tbuckley/cabot-search huggingface dataset:
A randomized phase III trial of gemcitabine (G) in combination with carboplatin (C) or paclitaxel (P) versus paclitaxel plus carboplatin in advanced (Stage IIIB, IV) non-small cell lung cancer (NSCLC): Update of the Alpha Oncology trial (A1–99002L)
Authors: J. Treat, C. P. Belani, M. J. Edelman, M. A. Socinski, R. H. Ansari, C. K. Obasaju, J. D. Bloss, D. M. Marinucci, R. B. Catalano, R. L. Comis
Journal: Journal of Clinical Oncology (2005)

LBA7025 Background: Two-drug regimens are the ‘standard of care‘ for treatment of advanced NSCLC. The role of non-platinum containing doublets continues to evolve. Gemcitabine and paclitaxel, a non-platinum-containing doublet needs to be prospectively compared to standard doublets. We are conducting a multicenter, randomized trial designed to compare the efficacy of gemcitabine-containing platinum and non-platinum doublet regimens with the most commonly used regimen of P+C to identify the combination associated with the best therapeutic index. We are now able to provide an update to the preliminary analysis of this ongoing trial previously reported. Methods: Between July 2000 and Nov 2004, 929 chemonaive patients (pts) with advanced stage (IIIB/IV) NSCLC, and ECOG PS < 2 were randomized to: (GC) G 1,000 mg/m2 IV on days 1, 8 plus C AUC 5.5, day 1 vs. (GP) G 1,000 mg/m2 IV on days 1,8 plus paclitaxel 200 mg/m2, day 1 vs. the control arm (PC) paclitaxel 225 mg/m2 plus carboplatin AUC 6.0, day 1. All three regimens were administered as 21-d cycles. The primary end point is overall survival (OS). Secondary endpoints are TTP, RR, and QoL analysis using FACT-L questionnaire. Results: At the time of this updated analysis, 681/929 pts have sufficient (> 6 mos) follow-up for response evaluation. (CR + PR = 39.5%; 95% CI 36% - 43%). Toxicity data are available for 812 pts. Pts characteristics include: (M/F 564/361), median age 64.1 years (range 32.7–91.0), ECOG PS (0–344/1–585), stage (IIIB-102/IV-827). The table summarizes response and toxicity data. Conclusions: All three regimens demonstrate similar activity as defined by objective tumor response. GC resulted in a higher incidence of uncomplicated grade 3/4 myelosuppression but was associated with less alopecia and neuro-sensory toxicity. TTP, OS and QoL data are being analyzed. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Bristol-Myers Squibb, Eli Lilly Eli Lilly Bristol-Myers Squibb, Eli Lilly Eli Lilly
Prospective NCCTG quality of life (QOL) study in adult newly diagnosed high-grade gliomas (HGG)
Authors: P. D. Brown, K. V. Ballman, T. A. Rummans, M. J. Maurer, J. A. Sloan, B. F. Boeve, R. M. Arusell, M. M. Clark, J. C. Buckner
Journal: Journal of Clinical Oncology (2004)

1524 Background: To assess QOL and the prognostic importance of QOL in adult patients with newly diagnosed high grade gliomas (HGG), QOL and outcome data collected in three prospective cooperative group clinical trial were analyzed. Methods: The QOL study was a companion protocol for three phase II protocols; 98–72-51 and 98–72-52 examined pre-irradiation and concurrent chemotherapy with radiation therapy for patients with anaplastic astrocytomas and glioblastomas (GBM) respectively, while N0074 investigated maintenance EGFR inhibitor after radiation was completed for GBMs. At study entry and at regular intervals, 5 self-administered forms were completed by the patient to assess (i) overall QOL (Linear Analogue Scale [LASA] and the Functional Assessment of Cancer Therapy-Brain [FACT-BR Version 4]), (ii) fatigue (Profiles of Mood States short form [POMS-SF] and the Symptom Distress Scale [SDS]), (iii) excessive daytime somnolence (Epworth Sleepiness Scale [ESS]), and (iv) depression (Profiles of Mood States short form [POMS-SF]). Results: Baseline and subsequent QOL data was available for 131 of 220 (60 %) patients enrolled in the 3 prospective trials. A significant proportion of patients became clinically distressed (QOL ≤ 50) at subsequent evaluations, while the majority of patients distressed at baseline remained distressed at subsequent evaluations. Increased fatigue (SDS, p=0.05), depression (p=0.05), and worse QOL (LASA, p=0.02) at baseline were predictive of worse survival. Subsequent development of clinical distress was not predictive of survival. Conclusions: A significant proportion of patients with HGG become clinically distressed after treatment. The majority of patients distressed at baseline remain distressed after treatment. Increased fatigue, depression, and worse QOL at baseline predict a worse survival. Interventional studies directed to improving QOL are needed. No significant financial relationships to disclose.
Correlation of FDG PET-CT with histologic response after neoadjuvant chemotherapy for soft tissue sarcomas
Authors: E. Y. Cheng, J. W. Froelich, J. C. Manivel, B. J. Weigel, K. M. Skubitz
Journal: Journal of Clinical Oncology (2009)

10583 Background: Surrogate endpoints for survival are needed to allow rapid assessment of new therapies without doing lengthy studies using a survival endpoint. Non-invasive assessment of treatment response is also needed to guide chemotherapy. FDG- PET-CT has potential for assessing response to treatment in sarcoma. This study's goal was to correlate FDG-PET-CT, along with standard CT, with histologic response after chemotherapy for high grade soft tissue sarcomas before resection. Methods: Patients with high grade soft tissue sarcomas &gt; 5 cm were enrolled in a prospective clinical trial and given ifosfamide/doxorubicin before tumor excision. FDG-PET-CT was performed at baseline before treatment, after cycle 1, &amp; just before surgery. Differences in both SUVmax (baseline to cycle 1 [B-1], baseline to surgery [B-3]) and CT criteria (RECIST 1 dimension [1D], RECIST 2D &amp; Choi) were compared to histologic response (&gt; or &lt; 90%) upon excision. Results: 25 patients were enrolled and 4 had disease progression prior to completing all 3 PET-CT's yielding 21 evaluable cases. 5 patients had SUVmax change of &lt;40%: 4/5 (80%) had histologic response &lt; 90% &amp; 1/5 (20%) had histologic response &gt;90%. 16 patients had SUVmax change of &gt;40%: 12/16 (75%) had histologic response &gt;90% &amp; 4/16 (25%) had histologic response &lt;90%. A scatterplot of SUVmax change (baseline to surgery), &amp; histologic response as continuous variables revealed a Spearman's correlation coefficient = 0.55 (p&lt;0.01). Conclusions: A cutoff value of 40% reduction in SUVmax from baseline to surgery appeared to differentiate histologic responders. Using this to define PET response, a correlation between PET response, as well as RECIST 1D and 2D, and histologic response was observed. Additional patient follow-up &amp; further study of FDG-PET-CT as a surrogate endpoint for histologic response and survival is warranted. [Table: see text] [Table: see text]
Patterns and consequences of missed work after diagnosis of breast cancer
Authors: M. Mujahid, N. K. Janz, S. T. Hawley, A. Hamilton, S. J. Katz
Journal: Journal of Clinical Oncology (2007)

9015 Background: Work loss is a potential adverse consequence of cancer. However, there is little research on patterns and correlates of paid work from diagnosis through initial treatment and the impact of missed work on family and finances. Methods: 2,030 women with non-metastatic breast cancer diagnosed from 8/05–5/06 and reported to the Los Angeles County SEER registry were identified and mailed a survey shortly after receipt of surgical treatment. Latina and African American (AA) women were over-sampled. Outcome measures included missed paid work (&lt;1 month, =1 month, stopped all together) and impact on finances (difficulty paying bills or cutting down on general expenses). We report results on a 50% respondent sample (N=742) which will be updated based on a final respondent sample of 1,400 patients (projected response rate, 72%). Results: Of the 440 women (59%) that worked prior to breast cancer, 35%, 26%, and 39% missed &lt;1month, =1month, or stopped working, respectively. African Americans and Latinas (especially those who primarily speak Spanish) were more likely to stop working as compared to whites [OR for stop working vs. missed &lt;1month: 3.5 (p&lt;.001); 4.0 (p&lt;.001) respectively]. Women receiving chemotherapy were also more likely to stop working after adjusting for other sociodemographic and treatment factors [ORs for stopped working vs. missed &lt;1month: 8.4 (p &lt;.001)]. Having sick leave and a flexible work schedule available through work was protective against work stoppage [ORs for stopped working vs. missed &lt;1month: 0.2 (p&lt;.001), 0.1 (p&lt;.001) respectively)] after adjusting for sociodemographic and treatment factors. Women who stopped work were more likely to report both difficulty paying bills, and the need to cut down on expenses compared to women who missed &lt;1month [ORs: 3.3 (p=.002); 3.6 (p&lt;.002) respectively]. Conclusions: Many women stop working altogether after a diagnosis of breast cancer, particularly if they receive chemotherapy, have limited resources, or are employed in vulnerable work settings. These women face adverse economic consequences. Clinicians and staff need to be aware of these adverse consequences of diagnosis and initial treatment particularly in ethnic minorities and low-income patients. No significant financial relationships to disclose.
The study of tamoxifen and raloxifene (STAR): Initial findings from the NSABP P-2 breast cancer prevention study
Authors: D. L. Wickerham, J. P. Costantino, V. Vogel, W. Cronin, R. Cecchini, J. Atkins, T. Bevers, L. Fehrenbacher, W. McCaskill-Stevens, N. Wolmark
Journal: Journal of Clinical Oncology (2006)

LBA5 Background: The STAR trial was designed to compare raloxifene to tamoxifen in terms of relative effect on invasive breast cancer risk and on other beneficial and detrimental outcomes associated with the use of tamoxifen. Methods: The trial opened on 7-1-1999, and accrual was completed November 4, 2004, with 19,747 women enrolled. To be eligible, a woman had to be postmenopausal with a 5-year predicted breast cancer risk of 1.66% as determined by the modified Gail model. Women were randomized and treated in a double-blinded fashion to receive 5 yr of therapy with either 20 mg per day of tamoxifen or 60 mg per day of raloxifene. The protocol-defined monitoring plan called for a final analysis and release of findings when 327 invasive breast cancer cases had been diagnosed in the total population. The mean age of the population at the time of entry into this trial was 58 yr, and the mean 5-yr risk of breast cancer was 4.04%. 93.5% of the women were white; 51.5% had a hysterectomy before entry into the study; 9.2% had a history of LCIS; 71.1% had at least one first-degree relative with a history of breast cancer. The average time on the study is 47 months. Results: There was no difference between the treatment groups in terms of effect on invasive breast cancer: 163 cases in women assigned to tamoxifen and 167 in women assigned to raloxifene (RR = 1.02, 95% CI = 0.82–1.27). The risk of invasive uterine malignancies was 40% less in the raloxifene group (36 in women assigned tamoxifen and 23 in women assigned raloxifene [RR = 0.62, 95% CI = 0.35–1.08]). The risk of non invasive breast cancer was less in the tamoxifen group (57 cases in those assigned to tamoxifen and 81 in those assigned to raloxifene [RR = 1.41, 95% CI = 1.00–2.02]). There were no significant differences between the treatment groups for any of the other invasive cancer sites or for cardiac events, osteoporotic fractures, or deaths. There were fewer thromboembolic events in women taking raloxifene than in those taking tamoxifen. Conclusions: Raloxifene is an effective alternative to tamoxifen for reducing the incidence of invasive breast cancer in postmenopausal women at increased risk of developing the disease and is associated with fewer endometrial cancers, deep vein thromboses, and pulmonary emboli. [Table: see text]
Organ preservation by weekly paclitaxel and carboplatin concurrent with radiation therapy in locally advanced laryngeal/hypopharyngeal carcinoma
Authors: M. Memon, A. Al Amro, N. Al-Rajhi, M. Rahal, M. El-Sebaie
Journal: Journal of Clinical Oncology (2005)

5564 Background: The goal of preserving laryngeal function and structure has dominated the development of newer treatment approaches. Radiotherapy with concurrent administration of cisplatin is superior to induction chemotherapy followed by radiotherapy or radiotherapy alone for organ preservation and locoregional control. This prospective phase II trial was conducted to evaluate the toxicity and organ preservation of weekly Paclitaxel (P), Carboplatin (C) and standard radiation therapy (RT) in previously untreated locally advanced laryngeal/hypopharynx (LA/HP) cancer. Material: Newly diagnosed patients (pt) with stage III-IV LA/HP carcinoma received weekly P (40/mg/m2 over 1 hour) and C (AUC:2) for 6 cycles starting on day 1 of RT which was given once daily for a total of 66.00Gy in 33 fractions. Re-evaluation with endoscopy, CT and PET scans was performed 6–8 weeks post RT. Salvage surgery was planned for residual, or recurrent, respectable disease. Result: 36 patients were included male: 23, median age 51, site: LA 20, HP: 16, Stage III/IV: 11/25. Tracheostomy tube was inserted for airway obstruction in 19 patients and 9 had tube feeding prophylactically. 75% of patients completed the planned therapy. Grade III-IV mucositis occurred in 48% of patients, while 2 patients developed grade IV skin necrosis around the tracheostomy tube. Hematologic toxicity was mild with febrile neutropenia in 4 patients. Weight loss was common and severe in 26% of patients despite admission for nutritional support of 9 patients. Local control for whole group was achieved in 22/36 (61%). With a median follow-up of 35 months, 16 patients (11 with LA and 5 with HP) are alive with no evidence of disease, two third of them with a functional larynx. Late complication in the form of laryngeal edema occurred in 1 patient. Conclusion: This combination proved feasible, with manageable toxicity, resulted in laryngeal preservation, and offered a high rate of disease control and survival in this population of locally advanced high risk LA/HP carcinoma. No significant financial relationships to disclose.
Modification in expression of EGFr, p53, and pTEN in non small cell lung cancer (NSCLC)
Authors: S. Bayle, F. Penault-Llorca, G. Robinet
Journal: Journal of Clinical Oncology (2006)

13151 Background: Treatment inhibiting tyrosine kinase domain of EGFr have proved dramatically efficient in NSCLC. Even if several studies have revealed predictors of treatment response, - such as gender, adenocarcinoma histology, gene mutations, or Asian origin-, response to treatment remains random and is not correlated with an initial overexpression of EGFr by the tumor. The efficiency of those EGFr inhibitors was only shown in second- or third-line treatments, and studies using them in first-line treatments, particularly when combined, had no positive outcome. We have therefore assessed the expression of EGFr in NSCLC before and after cisplatin-based chemotherapy to see if it modified the level of expression of either EGFr, or of molecules including its chain of activation, such as P53 or pTEN. Methods: Tumor samples were obtained from patients treated for NSCLC. We retrospectively studied the bronchial samples of all the patients treated for NSCLC in Brest University Hospital for 6 months. Patients with treatment response whose control samples were negative were not included. We extracted paraffin embedded samples from NSCLC before and after cisplatin-based chemotherapy. For all cases EGFr expression has been assessed with the Ventana CONFIRM TM EGFr 3C6 antibody, P53 expression with the DAKO P53 D07 kit, and pTEN expression with Novocastra antibody. Intensity was scored 0, 1+, 2+, 3+. Results: Data on 30 patients are available, 27 males and 3 females. 70% of tumors show overexpression of EGFr before chemotherapy, and 63.3% after, which has no stastistical significance. The same was observed for pTEN and P53, whose level of expression is similar before and after treatment. The level of expression of P53, pTEN, and EGFr is not correlated with gender or histological type. However, EGFr expression tends to increase after chemotherapy for the subsets of adenocarcinoma and women, but this remains statistically non-significant. Conclusions: Cisplatin-based chemotherapy does not seem to modify the expression of EGFr nor its chain of activation. However, the level of expression, particularly for EGFr, seems to be higher after chemotherapy for the subsets of adenocarcinoma and women. No significant financial relationships to disclose.
Does downstaging in patients (pts) with IIIA-N2 non-small cell lung cancer (NSCLC) and a response to induction chemotherapy (ICT) influence outcome with surgery (S) or radiotherapy (RT)? An exploratory analysis of EORTC 08941
Authors: J. P. Van Meerbeeck, G. W. Kramer, C. Legrand, E. F. Smit, A. Passioukov, G. Giaccone, N. Van Zandwijk, P. E. Van Schil
Journal: Journal of Clinical Oncology (2006)

7047 Background: In EORTC 08941, no difference in overall and progression free survival was observed in 332 pts with irresectable stage IIIA-N2 NSCLC, treated with either S or RT after a response to platinum-based ICT (van Meerbeeck, JCO 2005; 23, 1095s). Postoperative radiotherapy (PORT) was given to 40% of pts. In the S-pts, non-randomized exploratory comparisons showed a statistically significant benefit in outcome for (bi-)lobectomy vs. pneumonectomy (p = 0.0088) and for mediastinal lymphnodes (MLN) downstaged vs.non-downstaged pts (p = 0.0009). No difference was observed between S-pts treated with/without PORT. By randomizing after response to ICT, MLN-downstaging is assumed to be equally distributed among both treatment groups but cannot be formally retrieved in RT-pts. In order to compare the influence of MLN-downstaging in each treatment arm, we estimated in an exploratory analysis the outcome in subsets of S-pts and matched paired subsets of RT-pts. Methods: The subsets of 129 actually resected S-pts are defined as follows: (i) pts with MLN-downstaging at resection, (ii) pts without MLN-downstaging. Each subset was compared to a randomly selected subset of 154 actually irradiated RT-pts, matched on 4 baseline factors: histological subtype, gender, T stage, response to ICT. Kaplan-Meier estimates for overall survival (OS) and logrank p-values were then computed. Results: A match was feasible for 54/61 downstaged, 59/68 non-downstaged pts. Estimated OS (with 95% CI) for each S-subset and RT-matched pair subset is in the table . Conclusions: From these exploratory analyses, it appears that: 1. RT improves OS in MLN-non-downstaged pts; 2. S does not improve OS in MLN-downstaged patients. This should however be prospectively assessed. [Table: see text] No significant financial relationships to disclose.
Prevalence of pre-existing conditions and incidence of new medical conditions after diagnosis of non-small cell lung cancer
Authors: L. C. Koo, G. De Lissovoy, N. L. Hanna, E. Lyidick, M. Lambe, T. Higenbottam, M. H. Steinberg, P. Langmuir
Journal: Journal of Clinical Oncology (2006)

7152 Background: Patients with non-small cell lung cancer (NSCLC) are likely to have concurrent disease that affects treatment/prognosis. Estimates on the: 1) prevalence of pre-existing co-morbidities provides background information for clinical trials and patients, and 2) incidence of new conditions post diagnosis improves understanding of disease progression, treatment effects, and adverse event reports. Methods: Patients aged ≥66 with a primary diagnosis of NSCLC from 1991–1999 were identified in the SEER- Medicare linked database. ICD-9 codes from medical service claims (≥2) were analyzed to estimate comorbidity rates. Results: In the 12 months prior to NSCLC diagnosis, the prevalence for ischemic heart disease, cardiac dysrhythmias, and heart failure were 14%, 9%, and 8% respectively– indicating a substantial proportion of patients who might be poor candidates for surgery or cardio-toxic treatments. These prevalence estimates are likely to underestimate true prevalence due to the 1-year window of observation. For all 9 medical conditions, the incidence rates for new conditions were as much as 2 to 3 times higher than the prevalence rates for the same comorbidity before diagnosis. Conclusions: NSCLC patients have high prevalence of cardio-vascular conditions prior to diagnosis and many new medical conditions are detected post diagnosis as a result of increased detection, disease progression, and treatment. [Table: see text] [Table: see text]
Safety and efficacy of bevacizumab (Bev) when added to oxaliplatin/fluoropyrimidine (O/F) regimens as first-line treatment of metastatic colorectal cancer (mCRC): TREE 1 &amp; 2 Studies
Authors: H. S. Hochster, L. Welles, L. Hart, R. K. Ramanathan, J. Hainsworth, G. Jirau-Lucca, A. Shpilsky, S. Griffing, R. Mass, D. Emanuel
Journal: Journal of Clinical Oncology (2005)

3515 Background: Bevacizumab (Bev) added to IFL combination chemotherapy improves survival in mCRC. This randomized study assesses the safety & tolerability of each of three Oxaliplatin plus fluoropyrimidine regimens (bolus (b), infusional or oral fluoropyrimidine) alone in TREE1, and with Bev in TREE2. Methods: Eligibility: age ≥ 18; measurable untreated mCRC; PS ≤1. Primary endpoint: Grade 3/4 toxicities in the 1st 12 weeks (wk) of Rx; secondary endpoints: TTP, OS. Oxali-FU (in mg/m2) regimens consisted of: FOLFOX = O 85, leucovorin (LV) 350mg, 5FU bolus 400 & 2400 CIV x 46 hrs q 2 wk; bFOL = O 85 days (d) 1&15, LV 20 & bolus 5FU 500 d 1,8,15 q 4 wk; CapOx = O130 d 1, Capecitabine 1000 bid (850 for TREE2) for 14 d q 3 wk; Bev was added to each regimen (5 mg/kg q 2 wk or 7.5 mg/kg q 3 wk) in TREE2. Results: 147 pts were entered in TREE1 and 213 pts in TREE2. Selected gr 3/4 toxicity during 1st 12 wks of treatment is shown in table. Addition of B in TREE 2 caused increased gr 3/4 hypertension, impaired wound healing (5%) and bowel perforation (3%) in each arm. Confirmed ITT ORR (TREE1/2 respectively) = FOLFOX 39%/49%, bFOL 20%/34%, CapOx 29%/43% Conclusions: Grade 3–4 toxicity with first line Bev plus Oxaliplatin-based chemotherapy is acceptable and less than reported for IFL. All regimens of fluoropyrimidine administration are active but FOLFOX has best balance of response and toxicity. CapOX tolerance improved using reduced Cap 850 mg/m2 bid. Bev significantly improved RR (p=0.011, pooled logistic regression analysis) when added to Oxaliplatin-fluoropyrimidine chemotherapy. Additional efficacy data (TTP; OS) is not mature at time of abstract, but will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, sanofi-aventis Genentech, sanofi-aventis Genentech Genentech, Sanofi, sanofi-aventis Genentech, sanofi-aventis