tbuckley/cabot-search huggingface dataset:
High-dose-rate brachytherapy combined with external beam radiotherapy for localized prostate cancer: Correlation between clinical and dosimetric parameters and the incidence of rectal bleeding.
Authors: Shinji Kariya, Ichiro Yamasaki, Shingo Ashida, Kenji Tamura, Taro Shuin, Akihito Nishioka, Yashuhiro Ogawa
Journal: Journal of Clinical Oncology (2013)

213 Background: Several investigators have advocated that the alpha/beta ratio for prostate cancer is atypically low, and that hypofractionated radiotherapy or high-dose-rate brachytherapy (HDR-BT) regimens using appropriate radiation doses are expected to improve the local control rate for localized prostate cancer. However, the increase in the total biological effective dose (BED) may cause increased severity and incidence of normal tissue complications. The purpose of this study was to investigate what clinical and dosimetric factors affected the incidence of rectal bleeding after HDR-BT combined with external beam radiotherapy (EBRT). Methods: A total of 143 patients with localized prostate cancer underwent HDR-BT combined with EBRT. The fractionation schema for HDR-BT and EBRT was prospectively changed: 9 Gy x 2 + 2 Gy x 20 (BED 1.5 = 219 Gy, BED 3 = 139 Gy) in 57 patients (Group 1); and 9 Gy x 2 + 3 Gy x 13 (BED 1.5 = 243 Gy, BED 3 = 150 Gy) in 86 patients (Group 2). Median follow-up was 59 (range, 36 – 94) months. The toxicities were graded based on the National Cancer Institute-Common Terminology Criteria for Adverse Events v3.0. Results: Sixteen (11.2 %) and one patients developed Grade 2 and 3 rectal bleedings, respectively. There were no significant differences between Group 1 and Group 2 in the incidence of Grade 2 and 3 rectal bleedings (12.3% and 11.6%, respectively). Grade 2 and 3 rectal bleedings occurred much more in the patients receiving the antiplatelet therapy (AT) (19.4%) than those without a history of AT (9.8%) and in the patients with diabetes mellitus (DM) (37.5%) than those without DM (10.4%). However, neither AT nor DM were risk factors in univariate analysis. Regarding dosimetric factors, V75 &gt; 2cc, V90 &gt; 0.2cc, D2 &gt; 7 Gy, and D1 &gt; 7.4 Gy were statistically-significant risk factors. In multivariate analysis, DM was the only statistically-significant risk factor. Conclusions: BED escalation could be performed without severe rectal bleeding in HDR-BT combined with EBRT. V75 &gt; 2cc, V90 &gt; 0.2cc, D2 &gt; 7 Gy, D1 &gt; 7.4 Gy, and DM were risk factors for the incidence of rectal bleeding in HDR-BT combined with EBRT. Clinical trial information: 18-9.
Understanding the impact of primary care providers on treatment decisions for men with localized prostate cancer.
Authors: Archana Radhakrishnan, David Grande, Linda Crossette, Justin E. Bekelman, Craig Evan Pollack
Journal: Journal of Clinical Oncology (2016)

91 Background: Primary care providers (PCPs) play important roles for cancer patients across the care continuum and may help patients make treatment decisions in line with patients’ preferences. However, the extent of PCP involvement is poorly understood. We evaluated how frequently men with localized prostate cancer discuss treatment with their PCP and whether PCP involvement decreased use of definitive treatment, including among those eligible for surveillance according to clinical guidelines. Methods: We mailed surveys to men diagnosed with localized prostate cancer between 2012 and 2013 in the greater Philadelphia area. Patients reporting having a PCP at the time of diagnosis were asked whether their PCP helped decide how to treat their cancer. Definitive treatment was defined as having radical prostatectomy or radiation therapy. Unadjusted and multivariate logistic regression analyses were used to compare sociodemographic and clinical characteristics of patients who did and did not discuss treatment with their PCP. Similar analyses were used to determine effect of PCP involvement on definitive treatment, both overall and in subgroups of men eligible for surveillance (men &gt; 70 years, with limited life expectancy and with low-risk prostate cancer). Results: 3743 men were mailed a survey, 1757 responded, and 1139 were eligible for analyses. Overall, 438 (38.5%) discussed treatment with their PCP. In adjusted analyses, black men were more likely than white men (Odds Ratio 1.89; 95% Confidence Interval 1.22-2.91) and men with Medicare were more likely than men with private insurance (OR 1.61; 95% CI 1.03-2.51) to discuss treatment with their PCP. However, men who had treatment discussions with their PCP were not less likely to receive definitive treatment (p = 0.11), both overall and among those eligible for surveillance. Conclusions: Though a large proportion of men engaged in treatment discussions with their PCP, these discussions were not associated with differences in the receipt of definitive treatment among men with localized prostate cancer. Understanding the content of these discussions can inform interventions that can help patients make preference concordant treatment decisions.
Pharmacokinetics (PK) of free and total paclitaxel after equal doses of paclitaxel injectable emulsion and paclitaxel injection
Authors: A. R. Hanauske, L. Goedhals, H. Gelderblom, Y. Lee, A. Awada, J. B. Vermorken, C. Lübbing, A. Ruiz-Garcia, J. Pratt, M. B. Stewart
Journal: Journal of Clinical Oncology (2005)

2045 Background: Paclitaxel Injectable Emulsion (TOCOSOL Paclitaxel) is a novel tocopherol-based cremaphor-free formulation that allows a dose of paclitaxel to be infused over 15 minutes, and that has shown activity in Phase 2 trials in ovarian, non-small cell lung and bladder cancers (Lissianskaya et al., Bogdanova et al., Gorelov et al., ProcASCO, 2004). Methods: 36 patients with non-hematologic malignancies were enrolled in a multicenter study to receive single 175 mg/m2 doses of Paclitaxel Injectable Emulsion (TP) given over 15 minutes and CremophorEL-formulated Paclitaxel Injection (P) given over 3 hours. Doses were given as fixed-rate infusions, in random order, separated by at least 3 weeks. Blood samples to characterize the PK of free and total paclitaxel were obtained up to 120 hours after each dose; non-compartmental and compartmental PK analyses were performed. Adverse events and complete blood counts were assessed every 3 days. Results: The geometric mean ratio of free paclitaxel AUC values after equal 175 mg/m2 doses of TP and P was 1.67 (90% CI 1.56–1.79, p<0.0001) and that for total paclitaxel AUC values was 2.08 (90% CI 1.97–2.20, p<0.0001). Mean values for paclitaxel terminal elimination t½ were similar for TP and P. At this dose level, TP produced somewhat more neutropenia than P, however there were no episodes of febrile neutropenia or sepsis following either drug. There were no Grade 4 non-hematologic toxicities; the frequency and severity of Grade 1–3 non-hematologic adverse events was comparable between the two drugs. Full pharmacokinetic and clinical safety data will be presented. Conclusions: A 175 mg/m2 dose of TP given over 15 minutes produced a mean 67% higher exposure to free paclitaxel, and a mean 108% higher exposure to total paclitaxel, compared to an equal dose of P given over 3 hours. The differences in exposure may reflect differences in rate and/or extent of dissociation of paclitaxel from the tocopherol emulsion formulation compared to cremaphor-ethanol micelles. Single equal doses of TP and P were similarly tolerated. A Phase 3 comparative efficacy study is planned. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sonus Sonus Sonus
Predictors of lymph node metastasis and prognosis in early colorectal cancer patients with signet-ring cell and mucinous adenocarcinomas.
Authors: Baorong Song, Yongming Yu, Xiao Song, Xinxiang Li, Xiaoyu Dai, Sanjun Cai, Ye Xu, Guoxiang Cai
Journal: Journal of Clinical Oncology (2016)

717 Background: The local excision of early colorectal cancer is limited by the presence of lymph node metastasis. Signet-ring cell carcinomas and mucinous adenocarcinomas are two relatively infrequent histological subtypes. However, little is known about the predictors of lymph node metastases and prognosis to support the feasibility of local excision in early-stage signet-ring cell and mucinous colorectal adenocarcinomas. Methods: The Surveillance Epidemiology and End Results Database (1988 to 2006) from the National Cancer Institute was used to identify all patients with T1 adenocarcinomas, including conventional adenocarcinoma (AC), mucinous adenocarcinomas (MAC), and signet-ring cell carcinoma (SRC). The prevalence of lymph node metastasis was assessed, and the long-term survival rate in the above three types of colorectal cancer was calculated. Results: Final cohorts of 47,260 patients were eligible for analysis. SRC accounted for 0.3% and MAC accounted for 3.7% of the entire cohort of colorectal adenocarcinomas. Compared to AC, SRC and MAC more frequently presented at a younger age, were located in the proximal colon, and exhibited a higher grade. The incidence of lymph node metastasis in AC, MAC, and SRC was 5.8%, 10.8%, and 15.3%, respectively. Patients with SRC were associated with a worse prognosis, regardless of the tumor location. Patients with MAC of the rectum, but not the colon, were associated with a reduced implication of prognosis. After adjusting for other clinicopathological factors, SRC and MAC of the rectum were independently associated with a high risk of death (HR 2.70, CI 1.77-4.12 and HR 1.65, CI 1.38-1.98 for SRC and MAC, respectively). Histology was not found to be an independent prognostic factor in patients with colon cancer. Conclusions: MAC and SRC are two distinct subtypes of colorectal cancer that require special attention despite their relatively rare prevalence. T1 patients with SRC and patients with MAC of the rectum have higher incidences of lymph node metastasis (LNM), and with these adverse outcomes, local excision is not recommended. Although MAC of the colon has a high rate of LNM, the prognosis of this type is similar to that of AC.
Phase (P) I study of PF-00299804 (PF) combined with figitumumab (FI; CP-751,871) in patients (pts) with advanced solid tumors (ASTs).
Authors: E. Calvo, W. Ma, A. W. Tolcher, M. Hidalgo, J. Soria, R. Bahleda, A. Gualberto, L. J. Denis, R. D. Millham, A. A. Adjei
Journal: Journal of Clinical Oncology (2010)

3026 Background: Cross-talk between human epidermal growth factor receptor (HER) and insulin-like growth factor type I receptor (IGF-IR) signaling pathways involved in cell growth and survival has a role in resistance to antitumor therapies. Preclinical data suggest dual inhibition will be more effective than blocking either pathway alone; but combining targeted agents may exacerbate adverse events (AEs). This P1, multicenter, open- label, dose-finding trial is the first to combine PF, an oral, irreversible, small molecule inhibitor of HER1, -2, and -4 tyrosine kinases, with the IGF-IR inhibitor FI for pts with ASTs. Methods: Pts received intravenous FI once every 3 weeks + oral PF once daily, starting with PF 30 mg + FI 20 mg/kg. Endpoints included safety and recommended P2 dose (RP2D; both primary) and response. Results: 47 (of 64 planned) pts received PF (10–30 mg) + FI (10–20 mg/kg). Dose-limiting toxicities occurred at doses of PF 30 mg + FI 20 mg/kg (grade [G] 3 mucositis, n=3; G3 diarrhea, n=1) and PF 20 mg + FI 20 mg/kg (n=2: G2 intolerable mucositis). Dose regimens tolerated for multiple cycles included PF 10 mg + FI 20 mg/kg and PF 15 mg + FI 20 mg/kg; these two were identified as potential RP2Ds and two pt cohorts expanded (ASTs or advanced non-small cell lung cancer) and given PF + FI at these dose levels. Most AEs were G1/2, but AEs previously associated with PF appeared to be exacerbated and accelerated in patients receiving PF + FI. Common treatment-related AEs (TRAEs) were diarrhea (57%), dry skin (46%), mucosal inflammation (41%), and rash (39%). At doses of PF 20–30 mg + FI 10–20 mg/kg, a total of three pts discontinued due to TRAEs (G3 and 4 stomatitis; G3 urosepsis). AEs (mainly fatigue and diarrhea) led to dose reductions/interruptions in 11 pts. Clinical benefit was observed in 8/42 evaluable pts, with 2 partial responses (ovarian, salivary carcinoma). Full safety and efficacy data will be reported. Conclusions: PF + FI combination therapy is feasible with careful pt monitoring and has potential to provide clinical benefit. Two expansion cohorts are enrolling to confirm a maximum tolerated dose, further evaluate the safety, efficacy, and pharmacokinetics of PF + FI, and assess tumor mutations. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Chemotherapy Foundation, Pfizer Ardea Biosciences, Lilly, Pfizer
Assessing cytomegalovirus (CMV) specific immune recovery after reduced intensity conditioning allogeneic stem cell transplantation with monoclonal antibody (Alemtuzumab)
Authors: R. Lamba, D. G. Myers, U. Popat, C. M. Bollard, G. Carrum, R. Krance, H. E. Heslop, M. K. Brenner
Journal: Journal of Clinical Oncology (2005)

6650 Alemtuzumab appears to be of promise when incorporated as a lymphocyte-depleting agent in reduced intensity conditioning (RIC) stem cell transplants (SCT). However, there is a high incidence of CMV infection following Alemtuzumab based RIC, and the severity of post transplant immunosuppression produced by this antibody has not yet been well characterized. We studied the kinetics, pattern, and magnitude of CMV specific CD8 + T cells (CMV CTLs) reconstitution to ascertain the need for immune intervention. Thirty-eight patients underwent SCT with a RIC regimen (Fludarabine 120mg/m2, TBI 450 cGy, Alemtuzumab 40mg). The cumulative incidence of CMV infection at 1 year post-transplant was 60% (95% CI, 45%–78%) and early infection was common (median time to infection, 24 days range, 5- 95 days). Recovery of CMV specific CTLs was serially monitored in 13 patients, using assays with HLA A*2- NLVPMVATV and HLA B*7-TPRVTGGGAM tetramers. Analysis showed that 11/13 patients reconstituted CMV CTLs. One patient died early and one developed graft failure. In 7/11 patients, CMV CTLs appeared by 30 days after transplant, and in 10/11 patients by day 90. Average CMV CTLs detected at day 30 was 5.9% (95% C.I, 0–13%) and at day 90 was 7% (95% C.I, 0–17.5%). Strikingly, 5 of 6 patients developed rise in CMV CTLs with CMV infection. Mean CMV CTLs detected prior to CMV infection was 1.4% (95% C.I, 0–3.6%) compared to 7.3% (95% C.I, 0–23%) following infection, representing a mean 5.2 fold rise. Of the 11 patients who reconstituted CMV CTLs, only one developed CMV disease and CMV CTLs were first detected at 10 months. We conclude that there is high incidence of early CMV infection following Alemtuzumab/RIC stem cell transplant, commensurate with the early immune suppression produced by the post-transplant persistence of the antibody. However, CMV specific immune recovery in most patients occurred rapidly, and was accelerated in response to increase in viral load. Thus, immune intervention will only be required in the minority of patients in whom recovery of viral specific immunity is delayed. Monitoring CMV tetramer positive cells may help identify this vulnerable subgroup. No significant financial relationships to disclose.
Capecitabine and oxaliplatin as induction and concomitant with radiotherapy in rectal cancer: A phase II study.
Authors: J. A. Gutierrez, G. Martinez-Martinez, A. J. Silva, J. Gomez Rangel, M. Palmerin, M. Gutierrez, B. Garcia
Journal: Journal of Clinical Oncology (2011)

604 Background: Preoperative combined modality chemoradiation with fluoropyrimidine-based schedules is widely accepted as the current standard of care for localized rectal cancer. Current strategies have focused on intensifying the neoadjuvant systemic treatment to improve pCR. Methods: From January 2009 to January 2010, 18 patients with locally advanced rectal cancer (T3, any N, M0) were included according to Simon's design. Treatment was 2 cycles of capecitabine 1000 mg/m 2 bid (D1-14) and oxaliplatin 85 mg/m 2 (D1) every 3 weeks as induction followed by chemoradiation (45 Gy). During radiotherapy patients received 2 cycles of capecitabine 750 mg/m 2 bid (D1-14) and oxaliplatin 85 mg/m 2 (D1 and 8) every 3 weeks. Surgery was planned 5-10 weeks after completion of radiotherapy. The primary endpoint was pCR. Results: 18 patients were assessable for response. Median age was 55 y (41-65), 11 patients with ECOG performance status of 1 (61%), all 18 patients were staged as T3, 10 were staged N+ (56%). Of the 18 patients, 17 patients were given CRT and 13 patients (76%) underwent radical resection. Of the patients who did not underwent resection, 1 patient was considered unresectable at the time of surgery, 2 patients refused surgery because of clinical complete response and 1 patient experienced progressive disease to the spine after chemoradiation. During induction treatment 1 patient (6%) experienced grade 3-4 toxicity (diarrhea). During chemoradiation 1 patient (6%) experienced grade 3 diarrhea and nausea and 1 patient (6%) experienced grade 3 radio-induced dermatologic toxicity; overall grade 3-4 toxicity of 12%. No grade 4 toxicity or treatment related deaths were observed. Of the 13 patients who underwent resection, 12 patients (92%) had a complete resection (R0). Pathologic complete response rate was observed in 1 patient (6%) according to intent to treat. The study was closed after the first stage because it did not reach the minimum required number of pCR. Conclusions: Induction chemotherapy with capecitabine and oxaliplatin before chemoradiation is feasible. Given that we did not reach the prespecified pCR rate required to continue the trial, the study was closed after the first stage. No significant financial relationships to disclose.
Co-Treatment with JAK2 Inhibitor TG101209 and Panobinostat or hsp90 Inhibitor AUY922 Attenuates Mutant JAK2-V617F Levels and Activity in Human Myeloproliferative Disorder Cells
Authors: Yongchao Wang, Warren Fiskus, Kavita Natarajan, Anand Jillella, Cornelia Quadt, Peter Ataja, Ross Levine, Kapil N. Bhalla
Journal: Blood (2008)
A phase I/II, nonrandomized, feasibility/safety and efficacy study of the combination of everolimus, cetuximab, and capecitabine in patients with metastatic pancreatic cancer.
Authors: J. Wilmink, S. Kordes, H. Klumpen, D. Richel
Journal: Journal of Clinical Oncology (2011)

e14666 Background: Despite significant changes during the last decade in our molecular knowledge on pancreatic cancer, the prognosis and management of this disease has remained unchanged. Several phase III studies have demonstrated that TKI (erlotinib) and MoAb (cetuximab) mediated inhibition of EGFR in combination with chemotherapy have limited or no activity in pancreatic cancer. Because cross talk between EGFR/MAPK and PI3K pathways is a potential mechanism of resistance we explored the activity of multiple pathway inhibition by simultaneous inhibition of both EGFR and mTOR in combination with capecitabine. Methods: Patients with metastatic pancreatic cancer were first studied to determine the dose limiting toxicity (DLT) and the maximal tolerated dose (MTD) at a fixed dose of weekly cetuximab, whereas the dose of both capecitabine and everolimus were escalated in 2 dose levels, 600 mg/m2 and 800 mg/m2 bid for 2 weeks every 3 weeks and 5 and 10 mg daily continuously, respectively. At the MTD 23 additional patients were included to determine the efficacy of the combination. Results: Eighteen patients were treated in the phase I part with 2 different dose levels. Rash and mucositis were the DLT. On the basis of the observed DLT and overall safety, dose level 1: everolimus 5 mg daily continuously, capecitabine 600 mg/m2 bid for 2 weeks every 3 weeks and cetuximab 400mg/m2 first dose, thereafter 250 mg/m2 weekly, was recommended for further development. Among the 23 patients (9 received prior chemotherapy, 4 for metastatic disease) enrolled in the phase II part, 15 completed 3 cycles of treatment and could be evaluated according to protocol. Of these 15 patients there was 1 partial response and 4 patients with stable disease, of who 2 have disease stabilisation lasting more than 1 year. Most occurring grade 3 toxicities were rash (21%) and fatigue (21%). Conclusions: The combination of everolimus 5 mg daily continuously, capecitabine 600 mg/m2 bid for 2 weeks every 3 weeks and cetuximab 400mg/m2 first dose, thereafter 250 mg/m2 weekly is well tolerated, but the combination did not improve efficacy over what would be expected from chemotherapy alone.
Updated results of a randomized trial of 2 versus 5 years of adjuvant tamoxifen for women aged 50 years or older with early breast cancer: Italian Interdisciplinary Group for Cancer Care Evaluation study of adjuvant treatment in breast cancer 01 (SITAM 01)
Authors: M. Valentini, M. Belfiglio, F. Pellegrini, M. Sacco, A. Nicolucci
Journal: Journal of Clinical Oncology (2005)

528 Background: The study results in terms of disease-free survival (DFS) were already published (J Clin Oncol, 2003;21:2276–81). This is an update of the data relative to overall survival (OS) after 10 years of follow up. Methods: Women with breast carcinoma T1–3, N0–3, M0, aged between 50 and 70 years, were eligible for this multicentre randomized phase III trial. Patients event-free after 2 years of tamoxifen therapy (TAM) were randomly assigned to stop or continue TAM (20 mg/die) for additional 3 years. Primary end point was DFS. Secondary end points included OS and toxicity. A number of events of 514 was needed to detect a difference of 25% (log-rank test, P <.05) between the two treatment arms (1 - β = 0.90). Results: From 1989 through 1996, 1,901 patients were randomly assigned either to stop treatment (n = 958) or to receive TAM for 3 additional years (n = 943). Overall, 98% of patients had updated information about OS, of whom 549 had died. The median duration of postrandomization follow-up was 115 months (interquartile range 86–137). No statistically significant differences between the two arms was detected in the whole population (HR, 1.02; 95% CI, 0.86 to 1.22) as well as in ER-positive patients (HR, 0.90; 95% CI, 0.72 to 1.13). In the latter group, survival curves started to diverge only after 90 months, showing a trend in favor of the 5-year arm. The benefit of longer TAM was evident only in younger (age ≤ 55 yrs) ER-positive patients (HR, 0.56; 95% CI, 0.31 to 1.01), but not in older ones (HR, 0.98; 95% CI, 0.77 to 1.25). Conclusions: The benefits of longer TAM on OS start to emerge only after 9 years from diagnosis and seem to be more relevant in younger ER-positive women. No significant financial relationships to disclose.