tbuckley/cabot-search huggingface dataset:
Solid tumor cancer patients treated with zoledronic acid experienced reduced skeletal related events as compared to untreated patients in clinical practice claims database
Authors: H. T. Hatoum, S. Lin, M. R. Smith, V. Barghout, K. Koukouras, A. Lipton
Journal: Journal of Clinical Oncology (2007)

6596 Background: Patients (pts) with bone metastasis are at high risk for skeletal related events (SREs), leading to increased morbidity, mortality, and decreased QOL. Methods: To study the impact of zoledronic acid on SRE rates, follow-up duration (from 1st bone metastasis diagnosis to last claim) in treated pts as compared to the experience of non bisphosphonate-treated pts (untreated), and to investigate relative impact of zoledronic acid (ZA) frequency of administration using data from PharMetrics integrated claims database of 80 health plans across the U.S, from Jan 02 to Oct. 05. Results: There were 1,518 ZA treated-pts and 3308 untreated-pts, who met study inclusion criteria of having breast, prostate, or lung cancers, with confirmed bone metastasis and SRE experience. At baseline, breast cancer pts (N=1,799) had lowest Charlson Co-morbidity Index (CCI); lung cancer pts (N=2,413) had highest CCI (p&lt;0.05). Prostate cancer pts (N=622) were significantly older (p&lt;0.05). The average monthly ZA prescription rate (Rx) was 0.73 with average total Rxs of 7.82 over the follow-up duration. ZA use reduced monthly SRE rate by 30% from 0.41 ± 0.4 in untreated pts to 0.29 ± 0.3 in treated pts (p&lt;0.001) and prolonged follow-up durations in months from 9.4 ± 9.8 in untreated to 12.2 ± 9.0 in treated pts (p&lt;0.001). Regression models of SRE rate or follow-up duration as the dependent variable investigating the impact of ZA prescribing patterns indicated that pts who followed ZA label dose of 4 mg every q3, q4 experienced the lowest SRE rate (p&lt;0.001) and had longer follow-up duration (p&lt;0.005) as compared untreated pts. ZA use almost doubled time to 1st SRE from 101±165 days in untreated pts, to 185±210 days in treated pts (p&lt;0.0001). ZA also delayed time between 1st to 2nd SRE from 85 days in untreated to 111 days in treated pts (p&lt;0.05). Conclusion: Zoledronic acid significantly reduced SRE rate in cancer pts with bone metastasis by 30%, increased follow-up duration by almost 3 months, doubled time to 1st SRE, delayed time to 2nd SRE, with its label dose of 4 mg every 3 to 4 weeks achieving the best outcome. No significant financial relationships to disclose.
A multidisciplinary clinic to mitigate the impact of androgen deprivation therapy in prostate cancer: A pilot study.
Authors: Rahul Raj Aggarwal, Tammy J. Rodvelt, Michael W. Rabow, Greta Macaire, Regan Fedric, Geronima Cortese-Jimenez, Eric Jay Small
Journal: Journal of Clinical Oncology (2015)

218 Background: Androgen deprivation therapy (ADT) increases the risk of numerous metabolic toxicities, including weight and body fat gain, insulin resistance, and osteoporosis. Many of these toxicities can be mitigated with lifestyle changes and monitoring of cardiovascular and diabetes risk factors, however, these are not routinely implemented in clinical practice. We designed a pilot study to evaluate whether a structured multidisciplinary (multi-D) clinic can lessen the metabolic impact of ADT. Methods: Patients who started ADT within the past 6 months were enrolled in the year-long multi-D clinic consisting of monthly face-to-face visits and individualized counseling from registered dietitian, certified exercise physiologist, and symptom management specialist, and assessment of weight, body mass index, percent body fat, fasting glucose, lipids, and hemoglobin A1c on an every 3 month schedule. The primary endpoint for this pilot study was the patient adherence rate to the clinic visit schedule, with a targeted goal of greater than 80%. Secondary endpoints included maximal percent change from baseline in metabolic parameters as outlined above. Results: 22 patients were enrolled between November 2013 and May 2014. Participation in the multi-D clinic was high, with a 95% adherence rate to the clinic schedule. The mean maximal percent change from baseline in metabolic parameters is shown below in the Table. Conclusions: Conducting a multi-D clinic for men receiving ADT was feasible, with an adherence rate of over 90%. The metabolic impact of ADT during the 12-month clinic participation was minimal and compares favorably to historical controls, but may be due to selection bias. A randomized phase 2 study comparing multi-D clinic to usual standard of care is ongoing to validate these findings. [Table: see text]
Improved progression free survival (PFS), and rapid, sustained decrease in tumor perfusion among patients with advanced carcinoid treated with bevacizumab
Authors: J. C. Yao, C. Ng, P. M. Hoff, A. T. Phan, K. Hess, H. Chen, X. Wang, J. L. Abbruzzese, J. A. Ajani
Journal: Journal of Clinical Oncology (2005)

4007 Background: Carcinoid is a vascular tumor that expresses VEGF. Effective systemic therapy for advanced disease is lacking. We are evaluating anti-angiogenic therapy in a phase II study of Bevacizumab (BVZ) and PEG Interferon alpha-2b (PEGI) in patients with metastatic or unresectable carcinoid tumors. Methods: Patients on a stable dose of octreotide were randomly assigned to therapy with BVZ or PEGI for 18 weeks. After 18 weeks, the patients receive both drugs. Functional CT was used to monitor changes in blood flow (BF), blood volume (BV), and permeability surface (PS). PFS durations, calculated by Kaplan Meier method, were compared by log rank test. Results: Planned accrual of 44 patients is complete. 41 (20 BVZ, 21 PEGI) have completed at least 9 weeks of therapy. 35 (18 BVZ, 17 PEGI) patients have completed 18 weeks of octreotide plus BVZ or PEGI. We have previously reported decreased in tumor perfusion within 48 hours of treatment with BVZ by functional CT (ASCO 2004 abstr # 3013). We now also reported sustained decrease in tumor perfusion at week 18 (21 days after the previous dose of bevacizumab). By RECIST criteria, 3 PR (3 BVZ, 0 PEGI), 31 SD (16 BVZ, 15 PEGI), 6 PD (1 BVZ, 5 PEGI) have been observed. An additional patient achieved PR on BVZ + PEGI following PD on PEGI alone. Twenty-two patients remain on study. PFS duration was superior in the BVZ arm (P=.01). PFS rates after 18 weeks of monotherapy were 95% in BVZ versus 67% in PEGI arm. During the 18 weeks of monotherapy, ≥ 50% reduction in 5HIAA was observed in 21% on BVZ and 43% on PEGI. Overall, 46% achieved ≥ 50% reduction in 5HIAA. Conclusions: BVZ therapy is associated with suppression of tumor blood flow and prolongation of PFS duration in carcinoid tumors. Addition of PEGI may help to control hormonal output in patients refractory to octreotide. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech
Gene expression profiles in non-small cell lung cancers (NSCLCs) and in corresponding healthy lung tissues in smokers versus nonsmokers.
Authors: A. Szymanowska-Narloch, M. Skrzypski, M. Taron, H. Dienemann, W. Rzyman, M. Jarzab, T. Muley, E. Jassem, R. Rosell, J. Jassem
Journal: Journal of Clinical Oncology (2010)

1545 Background: Molecular characterization of NSCLC in non-smokers may provide new means for cancer prevention and treatment in these patients (pts). We assessed expression of genes potentially related to etiology of this disease in smoking vs. non- smoking NSCLC pts. Methods: We analyzed snap frozen tumor samples from surgically treated 31 nonsmoking and 54 smoking NSCLC pts, with corresponding normal lung tissue from 27 and 43 pts, respectively. Expression of 21 genes (including genes associated with smoking, kinases, hormonal receptors, growth factor receptors, transcription factors, genes indirectly involved in HPV infection pathways and other) was assessed by RT-PCR with use of microfluid cards (MFC). Analysis of RT-PCR was performed with relative quantification 2--ΔΔCT. Subunit 18S, POLR2A and ESD were used as normalization genes. Results: Five genes were significantly overexpressed in tumors of non-smokers vs. smokers: CSF1R (p < 0.0001), RRAD (p < 0.0001), progesterone receptor (PgR; p = 0.0004), TGFBR2 (p = 0.0027) and EPHB6 (p = 0.0033). Tumors in non-smoking females exhibited higher expression of RRAD (p = 0.0003), CSF1R (p = 0.0008) and PgR (p = 0.0009) compared to their smoking female counterparts. Healthy lung tissue in non-smoking females showed lower expression of CDKN2A (p = 0.0013) compared to smoking females. In both smokers and non-smokers expression of PgR and androgen receptor (both p < 0.0001) was lower, whereas expression of estrogen receptor 2 (ER2; p = 0.002) and IGF2 (p = 0.0014) was higher in tumors than in healthy lung tissue. Conclusions: Gene expression in NSCLC is strongly related to smoking history. Overexpression of ER2 in tumors suggests possible hormonal dependence. Some other molecular distinct features (e.g., IGF2 upregulation) may prompt new treatment strategies. No significant financial relationships to disclose.
Randomized trial of adjuvant equitoxic dose-escalated anthracycline (A)-containing regimen of doxorubicin, cyclophosphamide (AC) versus cyclophosphamide, methotrexate, 5-FU (CMF) for stage I-II breast cancer (BrCa): Can equitoxicity compensate for agent selection?
Authors: O. Pribylova, L. B. Petruzelka, K. Shumansky, J. J. Spinelli, J. Ragaz
Journal: Journal of Clinical Oncology (2005)

818 Background: Our past data (J. Ragaz, etal; ASCO; 1989, 8: 23) showed similar outcome of BrCa cases treated with varied cumulative delivered CMF dose (low, medium, high), providing the doses were equitoxic, as judged by comparable granulocyte nadir. Other published data agree on BrCa outcome benefit of anthracyclines (ANTHR) (i.e. AC) over CMF, with cardiotoxicity the limiting factor of ANTHR in long-term. Objective: The objective of this randomized trial was to confirm if dose escalation of each drug at each visit to reach equitoxicity (as judged by granulocytes) AC and CMF regimens would reach outcome equivalence. Methods: One hundred and four stage I-II BrCa patients (pts) were randomized to four cycles each of AC or CMF (A=60, C=600 mg/m2 q 21 days) versus CMF (C=500, M=40, F=600/m2 i.v. days 1+8 q 28 days). Both groups had dose of each drug escalated to 110% or 120% if granulocytes nadir was >1500, <2000, or >2000 on the day of therapy, resp. Outcome was five year DFS%. The two treatment groups were similar on age, ER, erbB2, and nodal status. Results: No difference between AC versus CMF was seen between ages <50 versus >50 or nodal status (N-ve versus +ve). Conclusions: Our data indicate that if equitoxic, CMF and AC regimens could be equivalent, with no significant differences for subsets based on ER, erbB2, age, or nodal status. Toxicity was acceptable and will be discussed. Further studies aiming for a maximum safe escalation to achieve targeted equitoxicity may be a required prerequisite, in order: 1) To achieve maximum effectiveness within routine guideline-recommended regimens; and 2) To determine the impact of new, more costly, and toxic chemotherapeutic agents and combinations, particularly as many standard regimens may not yet have been used to their maximum potential. No significant financial relationships to disclose.
Prospective Multicentric Molecular Study for Poor Prognosis Fusion Transcripts at Diagnosis in Adult ALL Patients - The LALA94 Experience.
Authors: Jean A. Gabert, Christophe Picard, Sandrine Hayette, Christelle Bilhou-Nabera, Jean-Michel Cayuela, Elizabeth Macintyre, Nicole Frenoy, Claude Preudhomme, Madeleine DuPont, Christian Bastard, Dominique Bories, Jean-Paul Vaerman, Frédéric Davi, Nicole Dastugue, Sophie Raynaud, Marina Lafage, Thierry Fest, Marie-Pierre Gaub, Véronique Lheritier, Xavier Thomas, Christiane Charrin, Claude Boucheix, Hervé Dombret, Denis Fiere
Journal: Blood (2005)
Survival benefit of post induction consolidation therapy in MCL (mantle cell lymphoma): A Polish Lymphoma Research Group (PLRG) retrospective multicenter analysis
Authors: W. Jurczak, A. Giza, D. Krochmalczyk, M. Sobocinski, D. Zimowska-Curylo, B. Stella-Holowiecka, P. Boguradzki, E. Kisiel, T. Wróbel, W. Knopinska-Posluszny, A. B. Skotnicki
Journal: Journal of Clinical Oncology (2009)

e19510 Background: In MCL, early intensification and consolidation of the first line therapy by ASCT is the treatment of choice. Elderly age and co-existing co-morbidities makes it however feasible for less than a third of patients. Methods: All MCL cases consulted in 8 PLRG centers within the last 5 years (n=140) were included in a retrospective analysis. Only 23% (n=32) were consolidated with ASCT, further 28% (n=40) by radioimmunotherapy (Ibritumomab), while in 49% (n=68) neither consolidation was performed. Rituximab was used in 36/72 patients subjected to consolidation and 25/68 treated without consolidation. There were no statistically significant differences in IPI, CS (clinical stage), frequency of extranodal manifestations and B symptoms between analyzed subgroups ( Table ) although patients subjected to ASCT were younger (median age 54 vs 62) and tend to have higher LDH (556 IU vs 473), while those who were not consolidated more frequently had a large tumor burden (defined as a mass &gt; 7 cm, 24 vs 15%). Results: There was a clear impact of consolidation on overall and progression-free survival (OS,PFS): at 5 years OS 65 vs 20 % (p= 0.0003 in Gehan Wilcoxon test); and PFS 40 vs 0 % (p= 0.0003 in Gehan Wilcoxon test). Rituximab used in the first line therapy further increased it's efficiency in terms of PFS, prolonging median time to progression from 15 to 26 months, however the OS benefit was seen only in consolidated patients (at 5 years 75% OS in those with Rituximab including induction followed by consolidation). Conclusions: With all limitations of retrospective analysis, it strongly supports the necessity of post induction therapy in MCL patients. The role of ASCT is established in younger patients, radioimmunotherapy may prove to be a feasible approach for the elderly and unfit ones. [Table: see text] No significant financial relationships to disclose.
Survival after radiation therapy for early-stage endometrial carcinoma: The Oslo study revisited after up to 43 years of follow-up.
Authors: Kristina Lindemann, Mathias Onsrud, Gunnar Kristensen, Claes Trope
Journal: Journal of Clinical Oncology (2012)

5008 Background: There is an ongoing debate regarding the benefit of radiation in patients with early stage endometrial carcinoma. Data on long time risk conferred by radiation is scarce. This study is a long-term follow-up on survival and secondary cancers of a previously published randomized study (Aalders J. et al., Obstet Gynecol 1980; 56: 419-27). Methods: Between 1968 and 1974, 568 patients with endometrial cancer FIGO stage I primarily treated with abdominal hysterectomy and bilateral salpingo-oophorectomy were included in the study. Patients were postoperatively randomized to receive either vaginal radium brachytherapy followed by external pelvic radiation 40 Gy (N=288) or brachytherapy alone (N=280). Survival data and data on incident secondary cancers were obtained by individual linkage to the Registry of Statistics Norway and Cancer Registry of Norway. By the end of follow-up at 1 November 2011, 45 (7.9%) patients were still alive. We used Cox proportional hazards model to estimate hazard ratios (HR) with 95% confidence intervals (95% CI). We also conducted analyses stratified by age groups. Results: After median 21 (range 0-43.4) years of follow-up there was no significant difference in overall survival or relapse free survival between treatment arms with HR of 1.12 (95% CI: 0.95-1.33) and HR 0.88 (95% CI: 0.55-1.40), respectively. Patients treated with external radiation had significantly lower risk of developing locoregional relapse (p&lt;0.001). However, women younger than 60 years had a significant poorer survival after external radiation (HR 1.36; 95% Cl: 1.06-1.76). In this patient group the risk of secondary cancer was significantly increased (HR 1.9; 95% CI: 1.23-3.03). Conclusions: We observed no survival benefit of external pelvic radiation in early stage endometrial carcinoma. In women younger than 60 years, pelvic radiation decreased survival, probably due to increased risk of subsequent second neoplasms. Adjuvant external radiotherapy cannot be recommended to this patient group. Those who have received such treatment might eventually benefit from prolonged post treatment surveillance with respect to secondary cancer.
Phase II trial of arsenic trioxide (ATO) and ascorbic acid (AA) with temozolomide (TMZ) in patients with metastatic melanoma (MM) with or without CNS metastases
Authors: T. E. Bael, B. L. Peterson, M. Thoreson, T. Richmond, J. Eyer, J. A. Gollob
Journal: Journal of Clinical Oncology (2005)

7553 Background: TMZ is commonly used to treat MM but has a response rate of only 10 to 15%. Melanoma resistance to TMZ may occur through upregulation of NF-κB and inhibition of apoptosis. ATO downregulates NF-κB activation and can arrest cancer cell growth and induce apoptosis. AA augments the effects of ATO by depleting glutathione stores. We therefore wanted to determine whether treatment with ATO and AA would augment the response rate to TMZ by increasing melanoma sensitivity to apoptosis. As both ATO and TMZ cross the blood-brain barrier, we also wanted to determine whether this regimen was active in MM patients with CNS disease. Methods: We developed a phase II trial combining TMZ with ATO/AA. The design called for the enrollment of 40 patients with stage IV melanoma and an ECOG PS of 0–2, and included early stopping rules for low response rate or toxicity. Prior therapy other than TMZ or DTIC was permitted. ATO was administered IV as a loading dose at 0.25 mg/kg/d x 5 days during week 0, and then twice weekly at 0.35 mg/kg x 8 weeks. Each dose of ATO was followed by a 1000 mg IV dose of AA. During each 8-week cycle, oral TMZ was given at 200 mg/m2/d x 5d on weeks 1 and 5. Results: Eleven patients have been enrolled to date, including 5 with CNS metastases, and 9 were evaluable for response. Common grade 1 and 2 side effects included edema (6), fatigue (4), rash (3), and elevated AST or ALT (3). Grade 3 and 4 side effects were nausea and vomiting (4), elevated AST or ALT (2), seizure (1), and renal failure (1). All 9 patients had progressive disease after 1 cycle of therapy. Conclusions: ATO and AA can be administered safely with TMZ on an outpatient basis with acceptable toxicity. No responses have been observed among the first 9 melanoma patients. The lack of activity will trigger early closure of the trial if the tenth patient currently on study does not have a major response. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cell Therapeutics
Clinical efficacy and immunogenicity of the optimized cryptic peptide TERT572Y vaccine (Vx-001) in patients with advanced non-small cell lung cancer (NSCLC)
Authors: K. Kosmatopoulos, E. Bolonaki, D. Aggouraki, E. Nikoloudi, P. Kanellou, E. Papadimitraki, A. Kotsakis, D. Mavroudis, V. Georgoulias
Journal: Journal of Clinical Oncology (2006)

17069 Background: BTERT 572Y , an optimized cryptic peptide homologous to TERT induces efficient antitumoral T cell cytotoxic immunity but not autoreactivity in vivo in HLA-A*0201 transgenic mice and healthy blood donors and prostate cancer patients (J. Clin. Invest., 2004, 113,425). Moreover, it was well tolerated and effective in eliciting specific T cell immunity in patients (pts) with advanced malignancies (ASCO 2005, abstr 2579). Methods: We evaluated its clinical efficacy, safety and immunogenicity in 13 HLA-A*0201 pts with advanced, stage IIIb (7 pts) and stage IV (6 pts), NSCLC. Three pts were in stable (SD) and ten pts in progressive (PD) disease following prior therapy. The vaccination protocol consisted of two subcutaneous injections of optimized TERT 572Y peptide followed by four injections of native TERT 572 peptide. Both peptides were emulsified in Montanide ISA51. Results: Eight pts completed the entire vaccination program, 4 discontinued due to PD and 1 is ongoing. The median follow up is 6.5 months (range 2.0–29.9). Three of 10 (30%) pts with prior PD developed SD for 6+, 7+ and 9 months. Overall clinical response was SD in 6 and PD in 7 pts. Median TTP was 8.1 months (range 3.7–9.1) for stage IIIb and 2.3 (range 2–6.9) for stage IV pts. Minimal grade I/II primarily skin toxicity was observed. ELISPot-detected TERT 572 specific CD8+ cells were demonstrated in all 7 pts tested. Conclusions: TERT 572Y peptide vaccine is well tolerated and effective in eliciting a specific T cell immunity. The disease stabilization observed in 30% of pts with previously progressive disease is very encouraging and deserves further evaluation. [Table: see text]
Capecitabine (X) chemoradiation in Chinese patients (pts) with advanced or relapsed rectal carcinoma
Authors: W. Shen, Y. Liu, J. Che, Z. Zeng, X. Ma, Y. Li, G. Li, R. Wang, W. Zhang, X. Liu
Journal: Journal of Clinical Oncology (2005)

3702 Background: Colorectal cancer is one of the most common malignancies in China. The oral fluoropyrimidine X is preferentially converted to 5-FU in tumor tissue by thymidine phosphorylase (TP). In addition, radiotherapy upregulates TP in tumor cells but not in normal tissues. We evaluated the synergistic effect and safety of X chemoradiation in Chinese pts with advanced or relapsed rectal carcinoma. Methods: 100 pts were enrolled between Jun 02 and Oct 03. All had measurable advanced or relapsed rectal carcinoma, KPS >60, adequate bone marrow, renal and hepatic functions. Prior radiotherapy to sites other than those evaluated in the trial and adjuvant fluoropyrimidines (>1 months previously) were permitted. Pts received radiotherapy at 1.8Gy/d for approximately 6 weeks (total dose 60Gy) plus X 825mg/m2 bid for the duration of radiotherapy. Results: 73 pts are evaluable. The remainder are not evaluable due to ongoing treatment. Baseline characteristics: 51 men, 22 women; median age 52 years (range 33–74). Measurable lesions: rectum 55%, pelvic 43%, skin 6%, liver 3%, lymph nodes 3%, other 3%. Number of metastatic sites: 1 (86%), 2 (11%), 3 (3%). 92% of pts completed 6 weeks of treatment; the remainder were treated for 5 weeks (1% for 4 weeks and 1% for 3 weeks). Anti-tumor efficacy is shown in the table. Median progression-free and overall survival have not yet been reached. The most common treatment related grade 1/2 adverse events (grade 1/2) were leucopenia 32%, hand-foot syndrome 26%, diarrhea 22%, nausea 11% and thrombocytopenia 10%. Grade 3 adverse events were rare: HFS 3%, diarrhea 3%, nausea 1%. Only 3 pts (4%) had grade 4 events (all thrombocytopenia). Treatment delays/dose adjustments resulted in improvement/cure for all grade 3 events from 2 weeks to 2 months. Conclusions: X chemoradiation is a highly active and well-tolerated regimen in Chinese pts with advanced or relapsed rectal carcinoma. No significant financial relationships to disclose.