tbuckley/cabot-search huggingface dataset:
Evaluation of the efficiency of an embedded palliative nurse practitioner in an oncology clinic.
Authors: Anne M. Walling, Sarah D'Ambruoso, Christopher Pietras, Jennifer Malin, Sara A. Hurvitz, Frances Watts, Bruce Ferrell, Ann Zisser, Neil Wenger
Journal: Journal of Clinical Oncology (2015)

146 Background: We embedded a palliative nurse practitioner in 2 oncologists’ clinics in March 2014 using a reproducible training program. After one year, patients with advanced cancer receiving care in the embedded model clinics, compared to other oncologists’ clinics, were more likely to have advance care planning performed and to die receiving hospice. In order to expand the intervention to other oncologists, we evaluated the efficiency in our model of care delivery. Methods: We reviewed overall caseload and a subset of patient encounters in depth to understand how much of the NP's practice could be conducted by other staff to inform alternate clinical models of palliative care delivery in an oncology clinic. Overall time spent and time spent per task (Symptom Assessment Basic (SAB), Symptom Assessment Medical (SAM), Symptom Assessment Psychosocial (SAP), Communication Basic (CB), Communication Complex (CC)) was recorded for 16 patient encounters. We also completed 3 days of time motion study in which a trained observer tracked the NP's daily activities from minute to minute. Results: After part-time clinical participation over the first year of the program, the NP had seen 68 initial consults and 141 follow-up consults, which were potentially billable. She also had 120 encounters where she met a patient with an oncologist and 158 email or phone encounters that were not billable. Mean duration of a visit was 56 minutes (range 40-70 minutes) and about half of this time was spent on symptom assessment and communication topics requiring an MD or NP (SAM and CC), whereas half of the time was spent on topics that potentially could be covered by an RN (SAB or CB) or an MSW (SAB, SAP, CB). Time motion study revealed that a significant amount of time was spent with email correspondence and talking with other providers for care coordination. Conclusions: Palliative care is time consuming and much of the work is not reimbursed by a traditional fee for service model. Approximately half of the time spent by the NP in our embedded program potentially could have been completed by an RN or other interdisciplinary staff with training in palliative care under supervision of a physician. We plan to add an RN case management component to our model of care delivery.
Comparison of outcomes of intensity-modulated radiotherapy and 3-D conformal radiotherapy for anal squamous cell carcinoma using a propensity score analysis.
Authors: D. A. Rothenstein, T. Dasgupta, J. F. Chou, Z. Zhang, J. L. Wright, L. K. F. Temple, L. Saltz, K. A. Goodman
Journal: Journal of Clinical Oncology (2011)

3555 Background: IMRT has been shown to reduce acute dermatologic and gastrointestinal toxicities when compared to 3DCRT in the treatment of ASCC; however, there has been concern that focal IMRT fields may lead to elevated rates of locoregional recurrence. We examined the efficacy of definitive chemoradiation (CRT) using intensity modulated radiotherapy (IMRT) as compared with 3D conformal radiotherapy (3DCRT) for patients (pts) with anal squamous cell carcinoma (ASCC). Methods: We retrospectively assessed 221 pts with ASCC treated with definitive CRT at MSKCC from 05/1991 to 01/2010. Of these pts, 44 received IMRT between 07/2005-01/2010, and 177 received 3DCRT between 05/1991-04/2007. Local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), colostomy-free survival (CFS), and overall survival (OS) were estimated by Kaplan-Meier methods and compared using a log-rank test. To account for biases arising from nonrandom allocation of pts to treatment groups, a propensity score analysis was performed using the potential confounding variables of age, gender, chemotherapy regimens, histology, T-stage and N-stage, to balance the covariates and allow for a more accurate estimate of the treatment effects. Results: Median follow-up time for survivors was 24.5 and 74.1 months for the IMRT and 3DCRT groups, respectively. The patients in the IMRT group received a median dose of 5,600cGy (mean 5,260cGy) to the primary tumor, compared to 4,500cGy (mean 4,739cGy) in the 3DCRT group. The IMRT and 3DCRT groups had similar durations of RT treatment with means of 41.5 and 41.4 days, respectively. The IMRT group had significantly (p<0.01) higher N-stage. The 2-year LRFS, DMFS, CFS, and OS was 88%, 83%, 96%, and 92%, respectively for the IMRT group and 81%, 88%, 91%, and 89%, respectively for the 3DCRT group with no significant difference between the groups. Longer treatment duration was associated with worse tumor control with every 10 days of delay resulting in a 31% increase in LR rate. Conclusions: In this large cohort of pts with ASCC treated with definitive CRT, use of IMRT, when compared to 3DCRT, does not appear to adversely affect outcomes.
AMG 386 in combination with sorafenib in patients (pts) with metastatic renal cell cancer (mRCC): A randomized, double-blind, placebo-controlled, phase II study.
Authors: B. I. Rini, C. Szczylik, N. M. Tannir, P. Koralewski, P. Tomczak, A. Deptala, K. Kracht, Y. Sun, M. Puhlmann, B. Escudier
Journal: Journal of Clinical Oncology (2011)

309 Background: AMG 386 inhibits angiogenesis by sequestering angiopoietin-1 and -2, thus preventing their interaction with the Tie2 receptor on endothelial cells. Combination with VEGF receptor inhibition has demonstrated additive effects in vivo. The efficacy and tolerability of sorafenib plus AMG 386, an investigational peptide-Fc fusion protein, were evaluated in mRCC pts. Methods: Treatment-naive pts with clear cell mRCC were randomized 1:1:1 to sorafenib 400 mgPO BID plus AMG 386 10 mg/kg (Arm A) or 3 mg/kg (Arm B) QW; or placebo (Arm C) IV QW. Endpoints were progression-free survival (PFS; primary); and (secondary) objective response rate (ORR), change in tumor burden, adverse events (AEs) and pharmacokinetics. Tumor assessment was performed at baseline and every 8 weeks thereafter. Results: 152 pts were randomized: Arms A/B/C, n=50/51/51. 60/61/61% of pts had intermediate and 40/39/37% had low MSKCC risk at baseline. PFS was similar in all 3 arms, whereas ORR was higher in the AMG 386 arms ( Table ). In Arms A/B/C the incidence of grade ≥ 3 AEs was 66/73/86% and serious AEs 36/49/28%. The most common AEs included diarrhea (70/67/56%; grade ≥3 8/10/8%), hand- foot syndrome (52/47/54%; grade ≥3 12/16/28%), alopecia (50/45/50%; grade ≥3 0/0/2%), and hypertension (42/49/46%; grade ≥3 18/20/14%). Median steady-state C max and C min for AMG 386 were similar to those reported previously. Sorafenib coadministration did not markedly affect AMG 386 exposure. Conclusions: Sorafenib plus AMG 386 was tolerable but did not improve PFS compared with sorafenib plus placebo. Increased ORR and the observed reduction in tumor burden are suggestive of an antitumor effect of AMG 386 in mRCC. [Table: see text] [Table: see text]
A phase I trial of depsipeptide in children with refractory solid tumors: A Children’s Oncology Group study
Authors: M. Fouladi, W. L. Furman, T. Chin, B. Freeman, C. F. Stewart, M. Krailo, P. J. Houghton, J. Wright, P. C. Adamson, S. M. Blaney
Journal: Journal of Clinical Oncology (2005)

8528 Background: Depsipeptide, a histone deacetylase inhibitor, has demonstrated potent antitumor activity against human tumor cell lines (including neuroblastomas) at IC50s < 10nM and in various xenograft models. Methods: A phase I trial of depsipeptide was conducted in children with recurrent or refractory solid tumors to determine the maximum tolerated dose (MTD), dose limiting toxicity (DLT) and pharmacokinetics (PK) of depsipepetide and to assess accumulation of histone acetylation (H3) in peripheral blood mononuclear cells (PBMNC). Depsipeptide was administered as a 4-hour IV infusion weekly × 3 consecutive weeks every 28 days. Dose levels were 10, 13, 17 and 22 mg/m2. PK and histone acetylation studies were conducted in the first course. Results: Of the 24 patients enrolled on this trial, 19 were assessable for toxicity (median age at enrollment: 13, range 2–21 years, 10 male). Three patients experienced DLT: one at 13 mg/m2 had asymptomatic reversible T wave inversions in leads II, III and AVF; one at 22 mg/m2 experienced asymptomatic and reversible sick sinus syndrome and another patient 22 mg/m2 had reversible, asymptomatic T wave inversions in leads II, III and AVF as well as asymptomatic ventricular tachycardia. Six patients have been enrolled at 17 mg/m2; the 6th patient has yet to be evaluated for toxicity. No objective responses have been observed. Two patients with PNET and ependymoma had stable disease for 4 and 5+ courses, respectively. At 17 and 22 mg/m2, the median (range) depsipeptide CL and terminal t1/2 were 12.4 L/hr/m2 (3.5 - 28.9) and 2.2 hrs (1.1 - 3.8), respectively. Median (range) depsipeptide AUC0–24hr at 17 mg/m2 was 1.8 μg-hr/mL (1.1 - 4.8), which is comparable to reported adult exposure at this dosage. Immunostaining in PBMNC demonstrated an accumulation of acetylated H3 between 2–6 hours after the start of the depsipeptide infusion which lasted for up to 20 hours after the end of infusion. Conclusion: Depsipeptide is relatively well-tolerated in children when administered weekly × 3 every 28 days. DLTs include asymptomatic EKG changes, ventricular tachycardia and sick sinus syndrome. Depsipeptide PKs in children are similar to those previously reported in adults.: No significant financial relationships to disclose.
Induction chemotherapy followed by chemoradiotherapy and TME for high-risk locally advanced rectal cancer.
Authors: P. Ding, M. R. Weiser, C. Hajj, L. Saltz, N. H. Segal, K. A. Goodman
Journal: Journal of Clinical Oncology (2011)

e14059 Background: Induction chemotherapy (ICT) followed by chemoradiation (CRT) may improve tumor downsizing and disease control among patients (pts) with locally advanced rectal cancer (LARC). We retrospectively assessed the safety and short-term efficacy of ICT followed by CRT and total mesorectal excision (TME) in pts with high-risk LARC with or without resectable metastases. Methods: We reviewed records of 34 consecutive stage III (n=15) or stage IV (n=19) pts with locally advanced rectal tumors treated with ICT followed by CRT between 12/06-1/10. Pts had high-risk primary tumors based on advanced T and/or N stage by endorectal ultrasound and/or MRI: T3 (n= 28), T4 (n=6) and N1 (N=9), N2 (n=19). Recurrence-free (RFS) and overall survival (OS) were estimated by Kaplan-Meier method. Results: Median age was 52 yrs, 65% were female. Pts received a median of 6 cycles of 5-FU based ICT combined with oxaliplatin (n=29), irinotecan (n=2), or both (n=3). CRT (median dose 50.4 Gy) was delivered with continuous infusion 5-FU; one pt did not complete the prescribed CRT. During ICT, 9 (27%) pts experienced grade 3+ heme toxicity. Grade 3+ heme or GI toxicity occurred in 3 (9%) and 2 (6%) pts, respectively during CRT. 7 pts did not undergo surgery due to: progression of disease (n=2); comorbid disease (n=2); or pt refusal (n=3). 27 pts proceeded to TME including 14 with clinical distant metastasis, 11 of whom underwent metastasectomy; 3 additional pts no longer had clinically identifiable liver (n=2) or sacral (n=1) lesions. All 27 pts had complete rectal resection, one had a circumferential margin < 1 mm. 17 pts had tumor response > 90% including 9 with pathologic CR. 2 pts had pathologic CR in resected metastasis. Post-op complications included: pelvic abscess (n=1) and pulmonary atelectasis (n=1). With a median follow-up of 25 mos, none of the 27 pts who underwent rectal resection developed local recurrence. The 3 yr RFS and OS among resected stage III pts was 63% and 100%, respectively; 3-yr OS for resected stage IV pts was 82%. Conclusions: ICT prior to CRT is associated with acceptable toxicity, substantial tumor regression, and promising clinical outcomes in pts with high-risk LARC, including pts with resectable metastatic disease.
Phase II and pharmacological study of oral paclitaxel plus cyclosporine A in anthracycline pretreated metastatic breast cancer
Authors: H. H. Helgason, C. M. F. Kruijtzer, A. D. R. Huitema, S. Marcus, W. W. Ten Bokkel-Huinink, M. E. Schot, J. H. Schornagel, J. H. Beijnen, J. H. M. Schellens
Journal: Journal of Clinical Oncology (2005)

652 Purpose: Paclitaxel is an important chemotherapeutic agent for metastatic breast cancer and often used as second line treatment. Due to its high affinity for the drug efflux pump P-glycoprotein (P-gp) in the gastrointestinal tract the oral bioavailability of paclitaxel is low and variable. We demonstrated that administration of oral paclitaxel plus, the P-gp and cytochrome P450 3A4 inhibitor, cyclosporine A (CsA) is safe and results in adequate exposure to paclitaxel. In this study we evaluated the activity, toxicity and pharmacokinetics of paclitaxel combined with CsA in patients with advanced anthracycline pre-treated breast cancer. Methods: Patients with measurable metastatic breast cancer were treated with weekly oral paclitaxel 90 mg/m2, bi-daily with 7 to 12 hour interval, combined with CsA (10 mg/kg) given 30 minutes prior to each dose of paclitaxel. Results: Twenty-nine patients with a median age of 50 years were entered. All patients had received prior treatments and 25 had received prior anthracycline containing chemotherapy. Nineteen patients had three or more metastatic sites. Total number of weekly administrations was 442 (median 15 administrations/patient) and dose-intensity of 97 mg/m2/week. Most patients needed treatment delay (median 8 administrations/patient) and seventeen patients needed dose reductions (median one/patient), mostly because of mild neutropenia. Treatment toxicities were neutropenia G 3/4 (54%), with three febrile episodes, short lasting nausea G 1/2, vomiting G 1/2, diarrhea G 1–3 in 90%, 75% and 71% of patients respectively. Grade 1/2 and 3 neuropathy and grade 1/2 arthralgia/myalgia, not resulting in treatment delays, were reported in 57%, 18% and 57% of patients respectively. In intention to treat analysis the ORR was 51.7% (95% CI 33.5% - 69.9%) and OS 16 months (95% CI 9 - 24). The ORR of 23 evaluable patients was 65.2% (95% CI 45.7% - 84.7%) with median TTP 6.5 months (95% CI 4 - 10). The pharmacokinetics revealed moderate inter-patient (33% in week 1 and 27% in week 2), and low intra-patient variability (17%) in the AUC. Conclusion: Weekly oral paclitaxel, combined with CsA, is active and well tolerated in patients with advanced breast cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration IVAX Research Eli Lilly
Phase I trial of RAD001 (R) and docetaxel (D) in castration resistant prostate cancer (CRPC) with FDG-PET assessment of RAD001 activity
Authors: R. W. Ross, J. Manola, W. K. Oh, C. Ryan, J. Kim, I. Rastarhuyeva, J. T. Yap, A. D. Van Den Abbeele, P. W. Kantoff, M. Taplin
Journal: Journal of Clinical Oncology (2008)

5069 Background: Improved therapy for CRPC remains an urgent need. CRPCs have frequent loss of the tumor suppressor gene PTEN with increased expression of mTOR driving tumor growth. R is a novel mTOR inhibitor with demonstrated in vitro synergy with docetaxel. We report a phase I trial of R/D in CRPC. Methods: Eligible patients (pts) had metastatic, chemo-naive CRPC with rising PSA and positive FDG-PET. Pts received R 10mg daily without D for two weeks and had re-staging FDG-PET. Metabolic response was evaluated using EORTC PET criteria. Pts were then treated at three dose levels: R 5mg/D 60mg/M2 (level 1), R 10mg/D 60 mg/M2 (level 2) and R 10mg/D 70mg/ M2 (level 3). Pts were treated in standard cohorts of 3 pts per dose level with expansion by 3 pts if a dose limiting toxicity (DLT) was observed. If two DLTs were seen that dose level was dose limiting. Pharmacokinetic (PK) levels of R were obtained after one week of R alone, days 8, 22, 29 and day 43 of R/D. Results: All screening FDG-PET scans were positive. Accrual was: 4 at level 1 (one not evaluable for DLT), 3 at level 2, and 8 pts at level 3 (2 not evaluable for DLT). There were no DLTs during R/D. Common toxicities were hematologic and fatigue. PK values of R were 1.5–26.8 ng/mL day 8, 5.0–32.9 ng/mL day 22, 4.5–55.4 ng/mL day 29, 4.1–21.8 ng/mL day 43 and 6.8–47 ng/mL on day 50. All pts had positive baseline FDG-PET; 10/14 pts had metabolic SD, and 4/14 pts had metabolic PR (two bone, one bone/soft tissue, one soft tissue). Of these 4 pts, 3 had PSA response after combined therapy (4th had 44% PSA decline): 3 had normalization of alkaline phosphatase (4th had 72% decline). Conclusions: R 10mg daily and D 70mg/M2 is safe in CRPC and these are the recommended doses for phase II. All pts showed high glycolytic activity in metastatic lesions and R inhibited the glycolytic activity of the CRPC after 2 weeks in a proportion of patients, presumably via inhibition of mTOR. Moreover, 3/4 of these pts had a subsequent PSA and/or alkaline phosphatase response to R/D. Data from tumor biopsies performed immediately prior to treatment will be available. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis
Clofarabine-Based Consolidation Improves Relapse-Free Survival of Younger Adults with Non-Favorable Acute Myeloid Leukemia (AML) in First Remission: Results of the Randomized ALFA-0702/Clara Study (NCT 00932412)
Authors: Xavier Thomas, Stéphane De Botton, Sylvie Chevret, Denis Caillot, Emmanuel Raffoux, Emilie Lemasle, Jean-Pierre Marolleau, Céline Berthon, Arnaud Pigneux, Norbert Vey, Oumedaly Reman, Marc Simon, Christian Recher, Jean-Yves Cahn, Olivier Hermine, Sylvie Castaigne, Karine Celli-Lebras, Claude Preudhomme, Christine Terré, Hervé Dombret
Journal: Blood (2015)
Results of the MARS study on the management of antiangiogenics’ renovascular safety in ovarian cancer.
Authors: Vincent Launay-Vacher, Nicolas Janus, Frédéric Selle, Francois Goldwasser, Olivier Mir, Jean-Philippe Spano, Jean Christophe Thery, Philippe Beuzeboc, Jean-Baptiste Rey, Christelle Jouannaud, Jean F. Morere, Stephane Oudard, Joseph Gligorov, Michel Azizi, Richard Dorent, Gilbert Deray, Isabelle Laure Ray-Coquard, Florian Scotte
Journal: Journal of Clinical Oncology (2013)

5567 Background: Anti-VEGF drugs (AVD) are widely used in cancer patients (pts). Hypertension (HTN) and proteinuria (Pu) are class-side-effects of AVD, related to the inhibition of the VEGF pathway. The MARS study has been conducted to assess the renovascular tolerance of these drugs in the clinical setting. Methods: This multicentric, prospective, observational study evaluated the renovascular safety of AVD in pts naive from any AVD, conducted in 7 centres in France, from 2009 to 2012, with a follow-up (f/u) of 1 year. Data collected included: gender, age, serum creatinine (SCr), HTN, hematuria (Hu) and dipstick Pu, at baseline and at each visit. Results: 1,124 pts were included. 79 pts had ovarian cancer (OC) and all received bevacizumab. Median age at inclusion was 61 years. Visceral, bone and cerebral metastasis frequencies were 74.1, 52.7 and 6.0%, respectively. HTN prevalence was 16.5%. Baseline renal assessment retrieved: Pu 36.0%, Hu 21.3%, mean aMDRD 83.0 ml/min/1.73m 2 and 5 pts with aMDRD&lt;60. The incidence of de novo Pu and HTA during f/u was 56.8 and 21.2% (Table). 88.9 % of pts with Pu at inclusion improved or remained stable. Among pts with de novo Pu, 64.0% afterwards improved/normalized. No Grade 4 Pu has been reported (at inclusion or during f/u). Renal function remained stable with a mean aMDRD of 83.2 at the end of f/u. 6.0% had grade 2 SCr increase (no grade 3-4). No thrombotic micro-angiopathy (TMA) was reported. Conclusions: These results on the renovascular safety of bevacizumab in OC patients showed that 1) TMA is rare, 2) Pu develops in 56.8% of the pts, however with only 1 Grade 3/4, 3) 21.2% developed HTN, and 4) aMDRD was stable. Furthermore, in case of a renovascular effect, investigators followed the recommendations from the French Society of Nephrology (Halimi JM. Nephrol Ther 2008) and no treatment withdrawal for unmanageable renovascular toxicity occurred. [Table: see text]
Phase II study of chemoradiation plus bevacizumab (BV) for locally/regionally advanced nasopharyngeal carcinoma (NPC): Preliminary clinical results of RTOG 0615.
Authors: N. Y. Lee, Q. E. Zhang, A. S. Garden, J. J. Kim, D. G. Pfister, J. Mechalakos, K. Hu, Q. Le, B. S. Glisson, A. T. C. Chan, K. K. Ang
Journal: Journal of Clinical Oncology (2011)

5516 Background: To present progression-free survival (PFS), overall survival (OS), distant metastases-free (DMF), loco-regional progression-free (LRPF), and toxicity rates of chemotherapy, IMRT and BV for NPC. Methods: Patients with NPC, WHO I-IIb/III, stage ≥T2b and/or + node(s) were given concurrent 3 cycles of BV (15mg/kg) and cisplatin (CDDP; 100mg/m2) with IMRT (70Gy) followed by 3 cycles of adjuvant BV (15mg/kg), CDDP (80mg/m2) and fluorouracil (1,000mg/m2/d) q3 weeks. Results: From 12/06 to 2/09, 44 patients enrolled and eligible for analysis. Patients were male (65.9%), Asian (52.3%), Zubrod 0 (75%), and WHO IIb or III (72.7%) with a median age of 48.5 years. Stages: T1 27.3%; T2a 9.1%; T2b 6.8%; T3 34.1%; T4 22.7%; N0 11.4%; N1 18.2%; N2 59.1%; N3a 4.5%; N3b 6.8%; IIB 11.4%; III 54.5%; IVA 22.7%; IVB 11.4%. Median dose was 70 Gy. Percentages of patients receiving 3 cycles of CDDP and BV during IMRT were 68.2% and 70.5% while 47.7%, 54.5%, and 52.3% received 3 cycles of adjuvant CDDP, fluorouracil, and BV, respectively. Median follow-up for surviving patients was 2.0 years (1.0-3.1). The 2-year PFS and OS were 71.7% and 90.9%, respectively. Five patients experienced DM with 2-year DMF rate of 90.8%. Nine patients experienced LR failures with 2-year LRPF rate of 80.7%. The apparently lower LR control might be related to attribution we applied in unclear cases, i.e., death from study cancer or unknown causes without documented progression are considered LR failure (n=3). No Grade 3-4 hemorrhage or Grade 5 toxicity was observed. Blood/bone marrow toxicity was the most common Grade 4 toxicity and 77.3% experienced Grade 3-4 mucositis. Conclusions: The combination of chemotherapy, IMRT and BV in treating NPC was feasible in a multi-institutional setting. When comparing RTOG 0615 vs RTOG 0225 and Intergroup 0099, the preliminary findings reveal similar PFS but favor RTOG 0615 for OS. These preliminary findings seemed to suggest that BV prolongs OS by slowing down the progression of disease in those not cured with chemoradiation. However, the findings from these comparisons will need to be confirmed in a randomized setting, preferably in patients at high risk for DM.