tbuckley/cabot-search huggingface dataset:
Prostate Biopsy: A Wealth of Information When Done and Interpreted Correctly
Authors: Peter R. Carroll
Journal: Journal of Clinical Oncology (2000)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.6.1161 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10715283 Prostate Biopsy: A Wealth of Information When Done and Interpreted Correctly Peter R. Carroll, MDxPeter R. CarrollSearch for articles by this author Show More University of California, San Francisco, San Francisco, CA https://doi.org/10.1200/JCO.2000.18.6.1161 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical Oncology
Phase II study of capecitabine in combination with cisplatin in advanced head and neck cancer: Preliminary results
Authors: V. Lorusso, N. Calvi, M. Ciccarese, G. Romano, A. Palumbo, S. Bonaduce, M. Santantonio, A. Latorre
Journal: Journal of Clinical Oncology (2007)

16502 Background: The cisplatin-5-fluorouracil (5-FU) combination is the current standard of treatment in head and neck cancer. However, this regimen is not devoid of toxicity, and it is not confortable, because its administration requires a central vein access for the continuous infusion (c.i.) of 5-FU. Capecitabine is an oral fluoropyrimidine, whose activity, mimic of c.i. 5-FU, is well known in malignancies as colorectal cancer and breast cancer. We are investigating the efficacy and tolerability of cisplatin and capecitabine combination in advanced head and neck cancer. Methods: Patients (pts) with untreated metastatic, recurrent, or inoperable head and neck cancer were enrolled. Eligibility criteria were: squamous histology, age 18 to 75 yrs, at least one measurable lesion according to RECIST criteria, ECOG performance status &lt;/=2, normal laboratory values. Pts received capecitabine (2,000 mg/m(2)/day, days 1 to 14) and cisplatin (100 mg/m(2), day 1) every 3 weeks. Results: Since June 2004, 25 pts were enrolled: 22 were male and 3 female; median age was 56 yrs (46–79 yrs). Primitive sites of disease were: 9 pts (36%) laryngeal, 5 pts (20%) oropharyngeal, 2 pts (8%) hypopharingeal, 4 pts(16%) rhynopharingeal, and 5 pts (20%) oral cavity. Two pts with lymphonode recurrence of laryngeal carcinomas achieved a complete response (8%) and 10 pts (40%) had partial response. Stable disease was observed in 6 pts (24%), and 7 pts (28 %) had progressive disease. By the intent-to-treat analysis, the overall response rate was 48% (95% CI, 30–65). At a median follow-up of 9.5 months (4.8–26.1 months) median TTP was 3.5 months (95% CI, 1.3–5.8), and median OS was 12.4 months (95% CI, 6.3–18.5). A total of 99 cycles of chemotherapy was delivered with a median of 5 cycles per pt (range 1- 6). Grade 3 neutropenia, anemia, and thrombocytopenia, were observed in 17%, 13%, and 1% of cycles respectively. Grade 4 anemia was observed in 2 pts (8%). With regard to non hematological toxicity, grade 3–4 asthenia, nausea and vomiting, stomatitis, diarrhoea and PPD were observed in 12%, 12%, 8%, 4% and 4% of pts, respectively. Conclusions The combination regimen of capecitabine and cisplatin showed a good antitumor activity with mild toxicity in patients with advanced head and neck cancer. No significant financial relationships to disclose.
Secondary cytoreduction and post-operative second line chemotherapy with gemcitabine &amp; cisplatin in recurrent epithelial ovarian cancer
Authors: N. Shami, S. Anwar, S. Asif, A. Shaharyar
Journal: Journal of Clinical Oncology (2005)

5161 Background: The role of secondary cytoreduction in recurrent epithelial ovarian cancer is not clearly defined. This study was designed to evaluate the efficacy of secondary cytoreduction and post operative 2nd line chemotherapy with gemcitabine and cisplatin in recurrent ovarian cancer. Methods: Patients who had undergone primary cytoreductive surgery, had received chemotherapy and showed a complete response but have developed subsequent recurrence were included. Evidence of measurable disease on imaging study was required. Abdomen was opened with a vertical incision, ascitic fluid/washings were removed, maximal cytoreduction was done to resect the tumor to <1 cm diameter. All patients were given gemcitabine 1250 mg /m2 on day 1 and 8 and cisplatin 70 mg/m2 on day 8 only. Cycles were repeated every three weeks. RECIST was used for response evaluation. Results: Forty-two patients were enrolled from Dec 98-Jun 03. Median age was 52 years (range 40 -68). Thirty-two had previously received cyclophosphamide and cisplatin while 10 had received paclitaxel and cisplatin. The disease free interval was more then 6 months in 28 patients and less then 6 months in 14. Optimal cytoreduction was achieved in 16(38.1%) only. Gut injury was seen in 3(7.1%) and bladder perforation in 4(9.5%). Among 16 patients with optimal cytoreduction, 6 had a CR while 10 showed a PR with chemotherapy whereas in patients with sub-optimal surgery CR was seen in 4 patients, PR in 16 and NR in 6. All patients who had a CR previously had DFI >6 months. Eight patients are still alive at a median follow up of 16 months (range 6–42 months). Conclusion: Secondary cytoreduction and postoperative second line chemotherapy with gemcitabine and cisplatin is a reasonable treatment option for patients with recurrent epithelial ovarian cancer who present after a disease free interval of more then 6 months. No significant financial relationships to disclose.
Clinical summary of 67 heavily pre-treated patients with metastatic carcinomas treated with GW572016 in a phase Ib study
Authors: E. C. Dees, H. Burris, H. Hurwitz, A. Dowlati, D. Smith, K. Koch, A. Stead, S. Mangum, J. Harris, N. Spector
Journal: Journal of Clinical Oncology (2004)

3188 Background: GW572016 is an orally active, potent, reversible inhibitor of ErbB1/EGFR and ErbB2 tyrosine kinases. ErbB2-containing heterodimers elicit potent mitogenic and survival signals; consequently simultaneous inhibition of ErbB1 and ErbB2 signaling is an appealing therapeutic approach. Methods: Patients with metastatic carcinomas that overexpressed ErbB1 and/or ErbB2 were randomized to one of five doses of GW572016 administered orally once daily on a continuous basis. Clinical response was initially assessed after 8 weeks of therapy and then every 2 months thereafter until evidence of disease progression or termination from study. Safety data was evaluated using NCI-CTC criteria. Results: Sixty-seven patients with a variety of carcinomas were treated with GW572016. Four partial responses (PR) were observed, all in women with paclitaxel and trastuzumab-resistant metastatic breast cancer. Two of the PRs occurred in women with recurrent inflammatory breast cancer. An additional 23 patients with a variety of carcinomas (e.g., non-small cell lung, breast, and colorectal) experienced disease stabilization ranging from 8 to 41 weeks. Common adverse events consisted of transient grade 1 and 2 rash and diarrhea (12 and 30% respectively). Five grade 3 drug-related toxicities (GI and rash) were reported in 4 patients. Neither skin rash nor diarrhea appeared to correlate with the dose of GW572016. Interstitial pneumonitis was not reported, nor was there evidence of cardiac dysfunction. A clear relationship to dose was not observed for either clinical response or adverse events. Conclusions: GW572016 is clinically active in heavily pre-treated patients with metastatic carcinomas overexpressing ErbB1 and/or ErbB2. GW572016 appears to be well-tolerated at the doses studied. The relationship between GW572016 serum concentration and either clinical response or toxicity is currently being investigated. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline
Margaret McCartney: Medicine is a bit of a giggle
Authors: M. McCartney
Journal: BMJ (2015)

Medicine is serious, pressurised, and stressful; it deals with death, life, ethics, human suffering, tragedy, hard statistics, and the Krebs cycle. It’s also a bit of a giggle.

I can hardly tell of the truly funny things that have happened in the consulting room, what with confidentiality and all. But some things get repeated often enough to be at least partly, and probably totally, mythical.

Take, for example, the GP on a house call whose patient complained of her washing machine being broken. Bemused, the doctor fixed the leaky connection, only to find later that he had called at the wrong house and that the “patient” had assumed he was an engineer.

Or the one about …
Phase I study of liposome encapsulated irinotecan (PEP02) in advanced solid tumor patients
Authors: L. Chen, T. Chang, A. Cheng, C. Yang, H. Shiah, J. Chang, G. Yeh
Journal: Journal of Clinical Oncology (2008)

2565 Background: PEP02 is a novel nanoparticle liposome formulation of irinotecan aiming to enhance tumor localization and improve pharmacokinetic properties of irinotecan and its active metabolite-SN38. The aims of the study are to define the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and pharmacokinetics (PK) of PEP02 in patients with advanced refractory solid tumors. Methods: Pts with advanced refractory solid tumors, ECOG PS 0–1, and adequate hematological, hepatic and renal functions were eligible. PEP02 was given as 90mins i.v. infusion, repeated every 3 weeks. The doses would have been escalated from 60, 120, 180 to 240 mg/m2 in a single-patient cohort accelerated titration design. PK samples were collected on days 1, 2, 3, 8 and 21. Results: A total of 11 pts (M/F 1/10; median age 47, range 41–67) were enrolled onto three dose levels, with 1, 6 and 4 pts at dose level I (60 mg/m2), II (120 mg/m2) and III (180 mg/m2), respectively. DLT was observed in 3 pts, including 1 at dose level II (grade 3 catheter-related infection) and 2 at dose level III (grade 3 diarrhea and febrile neutropenia in 1 and treatment-related mortality secondary to grade 4 diarrhea and neutropenia in 1). MTD was determined as 120 mg/m2. The PK of total irinotecan after PEP02 dosing were characterized by, i.e. after 120 mg/m2, low clearance (mean = 0.0591 L/m2/hr), small volume of distribution (mean = 1.8 L/m2, similar to plasma volume), and prolonged terminal half-life (mean=29.5 hr). The plasma concentration-time profiles of encapsulated irinotecan (PEP02) in each pt matched approximately with those of total irinotecan indicating that the release of irinotecan from liposomes occurred slowly over time. Comparing with published PK parameters after 125 mg/m2 of irinotecan, the Cmax of SN-38 after 120 mg/m2 of PEP02 was lower (9.2±3.5 vs 26.3±11.9 ng/mL), the terminal t1/2 of SN-38 was longer (75.4±43.8 vs 10.4±3.1 hrs) and the AUC of SN-38 was larger (710±395 vs 229±108 ng.h/mL). The best response of 10 evaluable pts was PR in 2 (cervical and pancreatic cancer) and SD in 3. Conclusions: The MTD of PEP02 monotherapy at 3-week interval is 120 mg/m2, which will be the recommended dose for future phase II studies. Preliminary data suggest that PEP02 exhibits encouraging pharmacokinetic, safety and efficacy profiles. No significant financial relationships to disclose.
Total blockade of the epidermal growth factor receptor with the combination of cetuximab and gefitinib: A phase I study for patients with recurrent non-small cell lung cancer (NSCLC)
Authors: C. L. Naret, S. Ramalingam, L. Beattie, S. D. Mayfield, H. Lu, C. Langer, C. P. Belani
Journal: Journal of Clinical Oncology (2006)

17045 Background: Cetuximab and gefitinib inhibit the epidermal growth factor receptor (EGFR) through different mechanisms. Preclinical evidence suggests that the combination of cetuximab and Gefitinib is synergistic and has shown antitumor activity in vitro and in xenografts (Matar et al, Clin Cancer Res, 2004). We are conducting a phase I study to determine the doses of the two agents that can be administered in combination. Methods: Patients (pts) with advanced NSCLC were eligible upon progression following 1 or 2 prior chemotherapy regimens. Gefitinib was administered at a dose of 250 mg/day for all cohorts. The dose of cetuximab was escalated in sequential cohorts of patients ( table ) and there will be no dose escalation above the approved doses for both agents (dose level 3). Paraffin-embedded tissue samples of the primary cancer were collected from all patients for analysis of EGFR mutations, gene amplification and protein expression. Results: From March to December 2005, 11 patients have been entered to the 3 planned cohorts. Patient characteristics include: 3 women and 8 men, with a median age of 63 years (range 51–77) and ECOG performance status (PS) of: 0 = 50%, 1 = 50%. A total of 26 treatment cycles were administered to the 11 pts with a median of 2 cycles per pt (range 1–8). Other observed adverse events include grade 1/2 skin rash and diarrhea. Of 8 evaluable patients, 4 had stable disease. No DLT has been experienced so far at the projected recommended phase 2 dose (dose level 3). The results of correlative studies will be presented at the meeting. Conclusions: The novel combination of cetuximab and gefitinib is safe and is associated with promising anti-cancer activity in recurrent NSCLC. [Table: see text] [Table: see text]
Phase II study of erlotinib (E) combined with fixed dose-rate gemcitabine (FDR-Gem) as first-line treatment for advanced adenocarcinoma of the pancreas (PDAC).
Authors: M. Milella, V. Vaccaro, I. Sperduti, E. Bria, A. Gelibter, G. Mansueto, L. Moscetti, T. Gamucci, E. Ruggeri, F. Cognetti
Journal: Journal of Clinical Oncology (2010)

e14565 Background: E combined with weekly Gem infused over 30 min provides a small, but statistically significant, survival advantage in advanced PDAC. Building on our previous experience with FDR-Gem, we have assessed activity and tolerability of E combined with FDR-Gem as first-line treatment for advanced PDAC. Methods: FDR-Gem was given weekly (1,000 mg/m2 at 10 mg/m2/min); E was given orally at 100 mg/d, continuously. Primary endpoint was 6-month PFS rate. Secondary endpoints were ORR (RECIST criteria), toxicity, OS and QoL. Results: From May 2007, 46 eligible pts were enrolled and are fully evaluable (M/F: 25/21; median age: 64 yrs, range: 35-81; median baseline CA19.9: 897 U/mL, range: 1-49,483; locally advanced/metastatic: 5/41). ORR was 11% (95% CI: 2-20%); disease control rate was 56% (95% CI: 42-71%); clinical benefit rate was 43% (95% CI: 26-59%). Only 3 pts (6%) experienced G4 toxicity (elevated transaminases, 1 pt; neutropenia, 2 pts); most common grade 3 toxicities were neutropenia (17%), thrombocytopenia (13%), anemia, and elevated transaminases (9% each). Survival outcomes are shown in the Table. E-related skin rash (any grade) was the most powerful predictor of longer PFS (p<0.0001) and OS (p=0.006) at multivariate analysis; conversely, Gem-related toxicities were associated with a worse survival outcome, although this effect did not reach statistical significance at multivariate analysis. Additional predictors of better outcome were female sex, CA19.9 reduction > 25%, and baseline PS 0-1 (only for OS). Conclusions: E combined with FDR-Gem is feasible and well-tolerated. Although overall results do not appear dramatically different from those obtained with FDR-Gem monotherapy, pts experiencing E-related skin rash (approximately 50%) derive a clear, highly significant (both statistically and clinically) survival advantage, thus supporting further investigation of pharmacodynamically based strategies (e.g., dose-to-rash) aimed at optimizing E treatment. Median (95% CI) 6-mo rate (%) 1-yr rate (%) PFS 14 wks (10-19) 30 11 OS 26 wks (9-44) 53 28 No significant financial relationships to disclose.
In Vivo Cytoreduction Studies and Cell Sorting–Enhanced Tumor-Cell Detection in High-Risk Neuroblastoma Patients: Implications for Leukapheresis Strategies
Authors: Lawrence B. Faulkner, Alberto Garaventa, Antonella Paoli, Veronica Tintori, Angela Tamburini, Laura Lacitignola, Marinella Veltroni, Maria Serena Lo Piccolo, Elisabetta Viscardi, Claudia Milanaccio, Annalisa Tondo, Serena Spinelli, Gabriella Bernini, Bruno De Bernardi
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To improve autologous leukapheresis strategies in high-risk neuroblastoma (NB) patients with extensive bone marrow involvement at diagnosis. PATIENTS AND METHODS: Anti-G D2 immunocytochemistry (sensitivity, 1 in 10 5 to 10 6 leukocytes) was used to evaluate blood and bone marrow disease at diagnosis and during the recovery phase of the first six chemotherapy cycles in 57 patients with stage 4 NB and bone marrow disease at diagnosis. A total of 42 leukapheresis samples from the same patients were evaluated with immunocytology, and in 24 of these patients, an anti-G D2 immunomagnetic enrichment step was used to enhance tumor-cell detection. RESULTS: Tumor cytoreduction was much faster in blood compared with bone marrow (3.2 logs after the first cycle and 2.1 logs after the first two cycles, respectively). Bone marrow disease was often detectable throughout induction, with a trend to plateau after the fourth cycle. By direct anti-G D2 immunocytology, a positive leukapheresis sample was obtained in 7% of patients after either the fifth or sixth cycle; when NB cell immunomagnetic enrichment was applied, 25% of patients had a positive leukapheresis sample (sensitivity, 1 in 10 7 to 10 8 leukocytes). CONCLUSION: Standard chemotherapy seems to deliver most of its in vivo purging effect within the first four cycles. In patients with overt marrow disease at diagnosis, postponing hematopoietic stem-cell collection beyond this point may not be justified. Tumor-cell clearance in blood seems to be quite rapid, and earlier collections via peripheral-blood leukapheresis might be feasible. Immunomagnetically enhanced NB cell detection can be highly sensitive and can indicate whether ex vivo purging should be considered.
The Altered Expression of Iron Metabolism Genes in Models of Liver Injury Suggests Iron Deficiency in Cholestasis and Inappropriate Regulation of Hepcidin in Hepatocellular Cirrhosis
Authors: KA Stuart, K Bridle, TL Murphy, A Sobbe, L Jaskowski, L Ostini, VN Subramaniam, LM Fletcher, DH Crawford
Journal: Hepatology (2011)
The development of the DCIS score: Scaling and normalization in the Marin General Hospital cohort.
Authors: Frederick L. Baehner, Steven M Butler, Carl N. Yoshizawa, Che Prasad, Diana B. Cherbavaz, Farid Jamshidian, Steven Shak
Journal: Journal of Clinical Oncology (2012)

190 Background: In selected low-risk patients with DCIS treated with wide local excision without radiation, the DCIS score was validated as a predictor of 10 year risk of an ipsilateral breast event (IBE - recurrence of in situ or invasive carcinoma) (p = 0.02) (Solin; SABCS 2011). As part of the development of the DCIS score, scaling from 0 to 100 and determination of risk group cutoff values was done using 100 patient DCIS samples from Marin General Hospital (MGH) selected to have a wide range of tumor characteristics. Methods: 100 patient specimens diagnosed with DCIS were provided by MGH. The Oncotype DX assay was performed, normalized expression levels for the 16 cancer related genes were determined, the DCIS Score and Recurrence Score (RS) were calculated. Distributions of the DCIS score, RS, and individual gene expression levels were described overall and by tumor characteristics. Treatment and pt outcome data were not available. Results: Samples for 96 pts had sufficient tumor and were evaluable; 47% had high nuclear grade, 52% comedo necrosis, 32% tumor size &gt;10 mm, and 9% were ER-negative by IHC. After scaling and risk group cutoff determination, the DCIS score was low risk (0-38) for 49%, intermediate risk (39-54) for 27%, and high risk (≥55) for 24% of pts (Table). The DCIS score was widely distributed within subgroups defined by each of the clinical and pathology characteristics. Proliferation gene expression levels were low in DCIS, on average, relative to prior studies in invasive breast cancer. 92% had a proliferation gene group score &lt;6.5, the threshold used when the RS is calculated; no threshold is used in calculating the DCIS score. Conclusions: Optimal scaling and risk cutoff determination for a wide range of all clinicopathologic characteristics provides for a wide distribution for the DCIS Score. [Table: see text]
A prospective investigation of tumor membrane fragments in the differentiation of benign and malignant adnexal masses prior to surgery
Authors: J. Draper, C. W. Helm, R. P. Edwards, D. S. Metzinger, D. D. Taylor
Journal: Journal of Clinical Oncology (2005)

5112 Background: Non-invasive methods of differentiating benign from malignant adnexal masses are urgently needed in order to spare women unnecessary surgery. Methods: We investigated whether the identification of tumor membrane fragments (TMF) in the serum can differentiate between benign and malignant adnexal masses in women prior to surgery. Informed consent was obtained and blood was taken before or at surgery and serum was extracted and stored at -700C. Relevant data was extracted from medical records. A control group was composed of women participating in an ovarian cancer screening study with no personal cancer history and with at least two consecutive normal annual ultrasound scans of the ovaries. TMF were isolated from sera and quantitated using a standard technique. Protein levels are reported in mg/ml. Statistical analysis was performed using Students t-test assuming unequal variances. Results: One hundred and eight women were included in the study with a mean age of 52 years (15–82). Eighty-six underwent surgery for an adnexal mass, 64 were benign, 22 malignant and there were 22 controls. Pathology of the cancers included ovarian cancer 18 (epithelial 15 including 5 low malignant potential, dysgerminoma 1, granulosa cell tumor 2,) and endometrial cancer 4. The FIGO stage included stage I=8, II=1, III= 6, IV=7. The mean TMF protein concentrations (mg/ml ±SD) versus control 0.669 ± 0.259 were benign mass 0.94 ± 0.67 (p=0.003) and malignant mass 1.19 ±0.904 (p=0.007). There was no significant difference of the protein levels between benign and malignant masses (p= ) but there was a trend which was greater when LMP ovarian tumors were excluded. There was no significant difference of TMF protein levels between early and more advanced stage of ovarian cancer, stage I= 1.292 ± 1.198, stage II-IV=1.14 ± 0.911 (p= 0.44). Conclusions: Tumor membrane fragments can differentiate women who are normal from those with an adnexal mass. Greater accuracy in differentiating benign from malignant masses may be possible with the detection of biomarkers associated with the membrane fragments. No significant financial relationships to disclose.