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1.
Roberto Petrioli Martina Chirra Luciana Messuti Anna Ida Fiaschi Vinno Savelli Ignazio Martellucci Edoardo Francini 《Clinical colorectal cancer》2018,17(4):307-312
Background
In the CORRECT (patients with metastatic COloRectal Cancer treated with REgorafenib or plaCebo after failure of standard Therapy) trial, regorafenib was proven to extend survival of patients with metastatic colorectal cancer (mCRC) that progressed after all available therapies. Grade 3 to 4 toxicity occurred in 54% of patients, and data on the activity and tolerability of regorafenib in elderly patients were scarce. The aim of this study was to evaluate the efficacy and safety of an alternative schedule, 2-week-on treatment and 1 week-off (2/1 schedule), of regorafenib for elderly patients with mCRC.Patients and Methods
Patients ≥ 75 years with mCRC who progressed after oxaliplatin- and irinotecan-based chemotherapy received regorafenib on a 2/1 schedule. Potentially frail subjects were identified by G8 screening tool and excluded. The 2-month disease-control rate was the primary endpoint, and the secondary endpoints included safety, progression-free survival (PFS), overall survival (OS), and objective response rate.Results
Between February 2014 and May 2017, 23 patients with mCRC were recruited at our institution. No partial or complete responses were observed, and the stable disease and disease-control rate were 52.2%. The median PFS was 4.8 months (95% confidence interval, 3.8-6.3 months), and the median OS was 8.9 months (95% confidence interval, 6.9-10.6 months). Adverse events were uncommon, and the most frequent grade 3 toxicity adverse events were hand-foot skin reaction (9%) and fatigue (9%). Toxicity-related dose reductions and discontinuations occurred in 5 and 2 patients, respectively.Conclusion
Regorafenib administered with a modified 2/1 schedule to patients who were aged ≥ 75 years and non-frail with treatment-refractory mCRC seems to be tolerable and achieve encouraging results in terms of PFS and OS. 相似文献2.
Matthias Unseld Magdalena Drimmel Alexander Siebenhüner Andreas Gleiss Daniela Bianconi Markus Kieler Werner Scheithauer Thomas Winder Gerald W. Prager 《Clinical colorectal cancer》2018,17(4):274-279
Background
Treatment sequencing for patients with refractory metastatic colorectal cancer (mCRC) has been highly debated. The thymidine-based nucleoside trifluridine/tipiracil (TAS-102) and the multikinase inhibitor regorafenib have demonstrated clinical benefits in randomized phase III trials compared with placebo. However, limited data are available on the most optimal therapy sequence involving TAS-102 and regorafenib.Patients and Methods
In the present retrospective, observational, real-life study, clinical data on mCRC patients treated with TAS-102 or an alternative salvage treatment at the Medical University of Vienna and University Hospital Zurich were collected from January 2013 to December 2016.Results
A total of 85 patients whose disease had progressed during fluoropyrimidine-based therapy (FBT) with or without an antibody were included. The disease control rate in patients treated with TAS-102 after FBT-based treatment was 24% compared with 35% in patients treated with regorafenib after FBT-based treatment (adjusted odds ratio, 1.75; 95% confidence interval, 0.41-7.47; P = .449). The progression-free survival (PFS) and overall survival (OS) for patients treated with TAS-102 was 2.8 months (quartile, 2.0-4.8 months) and 15.9 months, respectively. When the data were analyzed according to the subgroups of patients with or without an FBT-free period, the TAS-102–treated patients with a previous FBT-free interval had a PFS of 3.1 months and OS of 17.7 months compared with a PFS of 2.2 months and OS of 8.1 months for patients who received TAS-102 immediately after FBT.Conclusion
Our results have confirmed the efficacy of TAS-102 and regorafenib in the real-life setting. The treatment sequence analysis showed a tendency for longer PFS and OS for TAS-102–treated patients after an FBT-free interval. Prospective randomized data are needed to gain more information about the most beneficial therapy sequence in the salvage treatment of mCRC. 相似文献3.
Anthony Turpin Sophie Paget-Bailly Anne Ploquin Antoine Hollebecque Charlotte Peugniez Farid El-Hajbi Franck Bonnetain Mohamed Hebbar 《Clinical colorectal cancer》2018,17(1):e99-e107
Background
We studied the relationship between intermediate criteria and overall survival (OS) in metastatic colorectal cancer (mCRC) patients who received first-line chemotherapy with bevacizumab.Patients and Methods
We assessed OS, progression-free survival (PFS), duration of disease control (DDC), the sum of the periods in which the disease did not progress, and the time to failure of strategy (TFS), which was defined as the entire period before the introduction of a second-line treatment. Linear correlation and regression models were used, and Prentice criteria were investigated.Results
With a median follow-up of 57.6 months for 216 patients, the median OS was 24.5 months (95% confidence interval [CI], 21.3-29.7). The median PFS, DDC, and TFS were 8.9 (95% CI, 8.4-9.7), 11.0 (95% CI, 9.8-12.4), and 11.1 (95% CI, 10.0-13.0) months, respectively. The correlations between OS and DDC (Pearson coefficient, 0.79 [95% CI, 0.73-0.83], determination coefficient, 0.62) and OS and TFS (Pearson coefficient, 0.79 [95% CI, 0.73-0.84], determination coefficient, 0.63) were satisfactory. Linear regression analysis showed a significant association between OS and DDC, and between OS and TFS. Prentice criteria were verified for TFS as well as DDC.Conclusion
DDC and TFS correlated with OS and are relevant as intermediate criteria in the setting of patients with mCRC treated with a first-line bevacizumab-based regimen. 相似文献4.
Levent Korkmaz Hasan Şenol Coşkun Faysal Dane Bülent Karabulut Mustafa Karaağaç Devrim Çabuk Senem Karabulut Nuri Faruk Aykan Hatice Doruk Nilüfer Avcı Nazım Serdar Turhal Mehmet Artaç 《Surgical oncology》2018,27(3):485-489
Purpose
We aimed to investigate the prognostic effect of primary tumor resection (PTR) prior to bevacizumab-based treatments in unresectable metastatic colorectal cancer (mCRC).Methods
We retrospectively collected 341 mCRC cases with unresectable metastases at diagnosis. PTR was performed in 210 cases (the surgery group) and the other patients (n?=?131) were followed without PTR (the no-surgery group). All the patients were treated with bevacizumab combined chemotherapy regimens.Results
The median progression free survival (PFS) of the surgery group was 10.4 months (95% CI: 8.9–11.9), which was significantly better than that of the no-surgery group (7.6 months, 95% CI: 6.4–8.8, P=0.000). The median overall survival (OS) of the surgery group was longer than that of the no-surgery group (27.4 months vs. 18.3 months, respectively, P=0.000). The median PFS and OS of the surgery group were 10.4 months and 28.2 months, which were significantly longer than that of the no-surgery group in Kras-mutant patients (7.8 months and 18.3 months; P=0.004, P=0.028, respectively). There was no difference in terms of PFS and OS between the surgery and the no-surgery groups in Kras-wild type patients.Conclusion
Palliative PTR may improve the survival outcomes for unresectable mCRC patients. PTR may be preferred, particularly in Kras-mutant patients. 相似文献5.
Salvatore Siena Fernando Rivera Julien Taieb Marc Peeters Hans Prenen Reija Koukakis Gaston Demonty Claus-Henning Köhne 《Clinical colorectal cancer》2018,17(1):50-57.e8
Background
Köhne prognostic score is used to classify patients with metastatic colorectal cancer (mCRC) as high, intermediate, or low risk. Using data from 2 phase III trials, we analyzed survival in patients categorized according to Köhne prognostic category and virus-induced rapidly accelerated fibrosarcoma murine sarcoma viral oncogene homolog B (BRAF) mutation.Patients and Methods
PRIME (Panitumumab Randomized Trial In Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy) (first-line) and 20050181 (second-line) were studies of chemotherapy with or without panitumumab. Progression-free survival (PFS) and overall survival (OS) were analyzed retrospectively in rat sarcoma viral oncogene homolog (RAS) wild type (WT) and RAS WT+BRAF WT mCRC in each Köhne category, and in BRAF mutant (MT) mCRC.Results
In PRIME (n = 495) and 20050181 (n = 420), 53 (11%) and 44 (10%) patients, respectively, had BRAF MT mCRC. Of the RAS WT+BRAF WT/unknown populations, 85/267/90 and 82/211/83 were categorized as high/medium/low risk, respectively. PFS and OS hazard ratios (HRs), adjusted for Köhne group, for patients with RAS WT + BRAF WT/unknown mCRC favored panitumumab with chemotherapy versus chemotherapy alone in both studies. In PRIME, the PFS HR was 0.74 (95% confidence interval [CI], 0.61-0.90) and OS HR was 0.78 (95% CI, 0.64-0.95). In 20050181, PFS and OS HRs were 0.80 (95% CI, 0.65-0.99) and 0.78 (95% CI, 0.62-0.99), respectively. Median PFS and OS were lower in patients with BRAF MT mCRC than in any of the 3 risk categories for patients with RAS WT+BRAF WT/unknown mCRC.Conclusion
During first- and second-line treatment, Köhne prognostic score allows accurate risk classification in RAS WT mCRC. BRAF MT mCRC should be classified as high risk regardless of other parameters. Panitumumab with chemotherapy might provide survival benefits versus chemotherapy alone in RAS WT and RAS WT+BRAF WT/unknown mCRC, overall and across risk categories. 相似文献6.
Objective：The epidermal growth factor receptor （EGFR） inhibitors monoclonal antibodies （MoAbs） have already shown the therapeutic effectiveness in patients with metastatic colorectal cancer （mCRC）.But many patients resist to the treatment.The aim of this meta-analysis was to assess EGFR gene copy number （GCN） as a candidate predictive biomarker for resistance to anti-EGFR MoAbs in mCRC treatment.Methods：Systematic computerized searches of the PubMed,EMBase and Cochrane Library were performed.The primary endpoint was objective response rate （ORR）.The second endpoints included progression-free survival （PFS）,and overall survival （OS）.The pooled odd ratio （OR） and pooled sensitivity,specificity,and summary receiver operator characteristic （SROC） for ORR were estimated.The pooled hazard ratios （HR） for PFS and OS were also calculated.Results：Fourteen studies with 1,021 patients were included.Increased EGFR GCN was associated with increased ORR （OR=6.905; 95％ CI：4.489-10.620）.It was also found in wild-type KRAS mCRC patients,with the pooled OR of 8.133 （95 ％ CI：4.316-15.326）.GCN has medium value for predicting ORR,with the pooled sensitivity of 0.79 （95％ CI：0.73-0.84）,the pooled specificity of 0.59 （95％ CI：0.55-0.62）.In wildtype KRAS mCRC patients,the sensitivity and the specificity were 0.80 （95％ CI：0.70-0.87） and 0.60 （95％CI：0.53-0.66）,respectively.Increased EGFR GCN was associated with increased PFS （HR=0.557; 95％ CI：0.382-0.732） and OS （HR=0.579; 95％ CI：0.422-0.737）.Conclusions：This meta-analysis suggests that EGFR GCN represents a predictive biomarker for tumor response in mCRC patients treated with MoAbs regardless of KRAS mutation.mCRC patients with increased EGFR GCN are more likely to have a better response,PFS,and OS when treated with cetuximab or panitumumab. 相似文献
7.
Cristina Grávalos Alfredo Carrato María Tobeña Mercedes Rodriguez-Garrote Gemma Soler José Mª Vieitez Luis Robles Manuel Valladares-Ayerbes Eduardo Polo Mª Luisa Limón Mª José Safont Eva Martínez de Castro Pilar García-Alfonso Enrique Aranda 《Clinical colorectal cancer》2018,17(2):e323-e329
Introduction
The aim of this study was to evaluate the efficacy and safety of maintenance therapy with axitinib versus placebo following induction therapy in patients with metastatic colorectal cancer (mCRC).Patients and Methods
In this double-blinded, phase II trial, patients with mCRC who had not progressed after 6 to 8 months of first-line chemotherapy were randomized to receive axitinib (5 mg twice a day) (arm A) or placebo (arm B).Results
Forty-nine patients were included: 25 in arm A and 24 in arm B. The median follow-up was 26.07 months (95% confidence interval [CI], 18.44-31.73 months). Progression-free survival (PFS) rate at 6 months was 40.00% (95% CI, 21.28%-58.12%) in the axitinib arm versus 8.33% (95% CI, 1.44%-23.30%) in the placebo arm (P = .0141). The median PFS was statistically significantly longer in the axitinib group than in the placebo group (4.96 vs. 3.16 months; hazard ratio, 0.46; 95% CI, 0.25-0.86; P = .0116). Median overall survival was also longer in the axitinib arm but did not reach statistical significance (27.61 vs. 19.99 months; hazard ratio, 0.68; 95% CI, 0.31-1.48; P = .3279). Grade 3 to 4 treatment-related toxicities were experienced by 7 patients (28%) in cohort A and 1 patient (4%) in cohort B (P = .0488). The most frequent grade 3 to 4 treatment-related toxicities were hypertension, diarrhea, and asthenia. There were no toxic deaths. The study was prematurely closed because of slow recruitment.Conclusions
In our study, maintenance treatment with axitinib monotherapy showed a significant increase in PFS and a good safety profile. Axitinib should be further explored as a possible option for first-line chemotherapy maintenance treatment in patients with mCRC. 相似文献8.
Background
Progression-free survival (PFS) and time to progression (TTP) have been reported to correlate with overall survival (OS) in several cancer types. To our knowledge, however, the correlation between them is unclear.Methods
A literature-based meta-analysis was performed to assess whether PFS and TTP can be considered reliable surrogate end points for OS in a phase 3 clinical trial of advanced breast cancer (ABC). The median hazard ratios of PFS/TTP and OS were analyzed by determining their nonparametric Spearman rank correlation coefficients (Rs).Results
A total of 37 trials with 38 treatment arms and 14,966 patients were selected for analysis. The Rs between the median PFS/TTP and OS was 0.405 (95% confidence interval [CI], 0.191-0.582; P = .003), and the correlation coefficient between the hazard ratios of PFS/TTP and OS was 0.555 (95% CI, 0.277-0.748; P = .003). PFS/TTP was closely correlated with OS in the trials of targeted therapy-based treatment (Rs = 0.872; 95% CI, 0.619-0.962; P = .0001) and of PFS/TTP or OS benefit (Rs = 0.753 and Rs = 0.821, respectively) for ABC.Conclusions
Both PFS and TTP can be considered valid surrogate end points for OS in the trials of targeted therapy-based treatments and clinical benefits for ABC. Further research is necessary to clarify the surrogacy of PFS/TTP for OS in other trials of targeted therapy-based treatments for ABC. 相似文献9.
Shinji Nakamichi Hidehito Horinouchi Tetsuhiko Asao Yasushi Goto Shintaro Kanda Yutaka Fujiwara Hiroshi Nokihara Noboru Yamamoto Yoshinori Ito Shun-ichi Watanabe Yuichiro Ohe 《Clinical lung cancer》2017,18(6):e441-e448
Background
The optimal treatment strategy for locoregional recurrences developing after surgical resection in patients with non–small-cell lung cancer (NSCLC) is yet to be clearly established.Patients and Methods
To investigate the efficacy and safety of radiotherapy (RT) and chemoradiotherapy (CRT), we reviewed the consecutive data of patients with NSCLC with postoperative locoregional recurrences treated at the National Cancer Center Hospital between January 2000 and April 2010.Results
We reviewed the data of 74 patients (including 56 who received RT alone and 18 who received CRT) according to our study criteria. The median age was lower and the N factor at the recurrence site was higher in the CRT group compared with the RT group. Most patients received 60 Gy/30 Fr RT in both groups. The 2-year progression-free survival (PFS) rate, median PFS, and overall survival (OS) were 44.4%, 19.0 months (95% confidence interval [CI], 0-41.9 months), and 79.6 months (95% CI, 8.2-151.0 months), respectively, in the CRT group, although those were 25.0%, 10.6 months (95% CI, 8.7-12.9 months), and 33.1 months (95% CI, 17.9-48.3 months), respectively, in the RT group. The adverse event profile was acceptable, with no treatment-related death in either group. Multivariate analysis identified CRT as being significantly associated with a longer PFS and OS.Conclusion
CRT tended to yield better results than RT in terms of the survival outcomes, with acceptable safety profiles of both. We consider that a randomized study comparing RT and CRT is warranted to identify the optimal treatment strategy for patients with NSCLC with postoperative locoregional recurrences. 相似文献10.
Jonathan M. Loree Sean K. Tan Laurence M. Lafond Caroline H. Speers Hagen F. Kennecke Winson Y. Cheung 《Clinical colorectal cancer》2018,17(1):65-72
Background
With improved survival and longer duration of treatment, clinicians managing metastatic colorectal cancer (mCRC) increasingly consider intermittent (IC) or maintenance chemotherapy (MC), but the effect of these treatment modifications on real-world outcomes is unclear.Patients and Methods
Using a population-based cohort of mCRC patients who received combination chemotherapy, we aimed to describe the use of IC/MC and their effect on overall survival (OS).Results
Among 617 patients, 120 (19%) had periods of IC, 67 (11%) had periods of MC, and 53 (9%) had periods of both. Most (85.5%) modifications occurred in the first-line setting. The receipt of IC (median OS [mOS], 37 vs. 21 months; P < .0001) or MC (mOS, 36 vs. 24 months; P = .0015) was associated with improved mOS compared with continuous combination therapy. In multivariate analysis adjusting for age, sex, and regimen used at the time of treatment modification, IC (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.42-0.65; P < .0001), MC (HR, 0.71; 95% CI, 0.58-0.88; P = .002), and the combination (HR, 0.45; 95% CI, 0.33-0.63; P < .0001) were all associated with improved mOS. Among patients receiving MC, individuals with (HR, 0.69; 95% CI, 0.53-0.90; P = .005) and without (HR, 0.74; 95% CI, 0.55-1.00; P = .048) re-escalation to their original cytotoxic regimen had improved mOS compared with continuous therapy. The use of IC was associated with an improved OS compared with MC (HR, 0.65; 95% CI, 0.47-0.90; P = .009).Conclusion
In patients with mCRC, IC and MC are reasonable options to maintain quality of life and do not appear to negatively affect OS in carefully selected patients. 相似文献11.
Lijun Liang Lei Wang Panrong Zhu Youyou Xia Yun Qiao Jiang Wu Wei Zhuang Jiayan Fei Yixuan Wen Xiaodong Jiang 《Clinical colorectal cancer》2018,17(3):e443-e449
Background
Antiangiogenic therapy has shown improved clinical outcome in metastatic colorectal cancer (mCRC). After the failure of standard treatments, regorafenib and TAS-102 would be recommended for patients with mCRC, however, they have not been approved in China during this study period.Patients and Methods
This pilot study aimed to assess the efficacy and safety of apatinib, a novel oral inhibitor targeting vascular endothelial growth factor receptor 2, as third-line treatment for patients with mCRC refractory to standard therapies. In this retrospective study, all patients received apatinib treatment until progressive disease (PD), death, unacceptable toxicity, and curative surgery. The dose or treatment schedule was modified according to the physician's discretion according to the toxicity profiles.Results
Between March 2015 and June 2017, 36 patients were enrolled and eligible for evaluation of the safety and efficacy. One patient (2.8%) achieved complete response, 3 (8.3%) achieved partial response, 24 (66.7%) achieved stable disease, and 8 (22.2%) PD. The objective response rate and the disease control rate were 11.1% (4 of 36), and 77.8% (28 of 36), respectively. Moreover, the median overall survival (OS) since the initiation of first-line treatment was 33.2 months. The median progression-free survival (PFS) and median OS from apatinib treatment were 4.8 and 10.1 months, respectively. Intergroup analysis showed that there was no significant difference in median PFS and median OS between patients who were previously treated with and without bevacizumab. The most common Grade 3 to 4 adverse reactions were hand-foot syndrome, hypertension, and proteinuria.Conclusion
Our results suggested that apatinib was active as a third-line treatment of refractory mCRC with a manageable tolerability profile. In addition, preliminary data suggested that the efficacy of apatinib would not be affected by previous bevacizumab treatment. Further prospective randomized controlled clinical trials are urgently needed. 相似文献12.
Shirish M. Gadgeel Nathan A. Pennell Mary Jo Fidler Balazs Halmos Philip Bonomi James Stevenson Bryan Schneider Ammar Sukari Jaclyn Ventimiglia Wei Chen Cathy Galasso Antoinette Wozniak Julie Boerner Gregory P. Kalemkerian 《Journal of thoracic oncology》2018,13(9):1393-1399
Objective
The aim of this study was to assess the efficacy of maintenance pembrolizumab in patients with extensive-stage SCLC after treatment with platinum and etoposide.Methods
Patients with extensive-stage SCLC with a response or stable disease after induction chemotherapy were eligible. Pembrolizumab at a dose of 200 mg administered intravenously every 3 weeks was initiated within 8 weeks of the last cycle of chemotherapy. The primary end point of the study was progression-free survival (PFS) from study registration, with overall survival (OS) as a key secondary end point. Available tumor tissue was assessed for expression of programmed death ligand 1 (PD-L1) both in the tumor cells and in the surrounding stroma. Blood for circulating tumor cells was collected before the first, second, and third cycles of pembrolizumab.Results
Of the 45 patients enrolled, 56% were male and 22% had treated brain metastases. The median PFS was 1.4 months (95% confidence interval [CI]: 1.3–2.8), with a 1-year PFS of 13%. The median OS was 9.6 months (95% CI: 7.0–12), with a 1-year OS of 37%. Of the 30 tumors that could be assessed, three had PD-L1 expression (≥1%) in the tumor cells. A total of 20 tumors could be assessed for PD-L1 expression in the stroma. The median PFS in the eight patients with tumors positive for expression of PD-L1 at the stromal interface was 6.5 months (95% CI: 1.1–12.8) compared with 1.3 months (95% CI: 0.6–2.5) in 12 patients with tumors negative for this marker. No unexpected toxicities were observed.Conclusion
Maintenance pembrolizumab did not appear to improve median PFS compared with the historical data. However, the 1-year PFS rate of 13% and OS rate of 37% suggest that a subset of patients did benefit from pembrolizumab. 相似文献13.
Hiroki Ishihara Tsunenori Kondo Kenji Omae Toshio Takagi Jumpei Iizuka Hirohito Kobayashi Kazunari Tanabe 《Targeted oncology》2016,11(5):605-617
Background
Cancer cachexia is associated with patient outcomes.Objective
The objective was to evaluate the effect of cachexia on survival among patients with metastatic renal cell carcinoma (mRCC) who had received first-line sunitinib treatment.Patients and Methods
Seventy-one patients were retrospectively evaluated. Sarcopenia was diagnosed using sex-specific cut-offs for skeletal muscle index (measured using pre-treatment computed tomography) that were adjusted for body mass index. The modified Glasgow prognostic score (mGPS) was measured using C-reactive protein (CRP) and albumin levels (mGPS 2: CRP >1.0 mg/dL and albumin <3.5 g/dL; mGPS 1: CRP >1.0 mg/dL; mGPS 0: CRP ≤1.0 mg/dL). Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox proportional hazard models.Results
Forty-five patients (63.4 %) had sarcopenia, with 53 (74.6 %), ten (14.1 %), and eight (11.3 %) patients having an mGPS of 0, 1, and 2, respectively. Sarcopenia was associated with significantly inferior PFS and OS, compared to non-sarcopenic patients (PFS: 7.6 vs. 18.2 months, p?=?0.0004; OS: 22.3 months vs. not reached, p?=?0.0019). Higher mGPS was associated with inferior PFS and OS (mGPS 0, 1, and 2: PFS?=?11.5, 10.9, and 4.12 months, p?<?0.0001; OS?=?47.2, not reached, and 5.28 months, p?<?0.0001; respectively). Sarcopenia was an independent predictor of shorter PFS (p?=?0.0163), and mGPS was an independent predictor of shorter OS (p?=?0.0012).Conclusion
Sarcopenia and mGPS can predict outcomes among patients with mRCC who are receiving first-line sunitinib treatment.14.
Henry Chan Madeline Phillips Manjula Maganti Sophia Farooki Giovanni Piza Rodriguez Esther Masih-Khan Christine Chen Anca Prica Donna Reece Rodger Tiedemann Suzanne Trudel Vishal Kukreti 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(3):225-234
Background
Translocation t(4;14) has traditionally been classified as a high-risk cytogenetic feature in patients with multiple myeloma with shortened progression-free (PFS) and overall survival (OS) despite initial response to treatment. Recent data have shown an improved long-term survival in these patients treated with novel agents, such as bortezomib.Patients and Methods
We conducted a retrospective study on our patients with t(4;14) multiple myeloma treated with bortezomib-based induction between July 1, 2006 and June 30, 2014 to assess the real-world outcomes of these patients in a tertiary center.Results
Among the 75 patients analyzed, the median PFS was 33.5 months, and the median OS was 69.6 months after a median follow-up of 41 months. Even in the era of novel agents, patients who received frontline autologous stem cell transplant had a better PFS than those who received chemotherapy alone (median PFS, 24.2 months vs. 41.5 months; P = .01). Hypercalcemia at the time of presentation was found to be a significant predictor of progression (hazard ratio [HR], 10.1; 95% confidence interval [CI], 4.0-26.0) and death (HR, 9.4; 95% CI, 3.2-27.8), and co-harboring of del(17p) by fluorescent in situ hybridization with t(4;14) was associated with a significantly inferior OS (HR, 4.0; 95% CI, 1.4-11.4).Conclusion
Even in the era of novel agents, t(4;14) remains a negative prognostic marker. Frontline autologous stem cell transplant remains as an essential tool when treating these high-risk patients, but further prospective randomized studies are needed to determine the most effective strategy for this patient group. 相似文献15.
Consuelo Buttigliero Marcello Tucci Francesca Vignani Rosario F. Di Stefano Gianmarco Leone Clizia Zichi Daniele Pignataro Gaetano Lacidogna Pamela Guglielmini Gianmauro Numico Giorgio V. Scagliotti Massimo Di Maio 《Clinical genitourinary cancer》2018,16(4):318-324
Background
Neutropenia is a common side effect associated with docetaxel use. We retrospectively investigated the association between chemotherapy-induced neutropenia and survival in metastatic castration-resistant prostate cancer (mCRPC) patients receiving first-line docetaxel.Patients and Methods
Metastatic castration-resistant prostate cancer patients treated with first-line docetaxel, with known neutrophils value 10 days after first administration, were included in this retrospective analysis. Neutropenia was categorized in Grade 0 to 1 (G0-1), Grade 2 to 3 (G2-3), and Grade 4 (G4). Outcome measures were progression-free survival (PFS) and overall survival (OS).Results
Eighty patients were analyzed. Median PFS was 5.4 months in patients with G0-1 neutropenia, 6.9 months with G2-3 neutropenia (hazard ratio [HR] vs. G0-1, 0.69; 95% confidence interval [CI], 0.35-1.35; P = .27) and 9.5 months with G4 neutropenia (HR vs. G0-1, 0.30; 95% CI, 0.16-0.57; P < .0001). Median OS was 11.6 months in patients with G0-1 neutropenia, 25.5 months in patients with G2-3 neutropenia (HR vs. G0-1, 0.36; 95% CI, 0.16-0.80; P = .012) and 39.3 months in patients with G4 neutropenia (HR vs. G0-1, 0.19; 95% CI, 0.09-0.41; P < .0001). In multivariate analysis, the occurrence of severe neutropenia showed a statistically significant association with OS (HR G4 vs. G0-1, 0.14; 95% CI, 0.03-0.67; P = .013; HR G2-3 vs. G0-1, 0.42; 95% CI, 0.11-1.57; P = .20) and PFS (HR G4 vs. G0-1, 0.28; 95% CI, 0.09-0.86; P = .03; HR G2-3 vs. G0-1, 1.07; 95% CI, 0.38-2.96; P = .90).Conclusion
Docetaxel-induced neutropenia is associated with better survival of mCRPC. 相似文献16.
G.H.C. Tan C.A. Novo S. Dayal K. Chandrakumaran F. Mohamed T. Cecil B.J. Moran 《European journal of surgical oncology》2017,43(2):388-394
Background
The modified Glasgow prognostic score (incorporating C-reactive protein and albumin) predicts survival in patients with gastro-intestinal tract cancer but has not been evaluated in patients with peritoneal malignancy. The aim was to evaluate the modified Glasgow score preoperatively in patients undergoing complete cytoreductive surgery (CCRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei (PMP) of appendiceal origin.Methods
Prospectively collected data from patients with PMP of appendiceal origin following CCRS and HIPEC between January 2007 and December 2011 were analysed. The mGPS was calculated from preoperative C-reactive protein and albumin. Predicted overall survival (OS) and disease-free survival (DFS) for each mGPS score were calculated using the Kaplan–Meier model. In a separate analysis, a comparison was made between mGPS and Tumour Markers (TM).Results
260 patients were included in the study. The mGPS of 0, 1, and 2 were found in 111, 130, and 19 patients respectively. The median follow-up was 48 months. For mGPS-0, -1, and -2, the predicted OS was 82.2, 73.7, and 69.2 months and the DFS was 73.5, 62.9, and 54.4 months respectively. As mGPS increases, there is a reduction in long-term survival. There was no difference between mGPS and TM.Conclusion
Preoperative mGPS may be a cost effective prognostic tool for predicting OS and DFS in patients following complete CRS-HIPEC, and performs well compared to TM for predicting patients at high risk of recurrence. 相似文献17.
Purpose of Review
This paper reviews the development, mechanism of action, clinical efficacy, and safety of regorafenib and TAS-102. Through this review, we aimed to help clinicians make an appropriate choice in patients who progressed after standard therapies.Recent Findings
Regorafenib and TAS-102 have shown superior survival results compared with placebo in refractory metastatic colorectal cancer (mCRC). In the phase III CORRECT study, regorafenib showed significant improvement in overall survival (OS) and progression-free survival (PFS). TAS-102 was associated with OS and PFS benefit as well in the phase III RECOURSE study. However, the toxicity profiles were quite different between the two agents.Summary
Regorafenib and TAS-102 are approved for the management of refractory mCRC. Optimal treatment sequence for using these two novel agents is not defined yet. Safety profiles and patient’s condition should be considered before using these two agents in clinical settings. Further investigation is needed to identify the predictive biomarkers of both agents. These results will allow patients to benefit more from regorafenib and TAS-102.18.
Oliver Gautschi Sacha I. Rothschild Qiyu Li Klazien Matter-Walstra Alfred Zippelius Daniel C. Betticher Martin Früh Rolf A. Stahel Richard Cathomas Daniel Rauch Miklos Pless Solange Peters Patrizia Froesch Thilo Zander Martina Schneider Christine Biaggi Nicolas Mach Adrian F. Ochsenbein 《Clinical lung cancer》2017,18(3):303-309
Background
Pemetrexed and bevacizumab as single agents have been approved for maintenance therapy after platinum-based induction in patients with advanced nonsquamous non–small-cell lung cancer. It is currently unknown whether bevacizumab plus pemetrexed is superior to pemetrexed alone.Patients and Methods
We conducted a nonrandomized phase II trial with 2 sequential cohorts. In the first cohort, 77 patients were treated with 4 cycles of cisplatin, bevacizumab, and pemetrexed every 3 weeks, followed by bevacizumab plus pemetrexed maintenance until progression. In the second cohort, we treated 52 patients without bevacizumab, using maintenance with pemetrexed alone. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), adverse events, and the treatment costs of the 2 cohorts were compared.Results
The median PFS from the time of registration was 6.9 months in cohort 1 and 5.6 months in cohort 2. The ORR was 62.3% in cohort 1% and 44.2% in cohort 2. The PFS (hazard ratio, 0.7; 95% confidence interval [CI], 0.5-1.0; P = .041) and ORR (odds ratio, 2.1; 95% CI, 1.0-4.3; P = .049) were better in cohort 1 than in cohort 2. No OS difference was found (hazard ratio, 1.0; 95% CI, 0.7-1.6; P = .890) after a median follow-up period of 47 months for cohort 1 and 27 months for cohort 2. The rate of grade ≥ 3 adverse events was greater in cohort 1. The treatment costs per patient were on average 1.4 times greater for cohort 1.Conclusion
The addition of bevacizumab increased the ORR and PFS, but not OS, in our nonrandomized trial. Furthermore, the addition of bevacizumab was associated with greater toxicity and higher costs. 相似文献19.
Mohamed A. Kharfan-Dabaja Tea Reljic Hemant S. Murthy Ernesto Ayala Ambuj Kumar 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(11):703-709.e1
Introduction
It is common practice to refer patients to transplantation centers for allogeneic hematopoietic cell transplantation (allo-HCT) for blastic plasmacytoid dendritic-cell neoplasm (BPDCN) despite lack of randomized controlled trials. We performed a systematic review to assess the totality of evidence pertaining to the efficacy of allo-HCT in BPDCN.Methods
We searched the Cochrane, PubMed, and Embase databases through January 5, 2018, for studies on allo-HCT for BPDCN. Two authors independently reviewed all references for inclusion and extracted data related to benefits (overall [OS] and progression-free/disease-free [PFS/DFS] survival) and harms (relapse and nonrelapse mortality) from included studies. When appropriate, data were pooled using random-effects model.Results
Four studies (128 patients) were included in analysis. Pooled OS rate was 50% (95% confidence interval [CI], 41-59) for all patients. Among patients who underwent allografting whose disease was in first complete remission (CR1), pooled OS and PFS/DFS rates were 67% (95% CI, 52-80) and 53% (95% CI, 29-76), respectively. For patients who underwent allografting in > CR1, pooled OS and PFS/DFS rates were 7% (95% CI, 0-32) for both outcomes. Relapse rates were higher when reduced-intensity regimens were used (40% [95% CI, 25-56] vs. 18% [95% CI, 7-31]).Conclusion
This systematic review represents the best available evidence supporting allo-HCT in BPDCN, especially when offered in CR1. Use of myeloablative allo-HCT results in lower pooled relapse rates (18% vs. 40%). A prospective comparative study will be needed to determine the impact of intensity of the conditioning regimen on postallograft relapse. 相似文献20.
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
