tbuckley/cabot-search huggingface dataset:
Efficacy and tolerability of oxycodone for oxaliplatin-induced peripheral neuropathy and the extension of folfox therapy in colorectal cancer patients.
Authors: Makoto Nagashima, Mitsuru Ooshiro, Ayako Moriyama, Kengo Kadoya, Ayami Sato, Tomoaki Kitahara, Ryuichi Takagi, Tasuku Urita, Yutaka Yoshida, Hiroshi Tanaka, Takashi Oshiro, Shinichi Okazumi, Ryoji Katoh
Journal: Journal of Clinical Oncology (2014)

196 Background: The oxaliplatin-based regimen FOLFOX is widely used to treat patients with advanced colorectal cancer (CRC). However, dose-limiting toxicity after continuous oxaliplatin administration can lead to peripheral neuropathy. Several agents, including opioids, that have been employed to treat oxaliplatin-induced peripheral neuropathy (OIPN) have been examined in clinical settings regarding their protective and therapeutic effects. However, the pharmacotherapy of these agents has not yet been established. Therefore, we investigated the efficacy and tolerability of oxycodone for OIPN and subsequently with FOLFOX therapy in CRC patients. Methods: This was a single-center retrospective study of 64 CRC patients who underwent FOLFOX therapy at the Toho University Sakura Medical Center (Sakura, Japan). Controlled-release (CR) oxycodone was concomitantly administered to 29 patients (OXY group), whereas the additional 35 patients (non-OXY group) were not given oxycodone during the FOLFOX treatment course. The incidence and severity of OIPN and the number of FOLFOX cycles were measured and compared between the two groups. Neurological toxicities were assessed according to the Common Terminology Criteria for Advanced Events, version 3.0. Results: All study patients had OIPN. Most patients experienced grade 1 or 2 sensory neuropathy. Grade 3 sensory neuropathy was observed in two patients in the non-OXY group. All patients in the OXY group completed the scheduled FOLFOX therapy, whereas FOLFOX therapy was discontinued in ten patients in the non-OXY group due to severe peripheral neuropathy. The median numbers of FOLFOX cycles in the OXY and non-OXY groups were 13 (range, 6–46) and 7 (range, 2–18), respectively (P &lt; 0.05). The median cumulative oxaliplatin doses were 1072.3 mg/m 2 (range, 408.7–3385.3 mg/m 2 ) in the OXY group and 483.0 mg/m 2 (range 76.2–1414.1 mg/m 2 ) in the non-OXY group (P &lt; 0.05). Conclusions: Our findings indicate that CR oxycodone might attenuate the severity of OIPN and extend the use of FOLFOX therapy.
Circulating tumor cells (CTC): Assessment of treatment efficacy in metastatic breast cancer (MBC)
Authors: M. C. Liu, P. Shields, C. Isaacs, R. Warren, P. Cohen, M. Wilkinson, Y. Zhang, R. Shen, K. Luyegu, A. L. Gallagher
Journal: Journal of Clinical Oncology (2007)

10535 Background: Preliminary data in MBC suggest that ≥5 CTC/7.5 mL blood is associated with worse progression free survival (PFS) and overall survival (OS), and that the persistence of ≥5 CTC/7.5 mL blood after the initiation of therapy predicts for treatment failure (NEJM 2004. 351:781.). We are conducting a prospective clinical research study to validate the prognostic and predictive significance of this serum biomarker in MBC. Methods: Serial CTC levels are obtained in patients starting a new systemic treatment regimen for progressive, radiographically measurable MBC. 10 mL samples of peripheral blood are collected before the start of treatment and then at 3–4 week intervals. All subjects are followed prospectively for PFS and OS, and they are offered the opportunity to continue CTC testing upon disease progression. CTC enumeration is performed on a 7.5 mL blood volume using the CellSearch technology (Veridex, LLC; Warren, NJ). Epithelial cells are immunomagnetically separated and fluorescently labeled, and nucleated (DAPI+) cells with the EpCAM+, cytokeratin 8/18/19+, and CD45- phenotype are counted as CTC. Clinical outcomes are based on radiographic studies and physical examination in accordance with RECIST criteria. Results: 46 of 100 subjects have been accrued, and 33 have completed at least one radiographic staging evaluation with a median follow up of 7 mos (range 2–18 mos). Treatment for the 33 evaluable patients includes chemotherapy (27%), endocrine therapy (46%), and combination therapy with a biologic agent (27%). At baseline, 85% (28/33) had at least 1 CTC/7.5 mL (range 1–78), and 27% (9/33) had ≥5 CTC/7.5 mL. Median PFS was 2.57 months and 6.77 months for subjects with ≥5 vs &lt;5 CTC/7.5 mL at baseline, respectively (p=0.02). Conclusions: The current data validate the observation that baseline CTC levels correlate with PFS in patients with MBC and measurable disease. Patient accrual and data analysis are ongoing to confirm that persistent CTC levels ≥5/7.5 mL correlate with a lack of treatment efficacy and therefore are a reliable surrogate marker of disease responsiveness and PFS. [Table: see text]
The Ratio of Alternate BIRC5 (Survivin) Splice Variants Correlates with Refractory Disease and Poor Outcome in Children with Acute Myeloid Leukemia: A Report From the Children's Oncology Group,
Authors: Andrew S. Moore, Todd A. Alonzo, Robert B. Gerbing, Beverly Lange, Nyla A. Heerema, Janet Franklin, Susana C. Raimondi, Betsy A. Hirsch, Alan S. Gamis, Soheil Meshinchi
Journal: Blood (2011)
Correlative analyses between EGFR pathways and stroma-tumor profiles in head and neck cancer patients (HNSCC) on postoperative radiotherapy plus cisplatin (PORTc) plus or minus gefitinib (GORTEC-GETTEC CARISSA trial): Implications for sensitivity to gefitinib.
Authors: J. Thariat, D. Grall, M. Etienne-Grimaldi, F. Penault-Llorca, M. Francoual, G. A. Milano, D. De Raucourt, P. Garaud, R. Bensadoun, E. van-Obberghen Schilling
Journal: Journal of Clinical Oncology (2010)

TPS268 Background: PORTc is the standard treatment for resected poor-prognosis HNSCC. However, numerous patients fail. Anti-EGFR agent gefitinib is radiosensitizing. Gefitinib has FDA approval for EGFR-mutated lung cancer patients. CARISSA aims are: test the PORTc-gefitinib combination + identify a HNSCC subgroup sensitive to gefitinib. Prior CARISSA communication showed similar compliance to PORTc and no excessive toxicity. EGFR tyrosine-kinase domain mutations are anecdotic in HNSCC; Braf and Ras require investigations. Preliminary reports suggest that PTEN, pAkt, Ecadherin confer resistance to gefitinib in HNSCC. Human papilloma virus and tumor-stroma-EGFR pathways profiles are yet partially unknown in HNSCC despite publications on the role of stroma (matrix, tumor-activated fibroblasts) in tumor progression, invasiveness. The availability of operative samples was a unique opportunity to investigate the overall tumor behavior and response to gefitinib in regards to recent enlightenments on tumor biology. Methods: The CARISSA multicenter blinded phase II trial NCT00169221 (PORTc [A] ± gefitinib [B]) has a two-step randomization process: 1) patient agreement on having their biological samples (tumor + skin) analyzed (EGFR-binding, gene polymorphisms, Western Blotting of whole tumor lysates [WBl]/membranes [WBm], immunohistochemistry [IHC] of tumor/stroma on tissue microarrays [TMA]); 2) randomization postsurgery between A and B if pN + extracapsular spread or > 3pN+ ± positive margins ± lymphovascular emboli ± perineural invasion. Sensitivity to gefitinib is investigated using potentially predictive biomarkers: EGFR-pERGF, Akt-pAkt, PTEN, ERK-pERK, PAK1, FADD, cortactin, fibronectin, Src-pSrc, ILK by WBl, EGFR-pEGFR by WBm, same markers as WBl + p21, p16, Ki67, EGFRvIII, IGFR1, HER 2,3,4, amphiregulin, ERCC1, BRCA1, GSTpi, Ecadherin on TMA by IHC + Ras/Braf by in situ hydrization. The trial is planned to include 140 patients. Primary endpoint is three-year disease-free survival. Eighty-two patient samples have been collected. No significant financial relationships to disclose.
Developing an item bank to measure psychological distress in cancerpatients using Rasch models
Authors: A. Smith, R. Rush, P. Harvey, H. Swanson, G. Velikova, L. Wall, E. P. Wright, P. Selby, D. Stark, M. Sharpe
Journal: Journal of Clinical Oncology (2005)

8104 Background Psychological distress (PsyD) is common in cancer patients (CP). Self-report screening instruments are disappointing in detecting CP needing specialist intervention for PsyD, and CP with increased PsyD below psychiatric disorder, needing support within cancer care. Items assessing PsyD may fit on a single scale, so we may reduce the number of items CP must answer and tailor questions to CP own level of PsyD. We aim to apply Rasch analyses to instruments measuring PsyD, to develop a bank of items, and to evaluate how these items fit a unidimensional scale across the range of severity of PsyD (in logits). Methods A Rasch common-item equating analysis was applied to our database. The Beck Depression Inventory, General Health Questionnaire, Mental Health Inventory, State-Trait Anxiety Inventory, FACT Emotional Well-being scale, Patient Health Questionnaire, Hospital Anxiety and Depression Scale, and EORTC QLQ-C30 Emotional Functioning scale were analysed separately. Items that misfit the single scale (infit mean square >1.4) were removed. Then items from each instrument were added with common items as anchor points. Results A sample of 4923 CP provided an initial bank of 83 items. When 18 items were removed due to misfit, 65 items had infit and outfit mean square <1.4. No factor structure was evident in the residuals on principal components analysis, confirming a good unidimensional structure. Internal reliability was high (person separation index 0.85). Item locations ranged from -5 to +3 logits. Therefore many items assessed high levels of PsyD. Person abilities ranged from -5 to +1. Many CP reported low levels of PsyD. Limited overlap between item and person locations indicates a need to develop further items. Conclusions In a large sample of CP we have applied a Rasch model to items from widely used previously validated self-report PsyD questionnaires. Many items fit a single continuum of PsyD. Additional items may improve the item bank, leading in future to a fixed questionnaire and computer adaptive testing to measure PsyD in CP on a single continuum, using fewer items, tailored to the patient. No significant financial relationships to disclose.
Bevacizumab plus erlotinib in patients (pts) with carcinoma of unknown primary site: A phase II trial of the Minnie Pearl Cancer Research Network
Authors: J. D. Hainsworth, D. R. Spigel, D. S. Thompson, D. L. Shipley, J. D. Zubkus, M. A. Toomey, E. Burkett, F. A. Greco
Journal: Journal of Clinical Oncology (2006)

3033 Background: Targeted therapies inhibiting tumor angiogenesis or the epidermal growth factor pathway have demonstrated efficacy in a variety of solid tumors. In this multicenter phase II trial, we evaluated the efficacy of combined targeted therapy with bevacizumab plus erlotinib in pts with carcinoma of unknown primary site. Methods: Eligibility criteria included: metastatic adenocarcinoma or poorly differentiated carcinoma of unknown primary site; 1 or 2 previous chemotherapy regimens (previously untreated pts were eligible only if considered poor candidates for chemotherapy due to advanced liver or bone metastases); measurable disease; ECOG PS 0–2; no previous anti-angiogenic or EGFR inhibitor therapy; no active brain metastases; no active thromboembolic disease or bleeding abnormalities; adequate organ function; informed consent. All pts received bevacizumab 10mg/kg IV q 2 weeks and erlotinib 150mg PO daily. Pts were evaluated for response after 8 weeks; treatment was continued until tumor progression. Results: 51 pts entered this clinical trial between 4/04 and 7/05. Pt characteristics: median age 57; male/female, 22/29; ECOG 0/1/2, 5/43/3; previous chemotherapy, 75%. 49 pts (96%) received at least 2 months therapy and were evaluable for response. Objective responses occurred in 4 pts (8%) (all ongoing at 5+ - 19+ months); 30 pts (59%) had stable disease/minor response. After median follow-up of 13 months, median progression-free survival for the entire group is 6.2 months. Median overall survival is 8.9 months, with 42% of pts alive at 1 year. 1-year survival for previously treated vs. untreated pts: 41% vs. 46%. Toxicity with this regimen was consistent with previous reports; other than fatigue (12%), no grade 3/4 toxicity was observed in &gt; 10% of pts. Conclusions: The combination of bevacizumab and erlotinib has activity in pts with carcinoma of unknown primary site. Progression-free and overall survival results appear superior to our previous second-line results using a variety of chemotherapy regimens, and are similar to results with first-line chemotherapy. Future trials will evaluate bevacizumab/erlotinib as part of first-line therapy. [Table: see text]
Phase II trial of three-dimensional conformal radiation therapy for stage I non-small cell lung cancer (NSCLC) in elderly patients
Authors: Y. Niibe, K. Karasawa, R. Ieki, M. Shibuya, H. Kawamura, T. Umezawa, N. Hanyu, K. Hayakawa
Journal: Journal of Clinical Oncology (2004)

7230 Background: Conventional aggressive treatments for lung cancer are intolerable for the elderly patients, even in case of early stage disease, because many elderly patients have higher mortality and morbidity rates due to coexisting medical complications such as cardiovascular disease and chronic pulmonary disease. Recently, three-dimensional conformal radiation therapy (3D-CRT) has been performed to treat stage I non-small cell lung cancers (NSCLC), providing high dose of radiation to the tumors without increasing the dose to the surrounding normal lung tissue, which might improve curability without severe toxicities in elderly patients. Thus, we designed a phase II trial to evaluate the effectiveness of 3D-CRT for stage I NSCLC in elderly patients. Methods: Eligibility criteria was as follows: stage I pathologically proven NSCLC, age ≥ 70 years, a performance status (PS) of 0–3(ECOG), no limitations of respiratory status, V20 ≤ 20 %. Radiation therapy was planned with 6 MV X-ray, non-coplanar static 3D-CRT method. All patients were given 60 Gy or more in 3–4 Gy/ fraction. Results: Eighteen patients were registered in this trial between September 1999 and December 2002. Median age was 80.5 years (range, 70–87). As for T-stage, T1 was 13 and T2 was 5. As for PS, 0 was 1, 1 was 11, 2 was 4 and 3 was 2. Median follow-up time was 16 months (range, 4–41), median total dose was 66 Gy (range, 60–75), and median overall treatment time was 30 days (range, 25–38). One- and three-year local control rates were 92.9 % and 92.9 %, respectively. One- and three-year overall survival rates were 100 % and 69.2 %, respectively. Stratified by PS, 3-year local control rate of PS0–1 was 100 %, and that of PS2–3 was 75 %. Three-year overall survival rate of PS0–1 was 88.9 %, and that of PS2–3 was 50 %. As for toxicity, only two patients experienced grade 2 radiation toxicity of the lungs and all of the other events categorized into grade 0 or 1 (assessed by NCI-CTC criteria). Conclusions:This phase II trial demonstrates that 3D-CRT for stage I NSCLC in elderly patients was considered to be one of the most promising treatment methods, especially in case of good performance status. No significant financial relationships to disclose.
Final analysis of a phase I/IIa study with CV9103, an intradermally administered prostate cancer immunotherapy based on self-adjuvanted mRNA.
Authors: H. Kübler, T. Maurer, A. Stenzl, S. Feyerabend, U. Steiner, M. Schostak, W. Schultze-Seemann, F. vom Dorp, L. Pilla, G. Viatali, C. Hampel, S. Wedel, L. Trojan, K. Hiller, M. Sommerauer, D. Jocham, B. Scheel, T. Lander, K. Kallen, K. Miller
Journal: Journal of Clinical Oncology (2011)

4535 Background: CV9103 is a prostate cancer (PCA) vaccine that contains the four antigens PSA (prostate specific antigen), PSCA, PSMA and STEAP1 as self-adjuvanted full-length mRNAs. Methods: Patients with castrate resistant PCA with rising PSA and predominantly existing metastases (> 80%) were enrolled into a first-in-man phase I/IIa study. The primary endpoint was safety, the secondary immunogenicity. Three different dose levels (256µg, 640µg and 1280µg total mRNA) were tested in the phase I. Patients were vaccinated intradermally in weeks 1, 3, 7, 15 and 23. Blood samples were taken before the first and two weeks after the 2nd to 4th vaccination. Immune responses were assessed by ELISPOT (IFN-g), intracellular cytokine staining (IFN-g, TNFa), tetramer analysis (all ex vivo) or ELISA (PSA). Results: Three patients each were accrued at the low and medium dose level. One dose limiting toxicity, urinary retention, was observed at the high dose level which was expanded to six patients. A maximum tolerated dose was not defined. 389 AEs were reported, and 282 were classified as related. Of these, most were injection-site reactions or flu-like symptoms such as chills and fever. Of 21 serious adverse events, 7 were classified as related. With safety established, the high dose level was expanded by 32 patients (phase IIa). Immunomonitoring was possible in 33 of the 38 patients enrolled at the high dose level. Antigen-specific T-cells were detected in 79% of patients independent of their HLA-background. Importantly, 58% of the immunological responders reacted against multiple antigens. Immune responses were detected against all antigens regardless of cellular localization. The frequency of antigen-unspecific B-cells was increased in 74% patients. In 3 patients, an increase of preexisting anti-PSA antibody levels was measured. NK-cells showed a tendency for increased activation (CD25 and CD69). Individual patients had prolonged stabilization of PSA-levels after initial rises. One patient had a greater than 85% drop in his PSA-level. Conclusions: CV9103 was safe and well-tolerated and displayed an unexpectedly high level of cellular immunogenicity.
AR<sup>v567es</sup> as detected in circulating tumor cells: An innovative methodology for the detection of a prognostic and therapeutic biomarker.
Authors: Avani Atul Shah, Zhigang Kang, Ravi Amrit Madan, Jennifer L. Marte, James L. Gulley, William L. Dahut, Liang Cao
Journal: Journal of Clinical Oncology (2014)

112 Background: Increased androgen receptor (AR) expression and signaling is associated with the progression of prostate cancer. Constitutively active AR splice variants (ARVs) are thought to arise following castration and play a key role in progression. The most well studied variant, AR v567es , lacks portions of the ligand-binding domain, increasing expression of full-length AR and transcriptional activity of AR in human prostate cancer cell lines. Tumor-derived tissue can be difficult to obtain for molecular studies on patients (pts) with castration-resistant prostate cancer (CRPC), with circulating tumor cells (CTCs) representing a unique avenue to investigate changes at the molecular level. Methods: Forty-seven whole blood samples drawn from 36 pts with metastatic CRPC (mCRPC) were processed for CTC isolation followed by molecular characterization of cDNA using epithelial tumor markers and prostate cancer specific markers. Microfluidics devices used in this study for CTCs isolation and retrieval is a surface marker independent, label-free cell trap system developed to isolate CTCs based on cell size and deformability (Clearbridge Biomedics). The AR v567es was detected by multiplex digital PCR System (BioMark HD, Fluidigm) and confirmed by Sanger sequencing. Results: Four out of 36 pts and 6 out of 47 samples had the AR v567es. . The AR v567es amplified from three pts was confirmed by Sanger sequencing in which the ligand binding domain of the receptor was absent. Metastatic disease on presentation was seen in three out of four pts with the ARVs. The ARVs were detected late in the disease course, with the survival after assessment being brief (49, 106, and 200 days) for three out of four pts. One patient is still at 343 days. Due to the nature of this analysis it is unclear when these ARVs developed since baselines samples were not available. Conclusions: This is the first report of the AR v567es found in CTC-enriched peripheral blood samples from CRPC pts. This methodology can also be employed to find other ARVs, which could serve as potential biomarkers in pts, allowing for more appropriate treatment selection based on tumor evolution. This noninvasive method could significantly impact the molecular characterization and potentially the treatment science of CRPC.
Results from phase II trial of enzastaurin (LY317615) in patients with recurrent high grade gliomas
Authors: H. A. Fine, L. Kim, C. Royce, D. Draper, I. Haggarty, H. Ellinzano, P. Albert, P. Kinney, L. Musib, D. Thornton
Journal: Journal of Clinical Oncology (2005)

1504 Background: Gliomas are amongst the most angiogenic of all solid tumors and experimental evidence suggests that angiogenesis inhibition can be an effective approach for inhibiting glioma growth in vivo. PKC-β2 is an important signaling molecule in the induction of, and signaling through the VEGF pathway, thus making PKC-β2 an attractive therapeutic target. LY317615 is a PKC-β2 inhibitor with a potent antiangiogenic activity. We presented the preliminary result of phase II LY317615 clinical trial on 32 patients (pts) with recurrent malignant gliomas last year that demonstrated the antitumoral activity of LY 317615. (JCO, 2004 ASCO Ann. Meet. Proc., Vol 22, No 14S, 2004: 1511). We now report updated data on 85 pts (including original 32 pts) who were treated with LY317615. Methods: Treatment consists of oral LY317615 (fixed dose of 500 mg/day) administered daily on an every 6 week cycle. We stratified pts based on those taking enzyme inducing antiepileptic drugs (EIAED; Group B) and those not taking EIAED (Group A) and conducted pharmacokinetic (PK) studies. Results: To date 85 pts (70 pts in Group A and 15 pts in Group B) have been accrued to the trial and 79 pts were evaluable for response (72% GBM). Treatment (Tx) has been well tolerated with minimal drug-related toxicity > grade 1 (hematologic Grade (Gr) 2: 4 pts, Gr 3: 2 pts, Gr 4: 1 pt; hepatotoxic Gr 2: 1 pt). 36 pts have received more than 1 cycle of Tx (31 pts in Group A and 5 pts in Group B) and 13 pts have been stable on Tx for > 3 months and a number of other pts continue Tx with LY317615. Objective radiographic responses have been seen in 14 pts (10 GBM pts) that includes 1 complete response who is still receiving Tx 13 months after the enrollment. The Group B arm is closed and the accrual for GBM pts in Group A arm will be completed soon. Conclusion: LY317615 is well tolerated and appears to have promising antitumoral activity in a significant percentage of highly pretreated patients. We are still accruing pts to the trial and will present additional clinical and PK data to the ASCO meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Eli Lilly Eli Lilly