tbuckley/cabot-search huggingface dataset:
A phase I/II trial of sorafenib (S) with bevacizumab (B) in metastatic renal cell cancer (mRCC) patients (Pts)
Authors: J. A. Sosman, K. Flaherty, M. B. Atkins, I. Puzanov, D. F. McDermott, W. Vermeulen, K. Harlacker, A. Hsu, M. Rothenberg
Journal: Journal of Clinical Oncology (2006)

3031 Background: In an effort to enhance the efficacy of vascular endothelial growth factor (VEGF) pathway blockade in mRCC we initiated a Phase I-II trial of combination S and B to block VEGFR signaling and VEGF binding, as well as, platelet derived growth factor receptor β (PDGFR) signaling. Methods: Pts with measurable (RECIST) mRCC, adequate organ function, and PS 0–1 were eligible for this trial. Cohorts of 6 pts were enrolled at 3 sites to define the MTD and DLT of the combination of S and B. The schedule was B IV q 14 days and S daily with cycles of 28 days. Response and toxicity were assessed at the end of 2 cycles. Dose levels began with S at 200mg BID and B at 5 mg/kg (level 1) with the hope to reach phase II doses of both agents (S at 400mg BID and B at 10mg/kg). The MTD or the phase II dose of each agent would then be administered to up to 45 pts with mRCC, clear cell histology, and prior nephrectomy. Results: A total of 18 patients have been enrolled to date, with 15 completing their first response evaluation. Pts were median age 61 years (46–74 range); M/F: 15/3; PS: 0/1= 12/6; 17 clear cell, 1 chromophobe, 11 prior nephrectomy; 4 with prior cytokine therapy. Two pts in level 1 experienced DLT with recurrent and intolerable (grade 3) hand-foot syndrome (HFS). An additional 6 patients were treated at dose level -1 (S at 200mmg QD and B at 3mg/kg) with no DLTs. Six more pts have been treated at dose level 1 with Vit B6 at 300mg/d in an attempt to minimize HFS. Toxicity data in this cohort is incomplete. Additional toxicities among the 18 pts included grade 3 hypertension (4), grade 3 proteinuria (2), and grade 2 stomatitis (3). Responses including 4 objective PRs, and 4 pts with 20–30% regression have been seen in the 14 evaluated pts. Only 2 patients have had disease progression. Conclusions: The phase II doses for this combination have not yet been established, but will likely be lower than the full phase II doses of the individual agents. The toxicities from HFS (primarily) and hypertension and stomatitis appear to be limiting. Even at the initial low doses of S and B, significant anti-tumor activity has been observed. The completion of this phase I trial will be reported. The phase II studies in mRCC are highly anticipated. Support by phase I contract UO-1 CA099177 [Table: see text]
Bevacizumab for recurrent ependymoma
Authors: R. M. Green, T. Cloughesy, R. Stupp, L. M. DeAngelis, E. A. Woyshner, D. E. Ney, A. B. Lassman
Journal: Journal of Clinical Oncology (2009)

2060 Background: Ependymoma is a rare type of glioma, representing less than 5% of brain tumors in adults. Radiotherapy (RT) is commonly administered, but there is no standard chemotherapy. At recurrence ependymoma is notoriously refractory to therapy and the prognosis is poor. In recurrent glioblastoma, encouraging responses with bevacizumab have been observed. Therefore, we treated patients with recurrent ependymoma and anaplastic ependymoma with bevacizumab containing chemotherapy regimens. Methods: We retrospectively identified adults treated for recurrent ependymoma and anaplastic ependymoma with bevacizumab containing chemotherapy regimens. We determined radiographic response (Macdonald criteria) and estimated median time to progression (TTP) and overall survival (OS) by the Kaplan-Meier method. Results: There were six patients, four women and two men, with a median age of 29 years (range, 20–65). Prior treatment included RT in all and temozolomide in four. Bevacizumab (5–10 mg/kg) every other week was combined with cytotoxic agents: irinotecan (3), carboplatin (2), or temozolomide (1). Five patients achieved a partial response (83%); in one patient the disease was stable. Median TTP and OS were 6.5 (95% CI: 2.7–10.2) and 9.4 (95% CI: 6.3–12.6) months, respectively, with a median follow up of 18.7 months for the two surviving patients. One additional patient is initiating bevacizumab monotherapy (not included in this analysis). Conclusions: Bevacizuamb has efficacy in the treatment of recurrent ependymoma. Prospective study is warranted. [Table: see text]
Tumor survivin expression in locally advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemoradiation followed by surgical resection
Authors: M. J. Fidler, A. Seba, E. C. Farlow, S. Basu, K. Kaiser-Walters, D. Steker, J. Coon, A. W. Kim, P. Bonomi, L. P. Faber
Journal: Journal of Clinical Oncology (2009)

7595 Background: Recently tumor molecular markers have shown promise as prognostic and predictive indicators for survival in early and advanced stage NSCLC patients (pts.) treated with chemotherapy. The objective of this study was to correlate immunohistochemistry (IHC) markers of pre-treatment biopsies in locally advanced NSCLC patients treated with concurrent platinum based chemoradiation followed by surgical resection. Methods: This is a retrospective study that included stage III NSCLC pts who had adequate pre-treatment tumor specimens and were treated with platinum based chemotherapy regimens and concurrent thoracic radiation (40 Gy). Thirty three pts had sufficient pre-treatment tissue for IHC and were identified from a surgical database. Cells were stained by IHC for frequency (0–4) and intensity (0–4) of ERCC1, PTEN, and survivin and analyzed by log-rank and multivariate Cox PH regression for potential relationships to pathologic complete response (pCR), time to recurrence (TTR), and overall survival (OS). Results: Characteristics of 33 pts: 15 females; median age 61; 17 adenocarcinoma, 10 squamous(sq), 5 undifferentiated, 1 adeno-sq. Median OS was 23 months (mo) (5.9–140), and median TTR was 14.7 mo (3.5–121). Following chemoradiation, 9 patients had pCR. pCR was associated with improved TTR, p &lt; .027. ERCC1 and PTEN were not significantly related to OS, TTR, or pCR. High nuclear survivin frequency (&gt;2) was associated with worse OS, HR 0.4, p&lt; .045 and lower nuclear survivin intensity (&lt;4) was marginally associated with pCR, p&lt; .10. Conclusions: In this exploratory analysis, higher survivin expression was associated with worse prognosis in locally advanced NSCLC patients treated with chemoradiation followed by surgery. These results suggest that additional studies of survivin are warranted in NSCLC and that adding survivin inhibitors to chemoradiation is a reasonable strategy for locally advanced NSCLC with high survivin expression. No significant financial relationships to disclose.
The benefits of early integration of palliative care as a part of standard outpatient oncology care.
Authors: Piyush Srivastava
Journal: Journal of Clinical Oncology (2014)

18 Background: It is well known that palliative care (PC) services are skillful in aligning patients' goals of care with healthcare team’s plan of care and treating symptoms related to an advanced disease. The culture of PC is now focusing efforts upstream since earlier interaction fosters more thoughtful discussion of goals and more effective symptom management. Decreased or late access to PC services has traditionally been due to physician factors, including inaccuracies in prognostication, personal bias and lack of awareness of PC mission. With this understanding, we have consciously constructed a robust, standardized, formalized process in the oncology setting for patient identification and automatic referral to the outpatient PC clinic as a part of usual care to diminish the influence of oncologists. Methods: Due to the wide geographic area of our population, there are five ½ day outpatient PC clinics, two of which are embedded in outpatient oncology centers at two medical centers. These are staffed by an MD and RN, with option of chaplain and social work interventions. The Edmonton Symptom Assessment Scale serves as our tool to monitor patient’s clinical course. We have created a reproducible, patient selection and outreach process to make PC as part of ‘normal’ cancer care. Results: 330 oncology patients were seen over a 20 month period. Of these only 8 PC clinic patients received chemotherapy in the last 30 days prior to death vs 153 patients who were not seen in PC clinic. Within the last 14 days of life no patients who were seen in PC clinic received chemotherapy vs 54 patients who were not seen in clinic. This compares well to the national average of 10%. 55% were referred to hospice compared to the national average of only 11%. The average LOS for hospice was 50.8 days compared to the national average of 40.6 days. ER visits decreased by 15% and hospital admissions decreased by 63% for patients with PC clinic encounters. Subjectively, patient’s symptoms improved by 75%. Conclusions: These upstream encounters facilitate more thoughtful medical decision making for patients with terminal cancer diagnosis, improving quality of care and QOL and positively affecting hospital utilization.
Hepatoma and Renal Tubule Adenoma in Rats Fed Aflatoxin and Cyclopropenoid Fatty Acids&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: D. J. Lee, J. H. Wales, R. O. Sinnhuber
Journal: JNCI Journal of the National Cancer Institute (1969)

A crude aflatoxin preparation containing 50% aflatoxin B1 and 42% aflatoxin G1 was fed to weanling male rats of the Long-Evans strain to supply 18.4, 184, 552, and 736 parts per billion total toxin. Duplicate groups fed the 3 lower levels of aflatoxin also received Sterculia foetida oil that supplied 220 parts per million cyclopropenoid fatty acids (CPFA). During the 18-month experiment, of the rats fed aflatoxin, 34% developed renal tubule adenomas, 10% hepatocellular carcinomas, and 31% hyperplastic liver nodules. S. foetida oil caused a slight but significant decrease in growth rate, and a slightly higher incidence of total tumors (70% as compared to 59%) was found in the animals fed CPFA together with aflatoxins.
Randomized trial of three combinations of cisplatin with vindesine and/or VP-16-213 in the treatment of advanced non-small-cell lung cancer.
Authors: H M Dhingra, M Valdivieso, D T Carr, D F Chiuten, P Farha, W K Murphy, G Spitzer, T Umsawasdi
Journal: Journal of Clinical Oncology (1985)

One hundred sixty-seven evaluable patients with non-small-cell lung cancer were randomized to receive high-dose cisplatin and vindesine (PVD), or cisplatin and VP-16-213 (etoposide epipodophyllotoxin) (PVP), or cisplatin with VP-16-213 and vindesine (PVPVD). The patient distribution and characteristics were similar in all the treatment arms. The response rate differences (35% in PVD arm, 30% in PVP arm, and 22% in PVPVD arm) were not statistically significant (P = .33). Response durations were 43 weeks in the PVD arm, 20 weeks in the PVP arm, and 27 weeks in the PVPVD arm. Median survival was 29 weeks in the PVD and PVP arms and 28 weeks in the PVPVD arm. Median survival time of responding patients was 76 weeks in the PVD arm and 65 weeks in the PVP arm; 78% of patients were alive at 22+ to 87+ weeks follow-up in the PVPVD arm. Myelosuppression was similar in all three treatment arms. Significantly more azotemia occurred in the PVD arm than in the PVP and PVPVD arms (P = .002), and significantly more neuropathy in the PVD and PVPVD arms than in the PVP arm (P = .003 and .005). All the treatment arms have similar antitumor activity in non-small-cell lung cancer, but the PVP combination is slightly less toxic than the PVD and PVPVD treatment arms.
Illness understanding in patients with advanced lung cancer
Authors: J. S. Temel, J. A. Greer, S. Admane, V. A. Jackson, J. A. Billings, C. M. Dahlin, J. C. Jacobsen, C. D. Blinderman, T. J. Lynch, W. F. Pirl
Journal: Journal of Clinical Oncology (2009)

9515 Background: Accurate understanding of prognosis among terminally-ill patients impacts decision-making at the end of life. The goal of this study was to explore illness understanding in patients with advanced non-small cell lung cancer (NSCLC). Methods: As part of a larger randomized study of integrated versus standard palliative care in an ambulatory thoracic oncology clinic, we recruited 120 patients within eight weeks of diagnosis of incurable NSCLC with a performance status of 0–2. Prior to randomization, patients completed questionnaires on quality of life (FACT-L) and mood (HADS), as well as the following items regarding illness understanding: 1) “My cancer is curable” (yes/no); “The goals of my therapy are: to help me live longer” (yes/no), “try to make me feel better” (yes/no), “to get rid of all my cancer” (yes/no); and 3) “My current health status is: relatively healthy, seriously but not terminally ill, or seriously and terminally ill”). Results: Approximately one third of patients (n=39/116, 33.6%) believed their cancer to be curable. While most patients felt that the goals of therapy were to help them live longer (n=110/113, 97.3%) and feel better (n=102/102, 100%), 66.0% (n=64/97) also believed that getting rid of all of the cancer was a treatment goal. Only 13.9% (n=16/115) of patients believed that their current health status was seriously and terminally ill. Patients who reported greater depression and anxiety symptoms on the HADS were more likely than those without such distress to believe that their cancer was curable (OR=2.47, p=.03) and that one of the goals of treatment was to get rid of all of their cancer (OR=3.83, p=.02). Conclusions: Despite having an incurable illness, the majority of patients with advanced NSCLC do not view themselves as terminally ill or have an accurate understanding of the goals of anti-cancer therapy. Given that patients often make treatment decisions based on their prognostic awareness, many of these individuals, particularly those with comorbid mood symptoms, may be at risk of pursuing unsuitable choices for their care. Interventions are needed to promote greater understanding of prognosis and goals of therapy in this population. No significant financial relationships to disclose.
A phase Ib study of BKM120 combined with abiraterone acetate for castrate-resistant, metastatic prostate cancer.
Authors: Akash Patnaik, Justin Kung, Massimo Loda, Mary-Ellen Taplin, Rosina Lis, Philip W. Kantoff, Steven P. Balk, Glenn J. Bubley
Journal: Journal of Clinical Oncology (2015)

274 Background: There is cross-talk between PI3-kinase (PI3K) pathway and androgen receptor (AR) signaling pathways, respectively, which are both critical for cell survival in castrate-resistant prostate cancer (CRPC). The primary study objective is to determine the safety profile and MTD of BKM120 (B, pan-PI3K inhibitor) in combination with abiraterone/prednisone (A/P) in CRPC patients. The secondary objectives are to assess the impact of PTEN status on duration of response/time to progression in the expansion cohort, and to evaluate the impact of B on a PI3-kinase activation fingerprint in metastatic bone or lymph node tissue samples. An exploratory objective is to assess the effect of B on transcription of a set of AR-regulated genes in metastatic bone biopsy samples. Methods: The trial design involves a 14 day lead-in phase with B alone, to assess single-agent toxicity and perform correlative studies. A/P is combined with B at the end of 14 days using the standard 3+3 dose-escalation design with 3 dose levels of B, and participants are assessed for safety and MTD on the combination therapy. To determine PD impact of single agent B on the PI3K activation signature at a metastatic site, a mandatory CT-guided bone or lymph node biopsy is performed prior to B initiation and at the end of 2 weeks on B single-agent therapy. Immunohistochemical (IHC) stains for three markers (p-AKT, p-S6 and PTEN) are used to obtain a semi-quantitative PI3K activation score, based on the quartile levels of continuous staining scores of each marker. Results: Patient 1 had symptomatic bone pain improvement, marked decline in narcotic pain requirements and a biochemical decline in PSA from 156.5 to a PSA nadir of 9.2 within 4 weeks of combination therapy. Patient 3 had a symptomatic and &gt;90% biochemical improvement and has currently completed 15 cycles on treatment, and remains on study to date. RT-PCR analysis showed that the feedback circuitry between PI3K and AR signaling is heterogeneous in the metastatic prostate cancer-bone microenvironment, and dependent on tumor PTEN status. Conclusions: Preliminary data shows promising anti-tumor activity in CRPC patients from dual targeting of PI3K and AR pathways with B and A/P, respectively. Clinical trial information: NCT01741753.
Abstract 13753: The Impact of Previous Permanent Pacemaker on Outcomes After Transcatheter Aortic Valve Replacement
Authors: Marco A Magalhaes, Sa`ar Minha, Israel M Barbash, Salem Badr, Hironori Kitabata, Omar Alfazir, Pendyala Lakshmana, Joshua P Loh, Hideaki Ota, Itsik Ben-Dor, Rebecca Torguson, Fang Chen, Petros Okubagzi, William O Suddath, Kenneth M Kent, Lowell F Satler, Augusto D Pichard, Ron Waksman
Journal: Circulation (2013)

Background: Although pacemaker implantation during TAVR has not been associated with unfavorable short-term outcomes, patients with previous long-term ventricular pacing may develop singular left v...
IND.175: Phase I study of daily oral AZD2171, a vascular endothelial growth factor receptor inhibitor (VEGFRI), in combination with gemcitabine and cisplatin (G/C) in patients with advanced non-small cell lung cancer (ANSCLC): A study of the NCIC Clinical Trials Group
Authors: G. D. Goss, S. Laurie, F. Shepherd, N. Leighl, E. Chen, I. Gauthier, N. Reaume, R. Feld, J. Powers, L. Seymour
Journal: Journal of Clinical Oncology (2007)

7649 Background: AZD2171 is an oral an inhibitor of the tyrosine kinase activity of all VEGFR subtypes. Objectives: To determine recommended phase II dose (RPTD), dose limiting toxicity (DLT), toxicity, pharmacokinetics and efficacy of AZD2171 with G/C, in pts with untreated ANSCLC. Methods: Eligibility: stage IIIB/IV NSCLC; PS 0–2; no prior chemotherapy (CT) for advanced disease; adequate hematological, biochemical and end-organ function; no significant hemoptysis or bleeding. Treated stable brain metastases were permitted. G 1,250 mg/m 2 day 1 &amp; 8 and C 80 mg/m 2 day 1 was given q3 weekly with AZD2171 starting day 2 cycle 1. Planned dose levels (DL) of AZD2171 were 30 and 45 mg once daily PK assayed in cycle 1&amp;2, response (RECIST) every 2nd cycle. Results: 14 pts enrolled. 30 mg (5 pts) and 45 mg (9 pts). Pt characteristics (n=13) median age 56; 11 PS 0–1; 9 males. No DLTs seen in initial 3 pts at 30 mg dose; nor in 9 pts at 45 mg dose. Actual median dose intensity for AZD2171 in cycle 1 (C1) was similar to planned in C1 for both DL (200 mg and 300 mg)), but was higher for 30 mg vs 45 mg for subsequent cycles (150 mg vs 134 mg). At the 45 mg DL 13 dose reductions occurred in 9 pts. Grade 3 adverse events occurred in 2 of 3 30 mg pts (1 hypertension (HT), 1 fatigue); at 45 mg 6 pts of 9 pts had grade 3 events (HT, fatigue, diarrhea, voice changes); 2 pts had grade 4 toxicity (1 reversible CNS ischemia, 1 fatigue). PK: no effect of AZD2171 on gemcitabine PK Objective response: 9 pts are evaluable (4 too early At 30 mg-PR 2, SD 1; at 45 mg-PR 3, SD 3. 2 additional patients were accrued at the 30 mg DL. Conclusions: Toxicities of this combination are manageable and predictable. HT was easily controlled with a standardized treatment algorithm. MTD was not reached at the 30 or 45mg dose level, but 30mg of AZD2171 appears better tolerated in combination with G/C and is suggested as the RPTD. Encouraging anti-tumor activity has been observed which does not appear dose dependent at the doses tested. No significant financial relationships to disclose.
Physiotherapy and Occupational Therapy vs No Therapy in Mild to Moderate Parkinson Disease
Authors: Carl E. Clarke, Smitaa Patel, Natalie Ives, Caroline E. Rick, Francis Dowling, Rebecca Woolley, Keith Wheatley, Marion F. Walker, Catherine M. Sackley
Journal: JAMA Neurology (2016)

<h3>Importance</h3> It is unclear whether physiotherapy and occupational therapy are clinically effective and cost-effective in Parkinson disease (PD). <h3>Objective</h3> To perform a large pragmatic randomized clinical trial to evaluate the clinical effectiveness of individualized physiotherapy and occupational therapy in PD. <h3>Design, Setting, and Participants</h3> The PD REHAB Trial was a multicenter, open-label, parallel group, controlled efficacy trial. A total of 762 patients with mild to moderate PD were recruited from 38 sites across the United Kingdom. Recruitment took place between October 2009 and June 2012, with 15 months of follow-up. <h3>Interventions</h3> Participants with limitations in activities of daily living (ADL) were randomized to physiotherapy and occupational therapy or no therapy. <h3>Main Outcomes and Measures</h3> The primary outcome was the Nottingham Extended Activities of Daily Living (NEADL) Scale score at 3 months after randomization. Secondary outcomes were health-related quality of life (assessed by Parkinson Disease Questionnaire–39 and EuroQol-5D); adverse events; and caregiver quality of life. Outcomes were assessed before trial entry and then 3, 9, and 15 months after randomization. <h3>Results</h3> Of the 762 patients included in the study (mean [SD] age, 70 [9.1] years), 381 received physiotherapy and occupational therapy and 381 received no therapy. At 3 months, there was no difference between groups in NEADL total score (difference, 0.5 points; 95% CI, −0.7 to 1.7;<i>P</i> = .41) or Parkinson Disease Questionnaire–39 summary index (0.007 points; 95% CI, −1.5 to 1.5;<i>P</i> = .99). The EuroQol-5D quotient was of borderline significance in favor of therapy (−0.03; 95% CI, −0.07 to −0.002;<i>P</i> = .04). The median therapist contact time was 4 visits of 58 minutes over 8 weeks. Repeated-measures analysis showed no difference in NEADL total score, but Parkinson Disease Questionnaire–39 summary index (diverging 1.6 points per annum; 95% CI, 0.47 to 2.62;<i>P</i> = .005) and EuroQol-5D score (0.02; 95% CI, 0.00007 to 0.03;<i>P</i> = .04) showed small differences in favor of therapy. There was no difference in adverse events. <h3>Conclusions and Relevance</h3> Physiotherapy and occupational therapy were not associated with immediate or medium-term clinically meaningful improvements in ADL or quality of life in mild to moderate PD. This evidence does not support the use of low-dose, patient-centered, goal-directed physiotherapy and occupational therapy in patients in the early stages of PD. Future research should explore the development and testing of more structured and intensive physical and occupational therapy programs in patients with all stages of PD. <h3>Trial Registration</h3> isrctn.org Identifier:ISRCTN17452402