tbuckley/cabot-search huggingface dataset:
Phase II study of irinotecan and carboplatin in advanced non-small cell lung cancer (NSCLC): Updated results of an ongoing study
Authors: W. L. Read, L. Toles, E. Romvari, D. Adkins, H. McLeod, R. Govindan
Journal: Journal of Clinical Oncology (2004)

7364 Background: The outcomes for patients with metastatic lung cancer are dismal, with one-year survival rates of approximately 35%. We are evaluating the combination of irinotecan (I) and carboplatin (C) in patients with stage IIIB and IV non-small cell lung cancer. A preliminary report of this study was presented earlier (ASCO 2003, A 2704) Methods: Eligible patients include those with histological or cytological diagnosis of non-small cell lung cancer, no previous chemotherapy for metastatic lung cancer and performance status ECOG 0–1. The first five patients received I 250 mg/m2 over 90 minutes followed by C at an AUC of 5 over 1 hour. Subsequently the dose of I was reduced to 200 mg/m2 in due to poor neutrophil recovery in the first 5 patients. Chemotherapy cycles were repeated every 21 days. Patients were reevaluated every 2 cycles. Results: Of a planned 37 patients, 36 have been enrolled, of whom 27 (72%) completed 2 or more cycles and are evaluable for response. 14 women and 22 men have been enrolled, with a median age of 62. 126 cycles have been administered, 36 of which were delayed. 12 of 36 delays occurred in the first 3 patients, who received the higher (250mg/m2) I dose. 72% of patients received 2 cycles, 52% of patients received 4 cycles and 30% received all 6 cycles. Toxicities: The main toxicity is hematologic: 10 patients had grade 4 neutropenia, of whom 5 were hospitalized with neutropenic fever (13%). There have been 3 deaths on study: 1 neutropenic fever, 1 disease progression in lung and 1 transfusion-assocated lung injury; only the first was thought to be treatment related. Other toxicities included pancreatitis, diverticulitis and pericardial effusion. Responses: To date there have been five PR (26%) and 14 SD (51%); 8 patients (22%) developed PD during treatment. Median followup is 458 days. Conclusions: The regimen of I and C administered every three weeks is tolerable and convenient, with evidence of activity. The main toxicity is hematological. This study is actively accruing and nearing its completion. Pharmacogenomic data is also being collected on these patients, and will be correlated with toxicity / response. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca Aventis; Bristol-Myers; Lilly; Ligand; Pfizer
Rechallenge with trabectedin in patients with responding myxoid liposarcoma
Authors: R. Sanfilippo, F. Grosso, E. Virdis, C. Morosi, J. C. Tercero, A. Gronchi, S. Pilotti, M. D'Incalci, P. G. Casali
Journal: Journal of Clinical Oncology (2009)

10575 Background: To determine the efficacy of rechallenge with trabectedin (T) in patients with myxoid liposarcoma who were responding to T at the time of discontinuation but subsequently developed progressive disease. Methods: Since September 2002, 32 patients with recurrent or advanced myxoid liposarcoma received T at our institution within an expanded access program. We report herein 8 patients who received T for a median of 10 cycles (range 5–15) prior to discontinuation. We used RECIST criteria to classify patient response to therapy. During the initial administration of T, a CR had been observed in 2 patients, a PR in 3 patients, SD in 2 patients, and one had had tumor shrinkage but did not meet RECIST definition of PR. The median PFS was 24 months from treatment start, and 14 months (range 9–27) from treatment-end. In 6 of the 8 patients, the treatment had been discontinued in the absence of any evidence of disease: 4 patients had undergone complete surgical resection (R0) of residual disease and 2 patients had achieved a radiological complete response (CR). The other two patients stopped treatment voluntarily, one with a partial response (PR) and one with stable disease (SD). All these patients resumed treatment at the time of progression. Results: Following rechallenge with T, no PD was seen at first assessment, and no patients had to discontinue or reduce the dose due to toxicity. Response rate according to RECIST was 50%. At a median follow up of 7 months (range 2.7–12), the median TTP has not yet been reached. Treatment is still ongoing in 5 patients. Conclusions: Rechallenge with T can be beneficial in some patients with myxoid liposarcoma. If further data confirm this, treatment of progressing patients previously responding to T may include this option. Furthermore, studies on optimization of treatment duration upfront may be worthwhile. [Table: see text]
Utilization of genomic signatures for chemotherapy response in prospective clinical studies.
Authors: W. Barry, C. Acharya, M. B. Datto, H. K. Dressman, P. K. Marcom, N. Ready, G. S. Ginsburg, A. Potti, J. R. Nevins
Journal: Journal of Clinical Oncology (2010)

10513 Background: The development of genomic signatures as predictive biomarkers of chemotherapeutics provides the potential to guide therapeutic choice in instances where standard-of-care includes multiple options. A critical step is their application in clinical studies designed to evaluate the capacity to improve selection of drugs for the individual patient. However, the prospective use of microarray technologies and multigene models to a single patient sample in the context of a clinical trial requires several methodological advancements. Methods: We describe a strategy that makes use of a trial-specific reference tumor dataset to provide a source of information for normalization of microarray data between the preclinical training set (cell lines) and the single patient sample. Validations of chemosensitivity signatures are repeated under this strategy using historical datasets with split-sample and bootstrap approaches. Results: Genomic signatures for adriamycin, docetaxel and cisplatin are mapped to Affymetrix GeneChip HG-U133Plus2.0 platform. Prospective predictions of adriamycin sensitivity were associated with response to neoadjuvant treatment of 133 breast cancers (AUC = 0.76, p < 0.001). Prospective predictions of docetaxel (n=14, AUC = 0.92, p = 0.007) and cisplatin (n=49, AUC = 0.97, p = 0.0001) sensitivity discriminated between responders and nonresponders under first-line treatment of advanced ovarian cancer. Bootstrap analyses show the genomic signatures require that reference sets have similar characteristics to the investigations sample and be of sufficient size to capture variation in gene expression in the patient population. Conclusions: These results demonstrate the accuracy of the genomic signatures are comparable to retrospective assessments when properly applied to a single sample in the prospective setting. We further describe trial designs to test the efficacy of these signatures and an automated data analysis infrastructure to enable their use in a clinical context. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Expression Analysis, Inc.
Sequential chemotherapy of S-1/weekly paclitaxel in patients with peritoneal metastasis of gastric cancer
Authors: T. Yoshida, T. Osaragi, H. Murakami, T. Yoshikawa, A. Tsuburaya, O. Kobayashi, M. Sairenji
Journal: Journal of Clinical Oncology (2005)

4236 Background: The aim of this study is to clarify the survival benefit of sequential chemotherapy of S-1/weekly paclitaxel in patients (pts) with peritoneal metastasis of gastric cancer. Methods: A total of 91 gastric cancer pts, including synchronous peritoneal metasitasis in 66 and metachronous one in 25 pts, were treated with S-1 (80mg/m2/day for 4 weeks with 2 weeks rest) until progression. When S-1 was failed, pts then underwent paclitaxel (80 mg/m2 at day 1, 8, 15 every 28 days) if applicable. Of 66 synchronous disease, 9 were only positive for intra-peritoneal lavage cytology. Median age was 64 years (27–85). Fifteen pts had undergone prior chemotherapy. Performance status (PS) was 0 in 22 pts, 1 in 49 pts, and 2 in 20 pts. Results: S-1 was discontinued because of toxicity in 10 pts. Paclitaxel was applicable for 47 pts including PS0–2 in 36 pts, and PS3 in 11 pts. Overall median survival time (O-MST) after the initiation of S-1 was 300 days. O-MST was 256 days in pts with prior chemotherapy and 329 days in pts without one (p=0.02), and 356 days for PS0/1 and 234 days for PS2 (p=0.00), respectively. Median time to progression of S-1 was 173 days. MST after paclitaxel (P-MST) was 155 days. P-MST was 222 days and O-MST was 507 days in pts with PS 0/1/2 when paclitaxel was started. Conclusions: Sequential chemotherapy of S-1/weekly paclitaxel may benefit pts with peritoneal metastases, especially for pts with good PS. No significant financial relationships to disclose.
Contact Between Human Bone Marrow Stromal Cells and B Lymphocytes Enhances Very Late Antigen-4/Vascular Cell Adhesion Molecule-1–Independent Tyrosine Phosphorylation of Focal Adhesion Kinase, Paxillin, and ERK2 in Stromal Cells
Authors: Lisa J. Jarvis, Jean E. Maguire, Tucker W. LeBien
Journal: Blood (1997)
A phase I clinical trial of QBI-139, a human ribonuclease variant, in solid tumors.
Authors: L. E. Strong, J. A. Kink, B. Mei, M. N. Shahan, R. T. Raines
Journal: Journal of Clinical Oncology (2011)

TPS146 Background: RNA has been recognized as a drug target for cancer therapy, as evidenced by the ongoing clinical trials of RNAi and antisense therapies. An alternative approach that circumvents the delivery and stability issues of RNAi and antisense is to harness the activity of naturally occurring enzymes that degrade RNA. A series of human ribonuclease (RNase) variants have been generated with diminished binding to their natural inhibitor inside cells, which allows the new proteins to kill cancer cells. One of these RNases, called QBI-139, has shown efficacy against multiple tumor types in in vivo models of human cancer and was selected for a first in human clinical trial. Methods: Since QBI-139 showed efficacy against multiple cancers in model systems, a Phase I trial was designed for patients with advanced solid tumors (NCT00818831). Patients receive QBI-139 by intravenous infusion once weekly for three weeks with treatment repeating every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of three to six patients receive escalating doses of QBI-139 until the maximum tolerated dose (MTD) is determined. The inclusion/exclusion criteria are typical for the patient population. Twenty-nine patients have been treated to date (January 2011) without reaching dose limiting toxicity. The starting dose in the clinical trial was 3 mg/m2 while the most recently completed cohort was treated with a dose of 18.6 mg/m2. Dose escalation is ongoing. The primary outcomes of the trial are to evaluate the toxicity and tolerability of and the maximum tolerated dose for QBI-139 in patients with advanced refractory solid tumors. In addition, patient response to QBI-139 will be measured using the RECIST criteria and the pharmacokinetics of QBI-139 will be evaluated. Given the agent’s broad efficacy in model systems, one of the goals of the Phase I trial is to identify indications for the next clinical trial of QBI-139.
Molecular Advances in Severe Acute Respiratory Syndrome-Associated Coronavirus (SARS-CoV)
Authors: Ken Yan Ching Chow, Chung Chau Hon, Raymond Kin Hi Hui, Raymond Tsz Yeung Wong, Chi Wai Yip, Fanya Zeng, Frederick Chi Ching Leung
Journal: Genomics Proteomics & Bioinformatics (2003)

Abstract The sudden outbreak of severe acute respiratory syndrome (SARS) in 2002 prompted the establishment of a global scientific network subsuming most of the traditional rivalries in the competitive field of virology. Within months of the SARS outbreak, collaborative work revealed the identity of the disastrous pathogen as SARS-associated coronavirus (SARS-CoV). However, although the rapid identification of the agent represented an important breakthrough, our understanding of the deadly virus remains limited. Detailed biological knowledge is crucial for the development of effective countermeasures, diagnostic tests, vaccines and antiviral drugs against the SARS-CoV. This article reviews the present state of molecular knowledge about SARS-CoV, from the aspects of comparative genomics, molecular biology of viral genes, evolution, and epidemiology, and describes the diagnostic tests and the anti-viral drugs derived so far based on the available molecular information.
Long-Term Outcome Of 151 Patients With Relapsed APL Receiving Second-Line With Chemotherapy Or Arsenic Trioxide-Based Regimens
Authors: Pau Montesinos, David Martínez-Cuadrón, Concha Rivas, Salut Brunet, José David González-San Miguel, Vicente Rubio, Cristina Pérez, Félix Manso, Pedro Sánchez-Godoy, Lourdes Escoda, Elena Amutio, Mark Zijlmans, Mar Tormo, Marcos González, Chelo Rayón, María José Sayas, Josep-Maria Ribera, Guillermo Deben, José Hernández-Martín, Jordi Esteve, Edo Vellenga, Miguel Sanz
Journal: Blood (2013)
The effect of adjuvant radiation on survival for patients with resected localized or regional primary small cell carcinoma of the breast.
Authors: Felicia Hare, Jashmin Kirankumar Patel, Moon Jung Fenton, Michael Gary Martin
Journal: Journal of Clinical Oncology (2014)

87 Background: Primary small cell carcinoma of the breast (SCCB) is rare and prognosis, the role of radiation therapy and outcomes are largely undefined. Methods: Using case listing session of SEER 18 (1973-2010) we examined outcomes for patients (pts) with SCCB. Analyses were conducted with SEER*Stat 8.1.2, Microsoft Excel 2007 and GraphPad Prism 6. Comparisons were made using the chi-squared test and log rank test (Mantel-Cox); all p-values were 2-sided. Results: 199 pts with primary SCCB with staging were identified; median age was 65 (range 28-97); 98% were female. 84 (42%) had localized disease (dz), 77 (39%) had regional dz and 38 (19%) had distant dz. 95% of pts with localized dz and 88% of pts with regional dz had breast surgery. Median overall survival (OS) varied by stage (150 months [m] v 56m v 7m, p&lt;0.001) and radiation did not impact OS for pts with either localized (202m v 147m, p=0.477) or regional (52m v 75m, p=0.650) dz. For comparison 81,933 cases of small cell lung cancer (SCLC) were identified in SEER; 8% localized, 29%regional and 63% distant disease. Outcomes were superior for pts with SCCB with localized (150m v 16m, p&lt;0.001) and regional dz (56m v 13m, p&lt;0.001) but not distant dz (7m v 7m, p=0.043). Conclusions: SCCB presents at an earlier stage than and has a more favorable prognosis by stage for localized and regional dz than SCLC. Adjuvant radiation does not improve survival for patients with localized or regional SCCB.
Combination of vaccine with targeted chemotherapy reduced levels of CSC like (CD44<sup>+</sup>CD24<sup>- </sup>hematopoietic lineage negative {LIN<sup>-</sup>}) cells and improves outcome of cancer treatment
Authors: H. Akbulut, Y. Tang, K. G. Akbulut, J. Maynard, A. B. Deisseroth
Journal: Journal of Clinical Oncology (2008)

14001 Background: We studied the effect of a cancer vaccine on levels of CSC like cells. Methods: We compared the effect of the sc injection of Ad-sig-hMUC-1/ecdCD40L vector followed by two weekly sc injections of the hMUC1/ecdCD40L protein boost (vaccine) with 5-Fluorouracil (5-FU) intravenous (iv) chemotherapy (5FUCT), 5FUCT plus vaccine, and vector targeted 5-FU chemotherapy (VTCT) plus vaccine in a syngeneic mouse model of human MUC-1 (hMUC-1) expressing Lewis Lung Cancer Cells (hMUC-1LLC). 5FUCT was given iv at a weekly dose of 250 mg/kg. VTCT was administered by intratumoral injection (it) of 1x108 pfu of an AdCDIRESE1A adenoviral (Ad) vector system carrying a cytosine deaminase (CD) transcription unit followed by 10 days of intraperitoneal (ip) injection of 5- Fluorocytosine (5FC). Results: We found that the vaccine could induce an immune response against hMUC-1LLC in all groups. However, the mice injected with vaccine alone yielded significantly more IFN-gamma secreting T cells in ELISPOT assays than other groups given either 5FUCT or VTCT in combination with vaccine. Likewise, splenic T cells from the vaccine only group yielded significantly higher cell mediated cytotoxicity against hMUC-1LLC than the splenic T cells of the other groups. We found that while 5FUCT caused significant tumor shrinkage when compared to the control group, it also caused an increase in the ratio of CSC like to unfractionated cells (12.0% vs 7.4%). There were no significant increases in the ratio of CSC like/unfractionated cells of the 5FUCT plus vaccine group when compared to the controls (9.6% vs 7.4%). However, vaccine alone or in combination with VTCT decreased the CSC like/unfractionated cell ratio (4.68%, 4.96%, respectively). Interestingly, a decrease in the ratio of MUC1 expressing CSC like/unfractionated cells was seen with vaccine alone (0.12%) or in combination with 5FUCT (0.96%), or with VTCT (0.11%) when compared to 5FUCT alone (4.16%) or control (5.27%). Conclusions: These results suggest that combining vaccine with VTCT could suppress disseminated cancer by destroying CFC like cells. No significant financial relationships to disclose.
Survival benefit for multiagent chemotherapy but not dacarbazine in metastatic melanoma: A retrospective single institution study
Authors: A. Daud, A. Khan, S. Andrews, G. Collamat, R. Deconti
Journal: Journal of Clinical Oncology (2004)

7560 Background: The survival benefit of chemotherapy over observation in advanced melanoma is uncertain. Chemotherapy regimens have not been compared to observation to determine what benefit (if any) chemotherapy has in terms of survival. Methods: A retrospective analysis was done using a melanoma database at our center. All patients had documented melanoma and were treated between 1985 and 2003. 749 patients with Stage IV melanoma were identified. Of these, 194 patients had adequate records to be classified into one of the 4 groups. These groups included observation, DTIC alone, biochemotherapy and temozolomide with thalidomide. Patients in the observation group may have had vaccines but not chemotherapy or IL-2. All other groups received at least 1 cycle of treatment. Kaplan-Meier survival curves and Log rank tests were used to compare significance of prognostic factors. The Cox proportional hazards model was used to compare treatment effects. Results: The median survival of Stage M1c melanoma was 5.5 months. Survival was better in Stage M1a and M1b. No significant differences were found in survival between males and females. Survival was worse in patients older than 60. Log rank analysis showed that temo+thal and biochemotherapy were significantly better than DTIC treatment. In multivariate analysis, patients treated with either biochemotherapy or temozolomide and thalidomide lived significantly longer than those who received no chemotherapy while DTIC alone was not significantly associated with better survival. Conclusions: In this retrospective study, patients treated with multiagent regimens showed improved survival compared to observation. Treatment with DTIC alone did not significantly impact survival No significant financial relationships to disclose.
A randomized, double-blind, multicenter, phase II, three-arm, placebo-control study of apatinib as third-line treatment in patients with metastatic gastric carcinoma.
Authors: J. Li, S. Qin, J. Xu, W. j. Guo, J. p. Xiong, Y. Bai, G. Sun, Y. Yang, L. Wang, N. Xu, Y. Cheng, W. Zhe-Hai, L. Zheng, M. Tao
Journal: Journal of Clinical Oncology (2011)

4019 Background: Apatinib at a daily dose of 850mg was tolerable from our phase I study. The objective of this study was to evaluate the efficacy and safety of apatinib in patients with advanced or metastatic gastric cancer after failure of two lines of chemotherapy. Methods: Inclusion criteria were ECOG performance status ≤ 1, measurable disease and adequate organ functions. Patients were randomized to the placebo (A), 850mg qd (B), and 425mg bid (C) arm. Study treatment was continued as a 28-day cycle until progression or intolerable toxicity. Tumor assessments were performed after cycle 2, 3, and then every 2 cycle thereafter. The primary endpoint was progression-free survival (PFS). The secondary endpoints were disease-free control rate (DCR), objective response rate (ORR), and overall survival (OS). All adverse events were reported using CTCAE v3.0). COX analysis method was used. Results: 141 patients were enrolled. Results were presented in the table. Treatment-related toxicities of each arm was 8 (16.67%),13 (27.66%), 13 (50%), respectively, P=0.0021. The most common adverse events were hypertension and hand-foot syndrome. Conclusions: Apatinib once daily or twice daily has been shown to be active against gastric cancer with manageable safety profile. n PFS (M) Hazard ratio (95%CI) P Arm A 48 1.40 B vs A 0.353 (0.216, 0.578) <0.0001 B 47 3.43 C vs A 0.367 (0.224, 0.603) <0.0001 C 46 3.43 C vs B 0.997 (0.589, 1.689) 0.9909 OS(M) A 48 2.50 B vs A 0.525 (0.326, 0.845) 0.0080 B 47 4.83 C vs A 0.585 (0.363, 0.942) 0.0273 C 46 4.30 C vs B 1.191 (0.724, 1.961) 0.4908 ORR Arm % 95%CI Rate variance (95%CI) A 0.00 (0.0, 7.4) % B vs A (-0.61, 13.37) % B 6.38 (1.3, 17.5) % C vs A (3.31, 22.77) % C 13.04 (4.9, 26.3) % C vs B (-5.32, 18.64) % DCR Arm % 95%CI Rate variance (95%CI) A 10.42 (3.5, 22.7) % B vs A (15.56, 48.70) % B 42.55 (28.3, 57.8) % C vs A (12.17, 45.25) % C 39.13 (25.1, 54.6) % C vs B (-23.39, 16.55) %
Randomized study of systemic chemotherapy following complete excision of nonosseous sarcomas.
Authors: J H Edmonson, T R Fleming, J C Ivins, E O Burgert, E H Soule, M J O'Connell, F H Sim, D L Ahmann
Journal: Journal of Clinical Oncology (1984)

Between June 1975 and April 1981, 61 of the 177 eligible patients whose nonosseous sarcomas of extremity or trunk origin had been completely excised primarily or after local recurrences agreed to participate in a randomized study of adjuvant chemotherapy. Dermatofibrosarcoma, lymphomas, myeloma, Kaposi's sarcoma, and embryonal rhabdomyosarcoma were excluded as were patients with significant second primary cancers and those who received either preoperative or postoperative radiation therapy. After stratification by anatomic status of disease, site of origin, and histologic grade, a random one half of the 61 participants began alternating courses of vincristine/cyclophosphamide/dactinomycin, and vincristine/doxorubicin/dacarbazine at six-week intervals for one year. The control group was evaluated at six-week intervals without adjuvant chemotherapy, but these patients were offered this chemotherapy later if they had progressive disease excised. Although 30% of the 61 patients experienced local recurrence of disease within the first five years after randomization, and only 54% were continuously disease free for five or more years, 82% were surviving at five years (Kaplan-Meier calculations) with a median follow-up of 64.3 months. Partial suppression of distant metastasis by adjuvant chemotherapy was apparent in the overall study, in the extremity tumor category, and in the subgroup of patients who had received limb-sparing surgery; however, no survival advantage for chemotherapy-treated patients was demonstrated. The 30 adjuvant chemotherapy-treated patients received a total of three thoracotomies as compared with 17 salvage thoracotomies for the 31 control patients; however, salvage surgery for local recurrences has been similar in the two groups. Recent improvement in the survival of patients with soft-tissue sarcomas is not necessarily a result of adjuvant chemotherapy or radiation therapy.