tbuckley/cabot-search huggingface dataset:
Phase III study of gemcitabine [G] plus cetuximab [C] versus gemcitabine in patients [pts] with locally advanced or metastatic pancreatic adenocarcinoma [PC]: SWOG S0205 study
Authors: P. A. Philip, J. Benedetti, C. Fenoglio-Preiser, M. Zalupski, H. Lenz, E. O'Reilly, R. Wong, J. Atkins, J. Abruzzese, C. Blanke
Journal: Journal of Clinical Oncology (2007)

LBA4509 Background: Epidermal growth factor receptor [EGFR] pathway is a rational target for therapeutic intervention. This study tested the efficacy of an anti-EGFR monoclonal antibody and gemcitabine [G] combination in the Phase III setting in patients with advanced PC. Methods: Eligibility included locally advanced unresectable or metastatic PC; adequacy of organ function; performance status (PS) 0- 2; no prior EGFR therapy; no prior systemic chemotherapy except for adjuvant chemotherapy; and submission of tumor for EGFR immunostaining. The primary endpoint was overall survival. Secondary endpoints included objective response, time to progression, pain control, and quality of life. Assuming 6 months median survival, the study was designed to detect a median improvement to 8 months (1.33 hazard ratio) with 90% power, based on a one-sided 0.0125 test, and 704 eligible patients. Primary analyses used a Cox regression model, stratified for factors used in the randomization. Patients were stratified by PS, stageand prior pancreatectomy, and randomized to either G alone or G plus C. G was given at a dose of 1,000 mg/m 2 /wk for seven weeks out of 8, then 3 weeks on and one week off. C was given as a loading dose of 400 mg/m 2 on week 1 and then 250 mg/m 2 weekly. Results: 766 pts (735 eligible) with a median age of 64 (30–91) were enrolled by SWOG and CTSU between January 2004 and April 2006. Of those, 51% were males, 21.5% had locally advanced disease, and 13% had PS of 2. The study closed with full accrual. The median survival was 6 months in the G arm and 6.5 months in the G plus C arm for an overall HR of 1.09 (95% CI 0.93–1.27, p= 0.14) . The corresponding PFS was 3 months and 3.5 months, for G and G+C arms, respectively (HR =1.13, 95%CI .97–1.3, p=.058). The confirmed response probabilities were 7 % in each arm, and inclusion of unconfirmed responses yielded 14% in the G arm and 12% in the G + C arm.702 pts were evaluable for toxicity. 90 pts experienced at least one grade 4 toxicity; 14% on the G plus C, 11% on G alone. Conclusions: This study failed to demonstrate a clinically significant advantage of the addition of cetuximab to gemcitabine for overall survival, PFS and response in advanced PC. No significant financial relationships to disclose.
Physician practice of statin usage and lipid monitoring among patients with advanced lung cancer
Authors: T. Tanvetyanon, A. Choudhury
Journal: Journal of Clinical Oncology (2005)

8009 Background: The benefit of statins (HMG-CoA reductase inhibitors) for prevention of cardiovascular disease is well established; however, its use among patients with advanced cancers with limited life expectancy is controversial. Besides, the risk of liver dysfunction may increase among patients with liver metastasis or receiving chemotherapy. We investigate physician practices of prescribing statin and monitoring lipids among advanced lung cancer patients. Methods: Cancer registry at a large, suburban VA hospital was searched for deceased patients who presented with metastatic or stage IIIB non-small cell lung cancer (NSCLC) or extensive stage small cell lung cancer during 1999 to 2003. Patients were included if they were on statins at or after the time of cancer diagnosis, survived for at least one month after diagnosis, and had at least one documented contact with their physicians within 6 months before death. Results: Fifty patients met the search criteria: 49 were on statins at the time of cancer diagnosis, and 1 was started on statin afterward. Median age was 71 years, 26% had extensive stage SCLC, 52% metastatic NSCLC, and 22% stage IIIB NSCLC. Most had history of cardiovascular disease or diabetes. The overall median survival was 360 days. There were 42 patients (84%) who had statin prescription filled at least once after cancer diagnosis. Of these, 16 (38%) continued to have adequate supply until death. Median duration from the last statin medication until death was 72 days. Lipid was monitored at least once after cancer diagnosis in 26 patients (52%). Of these, the median duration from the last test until death was 149 days. Meanwhile, hospice referral before death was initiated in 31 patients (62%). Of these, the median duration from the date of hospice referral until death was 30 days. Conclusions: The majority of patients with advanced lung cancer who received statins continued this medication until near the date of death; lipid monitoring was also prevalent. Effort should be made to re-direct patients and physicians to other realistically beneficial interventions. No significant financial relationships to disclose.
A one-sample progression-free survival (PFS) hazard ratio estimate for planning a randomized phase II study (RP2) in mRCC utilizing evidence from RECORD-1.
Authors: S. A. Kovalchik, W. Mietlowski, A. C. Kay, N. Hollaender, E. Kpamegan, Y. Wang, M. H. Dugan
Journal: Journal of Clinical Oncology (2010)

e16515 Background: The era of cytostatic cancer agents requires alternatives to traditional response-based P2 studies. RP2 designs with a PFS endpoint have been proposed but generally require many more patients. Rubinstein et al. (2005) shows that 69 progression events are sufficient to detect a hazard ratio (HR) of 0.67 with 20% error rates. A PFS RP2 is feasible if a reliable estimate of the P2 HR can be obtained at the planning stage. Methods: We investigated whether evidence from a recent RCT can be used in combination with a phase I dose expansion cohort to estimate the RP2 HR for PFS. Using the methodology of Finkelstein et al. (2003) we evaluated the properties of a one-sample HR and log-rank statistic in a re- analysis of the RECORD-1 trial (Motzer et al. 2008) of everolimus for the treatment of mRCC, comparing against two-sample estimates. Also, simulation studies determined error rates of an mRCC phase I historical comparison (HCP1) study with 30-patients, using the placebo-controlled best supportive care (BSC) arm of RECORD-1 as the comparison group. A critical concern in single-arm studies is patient selection bias. We investigated whether stratification could provide some safeguard against identifiable sample discrepancies, focusing on the prognostic factor of any prior sunitinib treatment. Results: The two-sample analysis of RECORD-1 estimated a PFS HR of 0.332, 95% CI = (0.258, 0.427). The one-sample estimate was 0.347, 95% CI = (0.290, 0.415). For the HCP1 design, 22 events were sufficient to detect a HR of 0.67 with type I and type II error of 20%. Stratification was necessary to maintain these rates in the presence of significant selection bias. Conclusions: The one-sample methodology accurately estimates the HR outcome of a randomized trial but, for equal sample size, underestimates the variance by approximately 25%. We propose that a one-sample HR estimate has utility in establishing proof of concept for and planning of an RP2. Planning could be further improved by allowing multiple historical trials and incorporating the impact of intertrial variability. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis
Multicolor Fluorescence In Situ Hybridization (M-FISH) in Highly Aggressive B-Cell Lymphomas with 8q24/MYC Involvement Revealed the Heterogeneity of 13q Abnormalities with Unexpected Partial Gains.
Authors: Violaine Havelange, Geneviève Ameye, Evelyne Callet-Bauchu, Nicole Dastugue, Carole Barin, Dominique Penther, Lucienne Michaux, Anne Hagemeijer, Miikka Vikkula, Hélène Antoine-Poirel
Journal: Blood (2006)
Oral oncolytics: Patient-monitoring improvements in private practice.
Authors: Tallat Mahmood, Lindsey Redouty, Elaine McNamera
Journal: Journal of Clinical Oncology (2014)

215 Background: The use of oral oncolytics is becoming more common. These drugs have their own unique challenges in managing patient initiation, monitoring side effects and adherence. Methods: We conducted a baseline chart audit of patients prescribed oral oncolytics in our private oncology practice followed by a quality improvement program and subsequent reassessment. Information obtained included: prescription date, actual start date and any documented problems with the oral therapy. The baseline audit included patients from may of 2011 to July 2013. Subsequently we joined the Michigan oncology quality consortium’s oral chemotherapy collaborative and initiated the following: office procedures for identification of all patients on oral therapy, use of the Edmonton Symptoms assessment system (ESAS), and a self-care management education program including patient self-monitoring of symptoms with recommended initial treatments. A postintervention audit was conducted from August 2013 to March 2014. Results: We identified 25 patients in the first time period and 13 in the second. In the first time period we found only 13 of the 25 patients had an actual start date documented, and of these 13, 10 had a &gt;/=4 week delay prior to starting therapy, with 3/13 having a 2-4 week delay prior to start of therapy. 12 of the 25 patients discontinued their drug within the first month due to side effects without consulting their physician. After participating in the quality initiative, we identified only one patient without a documented start date, only 1/13 that had a &gt; 4 week delay from prescription date to starting the drug, with 12/13 having a less than 2 week lapse. We also found that there were no patients who discontinued the drug and only one dose reduction as directed by the physician. Conclusions: The introduction of new office procedures to easily identify all patients on oral therapy and improved patient management of symptoms at home with the use of self-care guidelines, and in the office with use of ESAS contributed to greater adherence to oral chemotherapy regimens.
ABV (doxorubicin [Adriamycin], bleomicin and vincristine) polychemotherapy regimen in HIV Kaposi’s Sarcoma: Uruguaian 10-year experience
Authors: G. Krygier, A. Sosa, A. Blanco, K. Lombardo, C. Castillo, A. Dutra, S. Cabrera, E. Savio, I. Muse, G. Sabini
Journal: Journal of Clinical Oncology (2006)

9559 Background: Kaposi’s sarcoma is the most common malignancy among HIV patients and is considered to be one of the AIDS defining conditions. This abstract illustrates our 10 year experience with the treatment of 32 Kaposi’s sarcoma HIV patients with the same therapeutic approach. Methods: Between 04/95 and 03/05 we recruited 32 previously untreated patients that were diagnosed with Kaposi’s sarcoma and treated at the Servicio de Oncologia Clinica (Universitary Clinicas Hospital) in Montevideo. All of them received the same iv polychemotherapy plan (Adriamycin 10mg/m 2 , Bleomycin 10 U/m 2 and Vincristine 1.4 mg/m 2 , every two weeks until tumor progression or severe toxicity). Results: 21 of the patients were good risk ones and the remaining 11 were poor risk patients (AIDS Clinical Trials Group staging classification). CD4 levels varied from 6 to 780/ml and the viral load ranges were 240 to 89000 copies. The patients received an average of 10.2 (4–21) polychemotherapy cycles. Grade 3–4 myelotoxicity was reported in 5 patients delaying the onset of the subsequent cycles. Grade 2 neurotoxicity was seen in 7 patients after 4, 5, 6, 8, 10, 11 and 13 cycles of ABV, changing vincristine for vinblastine (4mg/m 2 every two weeks) in these patients. All the patients achieved a partial response with improvements in CD4 levels and viral load. 13/32 patients experienced a relapse (3–29 months after last chemotherapy cycle). 3 patients were retreated with paclitaxel 135 mg/m 2 with 2/3 new partial responses of shorter duration. 5 patients received 4 additional ABV cycles achieving a new partial response. 5 patients refused further treatment dying due to progressive disease. One relapsed patient developed a second malignancy (High grade Non Hodgkin lymphoma) dying three months later. Conclusions: These data suggest that ABV regimen is still an effective treatment option for HIV-Kaposi’s sarcoma, specially in the undeveloped countries in which the cost of other better internationally approved options (liposomal doxorubicin and daunorubicin) makes them unaccesible for the majority of the population. No significant financial relationships to disclose.
Concomitant docetaxel plus gemcitabine versus sequential docetaxel followed by gemcitabine
Authors: A. Tomova, T. Brodowicz, V. Tzekova, C. Timcheva, C. Wiltschke, D. A. Gerges, J. Pawlega, S. Spanik, M. J. Inbar, C. C. Zielinski
Journal: Journal of Clinical Oncology (2008)

1106 Background: Docetaxel plus Gemcitabine represent an active combination in anthracycline pretreated advanced breast cancer patients (pts.). Impact of sequential administration of these drugs is unclear. This trial aimed to compare concomitant DG with sequential D->G in anthracycline pretreated advanced breast cancer patients. Methods: Pts. pretreated with anthracyclines in the (neo)adjuvant or metastatic setting were randomized to receive either: 8 cycles Gemcitabine 1,000 mg/m2 on days 1 and 8, plus Docetaxel 75 mg/m2 on day 8 (DG), or 4 cycles Docetaxel 100 mg/m2 on day 1, followed by four cycles Gemcitabine 1,250 mg/m2 on days 1 and 8 (D->G), in a 21-day schedule. The primary endpoint was time to disease progression (TTDP), secondary endpoints were overall response rate (ORR), response duration (RD), overall survival (OS) and toxicity. Sample size was calculated to be 430. Due to poor recruitment the trial was closed after randomization of 100 pts. Results: Between September 2002 and March 2006, 100 pts. at 14 centers in 7 countries were randomly assigned to DG (n=46) or D->G (n=54). The median age was 53 vs 55 years in DG and D->G arms, 52%/50% vs 55/47 were ER/PR positive, 23% vs 17 were HER2 positive, 52%/44% vs 42/47% had liver/lung metastases at baseline. Grade 3/4 adverse events encompassed leukopenia (29% in DG; 68% in D->G), neutropenia (49 vs 83%) (p<0.001 for both) and febrile neutropenia (4 vs 9%). One treatment-related death due to enterocolitis was reported in the DG arm. ORR, RD, TTDP and OS were similar in both arms. Conclusions: The present data suggest that sequential D->G treatment produced significantly more episodes of hematologic toxicity. Regarding efficacy no trend in favor of any regimen was observed. Efficacy Parameters DG (n=45) D->G (n=53) ORR (%) 31% 28% RD (months) 5.4 7.8 Median TTDP (months) 7.0 6.7 Median OS (months) 15.5 15.9 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly Eli Lilly
Tobacco use among radiation oncology outpatients
Authors: Y. I. Garces, K. P. Offord, I. T. Croghan, P. A. Decker, P. D. Brown, M. M. Clark, T. A. Rummans, R. L. Foote, R. D. Hurt
Journal: Journal of Clinical Oncology (2004)

1027 Background: Little is known about the prevalence of tobacco use in persons while they are receiving cancer treatments. The purpose of this survey was to describe the frequency of self-reported tobacco use among adult patients who are initiating radiation therapy, and their level of interest in receiving advice on tobacco use treatments. Methods: Of 395 consecutive patients seen between May - August, 2003, 214 consented to participate in our survey; 109 eligible patients refused, 51 were ineligible (hospitalized or <18 y.o.) and 21 were missed. Excluding ineligible or missed patients, our participation rate was 214/323 (66%). Three patients who did not return the survey were excluded, leaving 211/323 (65%) respondents (130 male, 81 female). Results: The most frequent primary sites were breast (16%), lung (16%), and gastrointestinal (15%). Of respondents, 1%, 8%, 17%, 20%, 24%, 22%, and 8% were stage 0, I, II, III, IV, had recurrent disease or disease staging was not applicable, respectively. The mean ± SD age was 58.3 ± 14.4 years (range 22–92 years). 10% (21) were current cigarette smokers (smoked in past 7 days), 8% (18) were recent ex-smokers (quit 8–90 days), 46% (96) were ex-smokers for >90 days and 36% (76) were never smokers. 63% of the current smokers and 53% of the recent ex-smokers agreed that they would like help in quitting their tobacco use or staying quit, respectively. Conclusions: Ten percent of radiation oncology outpatients at our institution are current cigarette smokers, and 8% are recent ex-smokers. The majority are receptive to receiving assistance from their radiation oncologist to help them quit smoking. Other tobacco use as well as interest and attitudes towards a tobacco use intervention and/or a relapse prevention program will be described. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration NIH Grant CA -90628; Eagles' Fraternal Order Cancer Fund
The ratio of membrane-bound form <i>Flt-1</i> mRNA to <i>VEGF</i> mRNA was correlated with tumor angiogenesis and prognosis in non-small cell lung cancer
Authors: K. Takenaka, F. Tanaka, H. Katakura, F. Chen, E. Ogawa, M. Adachi, H. Wada
Journal: Journal of Clinical Oncology (2005)

9586 Background: Angiogenesis is an essential process in development and progression of malignant tumors, and vascular endothelial growth factor (VEGF) and its receptors such as fms-like tyrosine kinase 1 (Flt-1) play critical roles in tumor angiogenesis. There have been reported two isoforms of Flt-1, membrane-bound form (mFlt-1) and soluble form. Experimental studies have revealed that mFlt-1 can act as a dual angiogenesis regulator, an angiogenesis inhibitor by trapping VEGF and an angiogenesis promoter in certain pathological conditions. In accordance with such complex function of mFlt-1 in tumor angiogenesis, clinical significance of mFlt-1 remains unclear. Methods: Expression of mFlt-1 mRNA along with VEGF mRNA was quantitatively evaluated by real-time RT-PCR in 79 resected non-small cell lung cancer (NSCLC) patients. Intra-tumoral microvessel density (IMVD) and mFlt-1 protein expression were assessed immunohistochemically. Results: Expression of mFlt-1 mRNA was positively correlated with mFlt-1 expression detected by immunohistochemical staining (P=0.099). Expressions of mFlt-1 mRNA and mFlt-1 protein were significantly higher in adenocarcinoma than in squamous cell carcinoma. Expression of mFlt-1 mRNA was positively correlated with VEGF mRNA expression. There was no significant difference in the mean IMVD according to mFlt-1 mRNA expression status or VEGF mRNA expression status. Next, the ratio of mFlt-1 mRNA to VEGF mRNA (mFlt-1/VEGF) was calculated. The mean IMVD for high mFlt-1/VEGF tumor was 57.0, which was significantly lower than that for low mFlt-1/VEGF tumor (148.5, P=0.004). The 5-year survival rate of high mFlt-1/VEGF patients was 69.6%, which was significantly higher than that of low mFlt-1/VEGF patients (41.6%; P=0.037). In contrast, expression status of mFlt-1 mRNA, mFlt-1 protein, or VEGF mRNA, did not provide a prognostic value. A multivariate analysis confirmed that high mFlt-1/VEGF was a significant factor to predict a favorable prognosis (P=0.043). Conclusions: The ratio of mFlt-1 mRNA to VEGF mRNA, not mFlt-1 mRNA alone, was inversely correlated with tumor angiogenesis, and was a significant prognostic factor. No significant financial relationships to disclose.
Ten cases of osteonecrosis of the jaws following a treatment by diphosphonate within the framework of bone metastasis of breast cancer and multiple myeloma: Experience in summer 2004 of a single center
Authors: M. M. Maerevoet, J. -L. J. Lenoir, L. Degols, P. Duprez, M. Donnay, L. Duck
Journal: Journal of Clinical Oncology (2005)

8271 In 2003 and 2004 Marx and Ruggerio defers 36 and 63 cases Osteonecros of the jaws (ONJ).Durie reported at the ASH 162 cases according to data’s of the WEB. The principal factor of risk is diphosphonate treatment, the dental care among cancer or osteoporotic patients. In our institution, we noted 9 cases ONJ by MM and Breast cancer(BC) patients treated by Zoledronate (Z). 6 patients receveid Pamidronate (P). The median times of P treatment is 26 month(M) for Z is 15.6 M, the median cumulative dose is 2433 mg for P, and 60.81 mg for Z.In contrast with the literature any patients as undergone dental care, one patient have total extraction dental 15 years ago.One ONJ arrival 9 month after the last perfusion of Z. The evolution of ONJ is in spite of the antibiotic treatments and the surgical care unfavourable in the majority of the cases, with infections of the jaw and soft tissues, pain,difficulties food intake and bad haleine.The quality of life is reduced. Conclusions: ONJ is related to diphosphonates time-dependant treatment. In contrast with the literature, in our series (only MM and breast cancer), any patient as undergone dental care, and every patient as treated by Z on time to ONJ presentation. The ONJ can arrival several month after the end of Z administration. The question as now open, optimal duration of diphosphonate treatment, the dosage and the frequency of the administration? Reférences: Marx; Pamidroante and Zoldronate induced avascular necrosis of the jaws, JOMF surg, 2003, 61: 1115–1118 Ruggerio, Osteonecrosis of the jaws associated with the use of diphosphonates, JOMF surg, 2004, 62:527–534 Durie, Osteonecrosis of the jaws in myeloma patients #756, ASH 2004 No significant financial relationships to disclose.