tbuckley/cabot-search huggingface dataset:
Reporting of serious toxicities of targeted cancer drugs in published reports of randomized phase III clinical trials (RCTs).
Authors: B. Seruga, L. Sterling, L. Wang, I. Tannock
Journal: Journal of Clinical Oncology (2010)

6028 Background: Information about safety of approved cancer drugs is updated regularly in drug labels on the basis of data from various sources. Here we compare serious toxicities of targeted cancer drugs obtained from the most recent drug labels to reporting of toxicities in articles describing RCTs that have evaluated these drugs. Methods: We searched for approved targeted cancer drugs with updated labels in years 2008/2009 in the U.S. Food and Drug Administration (FDA) website (FDA@Drugs). For each drug serious toxicities were identified in the
Predictors of clinical outcome in triple negative breast cancer: An institutional review
Authors: M. Dioca, M. D. Pereira, A. Adur, G. Liliana, C. A. Monica, L. Puricelli, A. M. Alvarez, E. Mickiewicz
Journal: Journal of Clinical Oncology (2008)

22180 Background: Triple negative (−) breast cancer (BC) is defined as lack of expression of estrogen, pregesterone and Her2 neu, being considered a high risk group. We study the pathological characteristics and the clinical outcome of a cohort of 64 consecutive triple negative(−) BC patients (pts) diagnosed at our institution. Methods: between january 1999 and june 2007, 64 (stage I to III) triple(−) BC pts. were retrospectively analyzed. All the Pts. had their receptor status and staining for Her neu by a single pathologist at the Institute of Oncology “Ángel H.Roffo”, (UBA). Univariate and multivariate analysis for the risk factors associated with relapse, and the log rank test for disease free survival (DFS), and overall survival (OS) was performed. Results: The median age was 52 years (range, 28–84 years).The median follow up time was 32 months (range, 3.−106). Overall, relapse rate is 42% (n=27), and 56 Pts (87.5%) are alive. Median DFS was 23 months (range, 3–106 months). Stage at the time of presentation was: 14 (22%) stage I; 29 (47%) stage II; 21 (31%) stage III. Pre-menopausal status was 46.6%, and 41% were limph node positive. Median OS: Stage I, II, and III was 33 (3–106), 30 ( 6–87), and 20 months (6–53) respectively, (p=0.0186). Median DFS: stage I, II and III was 33 (3–106), 27 (6–87), and 16 months (5–38) respectively, (p=0.0011). Pathological parameters analyzed ( nuclear grade, histologic grade, mitotic index and vascular invasion) were not significant predictors for DFS and OS by multivariate analysis, however vasculo-lymphatic invasion showed significance for both clinical outcomes in the univariate analysis, (p value 0.04 and 0.02, respectively). Conclusions: Triple (−) BC has an aggressive clinical course with significant risk of either local or systemic relapse and subsequent increased risk of death on short term follow up. In this triple (−) population only stage of disease was the only independent prognostic factor for DFS and OS. Between the pathological features analyzed only vasculo-lymphatic invasion seems to have prognostic significance. No significant financial relationships to disclose.
A pilot study of adjuvant chemotherapy with S-1 plus cisplatin for stage II-IV (M0) gastric adenocarcinoma.
Authors: Y. J. Lee, B. W. Kang, Y. S. Chae, S. J. Lee, J. H. Moon, J. G. Kim, S. K. Sohn, Y. Jang, S. W. Jeon, M. K. Jung, H. Y. Jung, W. Yu
Journal: Journal of Clinical Oncology (2011)

e14663 Background: We investigated the efficacy and safety of S-1 plus cisplatin as adjuvant chemotherapy in patient with curatively resected gastric adenocarcinoma. Methods: Korean patients with stage II-IV (M0) gastric adenocarcinoma who underwent gastrectomy with D2 lymph node resection were enrolled. S-1 was administered orally at 80 mg/m2 divided in two daily doses for 14 days and cisplatin was administered at 60 mg/m2 intravenously over two hours every 21 days. Patients received a maximum of six cycles. Results: From January 2006 to July 2010, 74 patients were enrolled in this study. The ratio of males to females was 45 to 29. The median patient age was 56 years (range, 22-71), and 51.4% (38/74) of the patients had a performance status of 0. The median number of chemotherapy cycles administered was 6 (range, 1-6). The median relative dose intensity was 86.4% for S-1 and 80.0% for cisplatin. With a median follow-up duration of 13.9 months, the median relapse-free survival (RFS) and overall survival (OS) have not yet been reached. RFS rate was 60.5% at 3-years and 15 relapse (20.3%) were documented among the 74 patients. The treatments were generally well tolerated. Grade 3-4 toxicities included neutropenia 35.1%, nausea 4.1%, asthenia 4.1%, thrombocytopenia 2.7%, vomiting 2.7%, infection 2.7%, anorexia 1.4%, fatigue 1.4%, abdominal pain 1.4%, and elevated AST/ALT 1.4%. Only 1 cycle of neutropenic fever occurred and there was no treatment-related death. Conclusions: Postoperative adjuvant S-1 plus cisplatin for 18 weeks were feasible in patients with stage II-IV (M0) gastric adenocarcinoma following complete surgical resection.
Quality of life, physical, and psychologic functioning in patients affected by end-stage head and neck cancer.
Authors: M. Airoldi, M. Garzaro, L. Raimondo, G. Riva, G. Pecorari, C. Giordano
Journal: Journal of Clinical Oncology (2011)

5537 Background: Primary head and neck squamous cell carcinomas (HNSCC) and their recurrences can heavily affect patient’s quality of life (QoL). Aim of our study was the evaluation of the impact of treatment on QoL, physical and psychological functioning of patients affected by recurrent end-stage HNSCC. Methods: The sample was composed by 34 patients affected by recurrent HNSCC. Primary tumour treatment was as follows: exclusive RT (radiotherapy) 18%, S+RT 55%, RT + chemotherapy (CT) 27%.In order to evaluate the late effects of RT we used the RTOG – EORTC late radiation morbidity score plus the DISCHE morbidity recording scheme. Psycho-oncological assessment included: HADS, MADRS, MINI MAC, EORTC QoL HN 35. Results: Among this population, 55% of pts relapsed on T, 15% on N, 21% on T+N and 9% on M. Recurrences were treated with S+CT 6%, RT+CT 21% and CT alone 73%. The late toxicity evaluation demonstrates that skin alterations, salivary glands impairment, subcutaneous fibrosis and mucous membrane alterations were the most relevant and severe damages. After a median follow-up of 60 ± 26 months, analysing RTOG-EORTC scale, high scores of skin and mucous membrane alterations are related (p<0.05) with higher levels of anxiety and depression, negative coping styles (reduction of fighting spirit, anxiety and depression) are increased by salivary and mucous membrane dysfunctions (p<0.05), moreover lower levels of QoL, in particular physical and social functioning, are correlated with higher levels of mucous membrane damages (p<0.05); all the mentioned above symptoms increase negative thoughts (p<0.05). DISCHE findings are superimpose able. Conclusions: In end stage HNSCC previous mucous, skin and salivary damages have a strong influence on QoL and coping styles. End stage treatments should evaluate previous toxicity and psychological profile. Treatment tailoring considering these parameters should be discussed with the patient. A negative impact of end stage therapies on mucosal and salivary functioning can deeply compromise QoL and depression profile.
Second-line systemic treatment for advanced cholangiocarcinoma.
Authors: Jane Elizabeth Rogers, Lindsey Law, D. Van Nguyen, Wei Qiao, Milind M. Javle, Ahmed Omar Kaseb, Rachna T. Shroff
Journal: Journal of Clinical Oncology (2014)

371 Background: Five-year survival for advanced cholangiocarcinoma (aCC) is reported at 5-10%. For advanced, unresectable patients, gemcitabine plus platinum (GEM-P) combination chemotherapy is common practice as first-line treatment with progression free survival (PFS) of 8 months and overall survival (OS) of 11.7 months. Data regarding chemotherapy treatment after first-line progression is limited. Methods: We performed a retrospective chart review of patients with aCC from 1/1/2009 to 12/31/2012 who received second-line chemotherapy at M.D. Anderson Cancer Center (MDACC). Median PFS was the primary endpoint. Secondary objectives included disease control rate (complete response + partial response + stable disease) and OS. Inclusion criteria: aCC diagnosis, progression on first-line therapy, and reimaging studies at MDACC. Exclusion criteria: patients who received localized treatment for aCC prior to second-line therapy or consolidative chemoradiation, mixed histology tumors, and those with a history of another malignancy. Results: 56 patients were identified, with the majority having intrahepatic aCC (95%). 80% of patients received gemcitabine based first-line treatment (GEM-P +/- erlotinib, GEM monotherapy). Second-line systemic treatment included GEM-P (19.6%), GEM + fluoropyrmidine (GEM-FU) (28.6%), fluoropyrmidine combination (FU-combo) (37.5%), and other consisting of chemotherapy or biotherapy monotherapy or combination (14.3%). Total median PFS was 2.7 months (95% CI = 2.3 to 3.8). Disease control rate was 50% with a median OS of 13.8 months (95% CI = 12 to19.3). No significant difference in PFS or OS was identified between the four second line treatment groups. A higher CA 19-9 at the start of second line treatment correlated with a worse survival (p= &lt;0.01). Conclusions: This retrospective study revealed a 50% disease control rate, median PFS of 2.7 months, and a potential for improvement in OS in patients who received second line systemic treatment. Agents that may be considered include GEM + FU, FU-combination therapy, or GEM-P if not given first line.
Engaging the cancer care team in advance care planning.
Authors: Tallat Mahmood, Jane Alcyne Severson, Laura Thompson
Journal: Journal of Clinical Oncology (2015)

14 Background: Engagement of oncologists and their care team is essential to ensure advance care planning (ACP) occurs for cancer patients. However, numerous barriers to ACP exists, including the availability of trained staff with competence and confidence to have discussions with patients as well as resources to ensure ACP is effectively and efficiently integrated into the oncology practice. Methods: A baseline audit to determine the presence of documented ACP discussions for patients with metastatic cancer was conducted, followed by a quality improvement program with subsequent reassessment. The baseline audit identified only 20% (10/50) compliance with documentation of such discussions. Subsequently, we joined the Michigan Oncology Quality Consortium’s (MOQC) ACP Collaborative where the care team (MA, RN, PA, MD) were taught how to request and complete a durable power of attorney, conduct ACP conversations, and document pertinent information in a standard EHR location. Results: A one-year post-intervention audit found that 80% (40/50) of patients with metastatic cancer had an ACP documented in their record - a four fold improvement. A post-implementation staff survey noted that the team improved their understanding of both the legal issues and importance of asking about advance directives as well as using the designated chart location to document. 100% of staff agreed or strongly agreed with the statement “I understand the importance of asking patients about advanced directives”. Staff gained confidence in how to talk to patients about advance directives again with 100% of staff agreeing or strongly agreeing with the statement,” I feel more confident now in how to talk to a patient about advanced directives”. Conclusions: It is critical that all members of the oncology care team understand the importance of ACP and that staff feel confident in how to have discussions with patients. While physician/patient discussion is both necessary and expected, patients often discuss their wishes and fears with others in the practice. It is critical that all members of the team understand the importance of and opportunities where they can both support patients’ wishes and direct patients to their oncologist if necessary for further discussion.
The impact of patient-related factors on the occurrence of febrile neutropenia in breast cancer patients receiving (neo-)adjuvant chemotherapy with 5-fluorouracil, epirubicin, and cyclofosfamide (FEC) x6 or FEC x3 followed by docetaxel (D) x3.
Authors: Christof Vulsteke, Alena Pfeil, Barbara Brouwers, Matthias Schwenkglenks, Robert Paridaens, Ruth Pettengell, Anne-Sophie Dieudonné, Sigrid Hatse, Patrick Neven, Diether Lambrechts, Hans Wildiers
Journal: Journal of Clinical Oncology (2013)

1078 Background: Recently we described the impact of genetic variability on severe toxicity in breast cancer patients receiving (neo-) adjuvant FEC chemotherapy (Annals of Oncology 2013, In Press). We now further assessed the impact of a wide range of patient-related factors on FEC toxicity in routine clinical setting. Methods: Patients with early breast cancer receiving (neo-)adjuvant 6 cycles FEC or sequential 3 cycles of FEC and 3 cycles D were retrospectively evaluated through electronic chart review for febrile neutropenia (primary endpoint; CTC 3.0). Age at diagnosis, body mass index, body surface area, number of cycles received, germline genetic polymorphisms, and baseline biochemical variables (white blood cell count, absolute neutrophil count, platelets, aspartate aminotransferase, alanine aminotransferase, total bilirubin and creatinine) were available for most patients (missing data &lt;10%). All patients had follow up for progression free survival (PFS) and overall survival (OS). Multivariate logistic regression analysis was performed including univariate associates of outcome with a p-value &lt;0.25. Results: We identified 1,031 patients treated between 2000-2010 with 6x FEC (n=488) or 3x FEC followed by 3x D (n=543). 174 (16.9%) patients developed febrile neutropenia during FEC. After logistic regression analysis febrile neutropenia was found to be significantly associated with carriers of the rs45511401 variant T-allele in the MRP1 gene found in 12% of patients (p= 0.03, OR1.99, CI 1.07-3.71) and with increasing serum creatinine values (p=0.05 OR 4.58/CI 0.99-20.98); all other investigated patient-related parameters were not retained by the model. At a mean follow up of 5.2 years, the occurrence of febrile neutropenia was not correlated with PFS and OS. Conclusions: In this study, only the baseline level of serum creatinine and germline genetic polymorphisms in the MRP-1 gene were predictive for the occurrence of febrile neutropenia in patients receiving FEC chemotherapy. The occurrence of febrile neutropenia did not seem to impact on outcome.
The impact of treatment intent on overall survival after radiofrequency ablation of colorectal cancer liver metastases: The Royal Marsden Hospital experience.
Authors: Khurum Hayat Khan, Anita Wale, James McCall, Nevin Wijesekera, Nasir Khan, Ian Chau, Gina Brown
Journal: Journal of Clinical Oncology (2014)

622 Background: 50% of patients with colorectal cancer will develop liver metastases (CLM), for many patients this will be the first and only site of metastatic disease. A minority of the patients will undergo surgical resection with curative intent, the remainder may be offered treatment with chemotherapy and local ablative techniques. Radiofrequency ablation (RFA) is increasingly used to treat patients deemed unsuitable for surgery, as an adjunct to or holding procedure before hepatic resection or for patients with recurrent disease. In addition some centres use RFA in the palliative setting. The aim of this study was to determine survival outcomes according to RFA treatment intent in patients with CLM. Methods: Clinical characteristics and survival outcomes of all patients with CLM treated with RFA between 2005-2011 were recorded. Patients were grouped according to the intent with which they underwent their first RFA procedure, namely "curative intent", "holding intent" or "palliative intent". Overall survival was compared between the groups using Kaplan-Meier survival analysis and Log Rank testing. Results: A total of seventy eight pts with CLM (M:F= 44:34), age (median=66, range 43-65 years), who underwent their first RFA procedure between 2005 and 2011 were identified. Thirty pts underwent RFA as a curative procedure (38%), 18 (23%) as a “holding procedure” before hepatic resection and 30 (38%) as a palliative procedure. The median OS for all patients was 25 months after first RFA treatment. Log Rank test showed survival was significantly different according to treatment intent; patients who underwent RFA as a holding procedure before hepatic resection had improved survival over those who underwent RFA with curative intent, who in turn had improved survival over those who underwent RFA with palliative intent (47 vs. 32 vs. 16 months, p = &lt;0.001). Conclusions: Our study demonstrates that patients do best if RFA is used as neo-adjuvant treatment prior to hepatic resection, compared to when it is used as curative or palliative procedure. Careful selection of pts is required to optimise outcomes for the pts receiving RFA.
Large-scale screening of ALK fusion oncogene transcripts in archival NSCLC tumor specimens using multiplexed RT-PCR assays.
Authors: T. Li, P. C. Mack, S. Desai, K. Kelly, J. Cooc, P. V. Danenberg, K. D. Danenberg, D. R. Gandara
Journal: Journal of Clinical Oncology (2011)

10520 Background: The ALK inhibitor crizotinib offers a new standard of care for patients with EML4-ALK fusion oncogene-positive advanced NSCLC. Two top priorities for its widespread clinical use are to determine: 1) the value of different screening methods for identifying the rare cohort of ALK-positive patients; and 2) the impact of crizotinib on tumor sensitivity to subsequent chemotherapy in ALK-positive tumors. Methods: We previously developed a panel of single and multiplexed RT-PCR assays suitable for rapid and accurate detection of all variants of ALK fusion oncogene transcripts, including all 9 known EML4-ALK fusion gene transcripts and ALK RNA level (Danenberg, ASCO 2010). The sensitivity and specificity on archival formalin-fixed, paraffin-embedded tumor specimens are 99% and 100%, respectively. Results: Between 07/10 and 12/10, 1889 NSCLC specimens in our database were screened for the presence of ALK fusion transcripts. We found 75 (4.0%) NSCLC cases with EML4-ALK fusion positivity, including 38 V1, 7 V2, 4 V3a, 20 V3ab, 4 V3b, and 2 V5a variants. All ALK-positive tumors were adenocarcinomas. Median age (range): 53.3 (33-84). Female/male: 35/40. No EGFR or K-Ras mutation were detected in ALK fusion-positive samples. Further investigation of those samples with high level of ALK expression is ongoing. Expression of chemotherapy-related biomarkers was available from 37 EML4-ALK-positive cases in the database: ERCC1 high/low (13/24), TS high/low/na (13/23/1), and RRM1 high/low/na (18/14/5). The clinical significance of drug target expression remains to be defined in large cohorts of patients with annotated clinical outcomes. Conclusions: Our panel of RT-PCR assays provides a tool for rapid, large-scale screening of NSCLC FFPE tissues for ALK fusion gene transcripts. Head-to-head comparison with other screening methods, such as IHC and FISH, will be required to identify optimal methodology for selection of patients for ALK inhibitor therapy; and will be tested in a developing SWOG trial.
5,10 methylenetetrahydrofolic acid with fluorouracil as treatment for advanced breast cancer in patients who failed prior treatment with anthracyclines and taxanes: A phase II study
Authors: J. Stewart, G. Berman, V. F. Semiglazov, H. L. Gomez, A. De La Cruz Vargas, S. Falcon, L. I. Akhmadullina, A. Guerrero, M. Varela, C. Martin
Journal: Journal of Clinical Oncology (2008)

1136 Background: Fluorouracil (FU) has response rate activity in metastatic breast cancer in the range of 17–23%. Although leucovorin (LV) modestly enhances FU activity, it has not been typically combined with FU in this setting. While LV must undergo metabolic activation, 5,10 methylenetetrahydrofolic acid (CoFactor, CF) directly modulates FU inhibition of thymidylate synthase without the need for metabolic conversion. CF + FU demonstrated enhanced efficacy and reduced hematologic toxicity compared to LV + FU in rodent models. We evaluated CF + FU in advanced metastatic breast cancer (mBC) patients. Methods: Patients had HER2/neu-negative taxane and anthracycline refractory mBC, fewer than 3 prior therapies for advanced disease, and performance status ECOG 0–2. Prior FU or capecitabine-based palliative chemotherapy was not allowed. Thirty-two patients were enrolled, and 31 received at least one dose of drug. A treatment cycle was 60 mg/m2 CF and 500 mg/m2 FU, weekly IV bolus for 6 weeks, repeated every 8 weeks. The primary endpoint of response rate was measured every 8 weeks using RECIST criteria. Results: Preliminary data are available on 21 patients. Treatment is ongoing in 17 patients. The median age is 52 years (range 39–76). The most common adverse events were grade 1/2 asthenia (33%), grade 1 nausea (24%), grade 1 hand-foot syndrome (24%), and grade 1 diarrhea (19%). Two patients reported 3 serious adverse events (abdominal pain, diarrhea, and pneumonia). Confirmed response data are available on 20 patients. The objective response rate (CR + PR) based on investigator assessment is 25% (1 CR, 4 PR, 10 SD, 5 PD). Complete data for all 31 patients will be reported. Conclusions: CF + FU is a safe, well tolerated, and active treatment in mBC. With the use of anthracycline and taxane-based regimens in the adjuvant setting, more treatment options are needed for advanced disease. The high level of activity and low toxicity of CF + FU suggests that this combination may be a good treatment option for mBC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration ADVENTRX Pharmaceuticals, Inc. ADVENTRX Pharmaceuticals, Inc.