共查询到20条相似文献,搜索用时 31 毫秒
1.
Kurt A Jaeckle Karla V Ballman Martin van den Bent Caterina Giannini Evanthia Galanis Paul D Brown Robert B Jenkins J Gregory Cairncross Wolfgang Wick Michael Weller Kenneth D Aldape Jesse G Dixon S Keith Anderson Jane H Cerhan Jeffrey S Wefel Martin Klein Stuart A Grossman David Schiff Jeffrey J Raizer Frederick Dhermain Donald G Nordstrom Patrick J Flynn Michael A Vogelbaum 《Neuro-oncology》2021,23(3):457
BackgroundWe report the analysis involving patients treated on the initial CODEL design.MethodsAdults (>18) with newly diagnosed 1p/19q World Health Organization (WHO) grade III oligodendroglioma were randomized to radiotherapy (RT; 5940 centigray ) alone (arm A); RT with concomitant and adjuvant temozolomide (TMZ) (arm B); or TMZ alone (arm C). Primary endpoint was overall survival (OS), arm A versus B. Secondary comparisons were performed for OS and progression-free survival (PFS), comparing pooled RT arms versus TMZ-alone arm.ResultsThirty-six patients were randomized equally. At median follow-up of 7.5 years, 83.3% (10/12) TMZ-alone patients progressed, versus 37.5% (9/24) on the RT arms. PFS was significantly shorter in TMZ-alone patients compared with RT patients (hazard ratio [HR] = 3.12; 95% CI: 1.26, 7.69; P = 0.014). Death from disease progression occurred in 3/12 (25%) of TMZ-alone patients and 4/24 (16.7%) on the RT arms. OS did not statistically differ between arms (comparison underpowered). After adjustment for isocitrate dehydrogenase (IDH) status (mutated/wildtype) in a Cox regression model utilizing IDH and RT treatment status as covariables (arm C vs pooled arms A + B), PFS remained shorter for patients not receiving RT (HR = 3.33; 95% CI: 1.31, 8.45; P = 0.011), but not OS ((HR = 2.78; 95% CI: 0.58, 13.22, P = 0.20). Grade 3+ adverse events occurred in 25%, 42%, and 33% of patients (arms A, B, and C). There were no differences between arms in neurocognitive decline comparing baseline to 3 months.ConclusionsTMZ-alone patients experienced significantly shorter PFS than patients treated on the RT arms. The ongoing CODEL trial has been redesigned to compare RT + PCV versus RT + TMZ. 相似文献
2.
Thomas J. George Alison M. Ivey Azka Ali Ji-Hyun Lee Yu Wang Karen C. Daily Brian H. Ramnaraign Sanda A. Tan Krista P. Terracina Thomas E. Read Long H. Dang Atif Iqbal 《The oncologist》2021,26(5):362-e724
Lessons Learned
- Treatment for patients with metastatic colorectal cancer (mCRC) typically involves multiple lines of therapy with eventual development of treatment resistance.
- In this single‐arm, phase II study involving heavily pretreated patients, the combination of sorafenib and capecitabine yielded a clinically meaningful progression‐free survival of 6.2 months with an acceptable toxicity profile.
- This oral doublet therapy is worthy of continued investigation for clinical use in patients with mCRC.
3.
Wencheng Zhang Cihui Yan Xuan Gao Xiaoxia Li Fuliang Cao Gang Zhao Jingjing Zhao Puchun Er Tian Zhang Xi Chen Yuwen Wang Yao Jiang Quanren Wang Baozhong Zhang Dong Qian Jun Wang Dejun Zhou Xiubao Ren Zhentao Yu Lujun Zhao Zhiyong Yuan Ping Wang Qingsong Pang 《The oncologist》2021,26(7):e1110-e1124
Lessons Learned
- Radiotherapy plus anti–PD‐1 antibody as first‐line therapy is safe and feasible in locally advanced esophageal squamous cell carcinoma (ESCC).
- Tumor‐infiltrating and peripheral lymphocytes were associated with patient survival.
- Further studies combining chemoradiotherapy with immunotherapy in locally advanced ESCC and exploration of predictive biomarkers are warranted.
4.
Christian Kollmannsberger Toni K. Choueiri Daniel Y.C. Heng Saby George Fei Jie Ruslan Croitoru Srinivasu Poondru John A. Thompson 《The oncologist》2021,26(3):182-e361
Lessons Learned
- The primary endpoint of this phase II study that evaluated the efficacy and safety of the investigational compound, AGS‐16C3F, versus axitinib in previously treated patients with metastatic renal cell carcinoma (mRCC) was not met.
- Median progression‐free survival, the primary endpoint, was 2.9 months with AGS‐16C3F and 5.7 months with axitinib (HR, 1.676; 95% CI, 1.107–2.537; p = .015), per investigator assessment
- The safety profile for each study drug was as expected, with the most commonly reported adverse events being fatigue (53%) and nausea (47%) in the AGS‐16C3F arm and fatigue (57%) and diarrhea (48%) in the axitinib arm.
- These results provide a benchmark for axitinib use in heavily pretreated patients with mRCC.
5.
Sandro Pignata Giovanni Scambia Alessandro Villanucci Emanuele Naglieri Mikel Arruti Ibarbia Federica Brusa Hugues Bourgeois Roberto Sorio Antonio Casado Dietmar Reichert Catherine Dopchie Beatriz De Rivas Luis Miguel de Sande 《The oncologist》2021,26(4):e658-e668
PurposeThe noninterventional, prospective NIMES‐ROC phase IV study () evaluated trabectedin plus pegylated liposomal doxorubicin (PLD) in real‐life clinical practice.Patients and MethodsEligible participants included adults with platinum‐sensitive recurrent ovarian cancer (PS‐ROC) who had received one or more cycles of trabectedin/PLD before inclusion according to the marketing authorization. The primary endpoint was progression‐free survival (PFS) according to investigator criteria.ResultsTwo hundred eighteen patients from five European countries were evaluated, 72.5% of whom were pretreated with at least two prior chemotherapy lines and received a median of six cycles of trabectedin/PLD (range: 1–24). Median PFS was 9.46 months (95% confidence interval [CI], 7.9–10.9), and median overall survival (OS) was 23.56 months (95% CI, 18.1–34.1). Patients not pretreated with an antiangiogenic drug obtained larger median PFS (p < .007) and OS (p < .048), largely owning to differences between the two populations. Twenty‐four patients (11.0%) had a complete response, and 57 patients (26.1%) achieved a partial response for an objective response rate (ORR) of 37.2%. Fifty‐nine patients (27.1%) had disease stabilization for a disease control rate of 64.2%. No statistically significant difference in PFS, OS, or ORR was observed by BRCA1/2 status and platinum sensitivity. Most common grade 3/4 adverse events (AEs) were neutropenia (30.3%), anemia (6.4%), thrombocytopenia (5.5%), and asthenia (5.0%). No deaths attributed to treatment‐related AEs or unexpected AEs occurred.ConclusionThe combination of trabectedin/PLD represents a clinically meaningful and safe option for patients with PS‐ROC regardless of prior treatment with an antiangiogenic drug, being comparable with previously observed outcomes in selected and less pretreated patients from clinical trials.Implications for PracticeThis noninterventional, prospective study, conducted in 57 reference sites across Europe, consistently confirmed that trabectedin plus pegylated liposomal doxorubicin (PLD) in routine clinical practice represents a clinically meaningful and safe option for women with platinum‐sensitive recurrent ovarian cancer. Although the study population represented a heterogeneous, older, and more pretreated population than those in prospective clinical trials, the combination of trabectedin plus PLD induced comparable clinical benefits, with a similar and manageable safety profile. Overall, these findings show that trabectedin in combination with PLD maintains antitumor activity when administered to heavily pretreated patients in real‐life clinical practice. NCT02825420相似文献
6.
Santiago Cabezas-Camarero María Nieves Cabrera-Martín Salomé Merino-Menéndez Mateo Paz-Cabezas Vanesa García-Barberán Melchor Sáiz-Pardo Sanz Maricruz Iglesias-Moreno Almudena Alonso-Ovies Pedro Pérez-Segura 《The oncologist》2021,26(6):e1018-e1035
BackgroundThere are still few data on the activity and safety of cetuximab‐based salvage chemotherapy after immunotherapy (SCAI) in patients with squamous cell cancer of the head and neck (SCCHN).Materials and MethodsThis was a retrospective study of patients with SCCHN who received cetuximab‐based SCAI after programmed cell death protein 1 or programmed cell death ligand 1(PD[L]1) inhibitors. Overall response rate (ORR) and disease control rate (DCR) with SCAI and with last chemotherapy before immunotherapy (LCBI) by RECIST 1.1, percentage change from baseline in target lesions (PCTL), progression‐free survival (PFS), overall survival (OS), treatment compliance, and toxicity were evaluated.ResultsBetween March 2016 and November 2019, 23 patients were identified. SCAI consisted of cetuximab‐based combinations (3‐weekly cisplatin‐5FU‐cetuximab [n = 2], weekly paclitaxel‐cetuximab [n = 17], weekly cisplatin‐cetuximab [n = 2], weekly carboplatin‐paclitaxel‐cetuximab [n = 2]). ORR was 56.5% (11 partial response, 2 complete response). DCR was 78.3%. Among 13 objective responders, median best PCTL was −53.5% (range, −30% to −100%). Median OS and PFS were 12 months and 6 months, respectively. In 10 patients receiving LCBI, ORR to LCBI was 40%, whereas ORR to SCAI achieved 60%. In LCBI‐treated patients, median PFS with LCBI was 8 months and median PFS and OS with SCAI were 7 months and 12 months, respectively. Reduced dose intensity of the chemotherapy and cetuximab components occurred in 82.6% and 52.2% of the patients. Grade 1 or 2 adverse events (AEs) occurred in all patients. Grade 3 or 4 AEs developed in 65%, being grade 3 in all of them except in one patient (grade 4 neutropenia). There were no treatment‐related deaths.ConclusionCetuximab‐based salvage chemotherapy after PD(L)1 inhibitors associated with high response rates and deep tumor reductions with a manageable safety profile. Subsequent lines of therapy may explain the long survival achieved in our series. These results invite to design studies to elucidate the best therapeutic sequence in patients with SCCHN in the immunotherapy era.Implications for PracticeCetuximab‐based salvage chemotherapy (SCAI) achieved high response rates in patients with recurrent/metastatic squamous cell cancer of the head and neck (SCCHN) after progression to PD‐1/PD‐L1 inhibitors. Objective response rate was higher than and progression‐free survival was comparable to that of chemotherapy administered before immunotherapy (IO). In most patients, SCAI consisted of weekly, well‐tolerated regimens. These observations have implications for current practice because of the limited evidence to date in SCCHN and the scant therapeutic options in this disease and invite to elucidate which may be the best treatment sequence for patients with head and neck cancer in the IO era. 相似文献
7.
Na Zhou Chuantao Zhang Dong Liu Kewei Liu Guanqun Wang Hua Zhu Jianli Zhang Man Jiang Ning Liu Xiaochun Zhang 《The oncologist》2021,26(3):e374-e381
Lessons Learned
- Apatinib combined with S‐1 was not superior to other chemotherapy regimens as first‐line therapy for advanced gastric cancer.
- There was a tendency for patients with lymph node metastasis to have prolonged median progression‐free survival and median overall survival, compared with patients with liver metastasis.
8.
Alex J. Liu Benjamin E. Ueberroth Patrick W. McGarrah Skye A. Buckner Petty Ayse Tuba Kendi Jason Starr Timothy J. Hobday Thorvardur R. Halfdanarson Mohamad Bassam Sonbol 《The oncologist》2021,26(5):383-388
IntroductionRecent classification of neuroendocrine neoplasms has defined well‐differentiated high‐grade neuroendocrine tumors (NET G3) as a distinct entity from poorly differentiated neuroendocrine carcinoma. The optimal treatment for NET G3 has not been well‐described. This study aimed to evaluate metastatic NET G3 response to different treatment regimens.Materials and MethodsThis was a retrospective study of patients with NET G3 within the Mayo Clinic database. Patients’ demographics along with treatment characteristics, responses, and survival were assessed. Primary endpoints were progression‐free survival (PFS) and overall survival. Secondary endpoints were objective response rate (ORR) and disease control rate (DCR).ResultsTreatment data was available in 30 patients with median age of 59.5 years at diagnosis. The primary tumor was mostly pancreatic (73.3%). Ki‐67 index was ≥55% in 26.7% of cases. Treatments included capecitabine + temozolomide (CAPTEM) (n = 20), lutetium 177 DOTATATE (PRRT; n = 10), Platinum‐etoposide (EP; n = 8), FOLFOX (n = 7), and everolimus (n = 2). CAPTEM exhibited ORR 35%, DCR 65%, and median PFS 9.4 months (95% confidence interval, 2.96–16.07). Both EP and FOLFOX showed similar radiographic response rates with ORR 25.0% and 28.6%; however, median PFS durations were quite distinct at 2.94 and 13.04 months, respectively. PRRT had ORR of 20%, DCR of 70%, and median PFS of 9.13 months.ConclusionAmong patients with NET G3, CAPTEM was the most commonly used treatment with clinically meaningful efficacy and disease control. FOLFOX or PRRT are other potentially active treatment options. EP has some activity in NET G3, but responses appear to be short‐lived. Prospective studies evaluating different treatments effects in patients with NET G3 are needed to determine an optimal treatment strategy.Implications for PracticeHigh‐grade well‐differentiated neuroendocrine tumors (NET G3) are considered a different entity from low‐grade NET and neuroendocrine carcinoma in terms of prognosis and management. The oral combination of capecitabine and temozolomide is considered a good option in the management of metastatic NET G3 and may be preferred. FOLFOX is another systemic option with reasonable efficacy. Similar to other well‐differentiated neuroendocrine tumors, peptide receptor radionuclide therapy seems to have some efficacy in these tumors. 相似文献
9.
Ghassan K. Abou-Alfa Robert Mayer Alan P. Venook Allison F. O'Neill Muhammad S. Beg Michael LaQuaglia Peter T. Kingham Rachel Kobos Olca Basturk Cameron Brennan Adam Yopp James J. Harding Stephen Leong John Crown Emir Hoti Gregory Leonard Michele Ly Mikaela Bradley Emily Valentino David Markowitz Alexander Zukiwski Ken Ren John D. Gordan 《The oncologist》2020,25(12):e1837-e1845
10.
Hironaga Satake Takeshi Kato Koji Oba Masahito Kotaka Yoshinori Kagawa Hisateru Yasui Masato Nakamura Takanori Watanabe Toshihiko Matsumoto Takayuki Kii Tetsuji Terazawa Akitaka Makiyama Nao Takano Mitsuru Yokota Yoshihiro Okita Koreatsu Matoba Hiroko Hasegawa Akihito Tsuji Yoshito Komatsu Takayuki Yoshino Kentaro Yamazaki Hideyuki Mishima Eiji Oki Naoki Nagata Junichi Sakamoto 《The oncologist》2020,25(12):e13443
Lessons Learned
- A biweekly TAS‐102 plus BEV schedule in patients with heavily pretreated mCRC showed equivalent efficacy with less toxicity compared with the current schedule of TAS‐102 plus BEV combination.
- Biweekly TAS‐102 plus BEV combination could reduce unnecessary dose reduction of TAS‐102, maintain higher doses, and possibly be effective even in cases without chemotherapy‐induced neutropenia (CIN).
- The prespecified subgroup analysis of this study showed an obvious association between CIN within the first two cycles and prognosis of biweekly TAS‐102 plus BEV.
11.
Elettra Merola Teresa Alonso Gordoa Panpan Zhang Taymeyah Al-Toubah Eleonora Pellè Agnieszka Kolasińska-Ćwikła Wouter Zandee Faidon Laskaratos Louis de Mestier Angela Lamarca Jorge Hernando Jaroslaw Cwikla Jonathan Strosberg Wouter de Herder Martin Caplin Mauro Cives Rachel van Leeuwaarde 《The oncologist》2021,26(4):294-301
BackgroundLong‐acting somatostatin analogs (SSAs) are the primary first‐line treatment of well‐differentiated advanced gastroenteropancreatic neuroendocrine tumors (NETs), but data about their efficacy in pancreatic NETs (panNETs) with Ki‐67 ≥10% are still limited.Materials and MethodsTo assess the clinical outcomes of advanced, nonfunctioning, well‐differentiated panNETs with Ki‐67 ≥10% receiving first‐line long‐acting SSAs in a real‐world setting, we carried out a retrospective, multicenter study including patients treated between 2014–2018 across 10 centers of the NET CONNECT Network. The primary endpoints were time to next treatment (TNT) and progression‐free survival (PFS), whereas overall survival (OS) and treatment safety were secondary endpoints.ResultsA total of 73 patients were included (68 grade [G]2, 5 G3), with liver metastases in 61 cases (84%). After a median follow‐up of 36.4 months (range, 6–173), the median TNT and PFS were 14.2 months (95% confidence interval [CI], 11.6–16.2) and 11.9 months (95% CI, 8.6–14.1) respectively. No statistically significant difference was observed according to the somatostatin analog used (octreotide vs. lanreotide), whereas increased tumor grade (hazard ratio [HR], 4.4; 95% CI, 1.2–16.6; p = .04) and hepatic tumor load (HR, 2; 95% CI, 1–4; p = .03) were independently associated with shortened PFS. The median OS recorded was 86 months (95% CI, 56.8–86 months), with poor outcomes observed when the hepatic tumor burden was >25% (HR, 3.4; 95% CI, 1.2–10; p = .01). Treatment‐related adverse events were reported in 14 patients, most frequently diarrhea.ConclusionSSAs exert antiproliferative activity in panNETs with Ki‐67 ≥10%, particularly in G2 tumors, as well as when hepatic tumor load is ≤25%.Implications for PracticeThe results of the study call into question the antiproliferative activity of somatostatin analogs (SSAs) in pancreatic neuroendocrine tumors with Ki‐67 ≥10%. Patients with grade 2 tumors and with hepatic tumor load ≤25% appear to derive higher benefit from SSAs. Prospective studies are needed to validate these results to optimize tailored therapeutic strategies for this specific patient population. 相似文献
12.
Sun Young Kim Ji Sung Lee Junho Kang Satoshi Morita Young Suk Park Junichi Sakamoto Kei Muro Rui-Hua Xu Tae Won Kim 《The oncologist》2021,26(6):e954-e962
BackgroundConcomitant use of proton pump inhibitors (PPIs) with capecitabine was suggested to be associated with poor outcomes in gastrointestinal cancers. We analyzed the differential impact of PPI use on capecitabine and fluorouracil using the data set from the AXEPT trial, a phase III randomized trial that demonstrated the noninferiority of mXELIRI (modified XELIRI: capecitabine plus irinotecan) to FOLFIRI (leucovorin, fluorouracil, and irinotecan), either with or without bevacizumab in patients with metastatic colorectal cancer.Patients and MethodsOut of the per‐protocol set (n = 620), patients with information on concomitant medications (n = 482) were included in this post hoc analysis. PPI use was defined as concomitant exposure of capecitabine and the use of any PPI for 20% or more of the study period. The treatment‐by‐PPI‐use interaction was examined after adjusting for stratification factors.ResultsOf the 482 patients, 49 (10.1%) used PPI. Among the PPI users, the mXELIRI group tended to have poorer overall survival compared with the FOLFIRI group. In contrast, among the nonusers, the overall survival of the mXELIRI group was significantly better than that of the FOLFIRI group. Similarly, a trend of worse progression‐free survival with mXELIRI compared with FOLFIRI was observed in PPI users but not in nonusers. Treatment‐by‐PPI‐use interaction was significant for overall survival and progression‐free survival.ConclusionThe significant interaction between PPI use and the type of fluoropyrimidine in terms of overall and progression‐free survival suggests that fluorouracil could be a more favorable option than capecitabine for patients with metastatic colorectal cancer using PPIs.Implications for PracticeThis study showed a significant interaction between the use of proton pump inhibitors (PPIs) and the type of fluoropyrimidines. This interaction mainly comes from the positive impact of PPIs in the survival outcomes in the fluorouracil arm rather than a negative impact of PPIs in the capecitabine arm. The possible drug‐drug interaction shown in this study suggests that fluorouracil, rather than capecitabine, could be a more appropriate choice of fluoropyrimidine for patients who are taking PPIs in the treatment of metastatic colorectal cancer. 相似文献
13.
Fei Xu Qiufan Zheng Wen Xia Quchang Ouyang Danmei Pang Zhongyu Yuan Yanxia Shi Roujun Peng Qianyi Lu Shusen Wang 《The oncologist》2021,26(5):e742-e748
Lessons Learned
- Fulvestrant 500 mg maintenance therapy showed a clinical benefit rate of 76% and median progression‐free survival of 16.1 months in patients who achieved objective responses or disease control after first‐line chemotherapy.
- Adverse events with fulvestrant maintenance therapy were consistent with the known safety profile of the drug.
14.
15.
Cissimol P. Joseph Sarah N. Abaricia Michelle A. Angelis Kathleen Polson Robin L. Jones Yoon-Koo Kang Richard F. Riedel Patrick Schöffski César Serrano Jonathan Trent Eric D. Tetzlaff Tuan Dong Si Teresa Zhou Ashley Doyle Sebastian Bauer Maria Roche Tracy Havnaer 《The oncologist》2021,26(4):e622-e631
BackgroundAvapritinib, a novel inhibitor of KIT/PDGFRA, is approved in the U.S. for the treatment of adults with PDGFRA exon 18‐mutant unresectable or metastatic gastrointestinal stromal tumors (U/M GISTs). We assessed the safety of avapritinib and provide evidence‐based guidance on management of avapritinib‐associated adverse events (AEs), including cognitive effects and intracranial bleeding.Materials and MethodsWe performed a post hoc analysis of data from a two‐part, single‐arm dose escalation/expansion phase I study (NAVIGATOR; ) in patients with U/M GISTs treated with oral avapritinib 30–600 mg once daily. The primary endpoints were safety and tolerability; the impact of dose modification (interruption and/or reduction) on progression‐free survival (PFS) was a secondary endpoint. Efficacy analyses were limited to patients who started avapritinib at 300 mg (approved dose).ResultsOf 250 patients enrolled in the study, 74.0% presented with KIT mutation and 24.8% presented with PDGFRA exon 18‐mutation; 66.8% started avapritinib at 300 mg. The most common treatment‐related AEs (any grade) were nausea (59.2%), fatigue (50.0%), periorbital edema (42.0%), anemia (39.2%), diarrhea (36.0%), vomiting (36.0%), and increased lacrimation (30.8%). No treatment‐related deaths occurred. Among 167 patients starting on 300 mg avapritinib, all‐cause cognitive effects rate (grade 1–2) was 37.0% in all patients and 52.0% in patients ≥65 years. Cognitive effects improved to a lower grade more quickly with dose modification (1.3–3.1 weeks) than without (4.9–7.6 weeks). Median PFS was 11.4 months with dose modification and 7.2 months without.ConclusionTolerability‐guided dose modification of avapritinib is an effective strategy for managing AEs in patients with GISTs.Implications for PracticeEarly recognition of adverse events and tailored dose modification appear to be effective approaches for managing treatment‐related adverse events and maintaining patients on avapritinib. Dose reduction does not appear to result in reduced efficacy. Patients'' cognitive function should be assessed at baseline and monitored carefully throughout treatment with avapritinib for the onset of cognitive adverse events. Dose interruption is recommended at the first sign of any cognitive effect, including grade 1 events. NCT02508532相似文献
16.
Dickran Kazandjian Alexander Dew Elizabeth Hill Elizabeth Gil Ramirez Candis Morrison Esther Mena Liza Lindenberg Constance Yuan Irina Maric Hao-Wei Wang Katherine Calvo Alina Dulau-Florea Joseph Roswarski Michael Emanuel Raul Braylan Baris Turkbey Peter Choyke Kevin Camphausen Maryalice Stetler-Stevenson Seth M. Steinberg William D. Figg Jennifer C. Jones 《The oncologist》2021,26(4):288-e541
Lessons Learned
- Despite the initial optimism for using immune checkpoint inhibition in the treatment of multiple myeloma, subsequent clinical studies have been disappointing.
- Preclinical studies have suggested that priming the immune system with various modalities in addition to checkpoint inhibition may overcome the relative T‐cell exhaustion or senescence; however, in this small data set, radiotherapy with checkpoint inhibition did not appear to activate the antitumor immune response.
17.
Margaret E. Gatti-Mays Fatima H. Karzai Sanaz N. Soltani Alexandra Zimmer Jeffrey E. Green Min-Jung Lee Jane B. Trepel Akira Yuno Stanley Lipkowitz Jayakumar Nair Ann McCoy Jung-Min Lee 《The oncologist》2020,25(12):1013-e1824
Lessons Learned
- Monotherapy with prexasertib demonstrated modest activity in BRCA wild‐type, recurrent triple‐negative breast cancer, highlighting the unmet need for combination treatment strategies.
- Neutropenia, anemia, and thrombocytopenia are common with the use of prexasertib but are manageable with supportive care measures. Prophylactic use of granulocyte colony stimulating factor should be considered to avoid dose reductions or treatment delays.
- Pharmacodynamic studies showed prexasertib treatment induced DNA damage in peripheral immune cells.
18.
Chun A. Changou Her-Shyong Shiah Li-Tzong Chen Servina Liu Frank Luh Shwu-Huey Liu Yung-Chi Cheng Yun Yen 《The oncologist》2021,26(3):e367-e373
Lessons Learned
- A PHY906 and capecitabine combination could be effective as a salvage therapy for patients with hepatocellular carcinoma (HCC) previously treated with multiple systemic therapies.
- This traditional Chinese medicine formulation can work with Western cancer chemotherapeutic agents to improve clinical outcomes or alleviate side effects for patients with advanced HCC.
19.
《Annals of oncology》2018,29(6):1423-1430
BackgroundThe addition of bevacizumab to temozolomide-based chemoradiotherapy (TMZ/RT → TMZ) did not prolong overall survival (OS) in patients with newly diagnosed glioblastoma in phase III trials. Elderly and frail patients are underrepresented in clinical trials, but early reports suggested preferential benefit in this population.Patients and methodsARTE was a 2 : 1 randomized, multi-center, open-label, non-comparative phase II trial of hypofractionated RT (40 Gy in 15 fractions) with bevacizumab (10 mg/kg×14 days) (arm A, N = 50) or without bevacizumab (arm B, N = 25) in patients with newly diagnosed glioblastoma aged ≥65 years. The primary objective was to obtain evidence for prolongation of median OS by the addition of bevacizumab to RT. Response was assessed by RANO criteria. Quality of life (QoL) was monitored by the EORTC QLQ-C30/BN20 modules. Exploratory studies included molecular subtyping by 450k whole methylome and gene expression analyses.ResultsMedian PFS was longer in arm A than in arm B (7.6 and 4.8 months, P = 0.003), but OS was similar (12.1 and 12.2 months, P = 0.77). Clinical deterioration was delayed and more patients came off steroids in arm A. Prolonged PFS in arm A was confined to tumors with the receptor tyrosine kinase (RTK) I methylation subtype (HR 0.25, P = 0.014) and proneural gene expression (HR 0.29, P = 0.025). In a Cox model of OS controlling for established prognostic factors, associations with more favorable outcome were identified for age <70 years (HR 0.52, P = 0.018) and Karnofsky performance score 90%–100% (HR 0.51, P = 0.026). Including molecular subtypes into that model identified an association of the RTK II gene methylation subtype with inferior OS (HR 1.73, P = 0.076).ConclusionEfficacy outcomes and exploratory analyses of ARTE do not support the hypothesis that the addition of bevacizumab to RT generally prolongs survival in elderly glioblastoma patients. Molecular biomarkers may identify patients with preferential benefit from bevacizumab.Clinical trial registration numberNCT01443676. 相似文献
20.
Pei Yang Wei Zhang Yinyan Wang Xiaoxia Peng Baoshi Chen Xiaoguang Qiu Guilin Li Shouwei Li Chenxing Wu Kun Yao Wenbin Li Wei Yan Jie Li Yongping You Clark C. Chen Tao Jiang 《Oncotarget》2015,6(38):40896-40906