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1.
Erin J. Song Jordan Torok Yuan Wu Junzo Chino Leonard R. Prosnitz Anne W. Beaven Chris R. Kelsey 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(2):145-151
Introduction
The purpose of this study was to evaluate the role of consolidation radiation therapy (RT) in advanced Hodgkin lymphoma (HL) in the setting of a complete metabolic response (CR) to chemotherapy (ChT).Patients and Methods
Patients with stage III/IV HL treated with ChT alone or combined modality therapy (CMT) between 1992 and 2012 were reviewed. Only patients in a CR according to positron emission tomography-computed tomography (PET-CT) or gallium imaging were included. Clinical end points were estimated using the Kaplan–Meier method and a multivariate analysis using the Cox proportional hazards model was performed.Results
Ninety patients were identified (46 CMT; 44 ChT alone). Median follow-up was 50 months. ChT (median 6 cycles) consisted primarily of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine; 74%) or an ABVD hybrid (10%). Post-ChT imaging consisted of PET-CT (71%) or gallium (29%). RT plans primarily included all initially involved sites of disease with a median dose of 21 Gy (range, 13-31 Gy). CMT was associated with improved 5-year progression-free survival (PFS; 88% vs. 65%, respectively; P < .001) and overall survival (97% vs. 78%, respectively; P = .002) compared with ChT alone. In multivariate analysis, age younger than 45 years (hazard ratio [HR], 0.23; 95% confidence interval [CI], 0.07-0.74; P = .013) and CMT (HR, 0.32; 95% CI, 0.11-0.96; P = .04) were independently associated with improved PFS. Secondary malignancies were comparable in both cohorts (5 with CMT, 4 with ChT), whereas cardiac events were slightly more frequent with CMT (5 vs. 2).Conclusion
Low-dose RT, administered to all sites of original involvement, was associated with improved PFS, even in the setting of a metabolic CR after ABVD. 相似文献2.
Brendan G. Coutu Christopher T. Wilke Jianling Yuan Qing Cao Matthew R. Vernon Chung Lee Veronika Bachanova Kathryn E. Dusenbery 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(1):65-73
Introduction
We evaluated the role of consolidative radiotherapy (RT) for patients undergoing high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) for relapsed or refractory diffuse large B-cell lymphoma (DLBCL).Materials and Methods
We reviewed the medical records of 72 consecutive patients who had undergone ASCT for relapsed or refractory DLBCL at our institution from 2006 to 2014. Pretransplant conditioning consisted of HDC and total body irradiation. Of the 72 patients, 13 received post-transplant consolidative RT at the discretion of the consulted radiation oncologist.Results
Consolidative RT was associated with significantly improved 2-year locoregional control (LRC) (92% vs. 68%; P = .04). However, no difference was seen in either the 2-year progression-free survival (PFS) (69% vs. 54%; P = .25) or overall survival (OS) (85% vs. 59%; P = .44). Analysis of the subgroup of 19 patients with persistent residual masses ≥ 2 cm on post-transplant imaging demonstrated a significant improvement in LRC (100% vs. 36%; P < .01), PFS (88% vs. 27%; P = .01), and OS (100% vs. 45%; P = .02) with consolidative RT.Conclusion
The use of consolidative RT after HDC and ASCT for relapsed or refractory DLBCL appears to significantly improve LRC. For patients with masses ≥ 2 cm after ASCT, improved 2-year PFS and OS were seen. Prospective trials are needed to further identify the patients who would derive the most benefit from consolidative RT in the ASCT setting. 相似文献3.
Khurum Khan Jayant K. Rane David Cunningham Sheela Rao David Watkins Naureen Starling Eleftheria Kalaitzaki Martin Forster Chiara Braconi Nicola Valeri Marco Gerlinger Ian Chau 《Clinical colorectal cancer》2019,18(1):64-71.e1
Background
Gastrointestinal (GI) cancer patients may not be considered for therapy with fluoropyrimidines (FPs) because of previous cardiovascular (CV) toxicity or preexisting risk factors; such patients may benefit from raltitrexed-based therapy.Patients and Methods
Patient, tumor, and treatment characteristics, as well as clinical outcomes of all consecutively treated patients with raltitrexed at the Royal Marsden Hospital between October 1998 and July 2011 were examined. GI cancer patients who developed CV toxicity as a result of FPs and those with significant CV risk factors receiving raltitrexed were included in this analysis.Results
A total of 247 patients (155 and 92 with CV FP-related CV toxicities and significant CV risk factors, respectively) treated with raltitrexed alone or in combination were examined after a median follow-up of 47.1 months. CV toxicity profiles of patients receiving capecitabine (n = 110) and 5-fluorouracil (n = 45) were largely similar. Of raltitrexed-treated patients, 13 (5%) experienced CV toxicities and 1 (< 0.1%) died as a result of myocardial infarction. The median progression-free survival (PFS) and overall survival (OS) were 36.0 months (95% confidence interval [CI], 26.5-48.6) and 44.3 months (95% CI, 33.1-56.8), respectively. The 5-year survival for early stage GI malignancies (n = 140) was 62.0% (95% CI, 50.1-71.9). Median PFS and OS were not reached in this group (interquartile range = 38.4 months to NR); median PFS and OS for advanced GI malignancies (n = 107) were 18.8 (95% CI, 11.9-25.7) and 23.7 months (95% CI, 17.0-26.9), respectively.Conclusion
A raltitrexed-based regimen is well-tolerated therapy with comparable efficacy to FPs in patients with GI malignancies with significant CV toxicities or risk factors. 相似文献4.
Kimberly L. Blackwell Khalil Zaman Shukui Qin Katherine H.R. Tkaczuk Mario Campone Daniel Hunt Richard Bryce Lori J. Goldstein 《Clinical breast cancer》2019,19(2):97-104.e4
Background
Despite the availability of several human epidermal growth factor receptor 2 (HER2)-directed treatments, many HER2-positive (HER2+) breast cancers eventually progress because of primary or acquired resistance.Patients and Methods
A 2-part, open-label, multicenter phase I/II study was conducted to determine the recommended dose of neratinib when administered with trastuzumab (part I), and to assess the antitumor activity of this combination in women with locally advanced or metastatic HER2+ breast cancer previously treated with at least 1 prior trastuzumab-based regimen (part II). Patients received oral neratinib (160 or 240 mg/d) once daily plus intravenous trastuzumab 4 mg/kg (loading dose) then 2 mg/kg weekly. Diarrhea prophylaxis was not permitted. The primary endpoint in part II was investigator-assessed 16-week progression-free survival (PFS).Results
Forty-five patients received neratinib plus trastuzumab (part I: neratinib 160 mg/d, n = 4; neratinib 240 mg/d, n = 4; part II: neratinib 240 mg/d, n = 37). In part I, there were no dose-limiting toxicities and the recommended neratinib dose was 240 mg/d. In part II, the 16-week PFS rate was 44.8% (90% confidence interval, 28.8%-59.6%), and the median PFS was 15.9 weeks (95% confidence interval, 15.1-31.3 weeks) in 28 evaluable patients. Three patients had durable clinical benefit lasting 9.4 to 9.7 years. Diarrhea was the most common adverse event (grade 3, n = 7 [15.6%]; grade 4, n = 0). No clinically significant cardiac toxicity was seen.Conclusions
Neratinib in combination with trastuzumab was well-tolerated and had encouraging antitumor activity in patients with advanced trastuzumab-pretreated HER2+ breast cancer. Durable responses can be achieved in some patients. 相似文献5.
Kevin H. Hall Kelly Valla Christopher R. Flowers Jonathon B. Cohen 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(2):89-94
Introduction
Intrathecal chemoprophylaxis is often administered to patients with diffuse large B-cell lymphoma (DLBCL) to lower the rates of central nervous system (CNS) relapse, although its benefit has not been well-described. Prognostic models, including the CNS-International Prognostic Index (IPI), have been developed to aid in identifying patients at highest risk for CNS relapse.Patients and Methods
We evaluated 112 patients diagnosed with DLBCL from 2009 to 2016 at Emory Healthcare and classified them as high (n = 44) or low risk (n = 68) for CNS relapse and compared CNS prophylaxis rates and relapse rates between groups. The primary outcome was to compare the CNS relapse rate in high-risk patients who received intrathecal prophylaxis with patients who did not.Results
Twenty-six patients (14 high-risk and 12 low-risk) received intrathecal prophylaxis. Only 4 of 112 patients experienced a CNS relapse, including 1 in the high-risk group and 3 in the low-risk group. Among 14 high-risk patients who received intrathecal prophylaxis, no patient experienced CNS relapse compared with 1 of 30 high-risk patients without prophylaxis (P = 1.0).Conclusion
Given the low rates of CNS relapse in this series, it is difficult to discern the impact of current risk stratification combined with intrathecal prophylaxis on outcomes. Our observation that many high-risk patients did not receive prophylaxis, whereas many low-risk patients received prophylaxis emphasizes the need for a standardized approach. 相似文献6.
Øystein Fluge Bård Mannsåker Anders Torp Ingvil Mjaaland Lars Helgeland Jan Klos Olav Mella Sigbjørn Berentsen Peter Meyer 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(2):125-135.e3
Background
The role of consolidative radiotherapy (RT) in advanced diffuse large B-cell lymphoma (DLBCL) is not established.Patients and Methods
In a population-based retrospective analysis of patients with DLBCL in Western Norway during 2003 to 2008, 170 consecutive patients admitted to Haukeland University Hospital (HUS) and 94 to Stavanger University Hospital (SUS) were included. The mean age was 64 years (range, 17-95 years), 147 patients (56%) were male, 80 patients (30%) had stage I/II, 126 patients (48%) stage III/IV, and 57 patients (22%) had primary extranodal disease.Results
There were no differences between hospitals in patient characteristics, use of rituximab, number of chemotherapy courses or cumulative doses, or in distribution of response categories after chemotherapy. The use of RT was significantly different: 17 patients (23%) received RT at SUS and 92 patients (65%) at HUS (P < .001). For 219 patients with International Prognostic Index (IPI) score of 0 to 3, 5-year cancer-specific survival (CSS) was 67% at SUS and 81% at HUS (P = .012). For 73 patients with complete response after chemotherapy there were no differences in survival between patients with and without RT. For 138 patients with any residual mass after chemotherapy, there were highly significant differences in favor of receiving RT (n = 81) versus no RT (n = 57): 5-year CSS 89% versus 69% (P < .001), and 5-year overall survival 82% versus 59% (P = .005). The effect of RT on residual mass was evident in most subgroups, mainly in low to intermediate risk, but not in high-risk (IPI 4-5) patients.Conclusion
With the limitations of a retrospective study, these data suggest that consolidative RT might improve survival in DLBCL patients with a residual mass after chemotherapy, also in advanced disease. 相似文献7.
AnnaLynn M. Williams Andrea M. Baran Carla Casulo Patrick Reagan Jonathan W. Friedberg Margaret Helber Jeremiah Moore Elizabeth Baloga Clive S. Zent Paul M. Barr 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(1):41-47
Background
As oral targeted agents, such as ibrutinib, become more widely used, understanding the impact of suboptimal dosing on overall survival (OS) and progression-free survival (PFS) outside of clinical trials is imperative.Patients and Methods
Data on ibrutinib discontinuation, dose reductions, and treatment interruptions were collected on 170 non-Hodgkin lymphoma and chronic lymphocytic leukemia (CLL; n = 115, 64%) patients treated with ibrutinib at a single institution. Ibrutinib dose adherence was calculated as the proportion of days in which ibrutinib was administered out of the total number of days ibrutinib was prescribed in the first 8 weeks. Kaplan-Meier curves and log-rank tests were used to compare conditional survival outcomes beyond 8 weeks in patients with ≥ 80% dose adherence and patients with < 80% dose adherence.Results
Median OS among those who discontinued therapy for progression was poor (n = 51, 1.7 months; 95% confidence interval, 0.3-3.7). Lower dose adherence (< 80%) was associated with significantly worse PFS (P = .002) and OS (P = .021). However, among CLL patients, lower dose adherence was only associated with worse PFS (P = .043). Patients with early dose reductions had significantly worse PFS (P = .004) and OS (P = .014). Patients with dose interruptions lasting > 1 week had worse PFS (P = .047) but not OS (P = .577).Conclusion
In this observational study, non-Hodgkin lymphoma and CLL patients experienced poor outcomes after discontinuing ibrutinib for disease progression. The inferior survival related to suboptimal dose adherence of ibrutinib was predominantly due to early dose reduction. These data confirm poor survival in CLL and lymphoma patients alike after ibrutinib discontinuation, and support recommendations for full dose at treatment initiation. 相似文献8.
Rami S. Komrokji Sheng Wei Adam W. Mailloux Ling Zhang Eric Padron David Sallman Jeffrey E. Lancet Sara Tinsley Lisa A. Nardelli Javier Pinilla-Ibarz Pearlie K. Epling-Burnette Alan F. List 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(3):157-161
Background
INCB024360 is an oral inhibitor of the enzyme indoleamine 2,3-dioxygenase (IDO), which catalyzes the degradation of tryptophan to kynurenine. Preclinical data suggest that IDO1 inhibition by INCB024360 will increase T cell proliferation, and decrease T regulatory cells and myeloid derived suppressor cells suppressive activity. We conducted a phase II study to explore activity and pharmacodynamics of INCB024360 in patients with myelodysplastic syndromes.Patients and Methods
All patients were treated with INCB024360 600 mg orally twice a day for at least 16 weeks. Fifteen patients were enrolled. The median age was 72 years. The International Prognostic Scoring System risk was low in 27% (n = 4), intermediate-1 in 47% (n = 7), and intermediate-2 in 27% (n = 4). All patients had prior azacitidine.Results
The best response was stable disease in 12 (80%) patients and progressive disease in 3 (20%) patients. The treatment was relatively well-tolerated. One patient developed hypothyroidism and adrenal insufficiency (grade 2), and 1 patient had low testosterone level. The mean IDO expression was 39% at baseline and 26% after treatment (n = 9; P = .4). The mean burst forming unit-erythroid changed from 72 to 191 colonies/106 (n = 5; P = .036), and the mean colony forming unit-granulocye, monocyte from 62 to 180 colonies/106 (n = 6; P = .5). The mean myeloid derived suppressor cell % (CD33Lin-HLA cells) was 29.5% at baseline compared with 27.6% after treatment (n = 9; P = .7). The mean T-regulatory effector memory cell % changed from 9.6% at screening to 7.4% at end of treatment (n = 14; P = .8). The mean kynurenine/tryptophan ratio decreased from 45 at baseline to 26 (42% reduction) at cycle 2, day 1 (P < .005).Conclusion
Future directions may include testing INCB024360 early in the course of the disease. 相似文献9.
Rick L. Haas Suzanne van Beek Anja Betgen Shaheen Ali Christoph J. Schneider Fenna Heres Diddens Astrid N. Scholten Folkert Koetsveld Peter Remeijer 《Practical radiation oncology》2019,9(2):115-122
Purpose
Many authors suggest that extremity soft tissue sarcomas (ESTS) do not change significantly in size during preoperative radiation therapy (RT). This cone beam computed tomography study investigates the justification to deliver the entire course with 1 initial RT plan by observing anatomic changes during RT.Methods and Materials
Between 2015 and 2017, 99 patients with ESTS were treated with either curative (n = 80) or palliative intent (n = 19) with a regimen of at least 6 fractions. The clinical target volume to planning target volume margin was 1 cm. Action levels were assigned by radiation technicians. An extremity contour change of >1 cm and/or tumor size change >0.5 cm required a physician's action before the next fraction.Results
A total of 982 cone beam computed tomography logfiles were studied. In 41 of 99 patients, the dose coverage of the initial treatment plan was fully satisfactory throughout the RT course. However, action levels were observed in 58 patients (59%). In 41 of these 58 patients, a contour increase of 5 to 23 mm was noted (29 tumor size increase only, 3 extremity contour increase, and 9 both). In 21 of 58 patients, a decrease of 5 to 33 mm was observed (20 tumor size decrease only and 1 tumor size decrease and extremity contour decrease). In 4 cases, contours initially increased and subsequently decreased. In 33 of 41 patients with increasing contours, the dose distribution adequately covered gross tumor volume because of the 1 cm planning target volume margin applied. For the remaining 8 patients (8%), the plan needed to be adapted.Conclusions
ESTS volumes may change substantially during RT in 59% of all patients, leading to plan adaptations resulting from increased volumes in 8%. Daily critical observation of these patients is mandatory to avoid geographic misses because of increases in size and overdosing of normal tissues when masses shrink. 相似文献10.
Brian I. Rini Thomas E. Hutson Robert A. Figlin Maria Josè Lechuga Olga Valota Lucile Serfass Brad Rosbrook Robert J. Motzer 《Clinical genitourinary cancer》2018,16(4):298-304
Background
Sunitinib malate, a targeted tyrosine kinase inhibitor, is standard of care for metastatic renal cell carcinoma (mRCC) and serves as the active comparator in several ongoing mRCC clinical trials. In this analysis we report benchmarks for clinical outcomes on the basis of International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups for patients treated with sunitinib for mRCC in a first-line setting.Materials and Methods
A retrospective analysis was performed on data from sunitinib-treated patients (n = 375) in the pivotal phase III trial of sunitinib versus interferon-α as first-line treatment for mRCC. Objective response rates (ORRs) were determined from independently reviewed radiologic assessments. The Kaplan–Meier method was used to estimate median progression-free survival (PFS) and median overall survival (OS) according to patient risk group.Results
Median PFS (95% confidence interval [CI]) was 14.1 (13.4-17.1), 10.7 (10.5-12.5), 2.4 (1.1-4.7), and 10.6 (8.1-10.9) months in sunitinib-treated patients in the IMDC favorable (n = 134), intermediate (n = 205), poor (n = 34), and intermediate + poor (n = 239) risk groups, respectively. Median OS (95% CI) was 23.0 (19.8-27.8), 5.1 (4.3-9.9), and 20.3 (16.8-23.0) months in sunitinib-treated patients in IMDC intermediate, poor, and intermediate + poor risk groups, respectively, and was not reached in the favorable risk group (>50% of patients were alive at data cutoff). ORRs (95% CI) was 53.0% (44.2%-61.7%), 33.7% (27.2%-40.6%), 11.8% (3.3%-27.5%), and 30.5% (24.8%-36.8%) in sunitinib-treated patients in IMDC favorable, intermediate, poor, and intermediate + poor risk groups, respectively.Conclusion
Results of this retrospective analysis show differences in patient outcomes for PFS, OS, and ORR on the basis of IMDC prognostic risk group assignment for patients with mRCC. 相似文献11.
Daichi Fujimoto Hiroshige Yoshioka Yuki Kataoka Takeshi Morimoto Tae Hata Young Hak Kim Keisuke Tomii Tadashi Ishida Masataka Hirabayashi Satoshi Hara Manabu Ishitoko Yasushi Fukuda Moon Hee Hwang Naoki Sakai Motonari Fukui Hitoshi Nakaji Mitsunori Morita Tadashi Mio Toyohiro Hirai 《Journal of thoracic oncology》2019,14(3):468-474
Introduction
Nivolumab is effective in the treatment of previously treated patients with advanced NSCLC. However, its radiological evaluation is challenging because of atypical patterns of response such as pseudoprogression. We examined the characteristics and outcomes of previously treated patients with NSCLC who were treated with nivolumab and experienced development of pseudoprogression.Methods
We conducted a 15-center retrospective cohort study of previously treated patients with advanced NSCLC who received nivolumab monotherapy. For the patients who showed pseudoprogression, we defined progression-free survival 1 (PFS1) as the time to Response Evaluation Criteria in Solid Tumors–defined first progressive disease and progression-free survival 2 (PFS2) as the time to Response Evaluation Criteria in Solid Tumors–defined second progressive disease or death.Results
Among the 542 patients included, 20% and 53% showed a typical response and progression, respectively. Of the 14 (3%) patients who showed pseudoprogression, most (n = 10) showed a response within 3 months of nivolumab treatment. The median PFS1 and PFS2 were 1.0 and 7.3 months, respectively. The median PFS2 was significantly shorter in the patients who showed pseudoprogression than the PFS of the patients with a typical response (p < 0.001). In contrast, patients showing pseudoprogression had significantly longer overall survival than did patients showing typical progression (p = 0.001).Conclusions
Pseudoprogression was uncommon, and the duration of response in patients who showed pseudoprogression was shorter than that in patients who showed a typical response. However, the survival benefit of pseudoprogression was markedly better than that of typical progression. Further research is required to elucidate the characteristics of and mechanisms underlying pseudoprogression. 相似文献12.
Yoshimasa Miyagawa Kazuhiro Araki Ayako Bun Hiromi Ozawa Yukie Fujimoto Tomoko Higuchi Arisa Nishimukai Ayako Kira Michiko Imamura Yuichi Takatsuka Yasuo Miyoshi 《Clinical breast cancer》2018,18(5):400-409
Introduction
Although eribulin and nab-paclitaxel are chemotherapy agents widely used for locally advanced or metastatic breast cancer (MBC), their predictive factors remain unknown. Because the absolute neutrophil-to-lymphocyte ratio (NLR) is a significant prognostic factor for early-stage breast cancer, we investigated its usefulness in terms of the eribulin or nab-paclitaxel treatment efficacy for MBC.Patients and Methods
A total of 85 patients with MBC treated with eribulin (n = 59) or nab-paclitaxel (n = 26) were recruited. NLR values were collected at baseline, after 1 cycle, after 2 cycles, and at the end of treatment. The NLR cutoff value was set at 3.Results
The progression-free survival (PFS) of patients with an NLR < 3 at baseline (median, 242 days; n = 24) was significantly better than that of patients with an NLR of ≥ 3 (median, 98 days; n = 35; hazard ratio, 0.37, 95% confidence interval, 0.18-0.71; P = .0032). Similarly, the overall survival was marginally significantly better in patients with an NLR < 3 who were treated with eribulin (P = .058). However, the NLR was not significantly associated with PFS or overall survival for patients treated with nab-paclitaxel. No significant association was found between the NLR during treatment and PFS in the eribulin group. The significance of the NLR for the efficacy of eribulin was consistent, irrespective of estrogen receptor status, previous anthracycline or endocrine use, and the number of previous chemotherapy regimens.Conclusion
A low NLR at baseline was significantly associated with improved PFS in patients treated with eribulin but not in those treated with nab-paclitaxel. Therefore, the baseline NLR might be clinically useful for selecting patients who would benefit from eribulin. 相似文献13.
Peter A. Kaufman Hans Wildiers Gilles Freyer Margaret Kemeny Anthony Gonçalves Guy Jerusalem Alison Stopeck Nandagopal Vrindavanam Florence Dalenc Nuwan Nanayakkara Benjamin Wu Cheryl A. Pickett 《Clinical breast cancer》2019,19(1):47-57
Introduction
Trebananib, a peptide-Fc fusion protein, blocks angiogenesis by inhibiting binding of angiopoietin-1/2 to the receptor tyrosine kinase Tie2. Trebananib plus trastuzumab and paclitaxel was evaluated in human epidermal growth factor receptor 2–positive breast cancer in an open-label phase 1b clinical study.Patients and Methods
Women with human epidermal growth factor receptor 2–positive breast cancer received weekly paclitaxel (80 mg/m2), trastuzumab (8 mg/m2 then 6 mg/kg every 3 weeks), and intravenous trebananib (10 mg/kg or 30 mg/kg weekly) beginning week 2. The primary end point was the incidence of dose-limiting toxicities. Secondary end points included incidence of adverse events (AEs), pharmacokinetics, and tumor response (objective response and duration of response).Results
Forty women were enrolled; 2 experienced dose-limiting toxicities (grade 3 ocular transient ischemic attack [10 mg/kg cohort] and grade 3 elevation in γ-glutamyl transferase [30 mg/kg cohort]). The most common treatment-emergent AEs were peripheral edema (n = 28), diarrhea (n = 27), alopecia (n = 26), fatigue (n = 24), and nausea (n = 24). Maximum observed concentration and area under the concentration–time curve increased proportionally with the trebananib dose. Objective response was confirmed in 31 patients. In the 10 mg/kg cohort, 16 patients (80%) experienced partial response, and none experienced complete response. In the 30 mg/kg cohort, 12 patients (71%) experienced partial response and 3 (18%) experienced complete response. Median (95% confidence interval) duration of response in the 10 and 30 mg/kg cohorts was 12.6 (4.3-20.2) and 16.6 (8.2-not estimable) months, respectively.Conclusion
This phase 1b study showed that trebananib was tolerated with manageable AEs at a dose up to 30 mg/kg weekly. Trebananib demonstrated anticancer activity, as indicated by objective response and duration of response. 相似文献14.
Shinji Atagi Junki Mizusawa Satoshi Ishikura Toshiaki Takahashi Hiroaki Okamoto Hiroshi Tanaka Koichi Goto Kazuhiko Nakagawa Masao Harada Yuichiro Takeda Naoyuki Nogami Yuka Fujita Takashi Kasai Kazuma Kishi Toshiyuki Sawa Koji Takeda Keisuke Tomii Miyako Satouchi Yuichiro Ohe 《Clinical lung cancer》2018,19(5):e619-e627
Introduction
In the phase III JCOG0301 trial, chemoradiotherapy (CRT) with daily low-dose carboplatin showed significant benefits in elderly patients with locally advanced non–small-cell lung cancer (NSCLC) compared with radiotherapy (RT) alone. However, the long-term patterns and cumulative incidences of toxicity associated with CRT and RT in elderly patients are not well elucidated. We report long-term survival data and late toxicities after a minimum follow-up of 6.4 years.Patients and Methods
Eligible patients were older than 70 years and had unresectable stage III NSCLC. They were randomly assigned to RT or CRT. Prognosis and adverse events data were collected beyond those in the initial report. Late toxicities were defined as occurring more than 90 days after RT initiation.Results
From September 2003 to May 2010, 200 patients (RT arm, n = 100; CRT arm, n = 100) were enrolled. Consistent with the initial report, the CRT arm had better overall survival than the RT arm (hazard ratio, 0.743; 95% confidence interval, 0.552-0.998; 1-sided P = .0239). The proportion of Grade 3/4 late toxicities were 7.4% (heart 2.1%, lung 5.3%) in the RT arm (n = 94) and 7.5% (esophagus 1.1%, lung 6.5%) in the CRT arm (n = 93). No additional cases of late toxicity (Grade 3/4) and treatment-related death have been seen since the initial report that was published.Conclusion
Long-term follow-up confirmed the survival benefits of CRT for elderly patients with locally advanced NSCLC. There was no observed increase in late toxicity with CRT compared with RT alone. 相似文献15.
Hideaki Miyake Takayuki Sugiyama Ryota Aki Yuto Matsushita Keita Tamura Daisuke Motoyama Toshiki Ito Atsushi Otsuka 《Clinical genitourinary cancer》2018,16(3):219-225
Background
The objective of the present study was to assess the oncologic outcomes of patients receiving second-line therapy against metastatic castration-resistant prostate cancer (mCRPC).Patients and Methods
The present study included 222 consecutive mCRPC patients with progression during initial androgen receptor-axis-targeted agent (ARATA) therapy with either abiraterone acetate (AA) or enzalutamide (Enz). Of these 222 patients, 108 subsequently received an alternative ARATA (AA-to-Enz, n = 49; Enz-to-AA, n = 59) and 114 received docetaxel (DTX; AA-to-DTX, n = 54; Enz-to-DTX, n = 60).Results
The prostate-specific antigen (PSA) level in the 114 patients receiving DTX was significantly greater than that in the 108 patients receiving ARATA. However, no significant differences were found in the remaining parameters between the 2 groups. The PSA response rate, PSA progression-free survival (PFS), and overall survival (OS) during second-line therapy in the DTX group (n = 114) were significantly superior to those for the ARATA group (n = 108; PSA response rate, 42.1% vs. 21.3%; median PSA PFS, 7.2 vs. 4.2 months; median OS, 17.5 vs. 14.5 months). Similar trends were confirmed by comparing these outcomes among 4 therapy groups, with significant differences (PSA response rate, Enz-to-AA vs. AA-to-DTX and Enz-to-AA vs. Enz-to-DTX; PSA PFS, AA-to-Enz vs. Enz-to-AA, AA-to-Enz vs. AA-to-DTX, Enz-to-AA vs. AA-to-DTX, and Enz-to-AA vs. Enz-to-DTX; and OS, Enz-to-AA vs. AA-to-DTX and Enz-to-AA vs. Enz-to-DTX). Furthermore, the introduction of DTX was independently associated with improved PSA PFS, but not OS, on multivariate analysis.Conclusion
Favorable oncologic outcomes can be expected with DTX treatment, rather than with alternative ARATA, for mCRPC patients after failure of an initial ARATA. 相似文献16.
Tianhong Li Bilal Piperdi William V. Walsh Mimi Kim Laurel A. Beckett Rasim Gucalp Missak Haigentz Venu G. Bathini Huiyu Wen Kaili Zhou Patricia B. Pasquinelli Srikanth Gajavelli Meera Sreedhara Xianhong Xie Primo N. Lara David R. Gandara Roman Perez-Soler 《Clinical lung cancer》2017,18(1):60-67
Background
Pharmacodynamic separation of pemetrexed and erlotinib avoids negative cellular interactions and results in antitumor synergy in erlotinib-resistant non–small-cell lung cancer (NSCLC) cells, independent of EGFR (epidermal growth factor receptor) genotype.Patients and Methods
Patients with platinum-treated metastatic nonsquamous NSCLC were randomly assigned 1:2 to pemetrexed alone (500 mg/m2 provided intravenously on day 1) or pemetrexed followed by erlotinib (150 mg provided orally once daily on days 2-17) every 21 days. EGFR genotype was centrally confirmed by Sequenom multiplex oncogenotyping assay. The primary end point was progression-free survival (PFS), which would be considered promising for future study if median PFS was ≥ 4.5 months.Results
Of 83 patients enrolled, 79 were randomized to either pemetrexed alone (n = 27) or in combination (n = 52). Fifty-nine (79%) of 75 eligible patients had tumors with confirmed EGFR genotype: 7 with activating mutations and 52 wild type. Median PFS was 4.7 and 2.9 months in the combination and pemetrexed-alone groups, respectively. In patients with EGFR wild-type tumors, median PFS was 5.3 and 3.5 months in the combination and pemetrexed-alone groups, respectively. Objective response rate (29% vs. 10%, P = .17), 6-month PFS (45% vs. 29%, P = .26), and 12-month PFS (23% vs. 10%, P = .28) were all higher in the combination arm. Rash (67% vs. 26%, P = .0007) and diarrhea (44% vs. 11%, P = .003) were significantly more common in the combination arm.Conclusion
In patients with unselected or EGFR wild-type advanced nonsquamous NSCLC, pharmacodynamic separation of pemetrexed and intercalated erlotinib had promising antitumor activity without new safety concerns. The combination merits further evaluation as maintenance or second-line therapy against new standards in patients with EGFR wild-type advanced NSCLC. 相似文献17.
E. Merfeld P. Gabani M.B. Spraker I. Zoberi H. Kim B. Van Tine J. Chrisinger J.M. Michalski 《Clinical oncology (Royal College of Radiologists (Great Britain))》2019,31(4):232-241
Aims
Angiosarcoma is a rare and aggressive malignancy with a poor prognosis. There is limited literature describing prognostic factors and guidelines for treatment. We aim to describe outcomes in angiosarcoma, including the impact of patient-, tumour- and treatment-related factors on prognosis.Materials and methods
Patients with non-metastatic angiosarcoma diagnosed between 2008 and 2017 were retrospectively reviewed. Univariable and multivariable Cox proportional hazards methods were used to evaluate factors associated with locoregional recurrence, distant failure and overall survival. The Kaplan–Meier method and log-rank statistics were used to compare outcomes among patients with and without a history of prior radiation therapy.Results
The cohort included 65 patients. The median age at diagnosis was 68 years (35–93). Nineteen patients had a history of receiving prior radiation therapy at the anatomic location of their angiosarcoma. Treatment modalities included surgery (n = 19), surgery + radiation therapy (n = 12), surgery + chemotherapy (n = 8), chemotherapy + radiation therapy (n = 7) and all three modalities (n = 14). The median follow-up was 18 (2–192) months. The 2-year locoregional control, distant control and overall survival were 61.8, 63.6 and 58.9%, respectively. On multivariable analysis, a history of previous radiation therapy was associated with inferior outcomes with respect to locoregional recurrence (hazard ratio 89.67, 95% confidence interval 8.45–951.07, P < 0.001), distant failure (hazard failure 3.74, 95% confidence interval 1.57–8.91, P = 0.003) and overall survival (hazard ratio 3.89, 95% confidence interval 1.56–9.60, P = 0.003). In patients with primary angiosarcoma, the rates of locoregional control, distant control and overall survival were 72.4, 73.4 and 65.1%, respectively, compared with 31.9, 41.1 and 45.1% in patients with radiation therapy-induced angiosarcoma (P = 0.001).Conclusion
Angiosarcomas that arise as a result of previous radiation therapy have worse outcomes compared with primary angiosarcomas. Although selection bias and compromise of clinical care in radiation therapy-induced angiosarcoma are partially to blame, differences in genomic profiles of the tumours need to be characterised to evaluate the underlying biological differences, as this may guide future treatment management. This study adds to the existing body of literature on angiosarcoma. Results from the current study are presented alongside previously published data to further characterise outcomes and prognostic factors on this rare and aggressive malignancy. 相似文献18.
Marco Maruzzo Umberto Basso Eugenio Borsatti Laura Evangelista Filippo Alongi Orazio Caffo Francesca Maines Sara Galuppo Rocco De Vivo Fable Zustovich Dario Palleschi Andrea Zivi Teodoro Sava Mariella Sorarù Roberto Iacovelli Maurizio Nicodemo Susanne Baier Lucia Fratino Vittorina Zagonel 《Clinical genitourinary cancer》2019,17(1):e187-e194
Background
Radium 223 was introduced for metastatic castration-resistant prostate cancer based on the results of a randomized controlled trial showing risk reduction for death and skeletal events. Our aim was to evaluate the outcome of patients receiving radium 223 in a real-world setting.Patients and Methods
We conducted a multicenter retrospective analysis in the Triveneto region of Italy.Results
One hundred fifty-eight patients received radium 223 in our region. After a median follow-up of 9.5 months, 75 patients died. The median overall survival (OS) was 14.2 months, and the median progression-free survival (PFS) was 6.2 months. Seventy-one (45%) patients achieved progression as best response. Thirty-seven (23%) patients stopped the treatment early because of progression. Eastern Cooperative Oncology Group performance status was prognostic for OS (18.4 vs. 12.3 vs. 7.5 months; 0 vs. 1, P = .0062; 0 vs. 2, P = .0002), whereas previous prostatectomy or docetaxel exposure were not. A neutrophil to lymphocytes ratio ≥ 3 significantly impacted OS (18.1 vs. 9.7 months; P < .001) and slightly impacted PFS (6.6 vs. 5.6 months; P = .05). Patients with a baseline alkaline phosphatase (ALP) value ≥ 220 U/L had worse OS and PFS (24.1 vs. 10.5 months; 7.2 vs. 5.5 months; P < .001). Patients with changes in ALP value achieved better OS (P = .029) and PFS (P = .002). There was no difference according to the line of therapy (0 vs. ≥ 1; P = .490). The main grade 3/4 toxicities were anemia, asthenia, and thrombocytopenia.Conclusion
This large real-world report confirms comparable OS and PFS data when compared with the pivotal study, as well as the predictive role of ALP and neutrophil to lymphocytes ratio. The definition of the optimal position of radium 223 in the treatment of metastatic castration-resistant prostate cancer has still to be defined. 相似文献19.
Suresh S. Ramalingam Maurice Pérol Martin Reck Ruben Dario Kowalyszyn Oliver Gautschi Martin Kimmich Eun Kyung Cho Grzegorz Czyzewicz Alexandru Grigorescu Nina Karaseva Shaker Dakhil Pablo Lee Annamaria Zimmerman Andreas Sashegyi Ekaterine Alexandris Gebra Cuyun Carter Katherine B. Winfree Edward B. Garon 《Clinical lung cancer》2018,19(3):270-279.e3
Introduction
Ramucirumab, a recombinant human immunoglobulin G1 monoclonal antibody receptor antagonist designed to block the ligand-binding site of vascular endothelial growth factor receptor-2 (VEGFR-2), was evaluated as second-line treatment in combination with docetaxel in patients with non–small-cell lung cancer in the REVEL trial (NCT01168973). Ramucirumab significantly improved overall survival (OS) and progression-free survival (PFS). We report age subgroup analysis results primarily on the basis of a 65-year cutoff.Patients and Methods
Patients were randomized 1:1 to ramucirumab with docetaxel or placebo with docetaxel (n = 1253). Of these, 798 were younger than 65 years (ramucirumab, n = 391; control, n = 407) and 455 were 65 years or older (ramucirumab, n = 237; control, n = 218). Treatment comprised 21-day cycles of 75 mg/m2 docetaxel with 10 mg/kg ramucirumab or placebo. Prespecified age subgroup analyses were performed, including OS, PFS, and objective response rate. Quintiles age analysis was conducted to establish a relationship between efficacy and age. The Lung Cancer Symptom Scale (LCSS) measured quality of life outcomes. Safety was assessed according to adverse events (AEs).Results
Patients younger than 65 years showed favorable OS outcomes with ramucirumab treatment (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.62-0.87; P < .001) and PFS (HR, 0.68; 95% CI, 0.59-0.79; P < .001). In patients 65 years or older, benefits of ramucirumab were not as evident; after model adjustment for prognostic factors, OS and PFS HRs were 0.96 (95% CI, 0.77-1.21; P = .04) and 0.87 (95% CI, 0.71-1.05; P = .03), respectively. Age analysis according to quintiles showed HRs favoring ramucirumab for all age groupings. LCSS scores and AEs did not considerably differ between age groups.Conclusion
In this subgroup analysis, true treatment effect differences on the basis of age have not been established, and treatment should not be deterred solely because of age. 相似文献20.
Paola Morelato Assunção Tamires Prates Lana Márcia Torresan Delamain Gislaine Oliveira Duarte Roberto Zulli Irene Lorand-Metze Carmino Antonio de Souza Erich Vinicius de Paula Katia Borgia Barbosa Pagnano 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(3):162-166