tbuckley/cabot-search huggingface dataset:
Improved detection of medullary thyroid cancer with radiolabeled antibodies to carcinoembryonic antigen.
Authors: M Juweid, R M Sharkey, T Behr, L C Swayne, A D Rubin, T Herskovic, D Hanley, A Markowitz, R Dunn, J Siegel, T Kamal, D M Goldenberg
Journal: Journal of Clinical Oncology (1996)

PURPOSE This investigation was undertaken to assess the targeting of established and occult medullary thyroid cancer (MTC) with radiolabeled monoclonal antibodies (MAbs) reactive with carcinoembryonic antigen (CEA). PATIENTS AND METHODS Twenty-six assessable patients with known (n = 17) or occult (n = 9) MTC were studied with radiolabeled anti-CEA MAbs. Scintigraphic images were collected to determine targeting of tumor lesions. RESULTS The targeting results of technetium 99m (99mTc)-,iodine 123 (123I)-, and iodine 131 (131I)-labeled anti-CEA antibodies (all directed against the same epitope of CEA) indicated that all these reagents were capable of detecting established and occult MTC. The sensitivity for detection of known sites of disease ranged from 76% to 100% for the various anti-CEA MAbs used, when compared with computed tomography (CT), magnetic resonance imaging (MRI), bone scan, or other imaging modalities. Moreover, the antibody scan was positive in seven of nine patients with occult disease (patients with negative conventional imaging studies, but who had elevated calcitonin and/or CEA levels). Three of seven patients underwent surgery and the disease was confirmed by histopathology in all three. CONCLUSION Anti-CEA MAbs are excellent agents for imaging recurrent, residual, or metastatic MTC. The high lesion sensitivity in patients with known lesions, combined with the ability to detect disease, may make these agents ideal for staging patients, monitoring disease pretherapy or posttherapy, and especially for evaluating patients with recurrent or persistent hypercalcitonemia or CEA elevations after primary surgery. Analogous to radioiodine in the evaluation of patients with differentiated thyroid cancer, radiolabeled anti-CEA MAbs may achieve a similar role in diagnosing and monitoring patients with MTC.
Patients’ preferences for adjuvant radiation therapy in early breast cancers
Authors: S. C. Pendlebury, V. Duric, D. Joseph, A. Rodger, A. Rodger, K. Taylor, R. Hedges, T. Corica, R. Smith, M. Stockler
Journal: Journal of Clinical Oncology (2007)

11083 Background: Adjuvant radiation therapy (ART) reduces the risk of local recurrence in women with breast cancers. In good prognosis tumours in older women the absolute benefits are small. The aim of this study is to determine the smallest improvement in local recurrence rates that women would consider sufficient to make their adjuvant therapy worthwhile. Methods: 95 women who had completed ART 2–4 years earlier for T1N0M0 breast cancers had their preferences elicited by 1 of 3 interviewers. Women were presented 3 sets of hypothetical scenarios about the risks of recurrence with and without radiation using baseline risks of 5%, 10%,and 20%without ART. The order scenarios were presented was allocated randomly. Results: The women’s median age was 63 years 54% had dependants, and 58% travelled 20km or less to their ART centre. A 1% reduction in risk of local recurrence was judged sufficient to to make ART worthwhile by 77% of the women. More than half the women judged ART worthwhile even if it conferred no benefit. 3–8% of the women judged even the maximum possible benefits insufficient to make ART worthwhile. Women’s preferences were almost identical for all 3 scenarios(Spearman’s rank correlations of 0.89 to 0.94). Preferences were unaffected by the order of scenario presentation, interviewer, participants age, cancer recurrence prior to interview,support during ART, dependants, distance to travel to ART, or time since completing ART. Conclusions: Most women judged small benefits in local recurrence sufficient to make ART worthwhile. Many women judged negligible benefits sufficient suggesting the importance of considerations other than the trade-off between direct benefits and harms. No significant financial relationships to disclose.
Metronomic antiangiogenetic biochemotherapy of non-small cell lung cancer patients with fractionated cisplatimum, oral etoposide, and bevacizumab
Authors: C. Remondo, C. Migali, I. Martellucci, F. Carbone, V. Ricci, R. Addeo, S. Del Prete, F. Fulfaro, G. Francini, P. Correale
Journal: Journal of Clinical Oncology (2009)

e19083 Background: Chemotherapy efficacy in advanced non small cell lung cancer (NSCLC) patients may be augmented if combined with bevacizumab, a monoclonal antibody to vascular endothelial growth factor (VEGF) with anti-angiogenetic activity. Metronomic chemotherapy is a newest approach which employs cytotoxic drugs at lower doses with very close and regular administrations, which has shown anti-angiogenetic effects, epigenetic attenuation of cancer phenotype and immune-modulation. Metronomic chemotherapy with cisplatinum and oral etoposide (mPE) has been tested in NSCLC patients with promising results. We have thus investigated a newest biochemotherapy regimen with mPE + bevacizumab (mPEBev regimen) in advanced NSCLC patients. Methods: This is a phase IB/II trial designed to evaluate toxicity, anti-tumor and biological activity of bevacizumab given at escalating doses in combination with mPE chemotherapy. Twenty-six patients with inoperable NSCLC and an ECOG≤2 were enrolled in the study and received every 21 days, iv. cisplatinum (30 mg/sqm, days 1–3), oral etoposide (50 mg/sqm, days 1–15) and bevacizumab (day 3) at different dose levels (no antibody/control group; 2.5; 5; 7.5; and 10 mg/kg). Results: The treatment resulted very active in those patients who received bevacizumab with a 95% objective response rate (19/20), with a median time to progression of 7.55 months. There were two early deaths at higher bevacizumab dosages: one due to a cardiovascular accident (7.5 mg/kg) and another to lung hemorrhage (10mg/kg). We reported also 4 cases of psychic depression and 4 cases of pneumonia which evolved into lung cavitation. A magnetic resonance monitoring showed a significant treatment-related blood perfusion reduction in the tumor site. It was also observed a progressive decrease in VEGF, thrombospondin-1 levels which were not dependent upon bevacizumab dose and were not observed in the controls. Conclusions: mPEBev regimen resulted very active in advanced NSCLC patients. Our metronomic biochemotherapy regimen with lower bevacizumab doses (2.5–5 mg/Kg) deserves to be investigated in further phase II-III trials. No significant financial relationships to disclose.
Abstract 17153: Effects of Age, Sex and Diabetes on Cardiac Stem Cells Characteristics and Left Ventricular Remodeling in Patients with Ischemic Heart Disease
Authors: Domenico D'Amario, Antonio M Leone, Antonella Lombardo, Antonio Iaconelli, Maria B Giannico, Francesca Graziani, Gina Biasillo, Andrea Macchione, Nicola Luciani, Costantino Smaldone, Irma Battipaglia, Massimo Massetti, Filippo Crea
Journal: Circulation (2012)

Cardiac stem cells(CSCs) have been utilized in the phase I SCIPIO trial reporting benefits of unexpected magnitude. However, a key question concerns whether a pool of functionally competent CSCs wi...
Phase I study of obatoclax mesylate (GX15–070MS), a bcl-2 antagonist, plus topotecan in relapsed small cell lung carcinoma and other solid tumors
Authors: A. B. Brown, C. Rudin, N. Rizvi, W. Travis, N. Takebe, L. P. James, S. Subzwari, L. Tyson, S. Markus, L. M. Krug
Journal: Journal of Clinical Oncology (2009)

3504 Background: Bcl-2 is a rational target in SCLC since it is overexpressed in 60%-90% of tumors and may play a role in resistance of SCLC to chemotherapy. Obatoclax is a small molecule BH3 mimetic that blocks bcl-2 binding to proapoptotic family members. Obatoclax has growth inhibitory effects in several solid tumor cell lines and xenografts, with at least additive effects in combination with topotecan. The primary objective of this study was to evaluate the safety profile and maximum tolerated dose (MTD) of obatoclax plus topotecan in patients with relapsed SCLC and other solid tumors. Methods: We conducted a phase I dose escalation study using a standard “3+3” design. Obatoclax was administered at 14 or 20 mg/m 2 over 3 hours on day 1 every 21 days. A subsequent cohort received obatoclax 14mg/m 2 on days 1 and 3. Topotecan was given at 1.25 mg/m 2 days 1–5. All patients received pegfilgrastim on day 8. Eligible patients were adults with solid tumors appropriate for treatment with topotecan. Patients with neurologically stable, treated brain mets were eligible. Results: 14 patients have been treated including 8 SCLC, 3 extrapulmonary small cell, 1 carcinoid, 1 Merkel cell and 1 melanoma previously treated with 1 or 2 lines of chemotherapy. Nearly all patients experienced neurologic toxicities during the obatoclax infusion which included ataxia, dysarthria, somnolence and/or mood alteration; these typically resolved 1–2 hours after completion of the infusion. The MTD of obatoclax was 20 mg/m 2 on day 1 with Dose Limiting Toxicities (DLT) including grade 3 neurotoxicity (2 pts) and febrile neutropenia. Hematologic toxicity included grade 3/4 anemia (6 pts), thrombocytopenia (5 pts) and neutropenia (5 pts). Other toxicities included mild nausea/vomiting, fatigue, pruritus, and constipation. Clinical activity was seen in patients with SCLC including 1 PR and 4 SD out of 7 evaluable. The median TTP for these SCLC patients was 11 weeks. Conclusions: The recommended phase II dose is obatoclax 14 mg/m 2 on days 1 and 3 with topotecan 1.25 mg/m 2 on days 1–5 in 21 day cycles. A phase II study in second-line SCLC is open. Supported by NCI U01-CA69856. No significant financial relationships to disclose.
Barriers to pain and fatigue management in medical oncology
Authors: B. R. Ferrell, M. Koczywas, T. Borneman, V. Sun, B. F. Piper
Journal: Journal of Clinical Oncology (2008)

9546 Background: The relief of symptoms is a critical aspect of supportive care in medical oncology. This NCI funded study compared usual care to an educational and systems change intervention in a Comprehensive Cancer Center. This paper presents data comparing the total N=184 patients including Breast (40%), Lung (25%), Colon (20%) or Prostate (15%) cancer. Based on the NCCN Pain and Fatigue guidelines, the intervention included a four part patient education program, professional education and strategies to integrate symptom management into routine oncology practice. Methods: This trial compared symptom management in outpatient oncology patients experiencing pain and/or fatigue who received either usual care (N=83) or the intervention (N=101). Outcome measures included the Pain and Fatigue Knowledge Scales, Psychological Distress Thermometer, City of Hope QOL Tool, Karnofsky Scale and Piper Fatigue Scale. Patients were assessed at baseline and 1 and 3 months post intervention endpoints. Results: To determine the immediate effect of the intervention and differences from the usual care condition, 2x2 repeated measures ANOVAs were conducted on instrument scales and single item measures. Post hoc analyses controlled for inflation of error using the lsd procedure. Compared to the usual care sample, the intervention had an immediate salutary effect on anxiety, depression, and social support (p=0.007, p=0.006, and p=0.048, respectively). Barriers to pain management decreased significantly only for the intervention sample. Knowledge of pain decreased in the usual care sample but increased significantly in the intervention sample (p<0.001). Fatigue decreased significantly in the intervention sample (p=0.006 to p<0.001) and often increased in the usual care sample. Knowledge of fatigue also increased significantly for the intervention sample (p<0.001), while falling in the usual care sample. Conclusions: Structured patient and professional education and systems change efforts can reduce barriers to pain and fatigue management resulting in improved outcomes for patients in treatment for solid tumors. No significant financial relationships to disclose.
An assessment of the causes of medication errors on the oncology ward of a large cummunity hospital
Authors: J. Killebrew, P. C. Fugitt, E. M. Prystas, C. D. Ford
Journal: Journal of Clinical Oncology (2005)

8246 Background: Medication errors are responsible for a significant morbidity and mortality in hospitalized oncology patients. Reducing errors requires an understanding of the established institutional processes of care, determining the areas of breakdown, and addressing problems by the identification of areas where effective processes are not being followed and appropriate changes in processes where indicated. Methods: Over the past two years, our nurses have reported 171 medication errors occurring on our oncology unit. Each error has been analyzed and classified into three subclasses: class 1 (errors resulting in incorrect orders being recorded in the physician written order, the nurse Kardex, and/or the hospital pharmacy computer), class 2 (as directed by current hospital process, a failure to properly cross-check the recorded orders (physician written order, Kardex, computer, orders on medication) against each other, and type 3 (errors in medication administration). Results: We found that the errors included 27 types of class 1 errors, 8 types of class 2 errors, and 14 types of class 3 errors involving physicians, ward clerks, pharmacists, and nurses. Medication errors included a class 1 error 22% of the time, a class 2 error (usually in association with a class 1 error) 14%, and a class 3 error 74%. We have discovered that a number of class 1 errors have no built in crosscheck in our current system. We found that both nurses and pharmacists unknowingly engaged in some practices that undermined the check and balance system. The project has also resulted in a much more rapid identification of the problem(s) underlying a given error and immediate feedback to those involved. Several suggestions to improve our processes have been submitted to hospital administration. Conclusions: An active hospital oncology medication errors identification program is helpful in multiple ways. Medication errors will be most effectively addressed by focusing on class 3 errors. No significant financial relationships to disclose.
Phase I trial of fixed dose rate infusion (FDRI) gemcitabine (GEM) with gefitinib in patients with advanced pancreatic carcinoma
Authors: B. Carneiro, R. Brand, E. Fine, R. Knop, J. Khandekar, W. Uhlig, G. Y. Locker
Journal: Journal of Clinical Oncology (2005)

4118 Background: Patients (pts) with metastatic pancreatic adenocarcinoma (PCa) treated with GEM using a FDRI have a longer survival than with 30 min infusion schedules1. Over 40% of metastatic PCa’s overexpress EGFR2. This study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of GEM using a FDRI in combination with gefitinib, an EGFR TK inhibitor in pts with PCa. Methods: Pts with advanced pancreatic cancer were given GEM at the FDRI of 10 mg/m2/min IV on days 1, 8, and 15 of a 28 day cycle. Dose levels of 1000, 1200 and 1500 mg/m2 were evaluated. Oral gefitinib 250 mg was given daily. DLTs were defined as two instances of grade III hematologic or IV non-hematologic toxicity or any grade IV hematologic toxicity. Four pts were treated at each dose level. Dose level escalation occurred in the absence of DLTs. Results: Four women and 8 men were enrolled. Median age was 61. All pts were PS 0 or 1 and had metastatic disease (83.3% liver; 16.6% lungs). Three pts received prior chemoradiation for pancreatic cancer, and one chemotherapy for lung cancer. Median cycles were 3 per pt. The MTD was 1200 mg/m2. Toxicity was predominantly hematologic. At 1500mg/m2, all 4 pts required dose reduction because of grade 3 granulocytopenia, and 1 pt had grade 3 anemia. One pt had grade 3 granulocytopenia at a dose of 1200mg/m2. Acneform rashes were mild with grade 1 in 6 pts (50%) and grade 2 in 2 pts (16.6%). One pt had grade 3 vomiting; no significant diarrhea or liver toxicity was seen. Median time to progression and overall survival were 3.6 months and 4.8 months, respectively. Conclusions: Combining FDRI gemcitabine with gefitinib is feasible and tolerable. Recommended phase II dose for GEM is 1200mg/m2 at FDRI of 10 mg/m2/min with gefitinib 250mg PO daily. 1 Tempero, M. Journal of Clinical Oncology 21(18):3402–8, 2003. 2 Uegaki, K. Anticancer Research 17:3841–7, 1997. Supported by a grant from AstraZeneca Pharmaceuticals Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca
Intra-arterial chemotherapy with docetaxel and cysplatin in combined treatment of patients with locally advanced squamouse cell head and neck cancer (SCHNC)
Authors: G. Adilbayev, D. Adilbay, G. Kim, D. Ahmetov
Journal: Journal of Clinical Oncology (2006)

15528 Background: Currently the main role in chemotherapy of head and neck cancer from the 90ths is related to taxans. To elevate the effect of combination docetaxel + cysplatin and to reduce their toxic influence to the organism we have studied intra-arterial path of delivery at the combined therapy of head and neck cancer. Methods: We treated 53 patients with locally advanced SCHNC(T3, T4). All patients received 2 courses of intra-arterial chemotherapy by catheterization the feeding arteries of tumor through the external carotid artery: docetaxel-80 mg/m 2 , cysplatin-100 mg/m 2 . Further, depending on the results of chemotherapy, there were performed radiotherapy and surgical treatment in necessary volumes. Results: By analyzing the effect of docetaxel + cysplatin combination in different tumor localizations, we have concluded that the best results have been achieved in oral cavity cancer: 9 (29.1%) patients with CR and 16 (51.6%) patients with PR. Worst results have been achieved in maxilla cancer: 0 CR and 14 PR (63.6%). Hematologic toxicity of chemotherapy has manifested only in 18.8% patients (I, II grade). Non-hemathologic toxicity: alopecia 67.9%; periphery neuropathy 11.3; mucositis 5.3%. Performing radiotherapy as the second stage after chemotherapy has increased the number of patients with CR, in patients with oral cancer up to 45.1% and with maxilla cancer up to 18.1%. All results has been confirmed by cytomorphology. As of now surgical treatment has been performed for 30 patients (56.6%). 86.8% patients have been followed up for 6 to 30 months. Conclusion: This neoadjuvant intra-arterial chemotherapy with docetaxel + cysplatin allows both increasing the results of combined therapy and reducing the toxicity of chemotherapy. No significant financial relationships to disclose.
Oxaliplatin and irinotecan plus granulocyte-colony stimulating factor (G-CSF) as third-line treatment in relapsed or cisplatin-refractory germ-cell tumor (GCT) patients: A phase II study
Authors: D. Farmakis, D. Pectasides, M. Pectasides, M. Nikolaou, M. Koumpou, A. Gaglia, A. Koumarianou, G. Aravantinos, T. Economopoulos
Journal: Journal of Clinical Oncology (2004)

4535 Background: Oxaliplatin is an active agent in patients with cisplatin-refractory GCT, while the combination of irinotecan with platinum compounds has also induced responses in such patients. Given the synergistic activity of the two agents, we investigated the efficacy and tolerability of their combination in patients with relapsed or cisplatin-refractory GCT. Methods: Eighteen patients with relapsed or cisplatin-refractory GCT were treated with oxaliplatin 85mg/m2 (days 1,15) and irinotecan 80mg/m2 (days 1,8,15) every 4 weeks for a maximum of 6 cycles. Results: All patients were assessable for response and toxicity. Seven patients (40%) achieved a favorable response (4 complete and 3 partial responses). One of the complete responders relapsed after 2.5 months and, despite treatment with high dose chemotherapy, he died 2 months later; the rest 3 patients are continuously disease-free for 11+, 14+ and 19+ months. The partial responders progressed subsequently and died after 2, 3 and 4.5 months, respectively. None of the patients with extragonadal mediastinal GCT responded to chemotherapy. The regimen had a good tolerance. Neutropenia (grade 3/4, 17%), neutropenic infections and sepsis were not common probably due to prophylactic G-CSF administration. Thrombocytopenia and anemia were not a serious problem. Grade 3/4 diarrhea and nausea/vomiting were noted in 22% and 28% of patients, respectively. Oxaliplatin-associated neurotoxicity was rather low; grade 3 peripheral sensory neuropathy was recorded in 11%. Conclusions: The combination of oxaliplatin and irinotecan is feasible and associated with significant clinical antitumor activity, mild and manageable toxicity and easy outpatient administration in patients with relapsed or cisplatin-refractory GCT. This combination offered a possibility for long-term disease-free status (17%), despite the poor prognostic features of the study group. No significant financial relationships to disclose.
Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms associated with overall survival in women with metastatic colon cancer
Authors: O. A. Press, W. Zhang, D. Yang, C. A. Haiman, M. Gordon, A. M. Schultheis, F. Nagashima, A. Sherrod, S. Iqbal, H. Lenz
Journal: Journal of Clinical Oncology (2006)

3600 Background: Methylenetetrahydrofolate Reductase (MTHFR) is a key enzyme regulating intracellular folate pool, which affects DNA synthesis and methylation. Recent studies found folate deficiency induces DNA damage because of impaired nucleotide-excision repairs in mouse model. Two MTHFR gene polymorphisms, C677T and A1298C are linked to altered enzyme activity. Numerous studies have shown these two polymorphisms associated with colon cancer risk and response to fluorouracil-based treatment in advanced colon cancer patients. One epidemiology study also demonstrated 1298CC genotype to be associated with a significantly lower risk of colon cancer in women, but not men. We tested whether these two polymorphisms were associated with clinical outcome in metastatic colon cancer patients treated with 5-FU/Oxaliplatin. Methods: Between 1992 and 2003, a total of 318 patients with metastatic colon cancer treated at the University of Southern California/Norris Comprehensive Cancer Center (USC/NCCC) or the Los Angeles County/University of Southern California Medical Center (LAC/USCMC), were eligible for this study. Peripheral blood samples were collected from each patient and genomic DNA was extracted from white blood cells using the QiaAmp kit (Qiagen, Valencia, CA). Two MTHFR gene polymorphisms (C677T, A1298C) were tested by PCR-RFLP method. Results: MTHFR A1298C gene polymorphism showed statistically significant differences in overall survival (OS) in female patients with metastatic colon cancer (P=0.025, logrank test). Patients with the AA genotype had an 18.7 months median OS compared with the heterozygous AC genotype, which had a 14.3 months median OS and the CC genotype, which had a 15.9 months median OS. Conclusions: There is no significant difference in clinical outcome in male patients. However, female metastatic colon cancer patients with a MTHFR A1298C polymorphism AA genotype have significantly better overall survival than those with heterozygous AC genotype or CC genotype. This data supports the role of MTHFR polymorphisms as an independent prognostic marker in female patients with metastatic colon cancer. Further prospective study is needed to confirm these preliminary findings. [Table: see text]