tbuckley/cabot-search huggingface dataset:
Phase II trial of cladribine and low-dose AraC alternating with decitabine in older patients with AML.
Authors: Tapan M. Kadia, Jorge E. Cortes, Gautam Borthakur, Guillermo Garcia-Manero, Elias Jabbour, Alessandra Ferrajoli, Srdan Verstovsek, Farhad Ravandi, Naveen Pemmaraju, Naval Guastad Daver, Marina Konopleva, Xuemei Wang, Hagop M. Kantarjian
Journal: Journal of Clinical Oncology (2014)

7031 Background: Treatment of AML in older patients (pts) is often complicated by poor tolerance to high dose chemotherapy and resistant disease. Lower intensity approaches employing more active combinations are needed. Cladribine works synergistically with araC and has been shown to improve survival when combined with standard-dose araC. Methods: We investigated the combination of cladribine and low-dose araC (LDAC) alternating with decitabine in pts aged > 60. Pts with adequate organ function and newly diagnosed AML (except APL) and high risk MDS were eligible. Induction was cladribine 5 mg/m2 IV over 30 min on d 1-5 followed by araC 20mg SQ BID on d 1-10. Consolidation was 2 cycles of cladribine 5 mg/m2 IV over 30 minutes on d 1-3 + araC 20 mg SQ BID on d 1-10 alternating with 2 cycles of decitabine 20 mg/m2on d 1-5, for a max of 18 cycles. Results: 59 pts have been enrolled with a median age of 69 yrs (range, 49-85), including 28 pts (47%) ≥ age 70 (Table). 29 pts (49%) had secondary or therapy related AML, 10 pts (17%) had therapy for an antecedent heme disorder, and 4 pts (7%) had a concurrent active 2nd malignancy while on study. Of the 55 pts evaluable for response, there were 32 CR (58%), 3 CRp (5%), and 2 PR (4%) for an overall response rate of 67%. With a median followup of 4+ months, median OS and median CR duration have not been reached. The 1-year OS estimate is 55%. The regimen was very well tolerated, with 0% 4-week mortality. There were no treatment-related grade 3/4 non-heme adverse events (AEs). Most common non-heme AEs were elevated bilirubin, constipation, nausea/vomiting, mucositis, diarrhea and rash. Conclusions: The low intensity program of cladribine+LDAC alternating with decitabine is a highly effective, well-tolerated, ambulatory regimen for older pts, including those with unfavorable-risk features. Clinical trial information: NCT01515527.Patient characteristics (N=59). Characteristic N (%) Median age [range] 69 [49-85] Cytogenetics Diploid 19 (32) -5/-7 20 (34) Complex without -5/-7 6 (10) Misc. other 10 (17) Insuff 4 (7) Molecular NPM1 10/54 (19) FLT3-ITD 6/54 (11) RAS 13/54 (24) Medians [Range] BM blast 30 [8-95] WBC 2.4 [0.5-51.3] Platelets 41 [4-447] Peripheral blasts 5 [0-88] LDH 597 [301-6498] Creatinine 0.91 [0.46-1.94] Bilirubin 0.6 [0.2-1.8]
Decisions about cancer treatment: Matching of actual to preferred roles and patient ratings of care.
Authors: Kenneth L. Kehl, Mary Beth Landrum, Neeraj K. Arora, Patricia A. Ganz, Michelle van Ryn, Jennifer W. Mack, Nancy Lynn Keating
Journal: Journal of Clinical Oncology (2014)

6533 Background: Shared decision-making in cancer treatment is an important aspect of high-quality care and is associated with improved outcomes. However, patients have different preferences regarding roles they want to play in treatment decisions. We assessed the association of patients' actual roles in decisions with ratings of their care and whether this association varied by preferred decision roles. Methods: In the Cancer Care Outcomes Research and Surveillance Consortium (CanCORS) cohort, a population- and health system-based study of lung and colorectal cancer patients, participants were surveyed about their preferred roles in treatment decisions and their actual roles in decisions about surgery, chemotherapy, and radiation. Among patients receiving treatments under consideration, we used logistic regression to assess associations between actual roles in decisions and patient-reported care quality, both overall and stratified by preferred roles, adjusting for clinical and demographic traits. Results: Among 8,191 decisions made by 5,170 patients treated with surgery, chemotherapy, and/or radiation, patients described 39.8% of decisions as patient-controlled, 47.1% as shared, and 13.1% as physician-controlled. Patients making these decisions more often reported preferring a shared role (58.5%) or a patient-controlled role (35.5%) than a physician-controlled decision role (6.0%). Overall, patients described excellent quality for 67.8% of treatments received. In adjusted analyses, patients reporting physician-controlled decisions were less likely to report excellent quality for each treatment than those reporting a shared role (OR 0.6, 95% CI 0.5-0.7). This association was similar regardless of preferred role (p for interaction=0.29). Conclusions: More active participation in treatment decisions for lung or colorectal cancer was associated with better reported care quality among patients receiving treatments under consideration. This effect did not vary by patients' preferred roles in treatment decisions. These findings underscore the importance of a shared approach to decision-making for all patients, even those who might prefer that physicians make final treatment decisions.
A randomized phase II study adding axitinib to pemetrexed-cisplatin in patients with malignant pleural mesothelioma (MPM): Clinical results of a single-center trial.
Authors: Wieneke A. Buikhuisen, Andrew D. Vincent, Marion M. Scharpfenecker, Catharina M. Korse, Arjan W. Griffioen, Renee van Pel, Paul Baas
Journal: Journal of Clinical Oncology (2013)

7528 Background: Since standard chemotherapy treatment does not lead to long-term survival, new treatment approaches are required. MPM is known for a high vessel count and high levels of vascular growth factors. Suppression of the neo-vasculature by adding the oral VEGF-TKI axitinib to standard chemotherapy may lead to improvement. This study had both clinical and translational objectives. We here report the secondary endpoints response, PFS, OS and toxicity. Methods: Treatment naïve patients with suspected or proven malignant mesothelioma and medically suitable for limited surgical intervention were eligible after informed consent. Patients were treated with pemetrexed (500mg/m 2 q3wk) and cisplatin (75mg/m 2 q3wk) and were randomised to daily axitinib (2x5mg tablets). Before treatment a thoracosopy was performed to confirm the diagnosis. After 3 cycles of chemotherapy a palliative pleurectomy was performed. During both interventions material was obtained for research purposes. Patients could receive an additional 2 cycles of chemotherapy. Results: From July 2009 until October 2012, 26 patients were randomised. Six consecutive patients who received chemotherapy plus axitinib to demonstrate the feasibility and safety of the study design, were also included. In total twenty patients received axitinib. There was one protocol violation in the control arm. Median age: 61 yrs (35 yrs – 75 yrs), 84% epithelial type, 94% WHO 0-1 and 6% WHO 2. Median follow up was 18 months. Toxicity: There was more grade 3, 4 toxicity in the axitinib group concerning neutropenia (40% vs. 9%; p=0.11). One patient in the axitinib group developed a CVA, one patient pulmonary emboli. No thromboembolic events occurred in the control arm. Partial response was observed in 35% of patients in the experimental arm vs. 27% in the control group (p=0.99). Median PFS was 8 months in the experimental arm vs. 8.3 months in the control arm. There was also no difference in overall survival 17 vs 18 months, respectively. Conclusions: Axitinib was well tolerated in combination with cisplatin and pemetrexed. There was no evidence of benefit in response rate, progression free or overall survival. Clinical trial information: NCT01211275.
Chemotherapy with a combination of consecutive low-dose cisplatin with ifosfamide and epirubicin (CLD-IEP) in sarcoma uteri
Authors: Y. Shimizu, K. Katase, T. Ishiya, Y. Takahashi, M. Yamada, S. Umezawa, K. Utsugi
Journal: Journal of Clinical Oncology (2006)

15016 Background: To evaluate the efficacy and toxicity of CLD-IEP for patients (pts) with sarcoma uteri. Methods: Eligible criteria were: a histologic proof of advanced or recurrent sarcoma uteri; measurable lesions; age between 18 and 75 yrs; WHO PS 0–3; WBC ≥ 3,000/μL; platelet count ≥ 100,000/μL; hemoglobin level ≥ 9 g/dL; adequate liver function; C-Cr ≥ 40 mL/min; no lung, heart, or brain disease; no previous neoplastic disease; no prior chemotherapy; and informed consent. The CLD-IEP regimen was ifosfamide 700 mg/m 2 infused over 2 hrs days 1 through 4; epirubicin 50 mg/m 2 bolus day 7; and cisplatin 15 mg/m 2 infused over 2 hrs days 1 through 5. The treatment was repeated at 4-week intervals. Results: To date, thirty-eight eligible pts (17 leiomyosarcoma [LMS], 4 endometrial stromal sarcoma, and 17 carcinosarcoma) were enrolled in this study and all pts were assessable for response, toxicity, and survival. The median age was 53 yrs (range, 37–77). Twelve pts received CLD-IEP in the neoadjuvant setting. Nine pts had prior radiotherapy. After a median of 4 cycles (range, 2–13), we observed objective responses in 22 pts (58%), with 5 (13%) CRs and 17 (45%) PRs (95% CI, 40% to 76%, 4% to 22%, 27% to 63%, respectively). Of 17 pts with LMS, 1 CR and 7 PRs (1 pt with good PR surviving more than 48 months after the start of CLD-IEP) were observed. Median overall survival time (MOS) after the start of CLD-IEP for all 38 pts was 17.5 months (range, 2.7 to 61.5). MOS was 20.8 months in the responders versus 9.9 months in the non-responders (Log-rank, p = 0.023). The median progression-free survival time of the responders was 10.5 months. NCI-CTC grade 3 or 4 leucopoenia, neutropenia, thrombocytopenia, and anemia occurred in 63%, 75%, 12%, and 18%, respectively. There was no significant nausea/vomiting, nephrotoxicity, or CNS toxicity. Conclusion: CLD-IEP regimen has significant to moderate anti-tumor activity with acceptable toxicity in pts with sarcoma uteri including LMS. No significant financial relationships to disclose.
Combination checkpoint immunotherapy and cytotoxic chemotherapy: Pembrolizumab (Pembro) plus either docetaxel or gemcitabine in patients with advanced or metastatic urothelial cancer.
Authors: Primo Lara, Laurel Beckett, Yueju Li, Mamta Parikh, Daniel Robles, Pawandeep Aujla, Chong-xian Pan
Journal: Journal of Clinical Oncology (2017)

398 Background: Metastatic urothelial cancer (mUC) is only modestly responsive to checkpoint inhibitor immunotherapy; e.g., the PDL1 inhibitor atezolizumab confers only a 16% tumor response rate (RR) in platinum-treated mUC. Chemotherapy is hypothesized to enhance tumoral neoantigen expression thus priming response to PD1-directed immunotherapy. Here we report results from the initial cohort of an investigator-initiated trial of Pembro plus either docetaxel or gemcitabine in platinum-treated mUC patients (pts). Methods: Primary endpoint was safety; secondary endpoints were overall RR and progression-free survival (PFS). Eligible pts had Zubrod PS 0-1, adequate end-organ function, and up to 2 prior lines of chemo (at least 1 platinum-based). Dose limiting toxicity (DLT) was any grade (Gr) 3+ non-heme toxicity, Gr3+ neutropenia w/ fever or infection, or Gr4 platelets (plts), or Gr3 plts with bleeding. In dose level (DL) 1, treatment consisted of Pembro 200 mg IV on D1 q3 weeks plus either docetaxel 75 mg/m2 on D1 (Arm 1) or gemcitabine 1000 mg/m2 on D1&amp;D8 (Arm 2). Results: Overall 12 pts were enrolled in DL1, six in each arm. Median age was 69 years (range 45-84), 8 (67%) male, &amp; 10 (83%) of white race. One pt in each arm had DLT: Gr3 hypophosphatemia in Arm 1, Gr3 diarrhea in Arm 2. Attributable Gr3+ toxicities were seen in 7 (54%). Most common Gr3+ AEs were anemia (5, 38%), fatigue (4, 31%), &amp; neutropenia (4, 31%). There were no treatment related deaths; 3 died from tumor progression (PD). As of 10/2016, 4 pts remain on active therapy. In total 4 pts had confirmed response (1 CR, 3 PR), 2 had stable disease (SD), and 6 had PD for an overall RR of 33% and Disease Control Rate (DCR) of 50%. Arm 1 had an overall RR of 50% (1CR, 2PR, 1SD) and DCR of 67%. Arm 2 had an overall RR of 17% (1PR, 1SD) and DCR of 33%. Median PFS (overall, Arm 1 &amp; 2) were 4.8, 5.7, and 3.7 months. Conclusions: Pembro 200 mg IV q3 weeks plus either full-dose docetaxel or gemcitabine is feasible in platinum-treated mUC pts. Encouraging anti-tumor activity for chemo-immunotherapy was seen in this ongoing study, particularly with Pembro+docetaxel. Further investigation of this approach is warranted. Clinical trial information: NCT02437370.
PROSPECT eligibility and clinical outcomes: Results from the pan-Canadian rectal cancer consortium.
Authors: Dominick Bosse, Jamison Mercer, Soundouss Raissouni, Kristopher Dennis, Rachel Anne Goodwin, Maria Jiang, Erin Diana Powell, Aalok Kumar, Richard M. Lee-Ying, Julie A. Price Hiller, Daniel Yick Chin Heng, Patricia A. Tang, Anthony MacLean, Winson Y. Cheung, Michael M. Vickers
Journal: Journal of Clinical Oncology (2015)

6594 Background: The current standard for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiation therapy (nCRT) followed by surgery. The PROSPECT trial (N1048) is investigating neoadjuvant FOLFOX with selective use of nCRT in patients (pts) with LARC undergoing low anterior resection (LAR). We evaluated outcomes of PROSPECT eligible and ineligible pts from a retrospective multi-institution database. Methods: Data from pts with LARC who received nCRT and had curative intent surgery from 2005 to 2014 were collected from 5 Canadian cancer centres. PROSPECT eligible pts included: cT3N0, cT2N1 and cT3N1 rectal adenocarcinoma, ECOG performance status (PS) ≤ 2, hemoglobin > 80 g/L, age > 18 years and receipt of LAR. Overall survival (OS), disease free survival (DFS), recurrence free survival (RFS), and time to local recurrence (TLR) were estimated using Kaplan-Meier method. Cox proportional hazards regression (MVA) was used to adjust for prognostic factors including circumferential resection margin (CRM), PS, clinical stage, pathological stage (ystg) and adjuvant chemotherapy (aCT), sex, age and RT dosage. Results: 1531 pts were included of whom 566 (37%) were considered eligible for PROSPECT. Eligible pts were more likely to have better PS (p = 0.0003), RT ≥ 45Gy (p = 0.001), negative CRM (p < 0.0001) and distance ≥ 5cm from anal verge (p < 0.0001). PROSPECT eligibility was associated with improved DFS (HR 0.75, 95% CI: 0.61-0.91), OS (HR 0.73, 95% CI: 0.57-0.95) and RFS (HR 0.68, 95% CI: 0.54-0.86) in univariate analyses. In MVA, RFS was improved for PROSPECT eligible pts (HR 0.75, 95% CI: 0.57 – 1.00, p = 0.0499), but not for OS and DFS. TLR was also similar (HR 0.95, 95% CI: 0.31-3.0) adjusting for CRM, ystg and aCT. The 3-year DFS for PROSPECT eligible pts was 79.1% compared with 71.1% for ineligible pts and the rate of freedom from local recurrence at 3 years was 97.4 v 96.8%, respectively. In comparison, the PROSPECT trial has estimated a 3-year DFS of 69-74% and a 3-year freedom from local recurrence of 96%. Conclusions: Real world data corroborate the eligibility criteria used in the PROSPECT study, identifying a subgroup of patients in whom recurrence risk is lower and where selective use of CRT should be actively examined.
A pilot study of the patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE) in a phase I clinical trial.
Authors: Rui Qin, Amylou C. Dueck, Daniel Satele, Julian R. Molina, Charles Erlichman, Ethan M. Basch, Jeff A. Sloan
Journal: Journal of Clinical Oncology (2013)

6587 Background: Recently the Patient-Reported Outcomes version of the CTCAE was developed to augment clinically graded adverse events with information reported directly by patients on clinical trials (Basch, 2009). The validation and potential application of PRO-CTCAE in phase I clinical trials are of great interest as toxicity is the primary endpoint. Methods: Selected PRO-CTCAE items (21 items measuring 12 symptomatic adverse events) corresponding to the major adverse events required to be graded clinically were collected in an ongoing phase I clinical trial of weekly cilengitide and paclitaxel in patients with advanced solid malignancies (NCT01276496). PRO-CTCAE was administered in a paper booklet by a clinical research associate prior to treatment on days 1, 8 and 15 of their regular visits. These PRO-CTCAE items were summarized descriptively in comparison to clinician-assessed CTCAE ver 4.0 (NCI, 2009) during the first cycle. As a pilot study to assess feasibility of PRO-CTCAE in phase I trials, PRO-CTCAE was not intended for determination of dose-limiting toxicity. Results: Twelve patients were accrued to two separate doses of cilengitide and paclitaxel. The median age was 56 (range 36—67) and half of patients were female. All patients had an ECOG performance score &lt;= 1. Over 90% of patients had received prior surgery and chemotherapy. All but one patient completed weekly PRO-CTCAE during the first cycle, the only patient refused to complete weeks 2 and 3 did not give a reason. PRO-CTCAE captured most of the symptomatic adverse events reflected in clinician-assessed CTCAE. Some symptomatic adverse events were not reported clinically by CTCAE but were reported by patients by PRO-CTCAE. Overall, PRO-CTCAE items indicated slightly more severe degree of symptoms experienced by patients than those reported in CTCAE. Conclusions: This is the first study that PRO-CTCAE items were integrated within regular study visits in a phase I trial. The administration of PRO-CTCAE has been proved feasible and fruitful, providing consistent and enhanced symptomatic toxicity from the patient point of view. The addition of PRO-CTCAE did not significantly increase patient burden. Clinical trial information: NCT01276496.
Phase I study of the combination of BKM120 and bevacizumab in patients with relapsed/refractory glioblastoma multiforme (GBM) or other refractory solid tumors.
Authors: Kent C. Shih, Peter Acs, Howard A. Burris, Lowell L. Hart, Rebecca A. Kosloff, Ruth E. Lamar, John D. Hainsworth
Journal: Journal of Clinical Oncology (2013)

e13045 Background: BKM120 is an oral pan-class I PI3 kinase (PI3K) inhibitor, with demonstrated CNS penetration. Enhanced PI3K signaling is common in GBM (56-75% of cases), and is associated with poor survival (Chakravarti et al, 2004). This phase I study was designed to determine the maximum tolerated dose (MTD) of BKM120 in combination with a standard dose of bevacizumab as treatment for patients with relapsed/refractory GBM or other refractory solid tumors. Methods: Patients with relapsed/refractory GBM or other refractory solid tumors for which bevacizumab was an appropriate therapy received BKM120 with bevacizumab in a standard 3+3 dose escalation design. Bevacizumab 10 mg/kg IV was administered days 1 and 15 of 28-day cycles, with escalating doses of BKM 120 self-administered daily. Patients were evaluated for response after 8 weeks; treatment continued until disease progression or unacceptable toxicity. Results: Twelve patients were treated at 2 BKM120 dose levels, DL 1 = 60 mg/day and DL 2 = 80 mg/day. DL 1 (n = 6) tumor types included: 2 GBM, 2 colorectal and 2 NSCLC with treated brain metastases. Dose-limiting toxicity (DLT) of G4 delirium was observed in 1 GBM patient. Three additional patients were enrolled, and no further DLTs occurred. DL 2 (n = 6) tumor types included: 3 GBM and 3 colorectal. DLTs were observed in 2 of 6 patients: 1 colorectal (G3 rash, G3 stomatitis, G3 dehydration, and G2 worsening vomiting), and 1 GBM (G3 ataxia and G3 mental status changes). 6 patients had CNS symptoms possibly related to treatment, including mood alteration (3 GBM and 1 colorectal), delirium, hallucinations, and mental status change (1 GBM patient each). Common treatment-related toxicities (all grades) included: dyspepsia (42%), nausea (33%), ALT elevation (25%), dehydration (25%), proteinuria (25%), rash (25%), and thrombocytopenia (25%). No objective responses were documented; however, 1 colorectal patient remains on treatment with stable disease for 8 months. Conclusions: The addition of BKM120 to standard dose bevacizumab was tolerated at a dose of 60 mg/day. A phase II study with this combination is currently underway in patients with relapsed/refractory GBM. Clinical trial information: NCT01349660.
Effects of intensive glucose control on microvascular outcomes in patients with type 2 diabetes: a meta-analysis of individual participant data from randomised controlled trials
Authors: Sophia Zoungas, Hisatomi Arima, Hertzel C Gerstein, Rury R Holman, Mark Woodward, Peter Reaven, Rodney A Hayward, Timothy Craven, Ruth L Coleman, John Chalmers
Journal: The Lancet Diabetes & Endocrinology (2017)
Dasatinib therapy for patients with Philadelphia-negative (ph-) myeloproliferative disorders (MPDs), including systemic mastocytosis
Authors: S. Verstovsek, E. Atallah, D. Thomas, J. Cortes, F. Ravanid-Kashami, C. Nicaise, I. Sams, F. GIles, H. Kantarjian
Journal: Journal of Clinical Oncology (2007)

7086 There are no curative medical therapies for Ph- MPDs. Over last several years several of the MPDs have been associated with the abnormal expression of selected tyrosine kinases (e.g. c-kit in SM) and others are suspected to be involved too. Therefore, we engaged in conducting a Phase II study with dasatinib, an orally available multi targeted kinase inhibitor, for patient with Ph- MPDs. Dasatinib is administered at 70 mg PO BID continuously (one month equals one cycle). Response is assessed every 3 cycles, and the therapy is discontinued in those without response after 6 cycles of therapy. Patients are observed for any toxicity; in such cases the dose of dasatinib is adjusted to 50 mg PO BID, then to 40 mg PO BID, or discontinued. The study is ongoing and has enrolled 55 patients; 44 are evaluable for response and toxicity, including 24 with SM (6 with aggressive SM, 4 with SM and associated hematologic non-mast cell disease and 14 with indolent SM with uncontrolled symptoms despite optimal supportive care measures), 10 CIMF, 6 HES, 3 unclassifiable MPD and one PV. Median age is 65 years (range, 27–75); 25 males and 19 females. The overall response rate in SM was 42% (10 pts). Of those, two patients (8%) achieved complete remission, one with SM-CIMF, and one with SM-HES. Both were c-KIT mutation negative and had low, not significant tryptase levels. Both were anemic (Hb 9.4g/dL) and failed erythropoietin therapy, and had abnormal WBC differential; one had low platelets (90×10 9 /L). Symptoms related to SM improved significantly in additional 8 patients, however, no significant response in percentage of bone marrow mast cells or blood tryptase levels have been observed so far. The 6 patients with HES had previously failed imatinib therapy and had no evidence of the FIP1L1-PDGFRA fusion transcript; one achieved complete remission (normalization of blood and bone marrow eosinophil percentage) while others did not respond. No responses have been recorded in patients with CIMF, PV and unclassifiable MPD. No grade 4 toxicity has been observed. Dasatinib is active in SM (overall response rate 42%) mainly by improving symptoms. Updated clinical results on all enrolled patients will be presented. No significant financial relationships to disclose.