tbuckley/cabot-search huggingface dataset:
Oxaliplatin (Ox) desensitization in colorectal cancer (CRC) patients: A single institution experience
Authors: S. Zubair, T. Joseph, C. Hamilton, K. Smith, M. Davies, P. Dore, A. Maraveyas
Journal: Journal of Clinical Oncology (2008)

15047 Background: Reported incidence of Ox hypersensitivity is 12–16%(Brandi G et al. Hypersensitivity reactions to oxaliplatin. Br J Cancer 2003; 89:477–81.). Ox is one of the most active agents in CRC and premature withdrawal may adversely impact on outcome. We implemented an Ox-desensitization protocol (Gammon D et al. Hypersensitivity reactions to oxaliplatin and application of a desensitisation protocol. Oncol 2004; 9:546–9.) in January 2006 and report our experience from January 2006 to December 2007. Methods: After patch test (PT); patients (P) were given inpatient desensitization treatment. Total dose was administered in serial dilutions from 1:1,000 to 1:1. Of 142 CRC patients receiving Ox 8 experienced allergic reaction for an institute incidence of 5.6%. NCI-CTC score grade (G) G2–3P, G3–2P, G4- 3P. Mean number of cycles received before reaction 4.5 range (1–13) and the mean total dose 700mg. 7 patients had stage IV disease and one stage III. 5 were female, mean age of 59.5 years. 7 patients had Ox-Modified De Gramont (MdG), 1 had Ox alone (coronary vasospasm with capecitabine). 6 reacted during their first course and 2 whilst being reintroduced after drug-holiday. 3 patients had desensitization having progressed through all other conventional lines of treatment. 6 patients had previous partial response (PR) to Ox-MdG. Results: PT was negative in 4 patients (omitted in 4). Mean number of further cycles received was 8.6 and mean dose received 1,266mg. All patients received treatment until at least one disease evaluation milestone (minimum 3 months). Response rate (#6): 1 CR, 3 PR, 1 SD and 1 PD. Survival (#7): 1 patient died (9 months), others alive at 3+, 8+, 10+, 11+, 20+ 22+ months from commencement of desensitization. Conclusions: Ox hypersensitivity can prematurely deprive CRC patients of effective treatment. We present our experience showing that perseverance with this treatment option using a desensitization protocol can be a useful addition to CRC treatment continuum, enhancing clinical benefit to these patients. No significant financial relationships to disclose.
Aflibercept versus placebo in combination with docetaxel/prednisone for first-line treatment of men with metastatic castration-resistant prostate cancer (mCRPC): Results from the multinational phase III trial (VENICE).
Authors: Ian Tannock, Karim Fizazi, Sergei Ivanov, Camilla Thellenberg Karlsson, Aude Flechon, Iwona Anna Skoneczna, Francisco Jorquera Orlandi, Gwenaelle Gravis, Vsevolod B. Matveev, Sevil E. Bavbek, Thierry Gil, Luciano S. Viana, Osvaldo Rudy Aren, Oleg Karyakin, Tony Elliott, Alison J. Birtle, Emmanuelle Magherini, Laurence Hatteville, Bertrand Tombal, Mark Rosenthal
Journal: Journal of Clinical Oncology (2013)

13 Background: Docetaxel/prednisone is standard first-line chemotherapy for mCRPC. Aflibercept (known as ziv-aflibercept in the US) is a recombinant human fusion protein that binds VEGF-A, VEGF-B and Placental Growth Factor (PlGF), thereby inhibiting angiogenesis. Methods: VENICE was a double-blind, randomized phase III study with overall survival (OS) as primary endpoint. Men with mCRPC, ECOG PS 0-2, adequate organ function and no prior cytotoxic therapy were treated with docetaxel (75 mg/m² iv q3w) and oral prednisone (5mg bid) and randomized double blind 1:1 to receive aflibercept (A) 6 mg/kg or placebo (Pbo), IV every 3 weeks. Pts were stratified by ECOG PS (0-1 vs 2). For final OS analysis, 873 deaths were required to detect a hazard ratio (HR) of 0.8 with 90% power (overall 2-sided α = 0.05). Results: From Aug 2007 to Feb 2010, 1224 patients (median age 68 yr, PS 0-1 96%) were randomized. Baseline characteristics were well balanced between arms. Median number of cycles was 8 (A) and 9 (Pbo). Median relative dose intensity was &gt;0.93 for A, Pbo and docetaxel. At final cut-off, median follow-up was 35.4 mos and 873 pts had died. Results for primary and key secondary endpoints with confidence intervals are in the table. Higher incidence of all grade hypertension, stomatitis, appetite disorders, diarrhea, dehydration, epistaxis, dysphonia, cough, headache and infections was observed in the aflibercept arm. Conclusions: Aflibercept in combination with docetaxel/prednisone given as first line chemotherapy for mCRPC did not lead to a statistically significant improvement in OS and added toxicity. (NCT00519285 sponsored by Sanofi and Regeneron Pharmaceuticals, Inc.) Clinical trial information: NCT00519285. [Table: see text]
Evaluating the hypothalamic-pituitary-adrenal axis (HPAA) in men receiving ketoconazole for castrate resistant prostate cancer (CRPC).
Authors: Rahul Raj Aggarwal, Vivian K. Weinberg, Eduardo V. Sosa, Amy M. Lin, Andrea Lynne Harzstark, Eric Jay Small, Lawrence Fong, Andrew Caleb Hsieh, Carl Formaker, Kathryn M. Koepfgen, Evelyn Hang, Terence W. Friedlander, Charles J. Ryan
Journal: Journal of Clinical Oncology (2013)

5077 Background: Serum adrenal androgen (AA) levels may be prognostic for survival in men with CRPC treated with androgen synthesis inhibitors (ASIs) including ketoconazole (keto) and abiraterone. We hypothesize that up-regulation of the HPAA and adrenocorticotropic hormone (ACTH) may contribute to therapeutic resistance on ASIs. The current study explores the relationship between ACTH, AA, testosterone (T) and estradiol (E) among CRPC patients (pts) treated with ASI + corticosteroids. Methods: Phase II study of keto (400 mg TID) + hydrocortisone (HC) (30 mg/day) in pts with CRPC. Pts who achieved ≥ 30% PSA decline from baseline at week 12 continued keto/HC until progression, at which point HC was replaced by dexamethasone (dex). Serum hormone (H) levels were measured (in AM) at baseline and every 4 weeks using standard assays. Statistical tests include Spearman’s rank test for correlation between baseline H levels; Wilcoxon matched pairs for baseline vs. week 4 distribution; and Fisher’s exact test for associations between H levels (dichotomized at median) with PSA decline. Results: Of 30 pts enrolled and 24 evaluable for PSA response, 13 pts (54%) achieved ≥ 30% PSA decline at 12 weeks. Baseline ACTH was positively correlated with DHEA (r = 0.40; p = 0.04) and cortisol (r = 0.52; p = 0.007). Change from baseline to week 4 in H levels is shown in table. There was a significant increase in pts achieving a PSA decline of &gt; 30% if there was a decrease in E at week 4 vs. no decrease (83% vs. 18%; p = 0.003). Baseline and changes in other H levels were not associated with PSA outcome at week 12. Conclusions: ACTH is positively correlated with DHEA and cortisol in CRPC pts. Declines in E may serve as an additional predictive marker of benefit for ASI therapy. These observations require prospective validation. Analyses exploring changes in ACTH at disease progression and impact of substituting dex for HC are ongoing. Clinical trial information: NCT01036594. [Table: see text]
Benchmarks for end of life care in a community oncology practice
Authors: J. R. Hoverman, K. Radebaugh
Journal: Journal of Clinical Oncology (2005)

8105 Background: There are efforts on many fronts to measure the quality of oncology care, particularly at the end of life. Yet benchmarks for community oncology practices are lacking. We undertook this study to: 1) assess the obstacles to obtaining data on end of life care and 2) establish benchmarks for quality improvement. Methods: Deceased patients were identified either through death certificates and obituaries or through a cancer registry. The charts were abstracted for the criteria that follow results. Results: 202 patients were identified in a community practice with two different sites served by six medical oncologists and 2 gynecologic oncologists over a period of two years. Of these 202 patients, 143 were deemed hospice appropriate (projected life span of 6 months or less, remained in the community, continued follow-up by our physicians). 105 of 143 were enrolled in hospice (73.4% of hospice appropriate or 52% of total). Of those enrolled mean length of enrollment was 28.6 days, median 21 days; average number of hospital days in the last 30 days was 2.6 (276/105) and the percent that had a new regimen of chemotherapy in the last 30 days was 1.9 (2/105). 51.4 (54/105) percent died at home, 26.7 (28/105) died in a freestanding hospice inpatient facility and 0.95 (1/105) died in the hospital. For 21% the place of death could not be determined from the record. In 22.9% (24/105) hospice enrollment occurred in the last 7 days of life. Conclusions: The constituents for good end of life care as identified by SUPPORT and the Promoting Excellence projects can be achieved in a community oncology practice. The overall hospice enrollment, resource utilization and achieved choice of place of death compare favorably with published data. The chief concern is the rate of late enrollments. Characteristics of the practice contributing to these results will be discussed, as will plans for quality improvement. No significant financial relationships to disclose.
Inguinal lymph node dissection for penile cancer: Predictors of lymph node metastasis.
Authors: Adam Luchey, Patrick Espiritu, Jared Gopman, Gautum Agarwal, Julio M. Pow-Sang, Wade Jeffers Sexton, Philippe E. Spiess
Journal: Journal of Clinical Oncology (2014)

386 Background: Inguinal lymph node dissection (ILND) for lymph node metastasis (LNM) of squamous cell carcinoma of the penis (SCCP) can be a curative surgical treatment. Having the potential to identify clinical and pathological factors that predict LNM is important because of the poor prognosis this diagnosis carries. Methods: A retrospective review of 51 patients that underwent inguinal plus pelvic lymph node dissection from 1999 to 2012 was preformed. Age, race, body mass index (BMI), significant lymphadenopathy on preoperative imaging (nodes &gt; 1 cm), palpable lymphadenopathy, and pathologic depth of invasion and diameter of the primary penile tumor along with associated lymphovascular invasion (LVI) were recorded and analyzed as potential predictors of LNM. Results: Median patient age was 65 and the median BMI was 29.3. Thirty-nine patients (76.5%) were white, 3 (5.9%) African American, and 9 (17.6%) were Hispanic. Median primary penile tumor diameter was 3.2 cm with 7, 29, and 15 patients having well, moderate, and poorly differentiated tumors. Pre-operatively, 32 patients (62.7%) had palpable lymphadenopathy on physical exam and 26 (51.0%) had significant lymphadenopathy on imaging (93% CT, 7% MRI), with 24 (47.1%) having both findings. Thirty-one patients (60.8%) who underwent ILND had pathological LNM. On univariate analysis, palpable nodes (p &lt; 0.001), nodes on imaging (p &lt;0.001), having both palpable nodes and nodes on imaging (p &lt; 0.001), age (p = 0.02), and LVI (p = 0.04), were significantly associated with LMN. On multivariate analysis, having nodes on imaging (p = 0.001) and age &lt; 65 years (p = 0.049) were significant for predicting LNM. Conclusions: In evaluation of patients with T1-T3 penile cancer, multiple factors were predictive of LNM in our series: palpable and radiographic nodes, younger than age 65 and LVI. Inguinal adenopathy defined as more than 1 cm appears to better predict occult nodal metastasis, however, this must be weighed in terms of the additional cost and clinical yield provided by widespread adoption of pelvic (CT or MRI) imaging in all patients with aggressive primary penile tumor phenotypes.
The effect of stereotactic ablative radiotherapy on time to change of systemic therapy in extra-cranial renal cell carcinoma metastases.
Authors: Chiachien Jake Wang, Xin Cai, Dong W. Kim, Lorel Huelsmann, Jeffrey John Meyer, Ivan Pedrosa, James Brugarolas, Vitaly Margulis, Robert D. Timmerman, Raquibul Hannan
Journal: Journal of Clinical Oncology (2016)

533 Background: Renal cell carcinoma (RCC) has traditionally been refractory to radiotherapy with conventional fractionation, although recent evidence suggests a response to higher doses per fraction. We evaluated local control of extra-cranial metastases from RCC treated with stereotactic ablative radiotherapy (SABR). Methods: RCC patients with extra-cranial metastases treated with SABR were retrospectively enrolled from a single institution between 2005 and 2015. A total of 188 lesions were identified from 91 patients. Radiation (8-60Gy) was delivered in 1-5 fractions (fx) using stereotactic guidance. Local control (LC) was determined by imaging according to RECIST 1.1. Results: Median age at the time of treatment was 62.4 years. Metastases were detected in bone (39.9%), lung (14.9%), liver (9.6%), lymph nodes (11.7%) and other sites (23.9%). Ninety-seven (51.6%) lesions reached curative intent while 91 (48.4%) only reached palliative intent. The most common radiation regimens were 20Gy/1fx, 30Gy/3fx, and 40Gy/5fx. One-year overall survival was 76.5% with a median follow up of 10.7 months. Patients treated with curative SABR showed a 2-fold median survival as compared to those treated with palliative therapy (3.97 year vs 1.43 year, p&lt;0.05). LC rates at 1 and 2 years were 91.4% and 89.7%, respectively. For the patients that failed, median time to local failure was 6.6 months. LC at 1 year significantly improved when treatment was curative (96.1% vs 84.9%, p&lt;0.05), while it decreased in a re-irradiation setting (94.8% vs 46.7%, p&lt;0.05). The median biological equivalent dose (BED) for the lesions that failed was 103Gy, corresponding to 6Gy x 5fx, and was significantly lowered compared to controlled lesions (BED 134Gy). Although 79% of patients developed new lesions within 1 year following SABR, 34.8% did not switch systemic therapy. Switching systemic therapy was delayed in patients treated with curative as compared to palliative SABR (13.4 vs 2.5 months, p&lt;0.05). Conclusions: SABR improved LC of extra-cranial RCC metastases and delayed change to systemic therapy. SABR may complement systemic therapy to improve outcome in the present patient population.
Financial implications of changes in the initial treatment of prostate cancer among Medicare beneficiaries.
Authors: M. A. Dinan, T. J. Robinson, T. M. Zagar, C. D. Scales, L. H. Curtis, S. D. Reed, K. A. Schulman, W. R. Lee
Journal: Journal of Clinical Oncology (2011)

6115 Background: The traditional treament approaches for localized prostate cancer have included androgen suppression, watchful waiting, open radical prostatectomy, external beam radiation therapy and interstitial brachytherapy. In the last decade a number of novel treatment options have been developed including minimally invasive radical prostatectomy (MIRP) and intensity-modulated radiation therapy (IMRT). Methods: In this study, we examined changes in the treatment of Medicare beneficiaries diagnosed with incident prostate cancer between 1999 and 2007. The primary outcome was utiliziation of radiation, surgery, or androgen suppression therapy in the first 12 months following newly diagnosed prostate cancer by year of incidence. Results: The study sample included 20 399 cases of incident prostate cancer identified between 1999 and 2007. Overall rates of surgery and radiotherapy within the first 12 months of diagnosis remained unchanged across the study period, however the proportion of beneficiaries receiving androgen suppression monotherapy decreased by half, with watchful waiting increasing from 16% to 23% of all beneficiaries. From 2002 to 2007, IMRT replaced 3-D conformal treatment as the most common method of prostate radiotherapy, and was used in two-thirds of all Medicare prostate cancer patients receiving any radiotherapy by 2007. During this same period, minimally invasive radical prostatectomy began to replace open surgical approaches, and was used in half of all radical prostatectomies by 2007. Conclusions: By 2007 IMRT had replaced 3D conformal radiotherapy (3D-CRT) as the predominant method of radiotherapy used in the Medicare prostate cancer population. With Medicare reimbursement for IMRT averaging $48,000 per beneficiary vs $22,000 for 3D-CRT, this trend has significant budgetary implications. The aging of the US population over the next decade will cause the number of men with newly diagnosed prostate cancer to climb. When combined with growth in the use of newer high-cost technologies, Medicare spending for prostate cancer will further accelerate.
Effect of extrahepatic disease on transarterial chemoembolization for metastatic carcinoid.
Authors: D. Arrese, E. Feria-Arias, H. Khabiri, G. Guy, C. R. Schmidt, M. H. Shah, M. Bloomston
Journal: Journal of Clinical Oncology (2011)

283 Background: Transarterial chemoembolization (TACE) is the locoregional therapy of choice for the management of patients with inoperable carcinoid liver metastases. Often, metastatic disease is not limited to the liver. The impact of extra-hepatic metastases on response and outcomes following TACE has not been described. Objective: We hypothesized that patients who have extra-hepatic disease would have similar tumor response and symptom control following TACE. Methods: We reviewed 198 patients that underwent TACE for inoperable carcinoid liver metastases. Two groups were identified, those with (N= 129) and without (N= 69) evidence of extra-hepatic disease at the time of TACE. Demographics, clinicopathologic characteristics, response to TACE, complications, and survival were compared. Results: The two groups were similar in demographics and histopathologic characteristics. Complications following TACE were similar. There was no difference between the groups with and without evidence of extrahepatic disease in symptomatic (76% vs 71%), biochemical (78% vs 90%) or radiographic response (35.0% vs 46%) to TACE. The group without extra-hepatic disease had a median survival of 88 vs 35 months with five-year survival of 65% vs 30% compared to patients with extra-hepatic disease at the time of TACE. Conclusions: Patients with extrahepatic metastatic disease from carcinoid tumor experienced shorter overall survival following TACE compared to those without extrahepatic disease. However, patients with extra- hepatic disease had similar symptomatic, biochemical and radiographic response to TACE compared to those with disease confined to the liver. Although the long-term prognosis for patients with extrahepatic disease is worse than those with liver-only metastasis, meaningful response to TACE is possible and should be considered. No significant financial relationships to disclose.
A phase I study of weekly oral topotecan in patients (pts) with relapsed small cell lung cancer (SCLC).
Authors: E. Kontopodis, L. Vamvakas, K. Kalbakis, N. K. Vardakis, G. Sfakiotaki, V. Georgoulias, S. Agelaki
Journal: Journal of Clinical Oncology (2011)

7081 Background: Oral topotecan represents a standard treatment in pts with relapsed SCLC. Oral topotecan 2.3 mg/m2/day for 5 days, repeated every 3 weeks is associated with severe hematologic toxicity in more than 50% of pts. The weekly administration of oral topotecan has not been studied. A phase I trial was conducted to determine the maximum tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of oral topotecan administered weekly in patients with relapsed SCLC. Methods: Pts with relapsed SCLC were treated with oral topotecan on days 1, 8, and 15, every 28 days. The dose was escalated in 0.5 mg/m2 increments from the starting dose of 3 mg/m2 until the MTD was reached. DLTs were defined as grade 4 neutropenia, febrile neutropenia, grade 4 thrombocytopenia, non-hematologic toxicity ≥ grade 3, or any toxicity precluding the administration of treatment on days 8 or 15 of the 1st cycle or on day 1 of the 2nd cycle. Results: Eighteen pts (median age, 56 years, 77.8% male) were enrolled. Performance status was 0-1 in 94.4%. Thirteen (72.2%) pts [6 (46.2%) with sensitive and 7 (53.8%) with refractory relapse] received oral topotecan as 2nd line and 5 (28.2%) as ≥3rd line treatment. Three DLTs among 6 pts were observed at the 4.5 mg/m2 dose level (grade 3 neutropenia and grade 2 thrombocytopenia on day 15 of the 1st cycle in 1 pt, grade 2 neutropenia on day 15 of the 1st cycle in 1 pt, and grade 2 neutropenia on day 1 of the 2nd cycle in 1 pt). The MTD was determined to be 4 mg/m2 (1 of 6 pts experienced a DLT consisting of grade 3 neutropenia on day 15 of the 1st cycle). Hematologic and non-hematologic adverse events included neutropenia (grade 2 in 16.7%, grade 3 in 11.1%), anemia (grade 2 in 27.8%, grade 3 in 5.6%) thrombocytopenia (grade 2 in 16.7%), nausea-vomiting (grade 2 in 5.6%), diarrhea (grade 2 in 5.6%), neurotoxicity (grade 2 in 5.6%) and fatigue (grade 2 in 33.3%, grade 3 in 11.1%). The response rate was 11.1%, the median time to tumor progression 2.3 months (range, 1.1-10.0) and the median overall survival 5.1 months (range, 1.5-10.2). Conclusions: The recommended phase II dose of weekly oral topotecan in pretreated pts with SCLC is 4 mg/m2 on days 1, 8 and 15 every 28 days.
Clinical benefit of chemosensitivity test for patients with advanced esophageal squamous cell carcinoma.
Authors: H. Kawasaki, S. Ikenaga, K. Hakamada
Journal: Journal of Clinical Oncology (2011)

e14540 Background: Patients who have undergone resection for advanced esophageal squamous cell carcinoma are at high risk of recurrence and early death. The role of the postoperative adjuvant chemotherapy in this population needs to be determined.There is a need for a clinical useful drug-response assay for carcinoma patients to individualize their chemotherapy. In our department, we start chemosensitivity test by HDRA method in December, 2008 for esophageal squamous cell carcinoma. Also, a utility of the preoperative chemotherapy (an FP treatment) for the stage II/III esophageal squamous cell carcinoma was shown by a report of JCOG9907 in 2008. Based on this report, even our department performs esophageal squamous cell carcinoma preoperative chemotherapy. We determined the chemosensitivity for 5-fluorouracil, cisplatin and Docetaxel in vitro in fresh human esophageal squamous cell carcinoma using the HDRA method. Subjects were 11patients who undergoing esophageal surgery from December 2008 to June 2009. Preoperative chemotherapy was performed to 7 patients. The carcinoma tissue was gathered by an operation sample and biopsy specimens in 5 patients. We compare a anticancer drug effect with a pathological factorial relation,pathological antitumor effect with results of chemosensitivity test in the preoperative chemotherapy case, and the sensitive results with biopsy specimens with an operation specimen. Results: Among 11 patients, we were able to judge it in 9 cases (82%). The rate of agreement of the results of chemosensitivity test and an effect of the preoperative chemotherapy was 71%. The rate of agreement of the results of chemosensitivity test for an operation sample and for biopsy specimens was 80%. Conclusions: The possibility that a CDDP sensitivity was in proportion to tumoral invasion depth was suggested. The chemosensitivity testing results of the operation specimen were in proportion to that of biopsy specimens. It was shown that the chemosensitivity test for the esophageal squamous cell carcinoma was useful.