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1.
T. Korkmaz S. Seber U. Kefeli E. Sari M. Canhoroz B. Oven E. Yildirim N. Yasar D. Aydin O. Balvan N. Sener S. Yuksel A. Mert O. Polat F. Yumuk O. Kanat M. Gumus N. S. Turhal 《Clinical & translational oncology》2013,15(7):535-540
Purpose
Small cell lung cancer (SCLC) has a high relapse rate despite being very chemosensitive. The efficacy of second-line treatment is dismal. Our aim was to evaluate the outcome of second-line treatment.Methods
We retrospectively assessed data of 120 SCLC patients who failed first-line treatment and received second-line treatment at three medical oncology centers.Results
Median age of group was 58. 82 % had an ECOG PS of 0–1 at the time of relapse. 39 % were at limited stage (LS) at the time of diagnosis. Patients who progressed more than 3 months after first-line therapy were categorized as having platinum-sensitive disease (PSD) (64 %). The number of patients who received platin-based combination treatment was 33 (27 %). The median OS time starting from the initiation of second-line treatment was 7 months. Multivariate analysis identified PS (p = 0.006), extent of disease at diagnosis (0.014) and PSD (0.001) as the independent prognostic factors for survival. Subgroup analyses of the patients with PSD indicated platin rechallenge yields higher progression-free survival, overall survival and overall response rate.Conclusion
Patients with good ECOG PS,who have PSD or initially presenting with LS, have a good prognosis and in patients with PSD, platinum-based therapy would be more appropriate. 相似文献2.
Zhenhua Fan Tao Ouyang Jinfeng Li Tianfeng Wang Zhaoqing Fan Tie Fan Benyao Lin Ye Xu Yuntao Xie 《Breast cancer research and treatment》2018,167(1):59-71
Purpose
The estrogen receptor (ER) is involved in control of progesterone receptor (PgR) expression and lack of PgR may be also a surrogate of altered growth factor signaling. The aim of this study was therefore to investigate PgR expression as predictive factor for response to neoadjuvant therapy and long-term outcome.Methods
Five thousand and six hundred and thirteen patients with primary breast cancer and positive ER expression from ten German neoadjuvant trials of anthracycline and taxane-based chemotherapy were included. Pathologic complete response (pCR), disease-free survival (DFS), distant disease-free survival (DDFS), overall survival (OS), and local recurrence-free survival (LRFS) were compared according to PgR expression.Results
The lack of PgR expression (1172 patients) was associated with grade 3 (38.4 vs. 26.3%; p < 0.001), nodal involvement (>cN2) (6.8% vs. 4.7%; p = 0.004), and HER2 positivity (36.2 vs. 22.3%; p < 0.001). pCR rates of PgR-negative tumors were higher in the entire cohort (13.8 vs. 7.5%; p < 0.001) and in the HER2-negative subgroup (11.2 vs. 5.8%; p < 0.001). In multivariable logistic regression, PgR negativity was an independent predictive factor for pCR overall (OR 1.76; p < 0.001) and in the HER2-negative patients (OR 1.99; p < 0.001). Patients with PgR-negative disease had significantly worse outcome (p < 0.001, respectively). Multivariable Cox regression analysis revealed that PgR was an independent prognostic factor for DFS, OS, DDFS, and LRFS.Conclusion
ER-positive/PgR-negative breast carcinomas are associated with higher response but also worse long-term outcome after neoadjuvant therapy. PgR negativity is an independent predictive factor for pCR after neoadjuvant chemotherapy in ER-positive HER2-negative breast cancer.3.
Junichi Kurebayashi Naoki Kanomata Toshiro Shimo Tetsumasa Yamashita Kenjiro Aogi Rieko Nishimura Chikako Shimizu Hitoshi Tsuda Takuya Moriya Hiroshi Sonoo 《Breast cancer (Tokyo, Japan)》2014,21(2):214-222
Purpose
Whether postoperative chemotherapy should be added to endocrine therapy or not is an important issue in patients with hormone receptor-positive and human epidermal growth factor receptor (HER)2-negative breast cancer. To identify patients who should be treated with additional chemotherapy, prognostic factors were investigated in breast cancer patients postoperatively treated with endocrine therapy alone.Patients and methods
Tumor samples and clinicopathological data were collected from patients who underwent curative surgery and were postoperatively treated with endocrine therapy alone between 1999 and 2003 in three different institutes. Expression levels of estrogen receptor (ER), progesterone receptor (PgR), and HER2 in primary tumors were centrally retested. Patients with ER-negative and/or HER2-positive tumors and/or with unknown nodal status were excluded from the study subjects. Immunohistochemical analysis of Ki67, HER1, insulin-like growth factor-1 receptor, and aldehyde dehydrogenase-1 was also performed. Prognostic factors were investigated by univariate and multivariate analyses.Results
A total of 261 patients were the subjects of this study. The median age was 59 years old, the mean tumor size was 1.9 cm, the node-positive rate was 20 %, and 65 % received tamoxifen alone. Distant metastases were observed in 11 patients at a median follow-up of 98 months, and four patients had died of breast cancer at a median follow-up of 99 months. Univariate analysis showed that marked lymphovascular invasion (LVI), PgR negativity, high Ki67 labeling index (LI), and high nuclear grade were significantly worse prognostic factors for distant metastasis. Multivariate analysis revealed that marked LVI [hazard ratio (HR) 21.8] and PgR negativity (HR 10.3) were independently worse prognostic factors for distant metastasis, respectively. Multivariate analysis also revealed that marked LVI (HR 287.3), PgR negativity (HR 25.1), and high Ki67 LI (HR 19.6) were independently worse prognostic factors for breast cancer-specific death, respectively.Conclusions
The results of this multi-institute cohort study indicated that endocrine therapy alone could not prevent distant metastasis in breast cancer patients with PgR-negative tumors and/or with tumors showing marked LVI or high cell proliferation. These patients may need postoperative adjuvant chemotherapy in addition to endocrine therapy. 相似文献4.
Valentina Fanotto Stefano Cordio Giulia Pasquini Caterina Fontanella Lorenza Rimassa Francesco Leone Gerardo Rosati Daniele Santini Riccardo Giampieri Samantha Di Donato Gianluca Tomasello Nicola Silvestris Filippo Pietrantonio Francesca Battaglin Antonio Avallone Mario Scartozzi Eufemia Stefania Lutrino Davide Melisi Lorenzo Antonuzzo Antonio Pellegrino Valter Torri Giuseppe Aprile 《Gastric cancer》2017,20(5):825-833
Background
Although second-line therapy is often considered for advanced gastric cancer patients, the optimal candidates are not well defined.Methods
We retrospectively collected baseline parameters, tumour features, and treatment data for 868 advanced gastric cancer patients exposed to multiple treatment lines at 19 Italian centres. Cross-tables and chi-square tests were used to describe categorical features. To predict the impact of clinical variables on progression-free survival and overall survival, Kaplan–Meier and Cox regression analyses were performed.Results
At the start of second-line therapy, median age was 64.8 years (25th–75th percentiles: 55.2–71.9 years). Overall, 43% of patients received single-agent chemotherapy, 47.4% a doublet, and 7.3% a triplet. Median second-line progression-free survival was 2.8 months (25th–75th percentiles: 1.8–5.2 months) and median second-line overall survival was 5.6 months (25th–75th percentiles: 2.9–10.0 months). Multivariate analysis showed that performance status, LDH level, neutrophils/lymphocytes ratio, and progression-free survival in the first-line therapy all impacted on prognosis. Based on these four prognostic factors, a prognostic index was constructed that divided patients into good, intermediate, and poor risk groups; median second-line overall survival for each group was 7.7, 4.5, and 2.0 months, respectively (log-rank p < 0.0001).Conclusions
Advanced gastric cancer patients with a favourable ECOG performance status, lower LDH levels, and a lower neutrophils/lymphocytes ratio at the start of second-line therapy seem to have better outcomes, regardless of age and intensity of treatment. A longer progression-free survival in the first-line therapy also had positive prognostic value. Our real-life study might help clinicians to identify the patients who may benefit most from a second-line therapy.5.
Daneng Li Linda M. McCall Olwen M. Hahn Clifford A. Hudis Harvey J. Cohen Hyman B. Muss Aminah Jatoi Jacqueline M. Lafky Karla V. Ballman Eric P. Winer Debu Tripathy Bryan Schneider William Barry Maura N. Dickler Arti Hurria 《Breast cancer research and treatment》2018,171(2):325-334
Background
In hormone receptor-positive advanced breast cancer, a progression-free survival benefit was reported with addition of bevacizumab to first-line letrozole. However, increased toxicity was observed. We hypothesized that functional age measures could be used to identify patients at risk for toxicity while receiving letrozole plus bevacizumab for hormone receptor-positive advanced breast cancer.Methods
CALGB 40503 was a phase III trial that enrolled patients with hormone receptor-positive advanced breast cancer randomized to letrozole with or without bevacizumab. Patients randomized to bevacizumab were approached to complete a validated assessment tool evaluating physical function, comorbidity, cognition, psychological state, social support, and nutritional status. The relationship between pretreatment assessment measures and the incidence of grade?≥?3 (National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0) adverse events was determined.Results
One hundred thirteen (58%) of 195 patients treated with letrozole plus bevacizumab completed the pretreatment assessment questionnaire. One patient was excluded due to missing adverse event data. The median age of patients was 56. Frequently reported grade?≥?3 adverse events were hypertension (26%), pain (20%), and proteinuria (7%). Two hemorrhagic events (one grade 5) and 1 thrombosis event occurred. Age?≥?65 years (p?<?0.01), decreased vision (p?=?0.04), and poorer pretreatment physical function measures (p?<?0.05) were found on univariate analysis to be significantly associated with increased incidence of grade?≥?3 adverse events. Upon multivariate analysis, age?≥?65 years (p?=?0.01) and decreased vision (p?=?0.04) remained significant. Univariable and multivariable logistic regression models demonstrated associations between age, vision, the ability to walk up flights of stairs, and grade?≥?3 adverse events.Conclusions
Age (≥?65 years), decreased vision, and impairments in physical function correlated with increased incidence of toxicity in patients receiving first-line letrozole plus bevacizumab. When evaluating therapy likely to increase toxicity, functional assessment measures can identify patients at increased risk for side effects who may benefit from closer monitoring.6.
Saori Fujiwara Mutsuko Ibusuki Satoko Yamamoto Yutaka Yamamoto Hirotaka Iwase 《Breast cancer (Tokyo, Japan)》2014,21(4):472-481
Background
Human epidermal growth factor receptor type 2 (Her2)/ErbB2 plays a key role in the initiation and progression of invasive breast cancer. However, the prognostic relevance to breast cancer patients of the other ErbB family members has long been a matter of debate.Methods
In a series of 250 primary invasive breast cancer patients, we performed a comprehensive analysis of ErbB1–4 at the levels of mRNA expression and gene copy number using real-time quantitative PCR. The relationship between the status of ErbB1–4 and the clinicopathological characteristics or prognosis was evaluated.Results
The mRNA expression of ErbB2, but not the other ErbB genes, was significantly correlated to copy number (P = 0.0005). ErbB3 and ErbB4 mRNA expression were positively correlated to each other (P < 0.0001). The mRNA expression of ErbB1/2 was inversely correlated to estrogen receptor (ER) and progesterone receptor (PgR) positivity, although mRNA expression of ErbB3/4 was positively correlated to ER and PgR positivity. Kaplan-Meier survival analysis showed that ErbB1 mRNA expression was associated with reduced survival. Neither ErbB2 nor ErbB3 mRNA expression had any association with survival, because half of the patients with Her2-positive tumors were treated with trastuzumab. High ErbB4 mRNA expression showed good prognosis with respect to breast cancer-specific survivalConclusions
ErbB3 and ErbB4 mRNA expression, as well as well as that of ErbB1 and ErbB2, could be histopathological factors. ErbB3 mRNA was highly expressed in ER-positive tumors and has controversial prognostic value. ErbB4 mRNA expression was well correlated with ER positivity and good prognosis, indicating that ErbB4 may contribute to ER-dependent growth. 相似文献7.
Yutaka Ueda Takayuki Enomoto Shinya Matsuzaki Eiji Kobayashi Toshihiro Kimura Kiyoshi Yoshino Masami Fujita Tateki Tsutsui Tadashi Kimura 《Cancer chemotherapy and pharmacology》2013,71(6):1411-1416
Purpose
The aim of the present study was to investigate, in ovarian carcinoma cases, the predictive association between the treatment-free interval (TFI) after an initial paclitaxel plus carboplatin (TC) therapy and the subsequent effectiveness of a second-line taxane-containing chemotherapy.Methods
Patients with a TFI < 6 months from the first-line TC therapy were treated with a combination chemotherapy using docetaxel and irinotecan; patients with a TFI ≥ 6 months were retreated with the same regimen as the initial TC therapy. The clinical data of these patients were retrospectively analyzed for this study.Results
The response rate of those with a TFI equal to 6–12 months was greater than that of those with a TFI < 6 months (p = 0.014) and less than that of those with a TFI > 12 months (p = 0.012). The progression-free survival of the cases with TFI equal to 6–12 months was longer than that of those with TFI < 6 months (p = 0.012) and shorter than that of those with TFI > 12 months (p = 0.0011). Overall survival of cases with a TFI equal to 6–12 months was longer than that of those with TFI < 6 months (p = 0.012) and shorter than that of those with TFI > 12 months (p = 0.0005).Conclusions
The effectiveness of using a second-line taxane-containing chemotherapy was shown to be predictable by the TFI after the first-line taxane-containing chemotherapy, implying that the theory of ‘taxane-sensitivity’ may be applied for second-line chemotherapy in the same way as that of ‘platinum-sensitivity’. 相似文献8.
Toni Roeke Marcelo Sobral-Leite Tim J. A. Dekker Jelle Wesseling Vincent T. H. B. M. Smit Rob A. E. M. Tollenaar Marjanka K. Schmidt Wilma E. Mesker 《Breast cancer research and treatment》2017,166(2):435-445
Purpose
The primary aim of the current study is to validate the prognostic relevance of the relative amount of tumour-associated stroma, the tumour-stroma ratio, in a large cohort of primary operable breast cancer patients.Methods
A retrospective cohort study was performed on women diagnosed and treated for primarily operable invasive breast cancer in the period from 1 January 1990 till 31 December 1999. Tumour-stroma ratio was estimated by microscopic evaluation of haematoxylin and eosin tumour slides. Two independent observers (k = 0.68) performed tumour-stroma ratio evaluation in a significant part of the cohort. The prognostic potential with respect to overall, recurrence-free and distant metastasis-free survival was evaluated.Results
A total of n = 737 women were evaluated. Median follow-up time was 11.5 years. High stromal content was an independent prognosticator for worse overall (hazard ratio 1.56, p = 0.002, 95% confidence interval 1.18–2.05), distant metastasis-free (hazard ratio 1.52, p = 0.008, 95% confidence interval 1.12–2.06) and recurrence-free survival (hazard ratio 1.35, p = 0.046, 95% confidence interval 1.01–1.81). In subgroups of hormone receptor-positive and lymph node-negative cases, high stromal content was also an independent prognosticator for worse outcome.Conclusion
Tumour-stroma ratio is an independent risk factor for worse overall, distant metastasis-free and recurrence-free survival in primarily operable breast cancer. However, detailed prospective studies with respect to tumour-stroma ratio are necessary to gain more insight in its prognostic potential in clinical practice.9.
K. Pliarchopoulou K. T. Kalogeras R. Kronenwett R. M. Wirtz A. G. Eleftheraki A. Batistatou M. Bobos N. Soupos G. Polychronidou H. Gogas E. Samantas C. Christodoulou T. Makatsoris N. Pavlidis D. Pectasides G. Fountzilas 《Cancer chemotherapy and pharmacology》2013,71(1):245-255
Purpose
RACGAP1 is a Rac GTPase-activating protein involved in cell growth regulation, cell transformation and metastasis. The aim of the present study was to explore the prognostic and/or predictive significance of RACGAP1 mRNA expression on disease-free survival (DFS) and overall survival (OS) in high-risk early breast cancer patients and compare it to that of Ki67 protein expression and to the Nottingham prognostic index (NPI).Methods
A total of 595 high-risk breast cancer patients were treated in a two-arm trial evaluating postoperative dose-dense sequential chemotherapy with epirubicin followed by CMF with or without paclitaxel. RNA was extracted from 314 formalin-fixed paraffin-embedded primary tumor tissue samples followed by one-step quantitative RT-PCR for assessing RACGAP1 mRNA expression.Results
High RACGAP1 mRNA expression (above the median) was associated with poor DFS (log-rank, p = 0.002) and OS (p < 0.001). High histological grade, as well as high Ki67 protein expression, was more frequent in the high-expression group of RACGAP1. Results of the Cox multivariate regression analysis revealed that high RACGAP1 mRNA expression independently predicted poor overall survival (Wald’s p = 0.008). High Ki67 protein expression was also an adverse prognostic factor for death (p = 0.016), while high NPI score values were not.Conclusions
High RACGAP1 mRNA expression, as assessed by qRT-PCR, was found to be of adverse prognostic significance in high-risk early breast cancer patients treated with dose-dense sequential chemotherapy. The utility of RACGAP1 mRNA expression in patient selection for treatment with aggressive chemotherapy regimens should be further explored and validated in larger cohorts. 相似文献10.
Objective
This retrospective analysis evaluates the clinical outcomes of extensive-stage small cell lung cancer (SCLC) patients who received second-line chemotherapy after platinum-based first-line chemotherapy, especially focusing on efficacy and toxicity between single-agent and combination chemotherapy.Methods
We retrospectively reviewed 193 patients who received second-line chemotherapy for extensive-stage SCLC. Patients relapsing or progressing beyond 90 days were defined as sensitive recurrence patients, and below 90 days as refractory recurrence patients. Survival curves were plotted using the Kaplan–Meier method. The Cox proportional hazard model was used for multivariate analysis.Results
138 patients received combination chemotherapy and 55 received single-agent treatment. The objective response rate (ORR) was 25.4 % in the combination group and 9.1 % in the single-agent group (p = 0.012). The disease control rate (DCR) was 65.2 and 34.5 %, respectively, (p < 0.001). The progression-free survival (PFS) was 3.80 months in the combination group and 2.13 months in the single-agent group (p = 0.001). In the sensitive recurrence group, the median PFS was 3.80 months in combination group and 3.23 months in single-agent group (p = 0.092). In the refractory recurrence group, the median PFS was 2.83 and 1.30 months, respectively (p = 0.001). The grade III/IV toxicity in single-agent group is much lower than the combination group (56.4 vs. 74.6 %, p = 0.013).Conclusion
Our retrospective data suggest a potential role of prolonging the PFS for combination treatment in extensive-stage SCLC second-line treatment, especially for the refractory recurrence patients, but with more toxicity as compared to single-agent. 相似文献11.
Yong Wha Moon Sun Young Rha Hei-Cheul Jeung Chan Kim Min Hee Hong Hyun Chang Jae Kyung Roh Sung Hoon Noh Byung Soo Kim Hyun Cheol Chung 《Cancer chemotherapy and pharmacology》2010,66(4):797-805
Purpose
We analyzed the natural history of advanced gastric cancer with sequential salvage chemotherapy following first-line treatment.Methods
We studied 532 patients with unresectable gastric adenocarcinoma who were treated at Yonsei Cancer Center (2000–2008). The patients were managed with multiple sequential salvage chemotherapy as allowed by performance status and toxicity profiles. The tumor response was assessed every two cycles.Results
Four hundred sixty patients received palliative chemotherapy and 72 received supportive care only. The median overall survival was 12.0 months for all patients, 12.1 months for the chemotherapy group, and 2.5 months for the supportive care group (P < 0.001). In the chemotherapy group, 87% received first-line chemotherapy, 47% second-line, 23% third-line, 9% fourth-line, and 3% fifth-line. Response rates were 24.8, 12.6, 10.9, 2.6, and 0% and disease control rates were 76.3, 60.1, 54.2, 54.2, and 53.3% for first- to fifth-line treatment, respectively. The median progression-free survival was 5.5, 3.4, 2.5, 1.9, and 2.0 months and overall survival was 12.1, 7.9, 5.5, 5.0, and 6.8 months. Performance status and metastatic pattern were consistent prognostic factors throughout salvage treatment.Conclusions
Clinical trials may be feasible in second- or third-line salvage chemotherapy for gastric cancer. Future clinical trials in these settings should take into account the low response rate, short progression-free survival, and the prognostic factors for optimal trial design. 相似文献12.
Taku Naiki Noriyasu Kawai Yoshihiro Hashimoto Takehiko Okamura Ryosuke Ando Takahiro Yasui Atsushi Okada Toshiki Etani Keiichi Tozawa Kenjiro Kohri 《International journal of clinical oncology / Japan Society of Clinical Oncology》2014,19(3):516-522
Background
The objective of this study was to evaluate the efficacy of a gemcitabine and docetaxel (GD) combination as a second-line treatment for patients with metastatic urothelial carcinoma (UC) after failure of first-line treatment with platinum-based chemotherapy.Methods
From June 2006 to January 2012, 38 patients with metastatic UC previously treated with platinum-based chemotherapy received GD therapy. This consisted of gemcitabine 800 mg/m2 and docetaxel 40 mg/m2 on days 1 and 8 of each 21-day cycle as second-line chemotherapy. All the patients were evaluated for toxicity and assessed every cycle by imaging. We analyzed the efficacy of GD as second-line chemotherapy in the follow-up study.Results
The median number of GD treatment cycles was 4 (range 2–9); the objective response rate was 47.4 %; and the median progression-free survival and median overall survival were 4.1 and 10.8 months, respectively. Univariate and multivariate analyses on the GD treated group showed that the existence of lung metastases was the only prognostic factor for tumor response. Grade 3 treatment-related toxicity included neutropenia (31.6 %) and thrombocytopenia (15.8 %), and only one patient with grade 4 toxicity had thrombocytopenia (2.6 %).Conclusions
The GD regimen as second-line chemotherapy was especially effective for lung metastatic UC and yielded favorable results in patients whose first-line platinum-based chemotherapy had failed. Given the safety and benefit profile seen in this study, a large prospective study is warranted to consider the potential utility of GD chemotherapy as a second-line for UC. 相似文献13.
Ji-Won Kim Jee Hyun Kim Seock-Ah Im Kyung-Hun Lee Jin-Soo Kim Tae-Yong Kim Sae-Won Han Yoon Kyung Jeon Do-Youn Oh Tae-You Kim In Ae Park 《Cancer chemotherapy and pharmacology》2013,72(5):1023-1029
Purpose
Epidermal growth factor (EGF) is a ligand for the epidermal growth factor receptor (EGFR). Human epidermal growth factor receptor 2 (HER2) shares common signal pathways and forms a heterodimer with EGFR. In this study, we investigated the clinical and pathologic implications of serum EGF levels in patients with HER2-positive metastatic breast cancer (MBC).Methods
We analyzed serum EGF levels from baseline serum samples of consecutive patients with HER2-positive MBC who received first-line trastuzumab plus taxane chemotherapy and correlated them with treatment outcomes and pathologic features.Results
A total of 50 women were analyzed. The median age was 47 years (range 27–72 years). Patients with high serum EGF levels (≥10.0 pg/mL) had significantly longer overall survival (47.0 months (95 % confidence interval (CI) 28.3–65.7 months) vs. 23.3 months (95 % CI 13.5–33.1 months); p = 0.009) with a tendency toward longer progression-free survival (p = 0.123). Serum EGF levels were not associated with hematologic or cardiac adverse events. Progesterone receptor-positive patients had significantly higher serum EGF levels than progesterone receptor-negative patients (24.3 pg/mL (range 9.5–69.0 pg/mL) vs. 12.3 pg/mL (range 0.0–59.5 pg/mL); p = 0.006).Conclusions
Our data suggest that high serum EGF levels may be associated with good prognosis in patients with HER2-positive MBC receiving trastuzumab plus taxane chemotherapy. In addition, serum EGF levels were associated with progesterone receptor positivity. 相似文献14.
Andrew Robinson Osama Souied A. Brianne Bota Nathalie Levasseur Carol Stober John Hilton Dalia Kamel Brian Hutton Lisa Vandermeer Sasha Mazzarello Anil A. Joy Dean Fergusson Sheryl McDiarmid Mathew McInnes Risa Shorr Mark Clemons 《Breast cancer research and treatment》2018,167(3):607-614
Purpose
Prospective information regarding the tolerability and efficacy of endocrine therapy (ET) alone and in combination with targeted agents in older patients in the metastatic setting is limited. This review summarizes available trial data in this population.Methods
We searched PubMed for Phase 2 or 3 trials with age-stratified patient cohorts (≥ 65 vs. < 65 years in most studies) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2?) advanced breast cancer treated with ET ± targeted agents.Results
We identified 19 studies reporting 10 clinical trials. Efficacy was similar in age-stratified subsets. There was a reduced disease progression risk for ET + everolimus, palbociclib, or ribociclib versus ET alone. In the first-line setting, median progression-free survival (mPFS) in older patients was 8.5, 26.2 months, and not reached with letrozole + temsirolimus, palbociclib, and ribociclib, respectively, and in younger patients was 9.0, 18.8 months, and not reached, respectively. In the second-line setting, older patients had mPFS of 6.8 and 9.9 months with everolimus + exemestane and palbociclib + fulvestrant, respectively, and younger patients had mPFS of 8.1 and 9.5 months, respectively. Tolerability was worse for combination therapy versus monotherapy. No age-related differences in discontinuations were observed for CDK4/6 inhibitors, although a higher rate of treatment discontinuation was observed for patients ≥ 70 years receiving everolimus + exemestane. Adverse event rates were similar in age-stratified subsets.Conclusions
ET + CDK4/6 or mTOR inhibitors are likely safe and effective in older patients with HR+, HER2? advanced breast cancer.15.
Jerevall PL Brommesson S Strand C Gruvberger-Saal S Malmström P Nordenskjöld B Wingren S Söderkvist P Fernö M Stål O 《Breast cancer research and treatment》2008,107(2):225-234
Background
The two-gene expression ratio HOXB13:IL17BR has been proposed to predict the outcome of tamoxifen-treated breast cancer patients. We intended to examine whether this ratio can predict the benefit of 5 years vs. 2 years of tamoxifen treatment of postmenopausal patients. A further objective was to investigate any prognostic effects of the ratio in systematically untreated premenopausal patients. Based on the current knowledge of HOXB13 and IL17BR, we hypothesized that these genes may have individual prognostic or predictive power.Patients and methods
Expression of HOXB13 and IL17BR were quantified by real-time PCR in tumors from 264 randomized postmenopausal patients and 93 systemically untreated premenopausal patients.Results
A high HOXB13:IL17BR ratio was associated with aggressive tumor characteristics, as were low levels of IL17BR alone. The ratio and HOXB13 alone predicted recurrence-free survival after endocrine treatment, with a benefit of prolonged treatment in estrogen receptor-positive patients correlated to a low ratio (recurrence rate ratio: RR = 0.39; P = 0.030), or low expression of HOXB13 (RR = 0.37; P = 0.015). No difference in recurrence-free survival was seen for the high ratio or high HOXB13 subgroups. The predictive value of HOXB13 and HOXB13:IL17BR was significant in multivariate analysis. In the systemically untreated cohort, only IL17BR showed independent prognostic significance.Conclusion
We conclude that the ratio or HOXB13 alone can predict the benefit of endocrine therapy, with a high ratio or a high expression rendering patients less likely to respond. We have also shown that IL17BR might be an independent prognostic factor in breast cancer. 相似文献16.
Akiko Kawano Takako Eguchi Nakajima Ichiro Oda Nobukazu Hokamura Satoru Iwasa Ken Kato Tetsuya Hamaguchi Yasuhide Yamada Hirofumi Fujii Yasuhiro Shimada 《Gastric cancer》2014,17(1):54-60
Background
There have been no reports on the incidence, characteristics, treatment outcomes, and prognosis of inoperably advanced or recurrent adenocarcinoma of the esophagogastric junction (AEGJ) in Japan.Methods
We investigated the clinicopathological characteristics, treatment outcomes, and prognosis for 816 patients with esophagogastric junctional and gastric adenocarcinoma who received first-line chemotherapy between 2004 and 2009.Results
Of 816 patients, 82 (10 %) had AEGJ. The patients with AEGJ had significantly more lung and lymph node metastasis, but less peritoneal metastasis, than those with gastric adenocarcinoma (GAC). The objective response rate to first-line chemotherapy was 23.3 % for patients with AEGJ and 22.6 % in patients with GAC (p = 0.90). The median survival was 13.0 months in AEGJ and 11.8 months in GAC (p = 0.445). In no patient was tumor site a significant prognostic factor (p = 0.472). In patients with AEGJ, ECOG PS ≥ 2, presence of liver metastasis, and absence of lung metastasis were significantly associated with poor prognosis.Conclusions
No significant differences were observed in treatment outcomes between advanced AEGJ and GAC. Therefore, the same chemotherapy regimen can be given as a treatment arm in future Japanese clinical trials to both patients with inoperably advanced or recurrent AEGJ and those with GAC. 相似文献17.
A. Carrato A. Gómez P. Escudero M. Chaves F. Rivera E. Marcuello E. González C. Grávalos M. Constenla J. Luis Manzano F. Losa J. Maurel R. Dueñas B. Massuti J. Gallego J. Aparicio A. Antón E. Aranda 《Clinical & translational oncology》2013,15(9):705-711
Purpose
To evaluate the efficacy and safety profile of the combination of panitumumab and irinotecan every 3 weeks in a phase II trial as second-line treatment in patients with advanced wild-type (WT) K-RAS colorectal cancer (CRC).Methods
Fifty-three patients received 9 mg/kg of panitumumab followed by 350 mg/m2 of irinotecan every 21 days until disease progression, unacceptable toxicity or consent withdrawal.Results
Median age of patients included was 67 years. All patients had previously received 5-fluorouracil, 84 % oxaliplatin and 8 % irinotecan as first-line treatment. Patients received a median of five infusions of panitumumab and irinotecan. On an intention-to-treat analysis, 12 patients (23 %) achieved partial responses and 22 patients (41 %) achieved disease stabilization. Median progression-free survival and overall survival were 4.5 and 15.1 months, respectively. The most frequent treatment-related severe toxicities per patient were diarrhoea (35.8 %), followed by skin rash (32.1 %), asthenia (18.9 %) and neutropenia (13.2 %). A significant association between clinical response and incidence and grade of skin toxicity was observed (p = 0.0032).Conclusion
This study shows that the administration of panitumumab plus irinotecan every 3 weeks is safe, active and feasible as second-line treatment in patients with advanced WT K-RAS CRC. 相似文献18.
Erion Dobi Fernando Bazan Armelle Dufresne Martin Demarchi Cristian Villanueva Loic Chaigneau Philipe Montcuquet Arben Ivanaj Jean Loup Sautière Yolande Maisonnette-Escot Laurent Cals Marie Paule Algros Anne-Sophie Woronoff Xavier Pivot 《International journal of clinical oncology / Japan Society of Clinical Oncology》2013,18(4):607-613
Background
This study searched for extra capsular tumour spread (ECS) as a prognostic factor for recurrence in terms of Disease Free Survival (DFS) and Overall Survival (OS).Patients and methods
For this study, from a retrospective database of the Doubs cancer registry, 823 eligible women with node positive breast cancer treated from February 1984 to November 2000 were identified. The following factors were evaluated: ECS, numbers of involved nodes, histological tumour grade, tumour size, status of estrogen and progesterone receptors, and age of patient. A Cox proportional hazards method was used to search for significant factors related to OS and DFS length.Results
In the multivariate analysis, factors related to DFS length were found to be: tumour grade (aHR 0.76, 95 % CI 0.61–0.96, p = 0.02), ECS status (aHR 0.7, 95 % CI 0.49–0.96, p = 0.03), progesterone (PgR) status (aHR 0.63, 95 % CI 0.44–0.85 p = 0.008), number of nodes involved (aHR 0.75, 95 % CI 0.56–1, p = 0.05). The multivariate analysis for OS found as significant factors: tumour grade (aHR 0.76, 95 % CI 0.61–0.95; p = 0.02) and PgR status (aHR 0.8, 95 % CI 0.56–0.99, p = 0.02).Conclusions
This study might suggest taking into account ECS status in the adjuvant decision-making process. 相似文献19.
Yukinori Ozaki Yuko Tanabe Nobuko Tamura Takuya Ogura Chihiro Kondoh Yuji Miura Kenichi Yoshimura Hidetaka Kawabata Toshimi Takano 《Breast cancer (Tokyo, Japan)》2018,25(3):343-349
Introduction
Although tamoxifen (TAM) plus ovarian function suppression (OFS) is considered as a standard adjuvant treatment for premenopausal women with hormone receptor-positive breast cancer, the optimal duration of OFS has not yet been established. This retrospective study was designed to assess the duration of OFS and the impact of the duration of OFS on the DFS in these patients.Methods
We retrospectively reviewed the data of premenopausal patients with breast cancer who received TAM + OFS (goserelin or leuprorelin) as adjuvant therapy between February 2004 and June 2015. The primary analysis was a comparison of the disease-free survival (DFS) between patients who received OFS for 3 years or less (OFS ≤ 3 years group) and those who received OFS for longer than 3 years (OFS > 3 years group).Results
We analyzed the data of 215 premenopausal patients diagnosed as having hormone receptor-positive breast cancer. A propensity score-matched model showed the absence of any significant difference in the DFS between the OFS ≤ 3 years group and OFS > 3 years group (6-year DFS rate, 93.2 vs. 94.0%; log-rank test p = 0.767).Conclusions
Our data showed that among premenopausal women with hormone receptor-positive breast cancer who received TAM + OFS as adjuvant endocrine therapy, there was no significant difference in the DFS between the OFS ≤ 3-year group and OFS > 3-year group. A randomized trial is needed to establish the optimal duration of OFS for these patients.20.
Daisuke Shimizu Takashi Ishikawa Mikiko Tanabe Takeshi Sasaki Yasushi Ichikawa Takashi Chishima Itaru Endo 《Breast cancer (Tokyo, Japan)》2014,21(5):557-562