tbuckley/cabot-search huggingface dataset:
Se-(methyl)selenocysteine (MSC) potentiates the antitumor activity of irinotecan against human tumor xenografts and protects against drug induced toxicity
Authors: Y. Rustum, S. Cao, F. Durrani, M. Fakih
Journal: Journal of Clinical Oncology (2004)

2068 Background: Selenium compounds induce specific molecular and cell cycle modulation and are in clinical development as chemopreventive agents. The effects of MSC on the antitumor efficacy and toxicity of irinotecan (IR) were evaluated in nude mice bearing HCT-8 & HT-29 colon and A253 & FaDu head and neck cancers. Methods: IR was administered by i.v. push weekly x 4 using the maximum tolerated dose (100 mg/kg/wk) and toxic doses (200 and 300 mg/kg/wk). MSC was administered orally 0.2 mg/mouse/day daily for 28 days and started 7 days prior to IR. Results were expressed in terms of complete tumor regression (CR) and partial tumor regression (PR, ≥ 50% tumor reduction) for antitumor activity and maximum body weight loss (MWL) and lethality for toxicity. Results: MSC significantly increased the CR and decreased host toxicity, and increased the MTD of IR from 100 to 200 mg/kg. With the dose of 300 mg/kg of IR alone, 100% lethality was observed, however, 80% of the animals protected from drug induced lethality and all were cured in three models and 50% cured in HT-29 when MSC was combined (see table below). Furthermore, MSC potentiated the antitumor activity of various anticancer drugs including taxol, doxorubicin, cyclophosphamide, cisplatin and oxaliplatin against these tumors and protect against drug induced specific organ (intestines, bladder and kidney) and hematological toxicities. Conclusion: MSC is highly effective in potentiating antitumor efficacy of anticancer drugs and protecting against drug induced toxicity. Clinical trials are initiated at our institute to investigate the safety and efficacy of regimens combining various chemotherapeutic agents with selenium compounds. No significant financial relationships to disclose.
Neoadjuvant therapy of gastric cancer with cetuximab added to both irinotecan and cisplatin, followed by surgical resection and adjuvant chemoradiation
Authors: H. Y. Ma, E. Newman, T. Ryan, G. Miller, U. Sarpel, H. L. Pachter, D. J. Cohen, H. Choi, J. D. Goldberg, H. S. Hochster
Journal: Journal of Clinical Oncology (2009)

e15552 Background: We previously demonstrated the efficacy of irinotecan (CPT) and cisplatin (Cis) combination therapy as neoadjuvant therapy for locally advanced gastric cancer [Newman E et al. J Gastrointest Surg. 2002.]. This trial was designed to add cetuximab (C) to both induction treatment and adjuvant chemoradiation (CRT) with bolus 5-FU/LV. Methods: Pts with untreated locally advanced (T3, T4 or N+) gastric/GE cancers were eligible. Neoadjuvant therapy consisted of Cis 25mg/m 2 + CPT 75mg/m 2 on d1,8 q21d x 4, C 400mg/m 2 on d1, then 250mg/m 2 qwk. Curative (R0) resection was performed 4–6 wks later. Adjuvant CRT with 5-FU/LV (425/20/m 2 qd x 5 on wks 1,14,19; 400/20/m 2 qd x 4 on wk 5, x 3 on wk 9) was given with C 250mg/m 2 qwk. Results: Since 11/05, 21 pts [median age 59 (32–82); 9 Caucasian, 11 Asian, 1 Hispanic; 15 male, 20 PS 0–1] received neoadjuvant therapy. The most common toxicities were gr 3 neutropenia (38%), gr 2 rash (33%), gr 2 fatigue (29%); gr 4 included 1 pt each of diarrhea, neutropenia, &amp; hypomagnesemia. 3 did not complete neoadjuvant therapy, due to gr 3 rash, diarrhea and GI bleeding (2 had gastrectomy; 1 lost to f/u). All 18 pts who completed neoadjuvant therapy were surgically explored. 4 had occult metastases, and went off study. 14 underwent R0 gastrectomy (see table); 8 were downstaged, 2 had stable disease, 4 were upstaged compared to the preoperative EUS. There was no postoperative mortality. Of 14 resected pts, 2 did not receive adjuvant therapy (prolonged postoperative recovery), 1 too early to assess, and 11 remaining receiving CRT. The most common toxicities for CRT were gr 3 nausea, gr 3 emesis, gr 2 and 3 fatigue, 3 pts each and 1 each of gr 4 neutropenia and thrombocytopenia. Among the 18 pts who completed neoadjuvant therapy, 5 died of disease, 1 is alive with disease, 12 remain NED with median f/u of 11.6mos (4.1–27.7mos). Conclusions: The addition of C to CPT/Cis as neoadjuvant therapy and to postoperative adjuvant CRT is well tolerated. The regimen induces a favorable pathologic response on the primary tumor. Ongoing evaluation includes K-ras mutation status on outcome and survival benefit. [Supported in part by a grant from BMS.] [Table: see text]
Trastuzumab cardiotoxicity: FDA review of four adjuvant breast cancer clinical trials leading to trastuzumab marketing approvals
Authors: K. Fedenko, P. Cortazar, P. Keegan, R. Pazdur
Journal: Journal of Clinical Oncology (2009)

e11520 Background: Trastuzumab can result in sub-clinical and clinical cardiac failure manifesting as congestive heart failure (CHF), and decreased left ventricular ejection fraction (LVEF). Methods: Data was reviewed from 9837 patients in four randomized trials (NCCTG 9831, NSABP B-31, HERA, and BCIRG-06) that supported trastuzumab HER2 overexpressing adjuvant breast cancer approval. Results: Trastuzumab can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death. Herceptin can also cause asymptomatic decline in LVEF. There is a 4−6 fold increase in the incidence of symptomatic myocardial dysfunction among patients receiving trastuzumab as a single agent or in combination therapy compared with those not receiving trastuzumab. The highest absolute incidence occurs when trastuzumab is administered with an anthracycline. Clinical trials NCCTG 9831, NSABP B-31, and BCIRG-06 included arms with doxorubicin- cyclophosphamide (AC) followed by a taxane plus trastuzumab. Among 32 patients receiving adjuvant chemotherapy from studies NCCTG 9831 and NSABP B-31 who developed CHF, one patient died of cardiomyopathy and all other patients were receiving cardiac medication at last follow-up. Approximately half of the patients recovered to a normal LVEF (defined as ≥ 50%) on continuing medical management at the time of last follow-up. In BCIRG-06 the incidence of CHF was six (6) fold higher in the AC followed by docetaxel plus trastuzumab arm as compared to AC followed by docetaxel. There was a lower incidence of CHF in the non-anthracycline TCH (docetaxel, carboplatin and trastuzumab) arm in BCIRG-06 comparable to trastuzumab monotherapy. Conclusions: Cardiotoxicity manifesting as sub-clinical and clinical cardiac failure is a known side effect of trastuzumab. In an era where trastuzumab is given earlier in the treatment of breast cancer (adjuvant setting), the safety of continuation or resumption of trastuzumab in patients with trastuzumab-induced left ventricular cardiac dysfunction has not been studied. No significant financial relationships to disclose.
FRI0299 Prevalence of Vertebral Fractures in Osteoporotic HIP Fractured Patients: The Focus Study
Authors: G. Arioli, P. Falaschi, G. Letizia Mauro, G. Iolascon, M. Invernizzi, M. Noale, M. Manfredini, G. Bernardi, C. Cisari
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Osteoporosis is a multifactorial systemic skeletal disease, characterized by low bone mass and microarchitectural modifications of bone tissue, with a consequent increase in fragility fractures [1]. Vertebral fractures are the most prevalent osteoporotic fractures and osteoporotic hip fractures are the most serious complication of osteoporosis resulting in increased mortality and high socio-economic cost [2,3]. The coexistence of these two pathological conditions in elderly patients has been previously described, leading to even worse functional outcomes than each one alone [4]. <h3>Objectives</h3> To determine the prevalence of vertebral fractures in osteoporotic hip fractured women and to evaluate the relationship between prevalence of vertebral fractures and pre-existing factors such us autonomy in daily life activity, quality of walking, numbers of falls, cognitive aspects and comorbidities. <h3>Methods</h3> 946 osteoporotic hip fractured women aged more than 60 years and with an X-ray evaluation of spine were consecutively enrolled in 25 Orthopaedic, Physical Medicine and geriatric centers in Italy. After spine X-ray morphometry patients were divided in two groups: previous vertebral fracture (F) and no previous fracture (NF). Moreover anamnestic, demographical and outcome related data (ADL, IADL, CIRS, SPMSQ, FAC and RANKIN scale) were collected. <h3>Results</h3> Prevalent vertebral fractures were present in 502 (54%) patients. 119 (13.7%) patients had at least one severe fracture. The F compared to NF group showed statistically significant worse scores regarding the pre hip fracture values of RANKIN, CIRS, SPMSQ, IADL and the overall number of falls (p&lt;0.001). Moreover the F group showed statistically significant lower values of serif 25(OH)D than NF group (p&lt;.0.001). <h3>Conclusions</h3> Previous Vertebral fractures in hip fractured patients are a common issue and negatively influence several functional and cognitive outcome measures in these patients. <h3>References</h3> NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis and Therapy. Osteoporosis prevention, diagnosis and therapy. JAMA. 2001;285:785–795 Sattui SE, Saag KG. Fracture mortality: associations with epidemiology and osteoporosis treatment. Nat Rev Endocrinol. 2014 Oct;10(10):592-602. Svedbom A, Hernlund E, Ivergård M, Compston J, Cooper C, Stenmark J, McCloskey EV, Jönsson B, Kanis JA; EU Review Panel of IOF. Osteoporosis in the European Union: a compendium of country-specific reports. Arch Osteoporos. 2013;8(1-2):137. Gonnelli S, Caffarelli C, Maggi S et al. The assessment of vertebral fractures in elderly women with recent hip fractures: the BREAK Study. Osteoporosis In.t 2013;24:1151-1159 <h3>Disclosure of Interest</h3> None declared
Cetuximab every second week with irinotecan in patients with metastatic colorectal cancer refractory to 5-FU, oxaliplatin, and irinotecan: KRAS mutation status and efficacy.
Authors: B. V. Jensen, J. V. Schou, H. H. Johannesen, I. J. Christensen, D. Nielsen, J. S. Johansen, E. V. H∅gdall, O. Larsen, M. Yilmaz, P. Pfeiffer
Journal: Journal of Clinical Oncology (2010)

3573 Background: Weekly (q1w) cetuximab (cet) is effective in all lines treatment of metastatic colorectal cancer (mCRC). Cet at 500 mg/m2 every second week (q2w) has similar pharmacokinetics to 250 mg/m2 q1w. In a retrospective study cet q2w with irinotecan (iri) (cetiri) was effective (3. Pfeiffer et al. 2008.). No phase II study on cetiri q2w related to KRAS status has been reported. Methods: Phase II study of cet 500 mg/m2 in 60 min. immediately followed by iri 180 mg/m2 in 30 min. q2w as third-line therapy in patients (pts) with mCRC resistant to 5-FU, iri and oxaliplatin. Response was assessed radiologically every 8 weeks and evaluated centrally according to RECIST criteria. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and compared with log-rank tests. Results: 163 patients (102 male, 61 female, median age of 63 yr, performance status 0/1/2 of 50/32/18%, number of metastatic sites, 1/2/>2 was 58/31/11%) were treated from 2006-9. KRAS tumor mutation status was known in 94% of pts. Grade 3/4 toxicity was similar to q1w administration (1, 2. Cunningham D et al. 2004.). No pts had complete response, 29 (18%) had partial response (PR), 104 (64%) stable disease (SD) and 28 (18%) progressive disease comparable to q1w schedule (Di Fiore F et al. 2008.). KRAS tumor mutation (M) was detected in 58 patients (38%) including 2 (3%) with a PR and 44 (76%) with SD. In KRAS wild-type (W) PR was seen in 26 (27%) and SD in 53 (56%). Pts with KRAS-W were more likely to have a PR than KRAS-M (p < 0.002). The high disease control (PR+SD) of 79% in KRAS-M patients was nearly double than reported in q1w schedule (2). For all pts, median PFS 4.3 m (95% CI: 3.8-5.1) and OS 10.8 m (9.2-12.8) were comparable to outcomes for q1w administration (1). PFS and OS were superior in pts with KRAS-W compared to KRAS-M tumors (PFS: 5.5 vs. 3.9 m, hazard ratio (HR) 1.6, p = 0.006; OS: 12.8 vs. 8.6 m, HR 1.56, p = 0.01). Conclusions: Cetuximab 500 mg/m2 q2w with iri is as effective and well tolerated as 250 mg/m2 q1w administration in the third-line therapy of patients with mCRC (1,2). Pts with KRAS-W mCRC appared to derive the most benefit from treatment with cetuximab. No significant financial relationships to disclose.
Rituximab is an effective treatment in cutaneous histiocyte predominant T-cell rich B-cell lymphoma
Authors: T. V. Hopkins, J. Floyd, T. Loy, N. Johnston, N. Shahab
Journal: Journal of Clinical Oncology (2005)

6744 Rituximab, an anti CD-20 monoclonal antibody, is efficacious in multiple subtypes of systemic B-cell non-Hodgkin’s lymphoma. Its use in cutaneous B-cell non-Hodgkin’s lymphomas is limited. Its use in primary cutaneous histiocyte predominant T-cell rich B-cell lymphoma is unknown. We report a case of a fifty-three year old white female who initially presented with a subcutaneous nodule on her right scapula. The lesion was excised and pathology was consistent with a Histiocytic predominant T-cell rich B-cell lymphoma. No further treatment was offered. Six months later a second nodule appeared on the opposite side of her back that was also excised. She was followed with observation for 5 years at which time a third nodule appeared on her back in approximately the same area as her initial lesion. After excision she received radiation therapy. Two months later a new lesion appeared on the left mid posterior calf. Following a negative staging workup, the lesion was excised and radiated. Within 7 months, she developed multiple nodules in the previously radiated area on the mid left calf. Restaging showed no systemic disease. Because of its success in other types of Bcell -non-Hodgkin’s lymphoma and relatively safe side effect profile, we opted to treat with single agent Rituximab at the standard dose of 375 mg/m2 weekly times four weeks. Follow-up at one month and three month intervals showed no regression. However, six months later she had complete resolution of all calf nodules. She continues to be in complete remission at her twelve month follow-up visit with no new lesions. The mechanism of this delayed response to Rituxan is unclear but should remind us of the virtue of patience and observation, before proceeding to more aggressive therapies. Even with this delayed response, Rituxan appears to be a viable option in the treatment of cutaneous or subcutaneous B-cell non-Hodgkin’s lymphoma, even those with a large component of T-cells or histiocytes. No significant financial relationships to disclose.
Recurrence patterns of Chinese patients with gastric cancer after complete resection
Authors: M. Lu, L. Shen
Journal: Journal of Clinical Oncology (2009)

e15667 Background: Recurrence after radical resection was the most important factor that influence the prognosis of patients with gastric adenocarcinoma. Focusing on the clinicopathologic features and recurrence patterns, this study aims to find the characteristics of recurrence pattern and the predictive factors of gastric cancer patients in China. Methods: This is a retrospective analysis of the gastric adenocarcinoma patients who accepted adjuvant treatment and follow up in our medical department after R0 resection. From June 1995 through June 2007, among 845 patients with R0 resection, 773 cases with detailed information of follow-up enrolled in this study. The location of first recurrence were reviewed. Recurrences location were categorized as locoregional, peritoneal, or distant. Locoregional recurrence was defined as dominant masses in the gastric bed, regional nodes or anastomotic recurrence. Peritoneal recurrence was documented by positive cytology in ascitic fluid, peritoneal nodules or ovaries with tumors involved. Distant metastases were defined as the specific organ or distant lymph nodes involved. Univariate and multivariate analyses were performed to identify predictive factors of recurrence patterns. Results: Till the last follow-up date in November 2008, 426 patients (55.1%) recurred, and 303(71.1%) recurred within 2 years after resection. The pattern of recurrence was locoregional in 240 patients (31%), distant in 261 patients (33.8%) and peritoneal in 88 patients (11.4%). On multivariate analysis, proximal location, the rate of positive lymph node &gt; 0.33, number of lymph node dissetion&lt;15 and operated in general hospital increase the risk of locoregional recurrence. Distant recurrence was significant associated with male gender, advanced T-stage, positive lymph nodes and number of lymph node dissection&lt;15; female gender, poor differentiation and advanced T-stage were high risk factors of peritoneal recurrence. Conclusions: Different recurrence pattern has remarkable relationship with various clinicopathologic factors. It is noteworthy that both locoregional recurrence and distant recurrence are associated with the number of lymph node dissection, confirming the importantace of lymph node dissection. No significant financial relationships to disclose.
Benefits of zoledronic acid compared with placebo in breast cancer patients with bone metastases based on analysis of pain, analgesic use, and performance status
Authors: K. Aogi, N. Kohno, H. Minami, S. Takashima
Journal: Journal of Clinical Oncology (2006)

10653 Background: We previously reported that zoledronic acid significantly reduced skeletal complications by 39% compared with placebo in breast cancer (BC) patients with bone metastases in a multicenter randomized trial conducted in Japan. To assess the effect of zoledronic acid in the maintenance of patient’s mobility or autonomy, we conducted a retrospective analysis of pain, analgesic use, and performance status (PS) among patients of this trial. Methods: 228 women with bone metastases were randomized to 4 mg zoledronic acid (n = 114) or placebo (n = 114) every 4 weeks for 1 year. At baseline and every 4 weeks during treatment, pain scores were assessed using the Brief Pain Inventory (BPI) on a scale of 0 to 10, and analgesic use was scored on a 4-point scale from none (0) to strong narcotics such as morphine (4). Eastern Cooperative Oncology Group (ECOG) PS was assessed at baseline and at study end. Results: Unlike patients receiving placebo who’s pain scores increased, patients treated with zoledronic acid had a significant decrease from baseline BPI composite pain score from week 4 to week 52: mean decrease of 0.86 in the zoledronic acid group at week 52 versus a mean increase of 0.62 in the placebo group; P &lt; .05. Patients treated with zoledronic acid had very little change in analgesic scores, whereas patients in the placebo group had a mean increase in analgesic score (approximately 0.5) by study end. Shift table analysis of ECOG PS showed that 61% of patients in the zoledronic acid group had no change in PS, and 28% had worsening of ECOG PS of at least 1 grade from baseline to study end. In comparison, 54% of patients in the placebo group had no change in PS, and 36% had worsening of PS. Approximately 10% of patients in both treatment groups had an improvement in PS. Conclusions: This analysis shows that treatment with zoledronic acid reduced pain and prevented a worsening of ECOG PS in a larger percentage of patients compared with placebo, consistent with the demonstrated reduction in the rate of skeletal complications. This suggests that zoledronic acid may improve quality of life and maintain autonomy and mobility in breast cancer patients with bone metastases. No significant financial relationships to disclose.
Plasma levels of total RNA and hTERT mRNA as biomarkers of response in rectal cancer patients receiving preoperative chemoradiotherapy.
Authors: S. Pucciarelli, E. Rampazzo, M. Briarava, L. Serra, C. Bedin, S. Lonardi, C. Mescoli, M. Digito, A. De Rossi, D. Nitti
Journal: Journal of Clinical Oncology (2010)

3648 Background: The levels of telomere-specific reverse transcriptase (hTERT) transcripts have been found to be a marker of colorectal cancer and tumor progression. Aim of the study was to investigate the role of plasma levels of total RNA and hTERT transcripts as marker of tumor response after preoperative chemoradiotherapy (pCRT) for rectal cancer. Methods: Pre- and post-pCRT plasma samples of 80 rectal cancer patients (median age, 62 years; male/female, 56/24) were available for the study. All patients received pCRT and, following the histopathology Dvorak tumor regression grade (TRG) classification, 45 of them were considered as non-responders (TRG 3-4-5) and 35 as responders (TRG 1-2). Quantification of RNA and hTERT transcripts (hTERT-AT) were performed by real time-PCR, using primer pair specific for HPRT and hTERT genes, respectively. Mann-Whitney Rank Sum Test was used to compare the levels of RNA and hTERT-AT between responders and non-responders at each time point. The Wilcoxon Signed Rank Test or the Paired t-test were used to compare pre- vs post-pCRT values in each subgroup. Results: In the responder group, the levels of RNA and hTERT-AT were significantly lower after pCRT compared to the baseline levels [RNA, n = 35: median (IQR) 252 (36-606) pg/mL vs. 1,335 (395-2,281) pg/mL, p < 0.001; hTERT-AT; n = 17: 0 (0-147) copies/mL vs. 728 (168-1054) copies/mL, p < 0.001)]. By contrast, no differences were observed in the nonresponder group [RNA, n = 45: median (IQR) 986 (382-2,765) pg/mL vs. 1,984 (685-3,175) pg/mL, p = 0.991. hTERT-AT, n = 30: 174 (0-562) copies/mL vs. 368 (0-733) copies/mL, p = 0.575]. Baseline levels of RNA and hTERT-AT were not associated with tumor response. After pCRT, the levels of RNA were significantly lower in responder (n = 35) than in nonresponder (n = 45) patients [median (IQR) 252 (36-606) vs. 986 (382-2765), p < 0.001)], whereas the levels of hTERT-AT in responder (n = 17) patients were not different from nonresponder (n = 32) patients (p = 0.105). Conclusions: The variations of plasma levels of RNA and hTERT transcripts between pre- and post-CRT may be useful markers of tumor response in patients receiving CRT for rectal cancer. No significant financial relationships to disclose.