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1.
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2.
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3.
Matthew Burge Christine Semira Belinda Lee Margaret Lee Suzanne Kosmider Rachel Wong Jeremy Shapiro Brigette Ma Andrew P. Dean Allan S. Zimet Simone A. Steel Sheau Wen Lok Javier Torres Melissa Eastgate Hui-li Wong Peter Gibbs 《Clinical colorectal cancer》2018,17(3):e593-e599
Background
The FIRE-3 [5-fluorouracil, folinic acid, and irinotecan (FOLFIRI) plus cetuximab versus FOLFIRI plus bevacizumab in first line treatment colorectal cancer (CRC)] study reported that first-line FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab resulted in similar progression-free survival (PFS) but improved overall survival (OS). A potential explanation is that the initial biologic agent administered in metastatic CRC (mCRC) affects later line efficacy of the other treatments. We sought to test this hypothesis.Materials and Methods
We interrogated our mCRC registry (Treatment of Recurrent and Advanced Colorectal Cancer) regarding treatment and outcome data for RAS wild-type patients receiving epidermal growth factor receptor inhibitors (EGFRIs) in second and subsequent lines. Survival outcomes from the beginning of EGFRI use were determined as a function of previous bevacizumab use and the interval between ceasing bevacizumab and beginning EGFRI use.Results
Of 2061 patients, 222 eligible patients were identified, of whom 170 (77%) had received previous bevacizumab and 52 (23%) had not. PFS and OS from the start of EGFRIs did not differ by previous bevacizumab use (3.8 vs. 4.2 months; hazard ratio [HR], 1.12; P = .81; 9.0 vs. 9.2 months; HR, 1.19; P = .48, respectively) for the whole cohort or when analyzed by the primary tumor side (HR for left side, 1.07; P = .57; HR for right side, 1.2; P = .52). PFS was significantly shorter with right-sided primary tumors when the interval between bevacizumab and EGFRI use was < 6 versus > 6 months (median, 2.2 vs. 6 months; HR, 2.23; P = .01) but not with left-sided tumors (median, 4.2 vs. 5.5 months; HR, 1.12; P = .26).Conclusion
Previous bevacizumab use had no effect on the activity of subsequent EGFRIs. The apparent effect of time between biologic agents in right-sided tumors might reflect patient selection. 相似文献4.
Peter Gibbs Volker Heinemann Navesh K. Sharma Julien Taieb Jens Ricke Marc Peeters Michael Findlay Bridget Robinson Christopher Jackson Andrew Strickland Val Gebski Mark Van Buskirk Huaqing Zhao Guy van Hazel 《Clinical colorectal cancer》2018,17(4):e617-e629
Background
The primary tumor side is emerging as a major prognostic factor for patients with metastatic colorectal cancer (mCRC). We examined the survival data from 2 randomized studies to determine whether the outcomes differ between patients with mCRC with right-sided primary (RSP) tumors and those with left-sided primary (LSP) tumors after selective internal radiation therapy (SIRT) plus mFOLFOX6 (folinic acid [leucovorin], 5-fluorouracil, oxaliplatin) chemotherapy, versus chemotherapy alone.Patients and Methods
Separate and combined analyses were performed on the data from the SIRFLOX and FOXFIRE global trials, which compared chemotherapy plus SIRT with chemotherapy alone for patients with mCRC liver metastases. The primary tumor side data were prospectively collected. The principal outcome measure was overall survival (OS) stratified by treatment and primary tumor side.Results
In the combined analysis of all 739 patients enrolled, SIRT had no effect on OS (median OS, 24.3 vs. 24.6 months; hazard ratio [HR], 1.021; P = .810). For the 179 patients (24.2%) with a RSP tumor, OS was improved with the addition of SIRT (median, 22.0 vs. 17.1 months HR, 0.641; P = .008). The addition of SIRT was not associated with a significant difference in OS among the 540 patients with a LSP tumor (median, 24.6 vs. 26.6 months; HR, 1.120; P = .264). A test of treatment interaction by primary tumor side was statistically significant for RSP and SIRT (P = .002).Conclusion
The addition of SIRT for patients with RSP tumors, but not for those with LSP tumors, was associated with a statistically and clinically significant OS gain. 相似文献5.
Dincer Aydin Mehmet Ali Sendur Umut Kefeli Basak Bala Ustaalioglu Ozhan Aydin Emre Yildirim Deniz Isik Melike Ozcelik Heves Surmeli Abdilkerim Oyman Selver Isik Nur Sener Ozlem Ercelep Hatice Odabas Mehmet Aliustaoglu Mahmut Gumus 《Clinical colorectal cancer》2017,16(1):78-83
Background
Small bowel adenocarcinomas (SBAs) are rarely seen tumors. Data regarding the use of chemotherapy together with bevacizumab in patients with advanced SBA are lacking. The aim of this study was the evaluation of treatment with bevacizumab in advanced SBA.Materials and Methods
Twenty-eight patients from 5 centers with a diagnosis of advanced SBA who received first-line treatments with modified FOLFOX6 (mFOLFOX6; oxaliplatin, leucovorin, and 5-fluorouracil) and FOLFIRI (leucovorin, 5-fluorouracil, and irinotecan) chemotherapy regimens were involved in the study. All patients were divided into 2 groups; those who received bevacizumab together with these chemotherapy regimens (Chemo+Bev group) and those who did not receive bevacizumab (Chemo group).Results
The median progression-free survival (PFS) and overall survival (OS) times of all population were 8.7 months and 16.9 months, respectively. The overall response rate was 43.7% in the Chemo group and 58.3% in the Chemo+Bev group. The median PFSs in the Chemo and Chemo+Bev groups were found to be 7.7 months and 9.6 months, respectively, and the median OSs were 14.8 months and 18.5 months, respectively. There was not a significant difference between the groups in terms of overall response rate, PFS, and OS.Conclusion
Although there was no significant difference in any of the outcomes, use of bevacizumab together with chemotherapy is a more effective treatment approach compared with chemotherapy alone, and it does not cause an excess of significant toxicity. 相似文献6.
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7.
Eiji Oki Takeshi Kato Hideaki Bando Takayuki Yoshino Kei Muro Hiroya Taniguchi Yoshinori Kagawa Kentaro Yamazaki Tatsuro Yamaguchi Akihito Tsuji Shigeyoshi Iwamoto Goro Nakayama Yasunori Emi Tetsuo Touyama Masato Nakamura Masahito Kotaka Hideki Sakisaka Takeharu Yamanaka Akiyoshi Kanazawa 《Clinical colorectal cancer》2018,17(2):147-155
Background
FOLFOXIRI (Fluorouracil, folinate, oxaliplatin, and irinotecan) plus bevacizumab improved progression-free survival (PFS) and overall survival in patients with metastatic colorectal cancer (mCRC), compared with FOLFIRI (fluorouracil, folinate, and irinotecan) plus bevacizumab, but significantly increased the incidences of adverse events. The efficacy and safety profiles of FOLFOXIRI plus bevacizumab in ethnic Asian patients have not been established yet.Patients and Methods
This study was an open-label, single-arm, multi-centered phase II prospective clinical trial in patients with mCRC who received FOLFOXIRI plus bevacizumab. The primary endpoint was the PFS rate at 10 months. Secondary endpoints included overall survival, response rate, and safety.Results
A total of 69 patients received FOLFOXIRI plus bevacizumab as induction therapy and were assessed for efficacy and safety. The PFS rate at 10 months was 75.2% and the median PFS was 13.3 months. Complete response and partial response were achieved in 2 (2.9%) and 47 patients (69.1%), respectively. Grade 3 and 4 adverse events with incidence rates exceeding 20% were neutropenia (72.5%), hypertension (34.8%), leucopenia (33.3%), and febrile neutropenia (21.7%). Significantly more patients with grade 4 neutropenia had single-heterozygous UGT1A1*1/*6 or *1/*28 (46.2%) than UGT1A1 wild-type genotype (*1/*1) (13.3%) (P = .004).Conclusions
FOLFOXIRI plus bevacizumab is considered an effective first-line regimen that improves the outcome of patients with mCRC regardless of ethnicity. In Asian patients, utmost attention should be paid to the possible onset of severe neutropenia or febrile neutropenia attributed to different types of UGT1A1*6 and *28 polymorphism, when FOLFOXIRI plus bevacizumab is administered. 相似文献8.
Charu Aggarwal Roger B. Cohen Eddy Yu Wei-Ting Hwang Joshua M. Bauml Evan Alley Tracey L. Evans Corey J. Langer 《Clinical lung cancer》2018,19(2):157-162
Background
Third-line treatment options are limited for patients with metastatic non–small-cell lung cancer (NSCLC). Etirinotecan pegol (NKTR-102) is a long-acting topoisomerase-I inhibitor. We conducted a single-arm phase II trial to evaluate its efficacy in third-line treatment.Patients and Methods
Patients aged ≥ 18 years with histologically proven NSCLC who had received 2 previous systemic therapy regimens, measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1, and adequate end-organ function were eligible. Etirinotecan pegol was administered at a dose of 145 mg/m2 intravenously once every 3 weeks until progression. The response was assessed every 6 weeks using Response Evaluation Criteria In Solid Tumors, version 1.1. The primary endpoint was the overall objective response rate. The secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. A Simon 2-stage design was implemented for futility.Results
From January 2013 to January 2015, 40 patients were enrolled. Their median age was 66 years (range, 19-85 years), 45% were female, 30% had an ECOG performance status of 0, 96% were current and former smokers, and 31 had adenocarcinoma. Patients received a median of 3 cycles (range, 2-15) of protocol therapy. The best response was a partial response in 2 patients. The treatment was well tolerated; 3 patients had grade 3 gastrointestinal toxicity attributable to therapy. The median PFS was 2.3 months (95% confidence interval [CI], 1.3-4.4 months), and the median OS was 7.1 months (95% CI 4.2-11.4 months).Conclusions
Etirinotecan pegol was well tolerated and led to 2 partial responses and disease stabilization with this third-line treatment of metastatic NSCLC. However, the study failed to meet its prespecified response rate endpoint. 相似文献9.
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10.
Magali Rouyer Eric François Antonio Sa Cunha Alain Monnereau Pernelle Noize Philip Robinson Cécile Droz-Perroteau Alise Le Monies de Sagazan Jérémy Jové Régis Lassalle Nicholas Moore Annie Fourrier-Réglat Denis Smith 《Clinical colorectal cancer》2018,17(2):129-139
Introduction
Few real-life data are available on cetuximab benefit. The EREBUS cohort was performed to assess metastases resection rate, use, safety, and survival outcomes in wild-type KRAS (Kirsten rat sarcoma viral oncogene) patients with initially unresectable metastatic colorectal cancer (mCRC) treated by cetuximab in real practice.Patients and Methods
The study cohort comprised patients initiating cetuximab between January 2009 and December 2010 in 65 French centers, with initially unresectable mCRC and wild-type KRAS. Kaplan-Meier analysis estimated 24-month probability of metastases resection and progression-free survival, and 36-month overall survival (OS). Cox proportional hazards models investigated factors associated with survival outcomes.Results
Among the 389 patients included, median age was 64 years, 67.4% were male, 77.9% had Eastern Cooperative Oncology Group performance status ≤ 1, and hepatic metastases were most frequent at baseline (n = 146 exclusively, n = 149 not exclusively, n = 94 nonliver only). Median duration of cetuximab use was 4.8 months. Metastases resection was performed in 106 patients (27.2%) (n = 60 liver exclusively, n = 33 not exclusively, n = 13 nonliver only). The 24-month probability (95% confidence interval) of metastases resection occurrence was 33.6% (28.5-39.3). Median progression-free survival was 9.2 (8.5-9.8) months for the total cohort and 13.0 (11.6-15.1) for those resected; median OS was 23.0 (20.6-26.3) months for the total cohort and was not reached after 36 months for those who were resected. The strongest factor associated with higher OS was metastases resection with complete remission (hazard ratio, 0.41; 95% confidence interval, 0.19-0.88).Conclusion
This cohort study highlights in French real-life practice the benefit of cetuximab in first-line mCRC therapy, notably in case of metastases resection with complete remission. 相似文献11.
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12.
Alessandro Pastorino Maria Di Bartolomeo Evaristo Maiello Vincenzo Iaffaioli Libero Ciuffreda Gianpiero Fasola Francesco Di Costanzo Giovanni Luca Frassineti Paolo Marchetti Carlotta Antoniotti Francesco Leone Alberto Zaniboni Giuseppe Aprile Chiara Zilocchi Alberto Sobrero Roberto Bordonaro 《Clinical colorectal cancer》2018,17(3):e457-e470
Background
Aflibercept combined with FOLFIRI (folinic acid, 5-fluorouracil, irinotecan) as second-line treatment of metastatic colorectal cancer (mCRC) significantly improved survival compared with FOLFIRI alone in the pivotal VELOUR (aflibercept vs. placebo in combination with irinotecan and 5-fluorouracil in the treatment of patients with metastatic colorectal cancer after failure of an oxaliplatin-based regimen) trial. No quality-of-life assessment was performed in VELOUR; therefore, the ASQoP (Aflibercept Safety and Quality-of-Life Program) trial was designed to capture the safety and health-related quality of life (HRQL).Patients and Methods
ASQoP was an international, open-label, single-arm trial evaluating the safety and HRQL of aflibercept combined with FOLFIRI administered in a real-life setting to 781 patients with mCRC, pretreated with an oxaliplatin-based regimen with or without bevacizumab. The Italian subset of ASQoP enrolled 200 patients from 28 institutions. The primary endpoint was safety; HRQL was a secondary endpoint, assessed by validated questionnaires (European quality of life 5-dimension instrument 3-level; European Organization for Research and Treatment for Cancer Quality of Life Questionnaire Core 30, version 3; and EORTC-CR29) at baseline, during treatment, and at the end of treatment.Results
The median age of the Italian ASQoP population was 63 years; the median number of aflibercept and FOLFIRI cycles was 7. Treatment-emergent adverse events were reported in 97.5% of patients. Hypertension (28.5%), neutropenia (27.5%; from laboratory data), asthenic conditions (20.0%), diarrhea (17.0%), and stomatitis (13.0%) were the most frequent (incidence, ≥ 5%) grade 3/4 toxicities. One toxic death occurred during the study period due to sepsis, without neutropenic complications. No significant worsening of HRQL was shown during treatment.Conclusion
Aflibercept combined with FOLFIRI was well tolerated when administered as second-line treatment for patients with mCRC in a real-life setting. It did not affect HRQL and showed similar rates of treatment-emergent adverse events as those observed in the VELOUR trial. No new safety signals were identified. 相似文献13.
Kenji Tsuchihashi Mamoru Ito Toshikazu Moriwaki Shota Fukuoka Hiroya Taniguchi Atsuo Takashima Yosuke Kumekawa Takeshi Kajiwara Kentaro Yamazaki Taito Esaki Akitaka Makiyama Tadamichi Denda Hironaga Satake Takeshi Suto Naotoshi Sugimoto Kenji Katsumata Toshiaki Ishikawa Tomomi Kashiwada Eishi Baba 《Clinical colorectal cancer》2018,17(4):e687-e697
Background
Assessment of patient factors is essential for selecting later-line chemotherapy in patients with metastatic colorectal cancer (mCRC). The efficacy, prognosis, and safety of each treatment regimen according to nutritional and inflammatory status still remain to be elucidated.Patients and Methods
A total of 550 patients with mCRC who were registered in the REGOTAS study (Regorafenib versus TAS-102 as Salvage-line in patients with colorectal cancer refractory to standard chemotherapies: a multicenter observational study, UMIN 000020416) and treated with trifluridine/tipiracil (TFTD) or regorafenib as a later-line therapy were retrospectively stratified according to the modified Glasgow Prognostic Score (mGPS), which divided patients into mGPS 0 to 2 by serum albumin and C-reactive protein, and compared.Results
The median overall survival (OS) of patients with mGPS 0, 1, and 2 was 10.0 months (95% confidence interval [CI], 9.2-11.6 months), 6.5 months (95% CI, 5.3-7.1 months), and 3.9 months (95% CI, 3.3-4.9 months), respectively. The median progression-free survival (PFS) with mGPS 0, 1, and 2 was 2.5 months (95% CI, 2.1-3.0 months), 2.0 months (95% CI, 1.9-2.3 months), and 1.7 months (95% CI, 1.4-1.9 months), respectively. There were significant differences by mGPS in both OS and PFS (all P < .001). No significant differences in OS and PFS were observed between the patient groups treated with TFTD and regorafenib in each mGPS group. In patients aged ≥ 65 years with mGPS 2, the OS and PFS were worse with regorafenib than with TFTD (OS: hazard ratio, 1.45; 95% CI, 0.93-2.25; P = .097; PFS: hazard ratio, 1.57, 95% CI, 1.01-2.44; P = .047), but there were no consistent trends observed as mGPS increased. The frequency of grade 3 and more adverse events was generally similar in each mGPS group. The multivariate analyses showed that mGPS was the strongest predictive factor for OS.Conclusions
The mGPS before later-line chemotherapy is strongly correlated with survival in patients with mCRC. 相似文献14.
Alex R. Menter Nikki M. Carroll Lori C. Sakoda Thomas Delate Mark C. Hornbrook Rakesh K. Jain Lawrence H. Kushi Virginia P. Quinn Debra P. Ritzwoller 《Clinical lung cancer》2017,18(2):189-197.e3
Introduction
Preclinical studies suggest that angiotensin system inhibitors (ASI) and bevacizumab improve tumor perfusion and chemotherapy efficacy. We performed a retrospective study to examine whether concomitant ASI use during carboplatin and paclitaxel (CP) without or with bevacizumab (CPB) was associated with improved overall survival (OS) in patients with advanced nonsquamous, non–small-cell lung cancer (NS-NSCLC).Patients and Methods
In a retrospective cohort study, adult patients diagnosed with stage IIIB or IV NS-NSCLC between 2005 and 2011 were identified from tumor registries at 1 of 4 Kaiser Permanente regions. Survival differences between those who did and did not receive ASIs concomitant with chemotherapy (CP or CPB) were assessed using propensity score–matched proportional hazard models. OS was measured from the initiation of chemotherapy until death, disenrollment, or December 31, 2012.Results
Of the 1465 CP and 348 CPB patients included, 273 (19%) and 78 (22%), respectively, received concomitant ASI. For CP patients with and without concomitant ASI exposure, median OS was 12.0 and 8.4 months, respectively (crude hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.63-0.84). For CPB patients, the comparable median OS was 14.9 and 11.9 months, respectively (crude HR, 0.77; 95% CI, 0.57-1.02). Using propensity score–matched cohorts, the HR for concomitant ASI use was 0.73 (95% CI, 0.61-0.88) for CP patients and 0.79 (95% CI, 0.51-1.21) for CPB patients.Conclusion
Concomitant ASI receipt during CP or CPB therapy for NS-NSCLC was associated with improved survival, although the association was only statistically significant in the CP group. 相似文献15.
Amandine Gouverneur Juliette Coutureau Jérémy Jové Magali Rouyer Angela Grelaud Sophie Duc Stéphane Gérard Denis Smith Alain Ravaud Cécile Droz Marie-Agnès Bernard Régis Lassalle Annie Forrier-Réglat Pernelle Noize 《Clinical colorectal cancer》2019,18(1):e150-e162
Background
Metastatic colorectal cancer (mCRC) is increasingly treated using targeted therapies. Their real-life evaluation is insufficient, especially in elderly and frail patients. The aim was to describe use, safety, and effectiveness of targeted therapies in first-line mCRC treatment according to age.Patients and Methods
Two field cohorts of patients initiating bevacizumab or cetuximab for first-line mCRC were pooled. Patients characteristics, use, and safety were compared between younger and elderly patients (<75 vs. ≥75 years). Two-year overall survival (OS) and progression-free survival (PFS) were estimated in both age groups using the Kaplan–Meier method adjusted on factors associated with death or progression identified with Cox multivariate modeling.Results
Eight hundred patients (n = 411, 51.4% bevacizumab) were included: 498 (62.3%) male, median age 64 years, 118 (14.8%) Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥2. Elderly patients (n = 126, 15.8%) were more often treated with 5-fluorouracil alone than younger. Severe adverse events were equivalent across age groups. ECOG-PS ≥1, abnormal hemoglobin, and abnormal alkaline phosphatases were associated with a higher risk of death; OS adjusted on these factors was similar between elderly and younger patients. ECOG-PS ≥1, lung metastases, abnormal hemoglobin, and abnormal creatinine clearance were associated with a higher risk of progression or death; PFS adjusted on these factors was similar across groups.Conclusion
Despite treatment adaptations, elderly patients could benefit from targeted therapies as younger without safety warning. 相似文献16.
A Phase II Clinical Trial of Apatinib in Pretreated Advanced Non-squamous Non–small-cell Lung Cancer
Fengying Wu Shijia Zhang Anwen Xiong Guanghui Gao Wei Li Weijing Cai Chunxia Su Xiaoxia Chen Fei Zhou Jing Zhao Shengxiang Ren Caicun Zhou 《Clinical lung cancer》2018,19(6):e831-e842
Objectives
Apatinib exhibits broad-spectrum antitumor activities by selectively inhibiting vascular endothelial growth factor receptor-2. This study evaluated the efficacy and safety of apatinib in patients with advanced non-squamous non–small-cell lung cancer who were heavily pretreated or not suitable to receive standard second-line chemotherapy.Patients and Methods
This was an open-label, single-arm phase II clinical trial (ClinicalTrials.govNCT02515435). Patients received 500 or 750 mg apatinib daily until progression, unacceptable toxicity, withdrawal, or death. The primary endpoint was the objective response rate. The secondary endpoints included disease control rate, progression-free survival, overall survival, and side effects. Apatinib administration was allowed beyond disease progression.Results
Between March 2015 and August 2016, 40 patients were enrolled. Among them, 6 (15.0%), 16 (40.0%), and 18 (45.0%) received apatinib as the second-, third-, and fourth-line or beyond treatment, respectively. The mean dosage of apatinib was 477.0 ± 85.3 mg/day. Thirty-eight patients were available for response evaluation; the objective response rate and disease control rate were 13.2% and 63.2%, respectively. The median progression-free survival was 3.06 months (95% confidence interval [CI], 2.20-4.14 months). The median overall survival was 7.69 months (95% CI, 5.36 months to not estimable). The most common treatment-related adverse events were hand-foot-skin reaction (30.0%), proteinuria (27.5%), oral mucositis (22.5%), fatigue (20.0%), and hypertension (17.5%). Nine patients received apatinib after progression, and the median duration of apatinib therapy beyond progression was 5.13 months (95% CI, 4.27-7.82 months).Conclusion
Apatinib shows promising efficacy and manageable toxicity in patients with advanced non-squamous non–small-cell lung cancer. Apatinib therapy beyond progression could provide further benefits in specific subpopulations. 相似文献17.
Raffaele Ratta Elena Verzoni Massimo Di Maio Paolo Grassi Maurizio Colecchia Giovanni Fucà Filippo de Braud Giuseppe Procopio 《Clinical genitourinary cancer》2018,16(4):e735-e742
Background
The purpose of the present retrospective analysis was to describe the trends in exposure to multiple lines of treatment and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) who started therapy in 2 different periods (period 1, 2004-2010; and period 2, 2011-2017).Patients and Methods
The proportion of patients who received subsequent lines of treatment after disease progression was compared between the 2 groups. OS was measured from the start of first-line treatment for metastatic disease to death or the last follow-up examination. Both univariate and multivariate analyses were performed.Results
A total of 500 patients were included in the study; 274 started treatment in period 1 and 226 in period 2. Of those patients who stopped first-line treatment because of disease progression, the patients in period 2 had a greater conditional probability to receive second- and third-line treatment compared with patients in period 1 (77.2% vs. 63.7%; odds ratio [OR], 1.93; 95% confidence interval [CI], 1.20-3.11; P = .0065; and 69.6% vs. 48.1%; OR, 2.48; 95% CI, 1.40-4.40; P = .002, respectively). The median OS improved from 22.8 months for patients in period 1 to 38.2 months for patients in period 2 (univariate analysis: hazard ratio, 0.65; 95% CI, 0.50-0.83; P = .001).Conclusion
Patients who started treatment during the past 5 years were exposed to a greater number of treatment lines compared with patients treated before 2011. Our data suggest that the increase of treatment options available and clinician expertise could be associated with better outcomes. 相似文献18.
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19.
Derek J. Jonker Patricia A. Tang Hagen Kennecke Stephen A. Welch M. Christine Cripps Timothy Asmis Haji Chalchal Anna Tomiak Howard Lim Yoo-Joung Ko Eric X. Chen Thierry Alcindor John R. Goffin Grzegorz J. Korpanty Harriet Feilotter Ming S. Tsao Ashley Theis Dongsheng Tu Lesley Seymour 《Clinical colorectal cancer》2018,17(3):231-239.e7
Background
Oncolytic reovirus pelareorep might preferentially infect and destroy rat sarcoma (RAS)-activated cells, and has preclinical and early clinical activity against colorectal cancer (CRC).Patients and Methods
After a 6-patient safety run-in, 103 patients with metastatic CRC were randomly assigned to standard first-line leucovorin/5-FU/oxaliplatin (FOLFOX6)/bevacizumab (FOLFOX/BEV) every 2 weeks with (n = 51) or without (n = 52) pelareorep 3 × 1010 tissue culture infective dose 50 on days 1 to 5 (cycles 1, 2, 4, and alternate cycles thereafter). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), quality of life, and correlative analyses.Results
At 13 months' median follow-up, PFS was inferior in the pelareorep arm (median 7 vs. 9 months; hazard ratio [HR], 1.59 [80% confidence interval (CI), 1.18-2.15]; P = .046). There was no statistical difference in OS (median, 19.2 vs. 20.1 months; HR, 1.22; P = .38). An increased ORR was observed with pelareorep (adjusted odds ratio, 2.52 [80% CI, 1.44-4.41]; P = .03), but with a shorter median duration of response (5 vs. 9 months; P = .028). Pelareorep patients experienced more hypertension and proteinuria, and were more likely to omit bevacizumab before progression. A trend to lower dose intensity and shorter oxaliplatin and bevacizumab treatment duration was observed with pelareorep.Conclusion
Combination pelareorep with FOLFOX/BEV was tolerable with an increased ORR, but PFS was inferior. Subgroup analysis of baseline variables including Kirsten rat sarcoma oncogene did not identify subgroups with PFS benefit. Decreased treatment intensity with standard agents likely contributed to the lack of benefit with pelareorep. Future studies might consider alternate pelareorep/chemotherapy strategies or combination therapy with novel agents. 相似文献20.
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