tbuckley/cabot-search huggingface dataset:
Effect of aprepitant on antiemetic protection in patients receiving moderately emetogenic chemotherapy plus high-dose cisplatin: Analysis of combined data from 2 phase III randomized clinical trials
Authors: R. J. Gralla, D. G. Warr, A. D. Carides, J. K. Evans, K. J. Horgan
Journal: Journal of Clinical Oncology (2004)

8137 Background: Addition of the NK1 antagonist aprepitant significantly enhanced the efficacy of a standard antiemetic regimen (5-HT3 antagonist + dexamethasone (D)) in patients receiving highly emetogenic chemotherapy (Poli-Bigelli 2003; Hesketh 2003). An initial sensitivity analysis suggested this benefit may extend to patients receiving additional moderately emetic chemotherapy (MEC); to further explore that observation, we analyzed data pooled from the above 2 large trials, for the subset of patients receiving MEC plus cisplatin. Methods: 1043 patients receiving their first cisplatin-based (≥70mg/m2) chemotherapy were randomly assigned to a control group (ondansetron (O) 32 mg iv and D 20 mg po on day 1; D 8 mg twice daily on days 2–4) or an aprepitant (A) group (A 125 mg po plus O 32 mg and D 12 mg on day 1; A 80 mg and D 8 mg once daily on days 2–3; and D 8 mg on day 4). Randomization was stratified for use of concomitant chemotherapy and gender. The endpoint was complete response (no emesis and no use of rescue therapy). Data were analyzed by a modified intent-to-treat approach and treatment comparisons made using logistic regression. Results: Among the 142 patients (aprepitant n=70, control n=72) who received additional MEC (in these studies, doxorubicin (dox) and/or cyclophosphamide (cyclo)), complete response rates were significantly higher with aprepitant v control for the overall, delayed, and acute phases (Table). Conclusions: Aprepitant markedly enhanced antiemetic control when added to O plus D in patients receiving MEC with cisplatin, demonstrating activity in one of the most difficult emetic settings and suggesting activity in MEC. Prospective trials are needed to confirm the potential benefit of aprepitant in patients receiving MEC only. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Research Laboratories Merck Merck Research Laboratories Merck; Merck Frosst Canada Merck
Rituximab, ifosfamide, carboplatin, and etoposide (RICE) compared with ICE in relapsed diffuse large cell lymphoma (DLCL) before autologous stem cell transplantation
Authors: D. C. Case, F. R. Aronson, K. S. Ebrahim, J. A. Hedlund, M. A. Boyd, K. A. Ault
Journal: Journal of Clinical Oncology (2007)

18532 Background: Retrospective cohort analysis suggests that the addition of rituximab to the ICE regimen (RICE) improved the complete response (CR) rate in relapsed DLCL and progression-free survival after transplantation (Blood 103:3684, 2004). We reviewed the results of two consecutive cohorts of patients treated with ICE and RICE prior to stem cell transplantation for CR rate, percent patients able to go to transplantation, and progression-free survival after transplantation. Methods: Adult patients (1996–2000) with relapsed DLCL received ICE chemotherapy [ifosfamide 1800 mg/m 2 IV q.d. x3, carboplatin 250 mg/m 2 IV day 1, and etoposide 75 mg/m 2 IV q.d. x3 along with mesna] every 28 days to maximum response. Responding patients who were clinically stable and able received high-dose chemotherapy with autologous stem cell support. Adult patients (2001–2004) with relapsed DLCL received ICE along with rituximab 375 mg/m 2 IV on day 1 of each cycle of chemotherapy. Patients in CR received autologous stem cell transplantation. Results: In the ICE series, 49 patients were treated with a 20% CR rate, and 10% went to transplant. Progression-free survival in those transplanted was 9, 12, 24, 36, and 81+ months (median 24 months). In the RICE series, 24 patients were treated with a 33% CR rate, and 25% were transplanted. Progression-free survival was 12, 18, 24+, 36, and 46+ months (median 24+ months). Myelosuppression was similar in each series. All patients were able to tolerate rituximab. The CR rate, percent of patients transplanted, and progression-free survival after transplantation appeared better with RICE but these differences were not statistically significant (P&gt;.05). Conclusions: In our small series, Rituximab added to ICE did not have a statistically significant impact. No significant financial relationships to disclose.
Safety analysis of randomized Belgian phase II trial of extended use of adjuvant temozolomide in newly diagnosed glioblastoma patients
Authors: Laurette Renard, P. M. Clement, Fatima Hammouch, T. Boterberg, V. Verschaeve, N. Whenham, C. Mitine, D. Devriendt, Jean-François Baurain
Journal: Neuro-Oncology (2010)
Bladder preservation strategy with induction chemotherapy (CT) followed by chemoradiotherapy (CRT) in bladder cancer
Authors: A. Ozkan, A. Mayadagli, M. Kocak, O. Demir, C. Parlak, S. K. Gul
Journal: Journal of Clinical Oncology (2008)

5081 Background: Aim of this study was to evaluate bladder conservative treatment of bladder cancer with induction CT followed by CRT after maximal TURBT. Methods: Thirty two patients who admitted to our clinic with histologically proven bladder cancer between April 2003 and June 2006 were enrolled to the study. All patients received 2 cycles of induction CT (gemcitabine 1,250 mg/m2/day d1, d8 and cisplatin 75 mg/m2 d1;q21) after maximal TURBT. Total 66 Gy of RT, starting at 42nd day of treatment, was given in 33 fractions concomitantly with gemcitabine given at a fixed dose of 200 mg/m2 weekly for 6 weeks. Results: Median age was 71 years (40–81), and 90.6% of cases were ≥ 60 years old. Four patients (12.5%) were female and 28 (87.5%) were male. Histopatological diagnosis was transitional cell carcinoma in all cases. Pathological stage was T1 in 5 cases (15.6%), T2 in 21 cases (65.6%), T3 in 1 case (3.1%) and T4 in 5 cases (15.6). Performance statuses were ECOG 0–1 in 29 cases and ECOG 2 in 3 cases. Radiological disease control was achieved in all cases, and response rates were CR in 56.2% and PR in 43.8. Cystoscopical response evaluation that could be performed to 25 cases showed pCR in 15 cases and pPR in 10 cases. At a median follow up period of 21.3 months (12–44.6), median OS and TTP were 36.3 months (95% CI:13–59.6) and 33.5 months (95% CI:13.8–53.2), respectively. One- and 2-year OS and PFS were 83.1% and 57.1, and 73.1% and 54.7%, respectively. Hematological and non-hematological toxicities were well tolerated. Most common hematological toxicities were anemia in 7 cases (21.6%) and leucopenia (WBC:3000–1000) in 6 cases (18.8%). Non-hematological toxicities were grade 1–2 nausea/vomiting (n:13, 40.6%), grade 1–2 skin reaction (n:10, 31.3%), uremia (n:11, 34.4%), grade 1–2 dysuria (n:13, 40.6%), grade 3–4 dysuria (n:2, 6.3%), grade 1–2 rectitis (n:11, 34.4%) and grade 3–4 rectitis (n:5, 15.6%). No factor except ECOG status showed impact on prognosis in both uni-and multi-variate analyses. Conclusions: Sequential use of TURB, gemcitabine/cisplatin-based combination chemotherapy, and gemcitabine containing CRT is feasible and may be considered a reasonable alternative in patients who are medically unfit for cystectomy or seeking an alternative to radical cystectomy. No significant financial relationships to disclose.
Chemotherapy safety initiative.
Authors: Maria Tomaro, Paula Silverman, Wendy Rowehl Miano, Amy Wakeling, Kathleen Gonzalez
Journal: Journal of Clinical Oncology (2013)

226 Background: The 2006 Institute of Medicine report "Preventing Medication Errors," stated that “medication errors harm at least 1.5 million patients every year…” Chemotherapy (CT) has a narrow therapeutic index and safety margin which can and does lead to fatal errors. University Hospitals Seidman Cancer Center (UHSCC), an National Cancer Institute (NCI) designated Comprehensive Cancer Center, dispensed 10,500 CT doses in 2012 and has taken an active approach to enhance CT safety. Methods: In the last quarter of 2012, a nurse coordinator (NC) for chemotherapy orders and a Chemotherapy Safety Governance Committee (CSGC) was conceptualized. The NC’s role would be to incorporate CT safety best practices into order set development. The charter for the CSGC includes 1) to establish cancer CT standards and operating procedures across the adult and pediatric oncology population; 2) to develop and oversee cancer CT order set infrastructure applicable to our hybrid electronic/paper current state; and 3) to lead performance improvement initiatives related to CT safety. Leading organizations involved in oncology practice and medication safety standard-setting (ASCO, Oncology Nursing Society, Institute For Safe Medication Practices, National Comprehensive Cancer Network, Journal of Cancer Research) were reviewed for recommendations for standards for CT order sets. Results: Thirty standards for a CT order template were identified by the NC. A comprehensive gap analysis was completed to compare the current inpatient and ambulatory CT order sets to these standards. Results of the gap analysis were brought to the CSGC, a multi-disciplinary group of cancer and quality clinicians and leaders over 6 meetings. Consensus was achieved on the application of these standards to CT order sets. Our new orders will adopt 100% of all identified standards for CT orders. Conclusions: The gap analysis led to the development of a CT order set template that maximizes safety by applying best-practice standards. This template is designed to be applicable to electronic and paper-based order sets and with minor variation, appropriate to all disease-based order sets. This template is currently being utilized to revise 330 electronic and 398 paper CT order sets at UHSCC. [Table: see text]
Postoperative radiotherapy results in soft tissue sarcomas
Authors: A. Aykanat, A. Yoney, M. Unsal, O. Kandemir, E. Berberoglu, A. Kucuk, S. Eskici, Y. Buyukpolat, M. F. Adatepe, S. Altin
Journal: Journal of Clinical Oncology (2006)

19513 Background: Postoperative radiotherapy results with higher local rates than surgery alone. In this trial we have evaluated and studied factors that affects local recurrence rates. Methods: A retrospective clinical study of 125 eligible patients with soft tissue sarcoma diagnosis from SB Okmeydani Educational Hospital-Oncology Department treated between 1998–2002 years was performed. Tumor size, surgery margin histopathologic grade and type were evaluated. At subgroup analysis local recurrense rates were studied in groups with or without postoperative radiotherapy. Results: In 125 patients, 70 were tumor free, 45 were tumor positive or with suspicious margin after the surgery. Subgroup of 25 patients which have tumor size smaller than 5 cm and negative margin had no radiotherapy and had no local recurrens. In an other group of 45 patients which have tumor size larger than 5 cm and tumor negative after excision 18 patients did not have any postoperative radiotherapy and 4 of them (% 22) had local failure. The rest of the 27 patients of this group who had postoperatif radiotherapy had 2 (% 7) local failure. Among 55 patients with positive or suspicious margins; 18 had no postoperative radiotherapy and there were 6 (% 33) local recurrens while the 37 patients with radiotherapy had 7 (% 18) local recurrens rates. Conclusions: In operable soft tissue sarcomas tumor size, hystopathological grade, postoperatif surgery margins are the most important factors which affects local recurrens rates. [Table: see text] No significant financial relationships to disclose.
The incidence and clinicopathologic features of metachronous gastric tumors after endoscopic submucosal dissection.
Authors: Sung Won Park, Yun Ho Lee, Dae Young Kim, Song I Bae, Won Jae Yoon, Soo Hyung Ryu, You Sun Kim, Jeong Seop Moon
Journal: Journal of Clinical Oncology (2015)

37 Background: Endoscopic submucosal dissection (ESD) has become a standard method of treatment for gastric tumors. The synchronous and metachronous development of two or more primary adenocarcinomas occurs in 10 to 20% of all cases of stomach cancer. Therefore, metachronous recurrence should be a consideration after ESD has been performed. The aim of this study was to review our experiences in the management of patients with synchronous and metachronous lesions, and to evaluate their incidence and clinicopathologic features. Methods: We reviewed 194 patients who underwent ESD for gastric tumors between January 2007 and December 2011. Synchronous lesions were defined as secondary gastric tumors detected within 6 months after the initial ESD. Metachronous tumors were defined as those detected more than 6 months after the initial ESD. We investigated the incidence and clinicopathologic features of synchronous and metachronous tumors after ESD. Results: In total, 20 patients (10.3%) had synchronous lesions and 19 patients (9.8%) had metachronous lesions. The annual incidence of metachronous tumors after ESD was 2.93%. The median period until discovery after initial ESD was 40.1 months. Female patients developed synchronous and metachronous tumors more frequently than male patients (p = 0.037). Patients with H. pyloriinfections developed tumors more frequently than those without (p = 0.04). There were no significant differences with respect to the type and differentiation of tumors. Conclusions: Synchronous and metachronous lesions of gastric tumors were considerably prevalent after ESD. Considering the results of this study, careful endoscopic investigation should be performed after ESD for female patients and those with H. pylori infections. However, further large-scale and longer prospective studies are needed.
Hepatic metastases (HM) from colorectal cancer (CRC): Resectability and survival after treatment with oxapliplatin or irinotecan + bevacizumab-based chemotherapy
Authors: I. Rubio, S. Carrera, A. Ruiz de Lobera, A. Sancho, P. Garrido, I. Marrodan, I. Díaz de Corcuera, A. Muñoz, E. Azkona, G. López-Vivanco
Journal: Journal of Clinical Oncology (2008)

15091 Background: In the last decade, CCR treatment has suffered great changes with the introduction of new agents, mainly since Bevacizumab approval by FDA as first line treatment. Treatment of hepatic metastases from CCR consists of chemotherapy and surgical rescue if possible. Methods: To review retrospectively patients (pt) diagnosed of HM from CCR treated with oxaliplatin-based chemotherapy (OXP) and to compare with pt treated with FOLFIRI+Bevacizumab (BVZ) in terms of: response rate, surgical rescue and survival. Results: From February-02 to Febuary-07, 82 pt were treated with: Oxliplatin 130 mg/m2 d1 + Capecitabine 1000 mg/m2/12 h days 2–15 (51 pt), FOLFOX 4 (5 pt), and FOLFIRI+Bevacizumab 5 mg/kg (26 pt). Patient characteristics: Sex, 52 male and 30 female. Median age: 66 (33–82). Tumour location: Right colon 14 pt, transverse colon 3 pt, left colon 8 pt, sigma 29 pt and rectum 28 pt. Number of hepatic metastases: 1–5, 36 pt; 5–10, 23 pt; > 10, 23 pt. Bilobar HM, 71 pt and unilobar, 11 pt. Overall response rate: 53.7%; OXP, 55% and BVZ, 50% (p=0.65). Overall median survival: 29 months (m); OXP, 26 m and BVZ, not reached (p=0.13). Median progression-free survival: 10 m; OXP: 8.83 and BVZ: 11.63 (p=0.14). HM resection: R0: 20 pt (24%); OXP 14/56 (25%); BVZ 6/26 (23%) p=0.85. Survival was longer in responders and resected patients. Non-significant factors: sex, location of primary tumour (colon/rectum), chemotherapy schedule (OXP vs BVZ), number of metastases (<5 versus >5). Conclusions: With these results, it does not seem to be differences in terms of response rate, surgical rescue and survival between patients treated with combinations of oxaliplatin and patients treated with irinotecan and bevacizumab. However, number of patients treated with bevacizumab is low and follow up is short, so it could be possible to change in next future. No significant financial relationships to disclose.
Chemotherapy dosing for Wilms tumor patients on hemodialysis: Experience of the National Wilms Tumor Study (NWTS)
Authors: J. H. Feusner, D. Green, P. Norkool, M. L. Ritchey
Journal: Journal of Clinical Oncology (2004)

8558 Background: There is very little published data re chemotherapy dosing for children with Wilms tumor (WT) on dialysis. Methods: The treatment and outcome of patients (pts) enrolled on NWTS protocols I-IV (1969 thru 1994) were abstracted from files in the NWTS data center. Results: Twenty-eight pts were identified who had been treated with chemotherapy while being dialyzed. Fifteen had bilateral disease. For the remaining with unilateral tumors, the initial stages were: I-5, II-5, III-1, IV-2. Histology was favorable in 26 and unfavorable in 2. Seven pts had the Denis-Drash syndrome and one the WAGR syndrome. At the time of dialysis, eighteen pts were being treated for either relapsed (14) or persistent (4) WT. The chemotherapy utilized was variable and included vincristine (VCR), actinomycin (AMD), doxorubicin (DOX), ifosfamide, etoposide, cisplatin, and carboplatin. The significant toxicities reported for agents used in > 2 pts are shown. The long term survival for this mixture of pts with different stages and treated in different eras was 39% at 9.9–22.5 years from initial diagnosis. Of the 17 deaths, 9 were directly due to WT and 8 to toxicity of end stage renal disease. Conclusions: This data suggests that VCR (definitely), and AMD and DOXO (probably) can be started at full dose in WT pts on dialysis. This is of note since there is some controversy in the literature re the need to dose adjust AMD and DOXO in pts with severe renal insufficiency. The data are insufficient to allow meaningful evaluation of other chemotherapeutic agents. Given the mixture of pts, disease states, and complicated renal failure treatments, their survival outcome is difficult to interpret. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration National Cancer Institute
Clinical outcomes of patients with gastrointestinal malignancies participating in phase I clinical trials.
Authors: Amit Mahipal, Nancy Burke, Georgine Wapinsky, Barbara Bertels, TzuHua Juan, Jae K Lee, Richard Lush, Daniel Sullivan, Aaron Denson
Journal: Journal of Clinical Oncology (2015)

428 Background: Early phase clinical trials play a pivotal role in drug development. However, limited data is available on the clinical outcomes of patients with gastrointestinal (GI) malignancies enrolled in phase 1 clinical trials. The aim of this study is to evaluate the clinical characteristics and survival of patients with GI cancers participating in phase 1 clinical trials. Methods: All consecutive patients with advanced GI tumors who participated in phase 1 clinical trials from 1/2007 to 12/2013 at Moffitt Cancer Center were included. Data for individual patients were extracted from the OnCore database and clinical charts. Only patients who received at least one dose of the study drug were included. Cox regression model was used to estimate multivariable adjusted hazard ratios and 95% CI. Results: 243 pts with GI malignancies who participated in phase 1 clinical trials were included. Median age was 62 years (26-82 years) with 55% of the patients aged &gt;60 years. Patients had the following disease types: pancreas (42%), colorectal (34%), gastro-esophageal (10%), hepatobiliary (13%) and others (2%). The distribution of patients for baseline variables are: male (55%), DVT/PE (12%), ECOG ≥1 (72%), prior systemic therapies ≥2 (59%), no. of metastatic sites &gt; 2 (31%), lung metastases (40%) and liver metastases (77%). Pts received treatment with chemotherapy only (14%), targeted therapy (41%), chemotherapy + targeted therapy (42%) and others (2%). The response rate was 4% with 38% achieving stable disease; 42% of pts had progressive disease. The median OS was 5.8 months (0.2-52.4). ECOG score of 0, prior systemic therapies &lt; 2 and absence of liver metastases were associated with better OS on multivariate analysis. Conclusions: This is the largest study to assess clinical outcomes in this patient population. Phase 1 clinical trials provide clinical benefit to patients with advanced GI malignancies and should be recommended as a treatment option in appropriate patients. [Table: see text]
Synergistic therapeutic activity of chimeric G250-TNF and IFNγ for the treatment of renal cell cancer
Authors: C. Renner, E. Oosterwijk, N. Adrian, J. Oosterwijk-Wakka, L. Cohen, G. Ritter, A. Knuth, C. R. Divgi, A. M. Scott, L. Old, S. Bauer
Journal: Journal of Clinical Oncology (2008)

16009 Background: Renal cell cancer (RCC) is a chemotherapy and radiation resistant disease with high morbidity and mortality when detected at advanced stage. RCC cells express the G250/CAIX antigen at high levels and can be targeted very efficiently with monoclonal antibodies. To deliver human tumor necrosis factor (TNF) we engineered a modified G250 antibody carrying TNF as dimerized CH2/CH3 truncated IgG1-TNF fusion protein which is able to induce TNF-receptor 1 and TNF-receptor 2 dependent bioactivity in a locally restricted manner. Methods: The N-terminal domain of human TNF was linked to the chimeric G250 antibody by molecular engineering. High-level expression of the recombinant fusion protein using NSO cells was achieved with about a 270 mg/l of culture supernatant. Cytotoxicity assays in vitro and biodistribution and efficacy assays in vivo were performed using standard methods. Results: We established an antibody fusion protein that consists of human TNF and chimeric antibody cG250. Bifunctional binding to the G250/CAIX target antigen and the TNR-1/R2 was not altered. Biodistribution studies in G250-positive RCC xenografted BALB/c nu/nu mice demonstrated a significant increase of tumor-to-blood ratios over time, indicating specific accumulation and retention of cG250-TNF at tumor sites. Furthermore, site specific TNF release resulted in growth inhibition of established G250-positive tumors and improved overall- and progression free survival. Anti-tumor activity could be enhanced by co-administration of low doses of non-targeted Interferon-γ (IFNγ) without significant increase of side effects. Administration of cG250-TNF and IFNγ resulted in synergistic biological activity and modulated several key effector components involved in blood coagulation, endothelial damage and angiostasis. Conclusions: The encouraging targeting and anti-tumor activity profile of cG250-TNF and the strong and stable expression pattern of CAIX/G250 in sporadic and inherited forms of RCC warrant clinical evaluation of this construct. No significant financial relationships to disclose.