tbuckley/cabot-search huggingface dataset:
Pathological complete response rates after neoadjuvant chemoradiation (CRT) for rectal cancer: Do novel agents have a role?
Authors: Muhammad Shaalan Beg, Jeffrey John Meyer, Xian-Jin Xie, Glen C. Balch, Amit G Singal
Journal: Journal of Clinical Oncology (2012)

e14165 Background: Preoperative concurrent radiation with either 5-fluorouracil (5FU) or capecitabine (CAP) is considered standard of care for T3-T4 and/or node positive rectal cancers with historical pathological complete response (pCR) rates ranging from 7-29%. There is lack of randomized data on the incorporation of bevacizumab (B) and cetuximab (C) with neoadjuvant chemoradiation (CRT). The aim of our study was to quantify pCR and adverse event rates for B-CRT and C-CRT in patients with rectal cancer. Methods: A systematic literature review using the Medline database and national meeting abstracts identified trials incorporating bevacizumab and cetuximab for neoadjuvant chemoradiation between 2000 and 2011. Pooled rates of pCR and frequency of grade 3-4 adverse events per patient with 95% confidence intervals (CI) using the adjusted Wald method, were calculated. Results: Out of 24 trials identified, 15 trials with a total of 457 (range 8-61) patients incorporated B-CRT. Five studies used 5FU, ten used CAP. A third chemotherapeutic agent was also included in 7 trials of B-CRT. There were 9 trials incorporating C-CRT with a total of 332 (range 20-50) patients. Two studies used 5FU, 7 used CAP, while four studies also included a third therapeutic agent. The pooled pCR rate for B-CRT of 20.8% (95% CI 17.3-24.8), was significantly higher than the 9.6% (95%CI 6.92-13.2) pCR rate for C-CRT (p&lt;0.001). The rate of grade 3-4 adverse events was significantly lower for B-CRT at 0.38 per patient studied (95% CI 0.34-0.43) compared to C-CRT at 0.55 per patient (95%CI 0.49-0.60) (p&lt;0.001). Surgery was performed in 92% of B-CRT and 94% of C-CRT patients. Conclusions: The addition of either B or C to conventional neoadjuvant CRT does not appear to yield higher pCR rates than those reported with conventional CRT alone. There is insufficient evidence to support routine use of novel agents in this treatment strategy for rectal cancer. Interestingly, although surgical rates are high in both groups, C-CRT has significantly lower rates of pathologic complete response and significantly higher rates of toxicity than B-CRT.
Glycosyltransferase Levels in Tumors Metastatic to Liver and in Uninvolved Liver Tissue 2
Authors: David Kessel, Elizabeth Sykes, Michael Henderson
Journal: JNCI Journal of the National Cancer Institute (1977)

Elevated levels of three plasma glycosyltransferases were associated with neoplasia in cancer patients, notably those with tumor metastatic to liver. We examined levels of sialyltransferase, galactosyltransferase, and fucosyltransferase in metastatic tumor and apparently uninvolved host liver tissue in attempts to delineate possible sources of elevated plasma enzyme levels. Highest levels of fucosyltransferase activity were found associated with tumor tissue; in contrast, sialyltransferase and galactosyltransferase activity was often highest at the tumor-liver interface.
Adjuvant chemotherapy for gastric carcinomas with positive lymph nodes: Experience with a weekly schedule of irinotecan + 5 FU + folinic acid
Authors: H. Jouhadi, S. Sahraoui, A. Acharki, A. Benider
Journal: Journal of Clinical Oncology (2004)

4258 Background: Locally advanced gastric carcinoma is very frequent in Morocco. In spite of a surgery often satisfactory and an adjuvant chemotherapy based on 5 FU+ Cisplatine, the 2 years survival remains low hardly passing the 50% . Moreover, the precarious performance status of patients make the haematological and renal toxicity of this protocol at the limit of the acceptability. The goal of this work is to evaluate the efficiency and the tolerance of a new protocol delivered in a weekly schedule including the irinotécan, the 5 FU and the folinique acid. Methods: It is a prospective study led between September 2000 and September 2001 that included 34 patient with gastric carcinoma. All patients had total gastrectomy with lymphadenectomy. Nodal involvement was present in 100 %. The middle age was of 43 years and the sex ratio of 5. On the histological plan, 28 patients had a well differentiated adenocarcinoma and 6 patients an undifferentiated carcinoma. The TNM stage was like follows: T3 in 29 cases and T4 in 5 cases; N1 in 19 cases, N2 in 10 cases and N3 in 5 cases. All patients were free of metastasis. The protocol of chemotherapy consisted in 8 weekly successive injections of: irinotecan 80 mg/m2 + 5 Fluorouracile: 750 mg/m2 + folinic acidic 20 mg/m2. Results: As regards to tolerance, a grade III neutropenia has been observed in 3 cases and a grade II diarrhea observed among 7 patients. at 2 years The disease free survival was 61%. Conclusions: The weekly schedule of irinotécan +5 FU + F.A is well tolerated. The 2 years DFS is increased with this protocol to 61%. These results are very promising and deserve to be confirmed on a large trial. No significant financial relationships to disclose.
Doxorubicin as adjuvant therapy for breast cancer: answers or more questions?
Authors: P P Carbone
Journal: Journal of Clinical Oncology (1989)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1989.7.5.554 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2709085 Doxorubicin as adjuvant therapy for breast cancer: answers or more questions? P P CarbonexP P CarboneSearch for articles by this author https://doi.org/10.1200/JCO.1989.7.5.554 First Page PDF © 1989 by American Society of Clinical Oncology
Abstract 18749: Avoidance of a Reload During the Therapeutic Shift From Clopidogrel to Ticagrelor in Patients With Acs Has No Influence on Residual Platelet Reactivity
Authors: Gianluca Caiazzo, Salvatore De Rosa, Daniele Torella, Mariella Micieli, Salvatore Giampà, Eleonora Palella, Carmen Spaccarotella, Annalisa Mongiardo, Elio Gulletta, Ciro Indolfi
Journal: Circulation (2013)

Background: Ticagrelor (TICA) was more efficient than clopidogrel (CLO) in preventing cardiovascular events after Acute Coronary Syndrome (ACS) in the PLATO trial. However, it was associated with a higher incidence of non-procedure related bleedings. Despite TICA therapy was always started with the administration of a loading dose in the PLATO trial, the loading dose could be unnecessary in patients with ongoing CLO therapy. Aim of the present study was to verify whether the administration of a loading dose is necessary to mantain the level of inhibition of aggregation during the switch from ongoing CLO to TICA therapy. Methods and Results: Fifty patients with ACS and on CLO treatment were randomly assigned to a starting dose of TICA of 90mg (Group 1) or 180mg (Group 2), on top of aspirin treatment. Platelet aggregation was measured using multiple electrode aggregometry (MEA) at 0, 2, 6, 24 and 72h after the switch, and verified through standard LTA aggregometry. No relevant difference in platelet aggregation between the two study arms was observed at baseline (p=0.256). Residual platelet aggregation measured using MEA was significantly reduced in both arms 2h after the first administration of TICA (both p&lt;0.001). Interestingly, no difference in aggregation was found 2 hours after the switch to TICA (176 72 vs 181 60 AUmin, p=0.281). Similar findings were confirmed with LTA. Conclusions: Therapeutic switch from ongoing clopidogrel therapy to ticagrelor without administration of a loading dose is clinically safe and is not associated to a lower degree of inhibition in patients with ACS. Avoiding the loading dose could be associated to a lower bleeding risk while mantaining the same level of aggregation. Larger trials are needed to confirm data from our proof-of-concept study.
Finite Androgen Deprivation Therapy (Adt) Plus Ipilimumab (Ipi) in Men with Hormone-Naïve Metastatic Prostate Cancer (Hn-Mpca)
Authors: S.K. Subudhi, A. Aparicio, A.J. Zurita, J.C. Araujo, P.G. Corn, S. Tu, X. Wang, D.R. Harris, K.A. Winslow, J. Gao, C.J. Logothetis, P. Sharma
Journal: Annals of Oncology (2014)
Temozolomide in rare brain tumors of the adult: a prospective study
Authors: R. Soffietti, A. Costanza, E. Laguzzi, E. Trevisan, R. Rudà
Journal: Journal of Clinical Oncology (2005)

1574 Background: Little is known about the role of salvage chemotherapy in adult patients with rare brain tumors relapsing after conventional treatments. Methods: Patients with histologically confirmed ependymomas (grade II and III WHO), medulloblastomas, germinomas, gliomatosis cerebri and brain stem gliomas, an age ≥18 yrs, and a Karnofsky performance status ≥ 60, who recurred after surgery and/or radiotherapy, were enrolled. Some patients had received a prior treatment with nitrosureas or platinum compounds. TMZ was administered at 200 mg/m2 for 5 days in cycles of 28 days up to tumor progression or unacceptable toxicity. Tumor response was evaluated according to Macdonald’s criteria basing on MRI. Results: Thirty-three patients were evaluable, with a median of 5 cycles of TMZ (range 1–18). Among ependymomas (11 pts) we observed 2 CR with TTP of 9–48+ months, 3 PR with TTP of 4–15 months, 5 SD (3 minor responses) with TTP of 7–44+ months and 1 PD. All responding (CR + PR) patients had grade III (anaplastic) ependymomas, and 2 of them displayed delayed responses (after 6 and 12 cycles respectively). All 3 patients with medulloblastoma had a SD (TTP 3–6 months) and 1 patient with a germinoma progressed under TMZ. Among patients with gliomatosis (12) we observed 1 CR (TTP 13 months), 1 PR (TTP 15 months), 5 SD (median TTP 8 months) and 5 PD. Four patients had a significant improvement in headache or seizures. The 6 patients with brain stem glioma (grade II) had 1 PR, 3 SD and 2 PD (median TTP 6 months). Myelotoxicity was mild, with 1 patient with grade IV thrombocytopenia. Conclusions: Temozolomide has activity in ependymomas (CR + PR 45%) and gliomatosis cerebri (CR + PR 16%). Further clinical and translational studies in these two tumor types are warranted. No significant financial relationships to disclose.
Costs of post-treatment surveillance for patients with ovarian cancer
Authors: K. S. Virgo, Y. Quang, R. Gibb, D. Mutch, F. E. Johnson
Journal: Journal of Clinical Oncology (2005)

5141 Background: The objectives of this study are to determine the range of recommended follow-up strategies for patients with ovarian cancer treated with curative intent and estimate the cost of follow-up. The ideal follow-up strategy of ovarian cancer patients after primary therapy is unclear because treatment of recurrent disease is rarely if ever curative and motivations for following patients vary widely. Methods: A 15-year literature review (1989–2003) was performed to find all published surveillance strategies for ovarian cancer. Only strategies that specified intervals for office visits and diagnostic tests for a full five years of follow-up were included. 2003 Medicare-allowed charges were used as a proxy to calculate the total costs of five-year follow-up for each strategy. Results: Medicare-allowed charges for 5-year follow-up of ovarian cancer patients ranged from $1,715 to $5,242, only a 2.06-fold cost differential over the 16 follow-up strategies identified. The average charge was $2,258. Charge ranges discounted at three and five percent were $1,589 to $4,931 and $1,513 to $4,742. Office visit and CA-125 were the most commonly used screening modalities. Conclusions: This study shows variation in costs of follow-up for ovarian cancer patients, even though only limited data suggest intensive monitoring has any value. Clinical trials are needed to identify an optimal surveillance strategy that addresses survival and quality of life benefits of early detection of relapse in the absence of curative treatment options. No significant financial relationships to disclose.
Phase I/II study of capecitabine plus irinotecan (XELIRI) in combination with bevacizumab as first-line therapy in metastatic colorectal cancer
Authors: I. Kocakova, S. Spelda, I. Kocak, R. Demlova, M. Simickova, R. Vyzula
Journal: Journal of Clinical Oncology (2006)

13504 Background: First-line treatment of metastatic colorectal cancer (MCRC) is based on regimens combining oxaliplatin or irinotecan with intravenous 5-fluorouracil (5-FU) and leucovorin (FOLFOX or FOLFIRI/IFL). A few phase II studies of capecitabine with irinotecan (XELIRI) proved to be comparable to FOLFIRI. Methods: A phase I/II study was conducted to assess the efficacy and tolerability of XELIRI + bevacizumab in MCRC. Indication for the therapy: histologically confirmed colorectal adenocarcinoma, metastatic inoperable disease, no prior systematic therapy for metastases, performance status 0–1, normal hematological, biochemical parameters, no other malignity. Therapy consisted of capecitabine 1000mg/m 2 bid on days 2–15 and intravenous irinotecan 250mg/m 2 on day 1, bevacizumab 7.5mg/kg on day 1, q 21 days. The response was evaluated after 2 or 3 cycles by RECIST criteria. Results: From March 2005 to December 2005 14 patients (pts) 9 males, 5 females with median age 53 years (range 39–67) have been included. 9 pts were initially disseminated, 5 pts relapsed after adjuvant therapy. Liver metastases were in 12 pts, number of metastatic sites was from 1 to 4, median 2. The overall number of cycles was 96, range 2–13, median 7 cycles. 13 pts have been evaluable for response. The CR occurred in 1 (7%) patient, PR in 10 (77%) pts, SD in 2 pts. During therapy CEA and Ca19–9 declined in all pts. Pretreatment level of CEA: median 32 μg/l, range: 2.4 - 9 265 μg/l. CEA at the response evaluation: median 5.3 μg/l, range: 1.2 - 573 μg/l. Pretreatment level of Ca19–9: median 119,7 kU/l, range: 0 - 4 692. kU/l. Ca19–9 at the response evaluation: median 17.4 kU/l, range: 0–666 kU/l. The toxicity: epistaxis in 1 patient, proteinuria &lt; 1 gram / day in 2 pts and granulocytopenia G3 in 1 patient. No other hematologic toxicity &gt; G2 has occurred. The therapy has been continued in all pts so far with median time of therapy 6 months. The time to disease progression and overall survival has not been reached yet. Conclusions: Irinotecan / capecitabine + bevacizumab has shown high efficacy with response rate 84% and low toxicity. The regimen seems to be appropriate for using in further phase II studies. No significant financial relationships to disclose.
The impact of radiotherapy technique on normal tissue dose in treatment of spinal vertebral metastases.
Authors: Richard S. Pieters, I-Lin Eric Kuo, Bruce A Bornstein, Thomas J. Fitzgerald
Journal: Journal of Clinical Oncology (2014)

179 Background: The optimal management of uncomplicated spinal vertebral metastases has yet to be determined. Preliminary evidence, suggesting single fraction therapy may be associated with fewer gastrointestinal side effects, did not report radiotherapy (RT) technique. Recent clinical experience with more advanced imaging and treatment delivery systems leads us to question if this approach is optimal given the radiation therapy dose to the surrounding normal tissues. The purpose of this study is to examine the impact of current RT techniques on normal tissue dose, which is known to affect acute tolerance of sensitive organs. The focus is on the bowel, an organ known for its radio-sensitivity which can impact quality of life. Methods: In a de-identified treatment planning CT of a patient with spinal metastases, the target volume of vertebrae from T9-L5 was defined and the normal bowel was outlined. Five RT techniques were planned: 1) the former standard, posterior/anterior (PA) 6MV field prescribed to a depth of 5 cm, 2) a PA 18MV field prescribed to a depth of 5 cm, 3) an opposed AP/PA dual energy plan, weighted posteriorly 2:1, 4) a 3-field 18MV plan (PA &amp; 2 posterior oblique fields), and 5) an intensity modulated radiotherapy (IMRT) plan, using 4 arcs. The last 3 techniques were optimized to minimize anterior dose to the bowel. Results: The 5 techniques delivered varying RT doses (Dmax%) to the bowel ranging from the highest (AP/PA dual energy plan) to the lowest (IMRT), expressed as a percentage of the prescription dose. Conclusions: Single fraction RT techniques, with the exception of IMRT, approach tolerance (Dmax%) for some bowel tissue, which may preclude retreatment. IMRT would also allow for dose escalation to the spinal target volume, possibly improving efficacy and reducing the need for retreatment. Future studies should report RT technique, dose and fractionation to optimize efficacy and tolerance. [Table: see text]
Falling demand for mefloquine threatens future of this important antimalarial, experts warn
Authors: Nigel Hawkes
Journal: BMJ (2016)

Negative publicity about the antimalarial drug mefloquine (Lariam) could reduce sales so much that its manufacturers, Roche, would stop making it, an adviser to the Ministry of Defence has warned.

Ron Behrens, a senior lecturer at the London School of Hygiene and Tropical Medicine, said the loss of mefloquine would be damaging. Although there are two other drugs, they also have side effects of comparable severity, and no new antimalarials are on the horizon.

“Mefloquine use has dropped off dramatically, even in the US where it was developed, as a result of media and public pressure,” he said at a background briefing at the …
Suicide attempted by self-immolation
Authors: N C Andreasen, R Noyes
Journal: American Journal of Psychiatry (1975)

The authors found that 14 individuals who had attempted suicide by self-immolation all had psychiatric illness (most were psychotic), and many had religious preoccupations. There was a reversal of the usual male to female ratios for burn injury and for successful suicide--all 5 completed suicides were women. Although self-immolation as social protest was widely publicized during the years surveyed, the authors note that these individuals all attempted suicide for personal and irrational rather than morally idealistic reasons.
Abstract 9809: Upregulation of Aldosterone by Steroidogenesis Acute Regulatory Protein (StAR) is Associated With Connective Tissue Growth Factor-Mediated Pulmonary Vascular Fibrosis in Pulmonary Arterial Hypertension In Vivo
Authors: Bradley A Maron, Sofia Annis, Stephen Y Chan, Joseph Loscalzo, Jane A Leopold
Journal: Circulation (2013)

Hyperaldosteronsim is associated with increased pulmonary vascular remodeling in patients with pulmonary arterial hypertension (PAH). In cardiomyocytes, aldosterone (ALDO) promotes collagen deposition by increasing levels of connective tissue growth factor (CTGF). The role of CTGF in ALDO-mediated vascular remodeling in PAH, however, is not known. We hypothesized that upregulation of CTGF by ALDO is a novel signaling mechanism that modulates pulmonary vascular fibrosis in PAH. To test this hypothesis, cultured human pulmonary artery endothelial cells were exposed to ALDO (10 -9 -10 -7 mol/l) for 24 hr and changes in CTGF levels were assessed by immunoblotting. Compared to vehicle control, ALDO induced a dose-dependent increase in CTGF expression (3.4 ± 0.2 vs. 6.7 ± 1.9 vs. 10.4 ± 1.6 vs. 17.6 ± 1.9 units, P=0.02). We next investigated the effect of ALDO on CTGF in PAH in vivo. Compared to controls, rats exposed to SU-5416 (20 mg/kg) and hypoxia (10% O 2 ) (Su/Hyp) for 21 d demonstrated increased pulmonary artery systolic pressure (PASP) (26 ± 2 vs. 81 ± 5 mmHg, P&lt;0.05), which was associated with a 397% (P&lt;0.02) increase in plasma ALDO levels. Next, we investigated changes in levels of steroidogenic acute regulatory protein (StAR) as a mechanism by which to account for hyperALDO in PAH. Compared to controls, immunohistochemistry revealed increased StAR in the pulmonary arterioles of Su/Hyp-PAH rats (19.2 ± 0.9 vs. 30.2 ± 0.5 units, P&lt;0.01) and in patients with PAH (14.3 ± 1.4 vs. 19.3 ± 0.9 units, P&lt;0.02). Immunohistochemistry revealed that compared to controls, Su/Hyp-PAH rats expressed increased levels of CTGF (88.1 ± 11.5 vs. 171.8 ± 5.9 units, P&lt;0.01) and collagen III (61.5 ± 18.7 vs. 126.5 ± 6.3 units, P&lt;0.01) in pulmonary arterioles. ALDO antagonism with eplerenone (0.6 mg/g chow) decreased CTGF and collagen III levels in SU/Hyp-PAH by 81% (p&lt;0.01) and 38% (P&lt;0.01), respectively, to decrease PASP (81 ± 5 vs. 62 ± 7 mmHg, P&lt;0.05). These data demonstrate that upregulation of StAR is associated with hyperALDO in PAH, which promotes vascular fibrosis through a mechanism involving CTGF. Identifying StAR and/or CTGF as novel treatment target(s) to attenuate pulmonary vascular fibrosis has potential therapeutic implications for patients with PAH.
A multicenter, randomized phase II study of the second-line maximum androgen blockade with an alternative antiandrogen combined with tegafur-uracil (UFT) for prostate cancer with relapse after initial hormonal therapy.
Authors: M. Takahashi, R. Kawabata, A. Kawano, Y. Murakami, Y. Sutou, T. Inai, S. Akazawa, T. Hamao, H. Hayashi, T. Fukawa, M. Takemura, Y. Yamamoto, K. Yamaguchi, H. Nakatsuji, T. Kishimoto, H. Izaki, T. Fukumori, H. Kanayama
Journal: Journal of Clinical Oncology (2011)

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Abstract 17959: Paradoxical Association of LDL Measures With the Risk of Incident Atrial Fibrillation
Authors: Samia Mora, Akintunde O Akinkuolie, Roopinder K Sandhu, David Conen, Christine M Albert
Journal: Circulation (2013)

Background: LDL cholesterol (LDL-C) is a strong risk factor for atherosclerosis but has an inverse (paradoxical) association with atrial fibrillation (AF). Cholesterol has stabilizing effects on ce...
Results from a randomized phase III trial of decitabine versus supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed AML.
Authors: X. G. Thomas, A. Dmoszynska, A. Wierzbowska, K. Kuliczkowski, J. Mayer, T. Shelekhova, J. Gau, W. Chou, R. Buckstein, J. Cermak, C. Kuo, A. O. Rocafiguera, V. Koza, F. Ravandi, H. Kantarjian
Journal: Journal of Clinical Oncology (2011)

6504 Background: We conducted a Phase 3 trial, the largest to date in older patients with acute myeloid leukemia (AML), comparing decitabine (DAC) to patient's choice with physician's advice (treatment choice – TC) of supportive care (SC) or low-dose cytarabine (AraC). Methods: In this open-label Phase 3 trial, newly diagnosed patients ≥65 years of age with de novo or secondary AML and poor- or intermediate-risk cytogenetics were randomized to two treatment groups: TC: either SC or 20 mg/m2 AraC subcutaneously once daily for 10 consecutive days, every 4 weeks; or DAC 20 mg/m2 as a 1-hour IV infusion once daily for 5 consecutive days, every 4 weeks. The primary endpoint was overall survival (OS). Results: Of 485 enrolled patients, 242 were randomized to DAC and 243 to TC. DAC patients had a median duration of treatment of 4.4 months versus 2.4 months for those on the TC arm. The protocol-specified final analysis with 396 (81.6%) deaths showed a statistically non-significant but favorable trend for increased OS for patients treated with DAC, with a median survival of 7.7 months (95% CI: 6.2, 9.2) versus 5.0 months (95% CI: 4.3, 6.3) in the TC arm. The HR was 0.85 (95% CI: 0.69, 1.04), and p=0.10. An updated unplanned OS analysis with 446 (92%) deaths showed the same median survival with strengthened evidence of the DAC effect (HR 0.82; 95% CI: 0.68, 0.99; nominal p=0.03). The secondary endpoint of CR+CRp rate was 18% (DAC) versus 8% (TC) with OR=2.5 (95% CI: 1.4, 4.8) and p=0.001. AE rates were consistent with the known DAC safety profile and without major differences between the treatment arms. The most frequently reported Grade 3 or 4 hematologic AEs were thrombocytopenia, anemia, neutropenia, and febrile neutropenia. Conclusions: Compared with the accepted standard therapies used in this study to treat older patients with AML, DAC showed an overall survival advantage and higher response rates without major differences in safety.