breast cancer initiating treatment on clinical trials with aromatase inhibitors or bisphosphonates.
Authors: A. Paner, K. S. Albain, P. A. Robinson, E. R. Gaynor, L. DiNunno, P. Camacho, S. S. Lo
Journal: Journal of Clinical Oncology (2010)

e11019 Background: We previously demonstrated that treatable secondary causes of bone loss (SCBL) are prevalent in breast cancer survivors (Camacho, JCO 2008). SCBL may amplify bone loss caused by aromatase inhibitors (AIs) or compromise response to bisphosphonates (BPs). Goals of our study were to determine the frequency of screening for osteoporosis and SCBL in patients (pts) enrolling onto clinical trials involving AIs or BPs, and to determine the prevalence of SCBL in this population. Methods: A retrospective chart review of pts enrolled between 2003-2009 in clinical trials involving treatment with AIs (MA-27, NSABP B-35, SWOG 0226, SOFT, MAP-3) and BPs (SWOG 0307, SWOG 0702) was conducted at a single institution. Charts were reviewed for bone density assessment with dual energy x-ray absorptiometry (DXA scan), and for SCBL including 25OH-vitamin D (25 OHD), parathyroid hormone (PTH) panel, thyroid stimulating hormone (TSH), 24 hr urine for calcium and creatinine. The WHO criteria were used to categorize pts into normal (T score ≥ -1), osteopenia, (T score <-1) and osteoporosis (T score ≤ -2.5) groups. Only MAP-3 study (9 pts) required DXA scan prior to enrollment. None of the studies required screening for SCBL. Results: Ninety-three charts were reviewed (58 on AI trials; 35 on BP trials). Overall 69/93 (74%) pts had DXA scans performed: 52/58 (88%) on AI and 17/35 (49%) on BP trials. Osteopenia was present in 26/52 (50%) pts on AI and 9/17 (53%) pts on BP trials. Ten (11%) pts had osteoporosis. 25 OHD levels were obtained in 45 (48%) pts, PTH in 30 (32%) pts, 24hr urine for calcium and creatinine in 19 (20%) pts, TSH in 29 (31%) pts. Of those pts screened, 24 (53%) had vit D deficiency, 6 (20%) had hyperparathyroidism, 2 (6%) had idiopathic hypercalciuria, and 1 (3%) had hyperthyroidism. Average time to screening for SCBL was 23 months. Conclusions: Osteopenia/porosis is common in patients enrolling onto clinical trials involving AIs and BPs. Screening for treatable SCBL occurs in the minority of patients, though the prevalence is high. Comprehensive evaluation of bone loss may be warranted prior to initiating AI or BP therapy. No significant financial relationships to disclose.
Long-term follow-up of autotransplant (AT)-supported high-dose melphalan (hdm) for multiple myeloma (MM): Update of Intergroup Francophone du Myelome (IFM), Southwest Oncology Group (SWOG), and Arkansas (ARK) Total Therapy (TT) trials
Authors: B. Barlogie, M. Attal, J. Crowley, J. Harousseau
Journal: Journal of Clinical Oncology (2009)

8519 Background: Clinical trial outcomes are usually published when statistical protocol objectives have been met, with short median follow-up not exceeding 5 years. Due to treatment innovations, MM survival beyond 10 years has become more common but formal long-term results are seldom reported. Methods: IFM, SWOG and ARK provide an update of their major trials. IFM-90: 1 AT v standard therapy (STD), IFM-94: 2 v 1 AT, IFM-9902: 2AT ± THAL, IFM-9904: 2AT for high-risk MM; SWOG-9321: 1 AT v STD; TT1: 2 AT with interferon, TT2: 2AT ± THAL, TT3: 2AT + THAL + bortezomib. Results: OS clustered in 3 groups with superior outcomes for TT3/TT2/IFM-99 v TT1 v IFM-94/ IFM-90/SWOG-9321 with 5/10/15-yr estimates of 70%/50%/TE v 57%/35%/20% v 43%/25%/15% (p&lt;0.0001). EFS also clustered in 3 groups with superior outcomes for TT3 v TT2 v remainder with estimates of 71%/TE/TE v 50%/35%/TE v 27%/ 15%/10% (p&lt;0.0001). Among phase III trials, added THAL in TT2 increased 10-yr OS/EFS from 40%/25% to 60%/40% (p=0.04/p=0.0005); 10-yr OS was 30% v 8% with 1 v 0 AT in IFM-90 (p=0.005), 31% v 21% with 2 AT v 1 AT in IFM-94 (p=0.08), and 20% for both arms of S9321. On multivariate analysis involving 2962 patients, OS was adversely affected by B2M &gt;=3.5mg/L (p&lt;0.001), LDH &gt;=ULN (p&lt;0.001), hemoglobin &lt;10g/dL (p=0.001) and albumin &lt;3.5g/dL (p=0.02). 2AT (65%) and THAL (21%) both contributed independently to superior OS (p&lt;0.001, p=0.002); among individual trials, IFM-9902 (19%) and TT2/TT3 (33%) both improved OS significantly (both p&lt;0.001). For each of the 3 major OS clusters, 228 patients could be matched on B2M, LDH, hemoglobin and albumin, with 10-yr OS/EFS estimates of 65%/30% for the TT3/TT2/IFM-9902 group significantly exceeding 30%/15% each for the other 2 groups (p=0.001/p=0.001). Conclusions: A 15-yr EFS plateau of 10% with older trials and superior 10-yr EFS/OS estimates of 50%/35% with recent studies emphasize that cure should be a realistic trial objective in contemporary MM therapy, requiring however very long-term follow-up beyond 15 years. [Table: see text]