tbuckley/cabot-search huggingface dataset:
Association of skin toxicity (ST) severity with clinical outcomes and health-related quality of life (HRQoL) with panitunumab (Pmab)
Authors: Y. Humblet, M. Peeters, S. Siena, A. Hendlisz, B. Neyns, A. Sobrero, M. Wolf, M. Woolley, R. Amado, E. Van Cutsem
Journal: Journal of Clinical Oncology (2007)

4038 Background: STs are associated with epidermal growth factor receptor (EGFr) inhibition. Studies of anti-EGFr inhibitors have shown associations between the severity of ST per clinical toxicity grading and response rate, progression-free-survival (PFS) and overall survival (OS). However a correlation between these endpoints and ST severity as measured by ST patient reported outcomes (PRO) and the impact of ST on HRQoL is unknown. We evaluated the associations among PFS, OS and ST PRO, and the impact of ST on overall HRQoL for Pmab. Methods: In a phase 3 study of mCRC patients (pts) with disease progression after treatment (tx) with standard chemotherapy, pts were randomized to best supportive care (BSC) ± Pmab 6mg/kg Q2W. ST was measured using modified NCI-CTC v3.0 grading criteria and a modified Dermatology Life Quality Index (mDLQI). HRQoL (EQ-5D and EORTC QLQ-C30 Global QoL subscale) and CRC symptoms (NCCN/FACT CRC symptom index, FCSI) were also measured. Analyses of ST with PFS and OS were restricted to pts in the Pmab arm with ≥ grade (gr) 1 ST that were progression-free at least 28 days. These analyses were adjusted for randomization factors. Hazard ratios (HR) and correlation analyses were used to determine relationships between PFS and OS to ST, and ST to overall HRQoL. Results: Tx with Pmab (n=231) prolonged PFS vs BSC alone (n=232; p&lt;.0001). The incidence of gr 2–4 ST was higher in the Pmab arm. OS was significantly prolonged in pts with more severe ST (gr 2–4 vs. gr 1; HR=0.67; p=0.0235). Lower mDLQI scores (worse ST) also predicted improved OS (Cox model, p&lt;0.0001). Similar results were seen with PFS. Pearson correlation coefficients showed that the minimum post- baseline mDLQI score was inversely associated with post-baseline median HRQoL and CRC symptom scores, suggesting that Pmab pts with more severe ST have a higher (better) HRQoL (p=0.0006, 0.0148, 0.2487) and improved CRC symptom scores (p=0.0649). Conclusions: Pts with gr 2–4 ST appear to experience longer PFS and OS compared to those with gr 1 ST. Pts reporting the greatest bother from their ST also tend to report better overall HRQoL and reduced CRC symptoms. [Table: see text]
Assessing alternative dosing strategies for granulocyte-colony stimulating factor (G-CSF) use with FOLFOX6 therapy for treatment of colorectal cancer in a prospective cohort.
Authors: Jordan Stinson, Yoo-Joung Ko, Carlo DeAngelis, Angie Giotis, Mark Pasetka
Journal: Journal of Clinical Oncology (2015)

771 Background: While clinical guidelines recommend an average of 11 injections of granulocyte-colony stimulating factor (G-CSF) per cycle of chemotherapy, few studies support alternative dosing strategies for G-CSF use by cancer type and chemotherapy regimen. Methods: From 2004 to 2013, 63 colon and 47 rectal cancer patients were recruited and monitored throughout the course of their FOLFOX6 therapy. G-CSF use was determined by a clinical pharmacist and tracked every week to ensure patients received an adequate number of injections and were compliant with each cycle. All patients received at least two cycles of G-CSF. Occurrence of neutropenia, febrile neutropenia, and thrombocytopenia were compared between patients receiving four and five injections per cycle. Results: There were 54 males and 56 females with a median age of 56. 104 patients received adjuvant chemotherapy with the remaining six being in the metastatic setting. 83 of 110 (75%) patients experienced no delays after initiation of G-CSF with 67 (61%) of those patients receiving four or five injections per cycle. The remaining 27 of 110 (25%) patients experienced a delay in treatment after at least one cycle of G-CSF completed (15 neutropenic delays, four FN delays, and 12 thrombocytopenic delays). Significantly, only seven of those 27 (26%) patients had a neutropenic delay that occurred as a result of a failed dosing strategy after G-CSF was initiated. Of these seven neutropenic delays, five (71%) were the result of a four dose injection pattern, but none were the result of the five dose injection pattern scheme. All other delays, after at least one cycle of G-CSF (74%), were caused by patients’ non-compliance The overall compliance rate with G-CSF injections was 93%. Conclusions: Only 7 of 110 (6.4%) patients experienced a G-CSF failure. It is recommended that G-CSF be administered on day 4, 6, 8, 10, and 12 of each FOLFOX6 cycle to maintain absolute neutrophil counts and prevent treatment delays.
Lenalidomide, bortezomib, and dexamethasone in relapsed/refractory multiple myeloma (MM): Encouraging outcomes and tolerability in a phase II study
Authors: K. C. Anderson, S. Jagannath, A. Jakubowiak, S. Lonial, N. Raje, M. Alsina, I. Ghobrial, R. Knight, D. Esseltine, P. Richardson
Journal: Journal of Clinical Oncology (2009)

8536 Background: Lenalidomide (Revlimid, Len), bortezomib (VELCADE, Bz; maximum tolerated dose [MTD] 15 mg/1.0 mg/m 2 ) ± dexamethasone (Dex; 20–40 mg; RVD) was well tolerated in a phase I study in relapsed/refractory MM patients (pts), with 58% ≥MR. This multicenter phase 2 study evaluated RVD efficacy and safety at the MTD. Methods: Patients received up to eight 21-day cycles of Len 15 mg (days 1–14), Bz 1.0 mg/m 2 (days 1, 4, 8, 11), and Dex 40/20 mg (cycles 1–4/5–8, days of/after Bz dosing). After cycle 8, patients with stable/responding disease received maintenance (Len, days 1–14; Bz, days 1, 8; doses per end of cycle 8; Dex 10 mg, days 1, 2, 8, 9) until progression or unacceptable toxicity. Pts with significant peripheral neuropathy were excluded. Results: Among 64 pts, 38 (59%) had relapsed and 26 (41%) refractory/relapsed MM. Median number of prior therapies was two, including Len (8%), Bz (55%), Dex (92%), thalidomide (77%), and stem cell transplant (SCT, 36%). Forty-one pts (64%) completed 8 cycles, 33 continue on maintenance, 22 discontinued early (11 due to progressive disease). Toxicities were manageable, primarily grade (G) 1/2 myelosuppression; 2 developed DVT on aspirin, 2 G3 atrial fibrillation, 1 G3 peripheral neuropathy. One pt died on-study (fungal pneumonia, possibly due to Dex). Overall response rate (62 evaluable patients) was 84% ≥MR, including 21% CR/nCR, 68% ≥PR, which was independent of high-risk features and prior treatment ( Table ). Median duration of response is 24 weeks (range 6–81). Time-to-events data including median time to progression, progression-free survival, and 1-year survival rates will be presented. Conclusions: RVD is active and well tolerated in pts with relapsed/refractory MM, including pts who have received prior Len, Bz, thalidomide, and SCT. Durable responses have been observed and appear independent of adverse cytogenetics and other recognized risk factors. [Table: see text] [Table: see text]
Lessons from ovarian cancer patients with more than 10 years survival
Authors: K. Kudoh, M. Takano, T. Kita, T. Yoshikawa, K. Furuya, Y. Kikuchi
Journal: Journal of Clinical Oncology (2006)

15059 Background: Purpose of this retrospective study is to explore predictive factors for long-term survival in patients with primary epithelial ovarian carcinoma. Methods: Total 161 patients treated from March 1983 to December 1994 at the National Defense medical College hospital were enrolled in this study. Profiles and characteristics of patients with long-term survival were retrospectively examined. Results: All patients with stage IA-B or IIA-B survived more than 10 years although 2 of patients with stage IA and IB tumor were dead of primary disease and one patient was dead of other disease after more than 10 years follow-up. More than half of patients with stage IC, IIC or IIIA-B survived more than 10 years, while 10-years’ survival rates of patients with stage IIIC or IV were only 10% with marked increase of death by primary disease. All patients with stage I or IIA-B without residual tumor after initial surgery survived more than 10 years. Although long-term survival rates of patients with stage IIC or IIIA-B were higher in patients without residual tumor after initial surgery, 6 out of 7 patients with stage IIIC or IV had residual tumor. Analysis of 70 patients with stage III or IV ovarian cancer revealed that residual tumor size, histologic types and response to initial chemotherapy affected significantly long-term survival. Conclusions: We demonstrated that predictors for long-term survival were stage, residual tumor size after initial surgery, histology and response to initial chemotherapy. [Table: see text] No significant financial relationships to disclose.
Epirubicin in patients with advanced or recurrent adenoid cystic carcinoma of the head and neck: A phase II study of the EORTC Head and Neck Cancer Cooperative Group
Authors: J.B. Vermorken, J. Verweij, P.H.M. de Mulder, F. Cognetti, M. Clavel, S. Rodenhuis, A. Kirkpatrick, G.B. Snow
Journal: Annals of Oncology (1993)
Cardiac function surveillance in patients during anti-cancer treatment: Initial experience with the CW-Doppler-based USCOM device and correlation to echocardiography and serum proBNP levels
Authors: V. Lange, S. Geiger, F. Brettner, V. Heinemann, H. J. Stemmler
Journal: Journal of Clinical Oncology (2008)

14648 Background: Cardiac function monitoring is essential during numerous anti-cancer treatments. For clinical routine, echocardiography is most commonly used for left ventricular systolic function surveillance. The primary goal of the present study was to determine the value of the CW-Doppler-based USCOM device (ultrasonic cardiac output monitoring) in monitoring the cardiac function of patients receiving anti-cancer therapy for various malignancies. Methods: 68 patients who received anti-cancer treatments [anthrazyclines (A) n=21, cetuximab (C) n=18, trastuzumab (T) n=10, bevacizumab (B) n=19] for mainly GI or breast cancers, were examined at 4 pre-defined times: T0 prior to first drug exposition, T1 subsequent to the first infusion, after 1 week (T2) and finally after 3 months of treatment (T3). Serum proBNP kinetics were compared to ejection fraction calculated by echocardiography (EFEcho; T0 and T3) and stroke volume measured by the USCOM device (SVUSCOM). Results: None of the patients developed clinically signs of overt heart failure. Parameters analyzed with the USCOM device (SVUSCOM) are in accordance to those measured by echocardiography (EFEcho) (→ table). Conclusion: The preliminary results of this study indicate a potential clinical value of the USCOM device in the cardiac function surveillance of patients during anti-cancer treatments. An outstanding advantage of the USCOM device is the less time needed (<1 min.) when compared to the well established but more time-consuming echocardiography. Further studies within more homogenous, pre-defined patient groups are initiated. T 0 T 1 T 2 T 3 Δ T0–3 (%) A SVUSCOM (ml) 75 84 83 64 85.3 A EFEcho (%) 68 - - 65 95.6 A proBNP (ng/ml) 208 286 234 310 149 C SVUSCOM (ml) 56 47 48.5 58 103.6 C EFEcho (%) 62.5 - - 72 115.2 C proBNP (ng/ml) 76.9 94.3 42.7 120 156 T SVUSCOM (ml) 70 55.5 80 76 108.6 T EFEcho (%) 63.5 - - 57 89.8 T proBNP (ng/ml) 126 116 132 113.4 89.9 B SVUSCOM (ml) 55 59 59 37.5 68.2 B EFEcho (%) 71 - - 67 94.4 B proBNP (ng/ml) 89.1 86.9 47.3 58.2 65.3 No significant financial relationships to disclose.
Low incidence of pneumonitis on SWOG 0023: A preliminary analysis of an ongoing phase III trial of concurrent chemoradiotherapy followed by consolidation docetaxel and gefitinib/placebo maintenance in patients with inoperable stage III non-small cell lung cancer
Authors: K. Kelly, L. E. Gaspar, K. Chansky, K. S. Albain, J. Crowley, D. R. Gandara
Journal: Journal of Clinical Oncology (2005)

7058 Background: Significant pneumonitis (≥ grade 3) is reported in up to 19% of patients (pts) with stage III non-small cell lung cancer treated with concurrent chemoradiotherapy (Werner-Wasik Proc ASCO: 2002). Among known risk factors for radiation (RT)-related pneumonitis is % total lung volume irradiated exceeding 20 Gy (TLV-20). SWOG 0023 is an ongoing randomized phase III trial incorporating three distinct treatment phases: concurrent cisplatin/etoposide (PE) plus thoracic RT, docetaxel consolidation and gefitineb (Iressa)/placebo maintenance. Each phase alone or in combination could contribute to pneumonitis, including interstitial pneumonitis (ILD) from Iressa. A preliminary analysis was conducted to determine the incidence, timing and severity of pneumonitis. Methods: Pneumonitis was defined by NCI CTC Version 2.0. Results: As of 12/02/2004, 516 eligible pts have been accrued. 406 pts are evaluable for concurrent chemoRT, 277 pts for consolidation, 82 pts for Iressa maintenance and 85 pts for placebo maintenance. The incidence of pneumonitis during each treatment phase is reported in the table below. Overall 20/406 pts (5%) discontinued treatment due to pneumonitis. Comparative data from relevant recent trials including SWOG 9504 (PE/TRT followed by docetaxel), RTOG 9410 (sequential versus concurrent versus experimental chemotherapy and TRT) and CALGB 39801 (concurrent paclitaxel and carboplatin (PC) plus TRT versus induction PC followed by PC/TRT) reported grade ≥ 3 pneumonitis rates of 5%, 2–6% (acute) and 11–13% (late) and 2–5% respectively. Conclusions: The incidence of significant pneumonitis currently observed in SWOG 0023 is low and compares favorably to prior reports in the literature. A detailed analysis to identify risk factors such as required RT to TLV-20 <35% is underway. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca Aventis
Prediction of outcome of TPF with or without cetuximab induction chemotherapy in head and neck squamous cell carcinoma (HNSCC) using the FLAVINO assay.
Authors: A. Dietz, A. Boehm, A. Reiche, G. Mueller, P. Kruber, U. Keilholz, D. Niederwieser, G. Wichmann
Journal: Journal of Clinical Oncology (2010)

5572 Background: Due to the fact that chemoradiation strategies in case of resectable HNSCC are increasingly promoted, individual response evaluation for better biology-based decision making is more desirable than ever. The purpose is to analyze combined effects of docetaxel (T), cisplatin (P), 5-fluorouracil (F), and cetuximab (Ce) on colony formation of HNSCC in the FLAVINO assay (short-time ex-vivo colony-forming assay – flavin-protecting conditions) and correlate these results with outcome of TPF induction chemotherapy (TPF-IC) prior to irradiation (70 Gy). Methods: Tumor-biopsies of 18 patients suffering from HNSCC (treated by TPF-IC ± Ce) were taken, minced, collagenase-digested, and exposed to T and/or P at half, two- and double their tolerable plasma levels ±Ce, as well as Ce or medium alone. After 72-h incubation, wells were washed and cultures ethanol-fixed. Following pan-cytokeratin staining of epithelial cells using a Cy2-labeled antibody, fluorescent colonies were counted. Results: 66.7% of the biopsies (12/18) formed >4 epithelial colonies and hence allowed for IC50 calculation. Of these 12 biopsies, 11 indicated P- and 5 T- suppressed colony formation, and 5 (41.7%) responded with reduced colony formation to Ce, while one responded to Ce with increased colony formation. The FLAVINO assay classified 11/12 HNSCC (91.7%) as TP-responders. Clinically, 11/12 patients including the patient reacting with Ce-induced colony formation showed sufficient TPF response, while 1 patient (8.33%) underwent surgery due to minor response. The HNSCC classified as non- responder developed a recurrence 9 month after irradiation. Within this small cohort, the FLAVINO assay predicted the outcome in 83.3% of cases with one false-positive (8.3%) and one false-negative case (8.3%) each. Conclusions: The identification of responders using the FLAVINO assay is mature and should be evaluated within clinical trials. No significant financial relationships to disclose.
Proteomic analysis for detection of NSCLC: Results of ACOSOG Z4031.
Authors: D. Harpole, K. V. Ballman, A. L. Oberg, G. Whiteley, R. Cerfolio, R. Keenan, D. R. Jones, T. A. D'Amico, J. Shrager, J. B. Putnam
Journal: Journal of Clinical Oncology (2011)

7003 Background: NCI CT Screening Trial demonstrated a significant decrease in lung cancer mortality. This will dramatically increase the number of suspicious nodules discovered by CT. Unfortunately CT scans have a high false-positive rate for lung cancer requiring invasive diagnostic intervention. This study aim was to prospectively determine whether the serum proteomic profile can predict the presence of primary NSCLC in patients with CT suspicious lung lesions. Methods: One-thousand seventy-four patients with a clinically suspicious stage I (cT1-2 N0 M0) lung lesion were enrolled in Z4031 between 02/2004 and 05/2006. Fresh-frozen and FFPE tumor with pre- and post-operatively blood were collected prospectively after informed consent. Ciba Chrome Blue was used to capture low molecular weight proteins in pre-operative serum (un-digested) followed by mass analysis on a prOTOF 2000 MALDI-TOF mass spectrometer (MS) in duplicate. The spectra were normalized and the maximum and sum amplitudes within a m/z bin were used as abundance values. Features were identified by m/z values. Results: 913 patients were eligible: 723 patients with NSCLC and 190 patients with benign nodules. Patients with NSCLC were older (median 67.2 yrs vs 59.7 yrs, p < 0.0001) and had larger nodules (57.9% vs. 29.3% ≥ 2.0 cm, p < 0.0001). Of patients with NSCLC, 28% were squamous, 61.3% were adenocarcinoma, and 10% were other NSCLC. 690 eligible patients had at least one analyzable spectra. The MS proteomic profiles failed to discriminate between the groups. The spectra contained only a handful of proteins per patient and bins that had statistically significant different abundance values were in the noise region of the data and did not contain proteins. Conclusions: The proteomic platform did not have sufficient sensitivity to detect low abundance proteins. Furthermore, the limit of detection for the newest MS platforms are not sufficient for discovering discriminate protein profiles due to the dynamic range of the human proteome. A targeted approach beginning with analysis of gene expression in tissue followed by confirmation of corresponding proteins in tissue, and then assessing these proteins in serum will likely be much more fruitful and is underway.
Correlation of Ki67, topo IIa, MRP1, p53 and p-gp with chemo-responsiveness and survival in patients with hepatocellular carcinoma (HCC)
Authors: W. Yeo, W. L. Wong, N. Wong, K. F. To, F. K. Mo, A. T. Chan, P. B. Lai, J. Koh, P. J. Johnson
Journal: Journal of Clinical Oncology (2006)

4139 Background: HCC is a common cause of cancer morbidity and mortality. For patients (pts) who are not candidate of curative surgery, chemotherapy (CT) is one of the main treatments but response has been poor due to drug resistance. In this study, using the pre-CT tumor biopsies of HCC pts who were entered into our recently reported phase III prospective randomized CT study (J Natl Cancer Inst 2005; 97(7): 536–539), we aimed to correlate selected biomarkers with CT responsiveness and survival. Methods: 188 HCC pts were entered into the CT study. They were separately consented for the present correlative study. CT response was based on WHO criteria. For the purpose of this study, pts were categorized into CT-‘responsive’ group (those who obtained clinical benefits and achieved CR, PR or SD) and CT-‘non-responsive’ group (those who developed PD). Immunohistochemical staining for Ki67, topo IIa, MRP1, p53 and p-gp were performed on the pre-CT tumor biopsies; findings of which were analyzed with conventional clinical variables to identify factors that influenced CT response and survival. Results: 149 pts had pre-CT tumor biopsies available and were thus included in the present analysis, 1 pt was not assessable for response; there were 75 pts in the CT-‘responsive’ group (23 PR and 52 SD) and 73 pts in the CT-‘non-responsive’ group. The overall median survival was 7.9 months. Using multivariate analysis, predictors of response to CT were Ki67 positivity (p = 0.0427; OR = 0.475), MRP1 positivity (p = 0.0323; OR = 0.429), age (p = 0.0027; OR = 1.056) and albumin level (p = 0.0130; OR = 1.108). Predictors of survival included Ki67 positivity (p = 0.0097; HR = 1.662), topo IIa positivity (p = 0.0358; HR = 1.566), total bilirubilin level (p = 0.0006; HR = 1.039) and ALT level (p = 0.0092; HR = 1.005). Conclusions: In addition to conventional factors, Ki67 and MRP1 positivity are predictors of response to CT, while Ki67 and topo IIa positivity are predictors of survival. The present study demonstrates that immunohistochemical staining of biomarkers can be instrumental in highlighting genes in the drug-resistant phenomenon of HCC. Acknowledgements: This study has been supported by the Direct Grant of Chinese University of Hong Kong, project no. 2041124. No significant financial relationships to disclose.
Phase II trial of continuous low-dose temozolomide (TMZ) for recurrent malignant glioma (MG) with and without prior exposure to bevacizumab (BEV).
Authors: M. Khasraw, L. E. Abrey, A. B. Lassman, A. Hormigo, C. Nolan, I. T. Gavrilovic, I. K. Mellinghoff, A. S. Reiner, L. M. DeAngelis, A. M. Omuro
Journal: Journal of Clinical Oncology (2010)

2065 Background: The prognosis of recurrent MG, including glioblastoma (GBM), grade 3 anaplastic astrocytoma (AA) and oligodendroglioma (AO) is poor, especially after BEV failure. Metronomic TMZ schedules have been proposed as salvage therapy for recurrent MG, with the goal of targeting angiogenesis through inhibition of endothelial cell proliferation and repair occurring during the resting period of conventional chemotherapy regimens. Metronomic TMZ may also overcome chemoresistance mediated by O-6-methylguanine-DNA methyltransferase (MGMT). Methods: In this prospective phase II study, pts with recurrent/progressive MG with no limit in number of recurrences were treated with continuous, daily TMZ (50 mg/m2) until progression. The primary endpoint was 6m-progression free survival (PFS). A Simon two-stage design was utilized (n = 37 planned GBM, with additional 10 AA/AO for exploratory analysis). Results: To date, 41 pts have been enrolled (GBM: 30, AA: 8, AO: 3; median age: 56 y, range 29-84; median KPS: 80, range 60-100; 14 were women). The MGMT promoter was methylated in 3 pts, unmethylated in 16 and not available in 22. In addition to standard chemoradiotherapy with TMZ, previous treatments included Bev in 16 pts, other cytotoxic agents in 6 and experimental targeted therapies in 8. Median followup of survivors was 10 m. In the GBM group, 6mPFS was 24% (95% CI 7.41); median PFS: 2 m; median overall survival (OS): 7 m; objective response rate (RR): 6.6%. Pts with prior BEV exposure fared worse than pts with no BEV exposure (6 m PFS 14% vs. 36%, p = 0.12; median OS 4 m vs. 18 m, p = 0.005). In the AA/AO group, 6 m PFS was 27% (95% CI 1.54), median OS was 16 m, RR = 9%. Grades 3 or 4 toxicities were limited to lymphopenia in 9 pts. Conclusions: This regimen was well tolerated in this heavily pretreated population. A modest increase in efficacy was observed in the overall GBM population, and results in non-BEV failures were particularly encouraging. Results in BEV failures are difficult to interpret due to lack of historical controls. This study highlights the need for stratification according to previous BEV exposure and new historical controls for future trials in recurrent MG. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Cepahlon, Eisai, Genentech, ImClone Systems, Schering-Plough, Sigma-Tau Genentech Brain Tumor Funders' Collaborative, Dana Foundation, Genentech, Keryx, National Brain Tumor Foundation, National Cancer Institute, Novartis, Pfizer, Schering-Plough, Sigma-Tau, Voices Against Brain Cancer