tbuckley/cabot-search huggingface dataset:
Intermittent chemotherapy in metastatic androgen-independent prostate cancer (AIPC): Initial results from ASCENT
Authors: T. M. Beer, C. W. Ryan, P. M. Venner, D. P. Petrylak, G. Chatta, J. Ruether, K. N. Chi, A. Arroyo, F. W. Clow
Journal: Journal of Clinical Oncology (2006)

4518 Background: Phase III studies document a survival benefit for 10–12 cycles of docetaxel-containing chemotherapy in AIPC. Further management of patients who complete chemotherapy in response status remains ill-defined. Single-institution phase II data suggest that re-treatment with the same regimen after a treatment holiday is feasible in selected patients. This approach was prospectively tested in a multi-institutional trial. Methods: ASCENT was a multi-institution randomized clinical trial designed to compare the activity and safety of weekly DN-101 (45 μg on day 1) plus docetaxel (36 mg/m 2 iv on day 2 for 3 weeks of a 4-week cycle) to placebo + docetaxel in patients with chemotherapy-naïve metastatic AIPC. ASCENT was the first large trial to prospectively evaluate intermittent chemotherapy. Patients could opt to suspend treatment if they had a confirmed ≥ 50% reduction in serum PSA and a serum PSA ≤ 4 ng/ml. PSA was monitored every 4 weeks (CT scans every 8 weeks in patients with measurable disease) during the treatment holiday. Treatment was resumed when serum PSA rose by ≥ 50% and was ≥ 2 ng/ml or for other evidence of disease progression. The study was not powered to compare treatment holiday outcomes between the two arms. Results: 250 patients were randomized 1:1. Overall PSA response rates were: DN-101: 63%, Placebo 52% (p = 0.07). Overall 18% (DN-101: 20%, Placebo: 16%) of patients entered the intermittent chemotherapy. The median duration of the first chemotherapy holiday was 16 weeks (range 4–74+) (DN-101: 15 weeks, Placebo: 16 weeks). Upon resumption of treatment after the first holiday, 50% of patients responded with a ≥ 50% reduction in serum PSA from their post-holiday baseline, 35% met criteria for stable PSA for at least 12 weeks, and 15% progressed on therapy. Conclusions: This is the first report of intermittent chemotherapy in AIPC prospectively tested in a large multi-institutional trial. This strategy results in a clinically meaningful duration of chemotherapy holidays and can be offered to a minority (18%) of patients. Upon re-treatment, most patients (85%) again respond or stabilize PSA values. [Table: see text]
The Registry Case Finding Engine (CaFE): An automated approach for cancer patient identification from unstructured, free-text pathology reports
Authors: D. A. Hanauer, A. M. Chinnaiyan, G. Miela, D. W. Blayney
Journal: Journal of Clinical Oncology (2006)

6080 Background: A vital component to maintaining an accurate cancer registry is the identification of patients with cancer. The University of Michigan Cancer Registry identifies more than 90% of all registry patients by manually reading free-text pathology reports and their associated SNOMED codes. This method is labor and time intensive and is subject to errors of omission. Methods: We created an application to scan free-text pathology reports to identify cases of interest to the registry. It uses a custom-made list of approximately 3,300 words, phrases, and SNOMED codes to positively identify relevant cases and to eliminate non-relevant cases, including those which may mention cancer-related terms. Experienced registrars reviewed 2,451 pathology reports and marked cases of interest to the registry; this served as the gold standard. These reports were also analyzed by the Registry CaFE. The time required for case identification was recorded for both processes. Results: Experienced registrars marked 795 (32.4%) cases as being of interest compared to the CaFE which marked 1,009 (41.1%). The sensitivity of the CaFE was 100% whereas the specificity was 87.1%. An analysis of the 214 errors made by the CaFE revelead that 30 cases (14%) were due to incorrect SNOMED codes assigned by our auto-coding system (Cerner Corporation, Kansas City, MO) and 89 (41.6%) were either skin squamous or basal cell carcinomas (most non-melanomatous skin cancers are not tracked in the registry). Registrars required an average of 21 seconds per pathology report whereas the Registry CaFE processed each report in less than a second. Conclusions: The Registry CaFE identified all relevant cases and correctly eliminated most cases that were not important; it is both effective and time-saving. Future efforts directed at improving the CaFE for squamous and basal cell carcinomas would yield the largest improvement in accuracy. No significant financial relationships to disclose.
Subgroup analysis of African American patients from a randomized phase 3 trial of gemcitabine (G) in combination with carboplatin (Cb) or paclitaxel (P) compared to P plus Cb in advanced (stage IIIB, IV) non-small cell lung cancer (NSCLC)
Authors: J. Treat, R. Gonin, M. Edelman, C. P. Belani, M. Socinski, R. Catalano, D. Marinucci, R. Ansari, R. Comis, C. Obasaju
Journal: Journal of Clinical Oncology (2007)

18066 Background: A relationship between race and prognosis in patients with NSCLC has been suggested with African Americans (AA) having higher incidence and lower survival rates compared to whites (W) with a similar stage of disease. However, due to under representation of AA in clinical trials there is little data to substantiate this hypothesis. To investigate the possibility of a race effect on the efficacy and safety of standard chemotherapy doublet regimens in AA pts, we conducted a retrospective subgroup analysis of our Phase 3 randomized trial comparing 3 regimens for advanced NSCLC (Treat, et al: Abst#7025, Proc ASCO 2005). Methods: A Phase 3 study in advanced (stage IIIB/IV) NSCLC chemonaive patients with ECOG PS &lt;2 was designed to compare the efficacy of a G-containing platinum regimen GCb (G 1000 mg/m 2 IV D 1, 8 plus Cb AUC 5.5, D 1) to a nonplatinum G doublet GP (G 1000 mg/m 2 IV D 1,8 plus P 200 mg/m 2 , D 1) and a reference regimen of PCb (P 225 mg/m 2 plus Cb AUC 6.0, D 1). Outcome and toxicity data of AA pts vs. W pts were compared. Survival (OS) was the primary endpoint with secondary endpoints being response rate (RR), time to progression (TTP) and toxicity. Data from all 3 arms were pooled for this analysis. Results: A total of 128 AA and 906 W pts were analyzed. There were no significant differences in the OS or TTP distributions in AA compared to W pts ( Table 1 ). The incidence and grade of hematologic toxicity in AA vs. W pts were comparable. AA demonstrated slightly lower incidences of Grade 3–4 constitutional (5.1% vs. 9.0%), hemorrhage (1.4 % vs. 2.5 %), and metabolic (4.4% vs. 7.0%) toxicities compared with W pts. Conclusions: Use of standard chemotherapy doublets as first-line chemotherapy in AA pts with advanced NSCLC demonstrated similar efficacy and safety compared to W pts treated under similar conditions. [Table: see text] No significant financial relationships to disclose.
Development of expression based biomarkers in NSCLC: A study of intratumor heterogeneity using FFPE tissue.
Authors: R. J. Holt, T. Davison, S. Dibben, J. Taylor, P. J. Kelly, I. Paul, P. Kerr, D. A. Fennell, R. D. Kennedy, J. A. James
Journal: Journal of Clinical Oncology (2010)

e21024 Background: There is considerable interest in the use of gene expression data to generate prognostic/predictive biomarkers from NSCLC tissue. Since individual tumors exhibit histological diversity, it is possible that different areas within tumors will exhibit distinct molecular profiles. This represents a potential problem for biomarker development. To date, intratumoral gene expression has primarily been studied to determine the feasibility of using small biopsies in expression studies. NSCLC studies describing EGFR mutations suggest that these tumors demonstrate tissue heterogeneity, however expression data is limited. We are currently developing a NSCLC prognostic signature using approximately 1,500 FFPE samples. The study of intratumoral gene expression in these samples will play a crucial role in allowing the development of a robust gene signature. Methods: 10 samples were selected (6 adenocarcinoma and 4 squamous carcinoma tumors). Between 3 and 5 blocks were taken from each sample, each representing different parts of the tumor. RNA was extracted from both macrodissected and whole FFPE sections and processed on the Lung Cancer DSA, a lung cancer specific microarray. Results: Bias and variations in gene expression were assessed at the intra and inter patient level and between adenocarcinoma and squamous samples. Gene expression data was fitted to a nested ANOVA model to assess the statistical significance of observed variations within and between samples and disease states. Univariate analysis of the measurement error for microarray data may not accurately reflect the impact of a multi-gene signature, therefore pseudo-signatures of varying lengths were generated from microarray data and the relationship between signature length and measurement error was assessed with measurement error generally decreasing with increasing signature size. Conclusions: Gene expression data indicated that variations in gene expression were present between blocks taken from a single patient. However, the variations in gene expression observed between individual patients and disease states were greater. We discuss the impact of signature size and heterogeneity on study design. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Almac Diagnostics
Phase II trial of docetaxel (D) / carboplatin (C) as treatment for first relapsed platinum-sensitive stage III/IV ovarian cancer
Authors: B. Goff, P. J. Paley, T. Gooley, L. A. Holmberg
Journal: Journal of Clinical Oncology (2004)

5051 Background: The optimal therapy to treat relapsed ovarian cancer remains elusive and patients who relapse ≥ 6 months after initial therapy are usually treated with platinum-containing salvage therapy. Docetaxel (D) alone has demonstrated some clinical responses in such patients. In a number of different cancers, treatment after Paclitaxel with D has yielded impressive clinical responses. Thus, it seemed reasonable to combine D and Carboplatin (C) to treat patients in first relapse with platinum-sensitive ovarian cancer. Methods: 21 patients have begun treatment with D 80 mg/m2 IV over 1 hour followed by C AUC6 (calculated by Calvert formula) IV over 30 minutes. Cycles were given every 21 days for a total of 6. Dose modifications occurred for hematological, neurological, hepatic or renal toxicity. Patients began therapy if platelet count was ≥ 100,000 cells/ul, ANC ≥ 1500 cells/ul, Total Bilirupin <2.0 mg/dl, SGPT/SGOT ≤ 1.5 X ULN with alkaline phosphatase ≤ 2.5 X ULN or SGOT/SGPT ≤ 5 X ULN with normal alkaline phosphatase. Karnofsky status had to be ≥ 60%. Grading of toxicity was according to NCI CTC. Results: Of the evaluated patients, 74% remain alive, with a median follow-up of 20.9 months (5–48). Fifty-eight % have progressed or relapsed. Initial response rates included 36.8% achieving a CR, and 31.6% a PR (the total CR+PR rate = 68.4%). An additional 15.8% had SD. Three patients who achieved a CR relapsed at 489, 261 and 95 days, the other four remain in CR. Eighty-four % of the patients developed grade 4 neutropenia. There were three separate cases of grade 3 non-hematological toxicity, including allergic reaction, nausea/dehydration and dermatitis. Thirty-two % of the patients developed an infection. One patient stopped therapy at physician's request for decreased performance status. Conclusions: Docetaxel and Carboplatin is not only a very well tolerated regimen with neutropenia the most common side effect but also a very active regimen in treating patients with first relapsed platinum-sensitive ovarian cancer. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis
Effect of low-dose, short-course sunitinib (Su) on tumor vasculature and tumor blood flow for enhancement of chemotherapy efficacy in breast cancer.
Authors: Andrea Li Ann Wong, Raghav Sundar, Samuel Guan Wei Ow, Ting Ting Wang, Thian-C Ng, Ching-Wan Chan, Mikael Hartman, Philip Iau, Sing Huang Tan, Bo Zhang, Choon Hua Thng, Maria Jannet Mogro, Pei Jye Voon, Shaik Ahmad Buhari, I Peng Thomas Soh, Boon C. Goh, Soo-Chin Lee
Journal: Journal of Clinical Oncology (2014)

1060 Background: Continuous VEGFR-I use may ablate vasculature and impede chemotherapy delivery, failing to improve outcome; in contrast, low-dose, short-course VEGFR-I may normalize vasculature and enhance drug delivery. Methods: We conducted a phase Ib followed by phase II randomized study in chemonaive breast cancer patients to evaluate 1 week treatment with low-dose Su before each cycle of neoadjuvant doxorubicin/cyclophosphamide (AC) and measured tumor blood flow, vascular and lymphatic density with serial DCE-MRI and biopsy, at baseline, after 1 week Su, and after cycles 1 and 4 AC. Results: Phase Ib enrolled 9 patients: 25mg Su (n=3) reduced tumor blood flow; 12.5mg Su (n=6) increased tumor blood flow reflected by plasma volume (Vp) on DCE-MRI and increased SMA/CD31 staining indicating normal vessels, and was used in phase II. 47 patients were randomized in phase II: 24 AC, 23 Su+AC. 68%, 43%, 68%, 92% had T3-4, N+, ER+, HER2- tumor. No significant change in DCE-MRI parameters, SMA/CD31 and podoplanin staining was seen with AC alone. In contrast, Su+AC increased plasma volume and blood flow on DCE-MRI after 1 cycle (Vp 11.5 vs 8.4, p=0.047; F 104 vs 87, p=0.077), and SMA/CD31 double staining after 1 and 4 cycles (22.2 vs 48.9 vs 63.8, p=0.036) reflecting better tumor perfusion from normalized blood vessels. Su+AC also reduced lymphatic density after 1 and 4 cycles (podoplanin 3.3 vs 1.0 vs 0.7, p=0.039). Of note, SMA/CD31 change occurred in patients with good histological response after 1 AC (p=0.036), while podoplanin change occurred in ypN0-1 patients at surgery (p=0.038), and not those with less favorable response. Su+AC led to better histological response (grade 4-5) after 1 cycle (54% vs 25%) and more breast conservation (24% vs 10%), but pCR & node negativity rates (6 vs 5%; 35 vs 33%) were similar to AC alone, and may be due to more dose delay/reduction/omission from neutropenia (29% vs 5%, p=0.087). Conclusions: 1 week of 12.5mg Su prior to AC normalizes tumor vasculature to improve perfusion and reduces lymphatic density, which correlated with early histological response and less nodal involvement after chemotherapy, providing proof of concept of potential efficacy of this strategy. Clinical trial information: NCT01176799.
VAD (vincristine, doxorubicin and high-dose dexamethasone) administered as intravenous bolus (IVB) injection as first-line treatment in multiple myeloma (MM)
Authors: A. C. Vendette, C. G. Ferreira, I. A. Small, B. Reinhard, A. Scheliga
Journal: Journal of Clinical Oncology (2004)

6709 Background: The combination of vincristine (VCR) and doxorubicin [Adriamycin (ADM)] as a 4-day continuous infusion (CI) via an indwelling catheter (IC) plus intermittent high-dose dexamethasone (DxT) is an effective primary treatment for induction therapy prior to hematopoietic stem cell transplantation in MM patients (pts). As an alternative for IC, which imposes logistic problems for outpatient administration, two recent studies reported that the IVB-VAD has a high objective response rate (RR) and a mild toxicity profile. However a cost comparison between CI- and IVB-VAD has not been reported so far. Methods: We analyzed retrospectively the clinical files of 36 pts treated with IVB-VAD as first-line treatment for MM at INCA between Jan1999 and Oct 2002. In parallel a detailed cost analyses was carried out in the records of pts treated with IVB- and CI-VAD. The IVB regimen consisted of bolus VCR 0,4mg and ADM 9mg/m2 plus DxT 40mg P.O. daily X 4. Results: There were 21 men and 15 women and the median age was 50 (28–64). At diagnosis the % of pts with Hb ≥ 11, PS≤ 2 and stage III were 91, 80,5 and 83,3, respectively. Seven pts have died and 29 are alive, 75% of them in first remission. In total, 127 cycles were administered and toxicity > grade 2 was rare, except for neutropenia (10,8%) and infection (35%). With a median number of cycles of 3,5, RR was 80% (complete and partial responses), but only 44% of the pts underwent autologous bone marrow transplantation. In line with the high RR, median overall and disease-free survival could not be reached, despite a median follow-up of 25 months. In terms of RR and toxicity, our results are akin to those previously reported. Further the pharmacoeconomic comparison, here for the first time reported, indicated a marked difference between being the CI cost 336% higher than IVB (US$ 1800 Vs 535 per patient). This more favorable pharmacoeconomic profile corroborates the advantages of IVB-VAD. Altogether we conclude the IVB-VAD is a feasible, safe and cost-effective regimen to be used as first-line treatment in MM pts. No significant financial relationships to disclose.
Cancer pain management: Safety and efficacy of transdermal fentanyl (TDF)
Authors: C. Caroti, C. Aschele, A. Gozza, M. D'Amico, C. Naso, L. Gallo, U. Folco, P. Pronzato
Journal: Journal of Clinical Oncology (2004)

8234 Background: Cancer patients with moderate-severe pain often require opioid analgesics. Methods: From October 2002 to November 2003, 62 outpatients underwent transdermal treatment with Fentanyl (TDF). All pts had been previously treated with other drugs according to the WHO analgesic scale. Pts characteristics: median age 64 years (range 44–84), M/F 29/33, median ECOG PS 0 (range 0–2). Primary tumors: 24 breast, 8 lung, 9 colorectal, 7 pancreas, 7 prostate, 7 others. Somatic pain was reported in 35/62 pts (56%), visceral pain in 12/62 pts (19%), 15/62 pts (24%) showed both types, with neuropatic features in 10%. Breakthrough pain was present in 24/62 pts (38%) requiring rescue medication. 47/62 pts (75%) received palliative chemo-radiotherapy. All pts were evaluated weekly with VAS (Visual Analogic Scale) and TIQ (Therapy Impact Questionnaire). A Geriatric Assessment with CIRS (Comorbility Index), ADL and IADL was performed for pts aged over 65 years (23/62; 37%) at the beginning of treatment and after two months. Median VAS starting value was 5 (range 3–8); TIQ showed also depression, cachexia and dispnea in 46–32-17% respectively; comorbidity in 87% of elderly people. 7 and 4 pts were ADL and IADL dependent respectively. Median TDF starting dose was 25 mcr/h (range 25–50). TDF was replaced every 72 h. TDF doses were increased depending on individual response to pain. Results: after the first two months, TDF showed a good pain control with a quickly VAS downloading already during the first week of treatment (median final VAS 1; range 0–7), without a significant TDF dose increasing. Application intervals had to be shortened to 48 h in 12/62 pts (19%). No interference with TIQ and ADL-IADL dependence was reported. Toxicity did not exceed grade 2. Pts receiving oral morphine as rescue medication showed nausea and vomiting( 12%), sleepiness (10%), and constipation (40%). 4/62 pts (6%) stopped treatment: 2 because of grade 2 toxicity and 2 for unfruitful pain control. Conclusions: TDF was safe and effective for both somatic and visceral pain. Compliance was good and toxicity mild also among elderly people. TDF should be therefore considered an useful medication for cancer pain management. No significant financial relationships to disclose.
Development of a model emergency oncology response system (EORS): The California oncology emergency master plan (COEMP)
Authors: R. Moss, P. Yu, C. Presant, J. Gonzalez, M. Lamb, S. Tucker
Journal: Journal of Clinical Oncology (2006)

6142 Background: Hurricane Katrina displaced patients (PT) and physicians (MD). Time &amp; resources were needed to match displaced PT with oncology (ONC) practices (PRC) for ongoing care. Disruption of care can be life-threatening to ONC PT who need to adhere to schedules &amp; monitoring. California (CA) is particular risk for natural disaster. In order to better support PT in a future emergency (E) MOASC &amp; ANCO created a model EORS with pilot implementation of select elements. Methods: MOASC &amp; ANCO prepared a multi-component COEMP. Joint calls &amp; meetings yielded a draft EORS approved by both society boards. Initial &amp; long-term funding is expected via granting mechanisms. Pilot implementation of specific elements began in 11/2005. Results: Goals of the COEMP are: Establish dedicated E ONC MD network; Create a voluntary ONC-specific PT medical record (MR) template &amp; secure data repository; Create &amp; test a functional E MD responder system for CA ONC MD; Develop liaison with relief providers (Homeland Security, FEMA, Red Cross); Strengthen existing role with Bio-Pharma (BP) for delivery of medicine (Rx) to displaced PT and PRC; Develop specific educational materials for the EORS (PT, MDs, Insurers, BP); Create &amp; distribute an EORS “PT Wallet Card” with PT national digital record (NDR) and E responder contacts. To prioritize components of the COEMP, a needs assessment, reviewing past E experience, response, and current capacity, has been initiated. The specific active components of the EORS include: 1-E ONC MD support network: ONC MDs have been invited to volunteer via email and at regional meetings. 2-Secure PT MR repository: MDs and PT will coordinate relevant MR, insurance, and E contact data, in locations (home of PT, w/relatives, NDR). 3-E coordinator MDs &amp; staff will respond to E calls from PT/MD via phone &amp; email. 4-Open dialogue with BP for E access to Rx for displaced PT. 5-Educational &amp; training for PRC and PT in printed &amp; electronic form. Conclusions: COEMP provides an initial E model for ONC. It may be applicable for state societies or national ONC groups. At ASCO 2006, MDs will be invited to participate and expand COEMP capabilities. Although we hope COEMP/EORS need never be used, its development will enable ONC practices to be more prepared for loco-regional E. No significant financial relationships to disclose.