tbuckley/cabot-search huggingface dataset:
Randomized, double-blind, placebo-controlled study of palifermin for the prevention of mucositis in patients receiving doxorubicin-based chemotherapy
Authors: S. Vadhan-Raj, J. C. Trent, S. R. Patel, D. M. Araujo, J. A. Ludwig, D. Bailey, X. Zhou, A. Gillenwater, A. El- Naggar, R. S. Benjamin
Journal: Journal of Clinical Oncology (2008)

9547 Background: Mucositis is a common complication in patients (pts) receiving chemotherapy (CT). Palifermin, a recombinant keratinocyte growth factor, has been shown to reduce mucositis when given as 3 doses both before and after intensive therapy with hematopoietic stem cell support. The purpose of this study was to evaluate the safety and efficacy of palifermin administered as a single dose prior to CT in pts receiving multi-cycle CT. Methods: 48 sarcoma pts were randomized 2:1 to palifermin vs placebo. All pts received doxorubicin (90mg/m2 by continuous infusion over 3 days) with ifosfamide (10 gm/m2over 4 days) or cisplatin (120 mg/m2 on day1). The blinded study drug (palifermin 180 mcg/kg or placebo) was administered IV 3 days prior to CT. The cycles were repeated at 3 weeks (max 6 cycles). Pts who experienced ≥ gr 3 mucositis received open label palifermin in subsequent cycles. Results: All 48 pts have been enrolled; 12 are still on treatment. There were 25 males and 23 females, with median age 41 (range, 15–64 yrs). So far, 7 pts have experienced severe (≥ gr 3 WHO criteria) mucositis, and received open label palifermin in subsequent cycles. None of the 7 pts experienced severe mucositis in the open label phase. The common side effects included feeling of thickness of tongue and oral mucosa, and altered taste. No serious adverse event related to the study drug was observed. Histopathologic evaluation of buccal mucosal biopsies in a few pts performed, revealed increased epithelial thickness and elevated proliferative index using Ki-67 marker after the study drug. The study is planned to be completed and un-blinded by May 2008. Conclusions: Palifermin alleviated severe mucositis in pts who previously experienced severe mucositis during multi-cycle CT. Parameters Blinded study drug cycle* Open-label Palifermin cycle* P value Wilcoxon signed-rank No. of pts with ≥ gr 3 mucositis 7 0 <0.001 Median cycle No. 2 3 Days of ≥ gr 3 6 (3–9) 0 (0–0) 0.016 Days of ≥ gr 2 9 (5–13) 0 (0–4) 0.016 Weight change (kg) −3.3 (−1.3–−8.9) +0.5 (−4.1–+1.7) 0.031 * Same dose CT Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen
A phase II study of gefitinib as a first-line therapy for advanced non-small cell lung cancers with epidermal growth factor receptor (EGFR) gene mutations
Authors: H. Asahina, K. Yamazaki, I. Kinoshita, S. Ogura, T. Ishida, H. Dosaka-Akita, H. Isobe, M. Nishimura
Journal: Journal of Clinical Oncology (2006)

13014 Background: Activating mutations in exon 18–21 of the epidermal growth factor receptor (EGFR) gene have been reported to be a predictor of response to gefitinib. We conducted a phase II study to evaluate the efficacy and safety of gefitinib as a first-line therapy for advanced non-small cell lung cancers (NSCLCs) with EGFR gene mutations. Methods: The primary endpoint was response rate (RR). Eligiblity criteria were stage IIIB or IV chemotherapy naive NSCLC, ECOG PS of 0–2, adequate organ functions, measurable lesions, and written informed consent. First, we examined EGFR gene mutations in exon 18–21 by direct sequencing of PCR products of DNA extracted from paraffin-embedded tissues. Those who had EGFR gene mutations received gefitinib 250 mg daily. This study, with a sample size of 14, had 90% power to support the hypothesis that true RR was ≥70%, and 5% significance to deny the hypothesis that true RR was ≤30%. Assuming an inevaluality rate ≤15%, we projected an accrual of 16 patients. Results: From Nov. 2004 to Jan. 2006, EGFR gene mutations were analyzed in tumor specimens from 82 patients. Twenty patients (24%) had EGFR gene mutations (16 with deletions in or near E746-A750, 4 with L858R). While there were no significant differences between mutation status and age, sex, histology, or the procedures to obtain tumor specimens, EGFR gene mutations were more frequently observed in never-smokers than in smokers (39% vs. 11%, p&lt;0.01). Sixteen patients (median age, 68; male/female, 3/13; adenocarcinoma/SCC, 15/1; current/former/never smoker, 2/1/13) were enrolled and treated with gefitinib. To date, best response is 2 CR, 7 PR, 1 SD and 1 PD (RR, 82%). Two patients had grade 3 toxicities, including 1 skin eruption and 1 liver dysfunction. One patient had grade 1 interstitial lung disease, leading to the termination of gefitinib treatment. Conclusions: Gefitinib is very active and well tolerated as a first-line therapy for advanced NSCLCs with EGFR gene mutations. No significant financial relationships to disclose.
Education for educating surgeons
Authors: G. Batstone
Journal: BMJ (1996)

though screening is demonstrably cost effective.4Foremost among the unresolved questions is the ability of physicians to treat bone disease once it is detected.The number ofknowledgeable physicians is increasing, but not enough for them to manage the 100-fold increase in caseload that could result from population screening.Today less than 5% of patients with fracture undergo densitometry, and less than one third of the potential patients with indications (for example, those taking corticosteroids or with malabsorption or hyperparathyroidism) are symptomatic.Barlow and col- leagues note that critics confuse clinical densitometry in patients showing symptoms or indications with screening.'Physicians must become educated about bone disease so that they can manage effectively the increased caseload that will result from justified use of densitometry, and they must not be misled by disingenuous arguments against screening.
Building on good data foundations
Authors: T. Bloom
Journal: BMJ (2015)

“Healthcare generates a vast rainforest of data that could be used more widely for research if barriers to access could be overcome,” say Ruth Gilbert and colleagues in an Editorial (doi:10.1136/bmj.h5897). The barriers include the cost of access and cumbersome application processes. And where are the incentives to provide data for research? Could we quantify the lost opportunities of research not done and do more to encourage data providers to list who has accessed their data and to what end?

Large scale imaging studies are now recruiting hundreds of thousands of volunteers, and we can expect thousands of incidental findings to crop up, say J M Wardlaw …
Asian race and breast cancer subtypes: A study from the California Cancer Registry
Authors: M. L. Telli, A. W. Kurian, E. T. Chang, T. H. Keegan, J. M. Ford, S. L. Gomez
Journal: Journal of Clinical Oncology (2008)

6618 Background: Distinct breast cancer subtypes have been identified by gene expression analysis. Little is known about the distribution of these subtypes among Asian women. Methods: Immunohistoch...
Interleukin-2 (IL-2)-based immunotherapy for the treatment of metastatic renal cell carcinoma (mRCC): An analysis of 422 consecutive patients treated between 1999 and 2008.
Authors: F. Donskov, H. K. Jensen, A. N. Jeppesen, K. Fode, H. Schmidt, M. Agerbaek, L. Broendum, H. von der Maase
Journal: Journal of Clinical Oncology (2010)

4591 Background: IL-2 is potentially curative in a subset of patients with mRCC. We assessed our 10 years experience of outpatient subcutaneous IL-2 based immunotherapy at a single institution. Methods: Between 1999-2008, 422 consecutive patients with progressive, non-resectable mRCC were treated with first-line s.c IL-2 and s.c. interferon-alpha (IFN) based immunotherapy. Treatment was given for a maximal duration of 9 months followed by surgery of residual disease, if applicable, and then followed by observation. Patients obtaining no evidence of disease (NED) were characterized in regards to well known prognostic features and correlated to the non-NED cohort. TKIs became available at our institution in 2006 and were given following relapse. Results: Overall response rate was 15%, which included 17 complete responses and 47 partial responses. Forty patients had surgical resection of residual disease following immunotherapy. Of these, 35 patients had vital tumor cells within resected residual lesions. A total of 36 patients (9%) obtained NED with a median follow-up of 76 months (range 10.2–131 mo). The median overall survival was 15.7 months (95%CI, 13.3-18.0 mo), the estimated 5-year survival rate was 15%, and the estimated 10-year survival rate was 10%. No patients obtaining NED had received TKI at any time. Patients obtaining NED (N=36) had the primary kidney tumor in place (28%), lymph nodes mets (36%), liver mets (14%), bone mets (17%), adrenal gland mets (14%) and lung mets only (19%). A total of 25 patients (69%) had 1 or 2 disease sites. 83% had baseline Karnofsky performance of 100 or 90. 94% had MSKCC favorable or intermediate prognosis. A detailed analysis of NED-patients compared with non-NED patients will be presented. Conclusions: IL-2 based immunotherapy, either alone or in combination with surgery, resulted in no evidence of disease in 9% of patients and an estimated 10-year survival rate of 10%. IL-2 based immunotherapy should still be a viable first line treatment option as this approach is potentially curative in selected patients with mRCC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis
Sorafenib for the treatment of metastatic renal cancer (MRC) in the real world: The Princess Margaret Hospital (PMH) experience
Authors: S. Chin, R. P. Riechelmann, L. Wang, I. F. Tannock, D. R. Berthold, M. Moore, J. J. Knox
Journal: Journal of Clinical Oncology (2007)

15568 Background: Sorafenib, an oral multi-kinase inhibitor, prolonged progression free survival (PFS) of MRC patients (pts) in second line when compared to placebo in a phase III trial (Escudier at al ECCO 2005). Grade 3/4 adverse events (AE) were reported in 12% of pts. Here we present sorafenib’s efficacy and safety in a less selected cohort of pts enrolled in the Bayer Expanded Access Program at PMH. Methods: Pts with MRC received Sorafenib 400 mg bid continuously until disease progression (PD) and/or clinical deterioration..Tumor response was measured by RECIST criteria. AE were graded by NCI common toxicity criteria. Summary statistics and logistic regression were used to describe the results. Results: From Nov 2005 to Aug 2006, 58 pts were enrolled: median age was 59 years (range 14–86), 47 (81%) were male, 48 (83%) had clear cell histology and 46 (79%) received Sorafenib in first line. None received prior kinase-inhibitors. Using the Motzer Prognostic Index, 29 pts (50%) were low risk, 21 (36%) intermediate and 8 (14%) poor risk. Grade 3/4 AE occurred in 37 pts (64%, 95% CI 50–76%): 15 (26%) pts had skin rash, 10 (17%) hand-foot syndrome, 4 (7%) hypertension, 4 (7%) fatigue, and 4 (7%) diarrhea. Thirty-six (62%) pts required dose reductions and/or treatment interruptions, most due to skin reactions and hand-foot syndrome. Median follow-up was 9 months (IQR range 2–11), the median PFS was 7.5 months (IQR range 5.4–11.3), and the best responses among 56 evaluable pts were: 10 (17%) confirmed partial responses (median duration: 6 months, range 4–11), 14 (24%) stable diseases for = 6 months and 10 (18%) early progression. Pts with bony mets progressed earlier than pts without bony mets. Abnormal creatinine clearance, age, performance status, line of treatment and presence of significant comorbid conditions were not associated with grade 3/4 AE in univariate analysis. Conclusions: Sorafenib is effective in a ”real world”, less selected patient population with MRC but leads to more toxicity than described previously. [Table: see text]
ERCC1 and beta tubulin class III (BT-III) expression by quantitative immunofluorescence (IF) in the responder and non-responder group of patients with advanced non-small-cell lung cancer after 2 cycles of cisplatin (P) and vinorelbine (Vn) chemotherapy
Authors: S. Park, J. Park, S. Kim, M. Kim, H. Kim, K. Nam
Journal: Journal of Clinical Oncology (2008)

19065 Background: Recent data indicates that ERCC1 expression correlates with platinum responsiveness in adjuvant therapy and in stage IV disease. BT-III expression has been correlated to sensitivity to anti-tubulin agents. We investigated whether ERCC1 and BT-III expression level is correlated with clinical responsiveness in the patients treated with PVn chemotherapy utilizing a novel quantifiable IF method to assess ERCC1 and BT-III expression. Methods: We retrospectively studied 36 patients who received the first line chemotherapy of P 60 mg/m2 D1 and Vn 25 mg/m2 D1, D8 q 3 weeks and were categorized into 2 groups of responder(R) and non-responder(nR) (defined as more than partial response and as stable disease or progressive disease, respectively, after 2 cycles of chemotherapy). Paraffin embedded tumor specimens were analyzed by quantitative IF staining for ERCC1 and BT-III expression using anti-ERCC1 (clone 8F1, GeneTex) and anti-beta tubulin class III (clone SDL.3D10, Sigma-Aldrich) respectively. The intensity of IF was measured quantitatively with a digitalized microscopy system (expression level from 0 to 10) and expressed as the mean of the average fluorescence per pixel. Results: Among 36 patients who received the first line PVn chemotherapy 2 cycles, R was 19 and nR 13 (RR 59%). 32 tumor specimens were available for IF staining, but 26 cases were analyzable by quantitative IF staining (excluded 3 cases each from R and nR). ERCC1 expression in R ranged from 1 to 8 (mean 3.17, SD 1.76) and that in nR ranged from 1.5 to 10 (mean 4.94, SD 2.55, p=0.063). BT-III expression in R ranged from 1 to 9.7 (mean 3.87, SD 2.20) and that in nR ranged from 0.5 to 9.7 (mean 3.08, SD 3.02, p=0.474). R/nR ratio in high(+) ERCC1/high(+)BT-III was 3/1, +/low(−) 3/5, −/+ 5/2, −/− 4/3. Conclusions: Clinical responsiveness of cisplatin and vinorelbine chemotherapy in the patients with advanced non-small-cell lung cancer was good and we observed a tendency toward correlation between ERCC1 expression and clinical responsiveness but poor correlation in terms of BT-III expression within the limitations of small sample size. No significant financial relationships to disclose.
A phase I study with CP-4055 in patients with hematologic malignancies
Authors: S. M. O'Brien, N. Vey, D. A. Rizzieri, H. M. Kantarjian, T. Prebet, F. Ravandi, T. F. Jacobsen, B. I. Nilsson, K. Staudacher, F. J. Giles
Journal: Journal of Clinical Oncology (2008)

2532 Background: CP-4055 (ELACYT, cytarabine 5’-elaidic acid ester) is a novel derivative of cytarabine, CP-4055 is independent of nucleoside transporters for cellular uptake. This first study in patients (pts) with hematologic malignancies aims at determining the maximum tolerated dose (MTD) and the preferred infusion time in this population. Methods: Pts received IV CP-4055 over 2–4 hours (2–4 hr IV, Arm A) or 24 hours (CIV, Arm B) in a day (d) 1–5 q3w schedule. The starting dose was 300 mg/m²/d (Arm A) and 200 mg/m²/d (Arm B), with standard definitions of DLT. Dosing increments were by 50% until nonhematologic toxicities, and thereafter by 30% (3+3 pts per dose level). Results: In the ongoing study, 66 pts [43 male, median age 61 yrs (range 21–92); AML (57pts), BAL (1), MDS (1), ALL (3), CML-BP (2), CMML-AML (2), average 2–3 lines prior chemotherapy (range 0–7)] have been treated at 4 centers. 7 pts are ongoing. MTD has been determined at 2500 mg/m²/day for both Arm A and B. All DLTs were reversible elevations of LFTs. Nausea, diarrhea, fever, thrombocytopenia, elevation of liver function tests (LFTs), constipation and anemia were the most common possibly related AEs. 1 CR (maintained after 4 courses), 1 CRp and 2 PR were reported at doses 875 - 2,000 mg/m2/d (all AML, age 50–92 yrs). 10 pts with stable disease/mild myelosuppression received > 2 courses of CP-4055. 1 pt was referred to stem cell transplantation. Conclusions: Patients with hematologic malignancies tolerate CP-4055 well. The MTD was 2500 mg/m²/d for both 2–4 hr IV and CIV. Clinical activity has been observed with minimal nonhematologic toxicity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Clavis Pharma ASA Clavis Pharma ASA Clavis Pharma ASA Clavis Pharma ASA
Relapsing low-grade glioma treated with bevacizumab and irinotecan as third-line therapy.
Authors: A. Menendez, W. Arias Sifontes, A. G. Menendez Rivera
Journal: Journal of Clinical Oncology (2010)

e12556 Background: A 63-year-old Hispanic patient was diagnosed as right side fronto-temporal grade 2 astrocytoma with gemistocytic changes on 10/2006. He underwent subtotal resection with placement of carmustine wafer, fractionated RT (6,300 cGy) and temozolomide 75 mg/m2 for 42 ds. He received mantainance therapy with temozolomide 150 mg/m2 for 5 days every 28 ds. Following relapse after 10 months he underwent stereotactic radiosurgery but 4 weeks later his condition worsened; an MRI showed progression of tumor size with edema involving the right basal ganglia, frontal and temporal regions. CCNU/procarbazine was started but stopped after 7 ds because of severe vomiting. He presented 4 months later in a stuporous state with left side paralysis and expressive-receptive aphasia. Methods: On 04/2008 therapy was started with bevacizumab (Bv) 10 mg/kg and irinotecan (Iri) 340 mg/m2 every 2 weeks. Results: 24 hrs after treatment he began to open eyes, moved his left fingers and toes and understood words. Further improvement was seen after each cycle; he could resume work and walk with a walking device. A brain MRI after the fifth dose of Bv-Iri revealed a 47% reduction in tumor size and almost complete resolution of edema. Before the sixth dose he developed bowel obstruction, one week later underwent the first of several laparotomies and eventually died of abdominal sepsis. Conclusions: Although low-grade gliomas are considered chemotherapy-resistant recent reports indicate some response to temozolomide.Bev-Iri has been used for high-grade gliomas with promising reports in glioblastoma multiforme. Our case showed high-risk features: subtotal resection, older than 40 yr, tumor beyond middle line and third line of therapy. However, an impressive clinical response was accompanied by a substancial reduction in tumor size. This response suggests that Bev-Iri has some activity for low-grade gliomas especially considering that only 5 doses could be given. These findings warrant further evaluation in well designed randomized, controlled trials. No significant financial relationships to disclose.
Sunitinib (SU) in combination with pemetrexed (P) in patients (pts) with advanced solid malignancies: A phase I dose escalation study
Authors: L. Q. Chow, D. J. Jonker, S. A. Laurie, J. A. Call, S. G. Diab, G. Goss, M. McWilliam, E. Wang, R. Chao, S. G. Eckhardt, D. R. Camidge
Journal: Journal of Clinical Oncology (2008)

3566 Background: SU is an oral multitargeted tyrosine kinase inhibitor of VEGFRs, PDGFRs, KIT, FLT3, CSF-1R, and RET, approved multinationally for the treatment of advanced RCC and imatinib-resistant/intolerant GIST. NSCLC xenograft data indicate SU enhanced the antitumor activity of P and support studies with SU+P. This ongoing, open-label, phase I study investigated the maximum tolerated doses (MTDs), safety, pharmacokinetic (PK) profile and efficacy of SU+P in pts with advanced solid malignancies. Methods: Successive pt cohorts received escalating daily doses of oral SU at 25, 37.5, or 50 mg on continuous 3-wk cycles (continuous daily dose [CDD] schedule) or for 2 wks of a 3-wk cycle (2/1 schedule) with escalating doses of P at 300–500 mg/m2 IV q21d. MTD was defined as the highest dose at which 0/3 or 1/6 pts had dose-limiting toxicities (DLTs) during cycle 1. Safety was evaluated and PK profiles were analyzed for SU, P and SU+P. In pts with measurable disease, objective response was determined by RECIST. Results: As of Dec 2007, 20 pts received SU (CDD) + P in 4 dose-escalation cohorts (NSCLC n=3). DLTs included febrile neutropenia (n=1; SU 37.5 mg + P 500 mg/m2), grade (G) 3 anorexia ≥7 days and G5 cerebral hemorrhage (each n=1; SU 50 mg + P 500 mg/m2). MTD was established as SU 37.5 mg (CDD) + P 500 mg/m2. Non-hematologic, all causality ≥G3 AEs (≥2 pts) included: fatigue (n=5), anorexia (n=3), febrile neutropenia, syncope, and hypoxia (each n=2). G4 lab abnormalities included lymphopenia (n=2), neutropenia, thrombocytopenia and leucopenia (each n=1). Two G5 AEs were reported: cerebral hemorrhage (considered possibly related to SU) and sudden death (considered related to underlying disease). PK data revealed no clinically significant drug-drug interactions with co-administration (all dose levels). To date 1 pt (cholangiocarcinoma, SU 37.5 mg + P 300 mg/m2) had a documented PR maintained >12 cycles and 8 pts have SD (5 pts with SD >3 months, [NSCLC n=1] range 3.0–6.5+ months). Data will also be presented on the ongoing 2/1 schedule cohort. Conclusions: SU 37.5 mg/day (CDD schedule) + P 500 mg/m2 q21d has a manageable safety profile and shows preliminary evidence of efficacy. Further studies of SU+P are planned in additional pt populations including NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Pfizer
Optimal criteria of treatment change for advanced gastric cancer patients with nonmeasurable peritoneal metastasis alone.
Authors: Hiroko Hasegawa, Kazumasa Fujitani, Shoichi Nakazuru, Motohiro Hirao, Eiji Mita, Mitsugu Sekimoto, Toshimasa Tsujinaka
Journal: Journal of Clinical Oncology (2013)

103 Background: Palliative chemotherapy is the mainstay for the treatment of advanced gastric cancer (AGC) patients with peritoneal metastasis. In general, chemotherapy regimen is changed when patients show disease progression on CT scan. However, nearly 40% of these patients have no measurable lesions. It remains uncertain how clinicians can decide the timing of treatment change for AGC patients with non-measurable peritoneal metastasis alone. Methods: There were 217 patients with primary unresectable or recurrent gastric cancer at our institution between April, 2005 and March, 2012. Among them, 50 patients, who had histologically proven non-measurable peritoneal metastasis alone, were retrospectively identified and investigated in this study. They underwent measurements of tumor markers (TM) every month and abdominal CT scan every 2 months. For these 50 patients, chemotherapy regimen was changed based on the following different 2 criteria; 1. elevated TM and/or aggravated clinical symptoms alone (n=21), 2. radiologically confirmed disease progression (n=29). We assessed whether these two different criteria have any impact on overall survival (OS) by univariate and multivariate analyses. Results: Median survival time of all 50 patients was 604 days. Multivariate analysis identified pre-treatment performance status of 0-1 (hazard ratio (HR) 0.211, 95% confidence interval (CI) 0.045–0.998, P=0.049), initial hemoglobin level of 10 mg/dl or more (HR 0.114, 95% CI 0.014–0.936, P=0.043) and the TM / symptom based treatment change (HR 0.124, 95% CI 0.043–0.360, P=0.001) as significant prognostic factors for favorable OS. Conclusions: Early decision making of treatment change based on elevated TM and/or aggravated clinical symptoms alone might contribute to longer OS in AGC patients with non-measurable peritoneal metastasis alone.