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1.
Kim ST Uhm JE Lee J Sun JM Sohn I Kim SW Jung SH Park YH Ahn JS Park K Ahn MJ 《Lung cancer (Amsterdam, Netherlands)》2012,75(1):82-88
Purpose
Gefitinib and erlotinib are potent EGFR TKIs, with antitumor activity. In this randomized, single-center, non-comparative phase II trial, the efficacy and safety of gefitinib and erlotinib was evaluated as the second-line therapy for advanced non-small cell lung cancer (NSCLC).Patients and methods
Patients with locally advanced, metastatic stage IIIB/IV NSCLC who failed first-line chemotherapy and had either EGFR mutation or at least two out of three clinical factors associated with higher incidence of EGFR mutations (female, adenocarcinoma histology, and never-smoker) were eligible.Results
A total of 96 (48 per arm) patients were randomly assigned to gefitinib- or erlotinib-arm, respectively. Baseline characteristics were well-balanced between the two arms. The response rates (RR) were 47.9% in the gefitinib arm and 39.6% in the erlotinib arm. Median PFS was 4.9 months (95% CI, 1.3-8.5) in the gefitinib arm and 3.1 months (95% CI, 0.0-6.4) in the erlotinib arm. The most common grade 3/4 toxicity was skin rash. Exploratory analyses showed that there was no significant difference in RR and PFS in the gefitinib arm compared to the erlotinib arm (RR (%) 47.9 vs. 39.6, p = 0.269; median survival (months) 4.9 vs. 3.1, p = 0.336). There was no significant difference in QOL between the two arms.Conclusion
Both gefitinib and erlotinib showed effective activity and tolerable toxicity profiles as second-line treatment for the selected population of NSCLC. We may consider conducting a phase III trial to directly compare the efficacy and toxicity between gefitinib and erlotinib in an enriched patient population. 相似文献2.
Jenn-Yu WuShang-Gin Wu Chih-Hsin YangYih-Leong Chang Yeun-Chung ChangYa-Chieh Hsu Jin-Yuan Shih Pan-Chyr Yang 《Lung cancer (Amsterdam, Netherlands)》2011,72(2):205-212
Introduction
Erlotinib and gefitinib are tyrosine kinase (TK) inhibitors of epidermal growth factor receptor (EGFR) that are effective in treating non-small cell lung cancer (NSCLC). This study aimed to compare their clinical uses and the influence of EGFR mutation.Methods
The usages of erlotinib and gefitinib in advanced NSCLC were analyzed. Clinical data and EGFR mutational status of tumors were collected.Results
Seven hundred and sixteen (716) patients received gefitinib (n = 440) or erlotinib (n = 276) for stage IIIb or IV NSCLC. Erlotinib was prescribed more frequently than gefitinib in males (58.2% vs. 41.8%, p < 0.001), smokers (60.5% vs. 39.5%, p < 0.001), and non-adenocarcinoma (70.6% vs. 29.4%, p < 0.001). Of the 716 study patients, 327 underwent testing for EGFR mutations (170 with mutant EGFR and 157 with wild-type EGFR). Adenocarcinoma in patients with mutant EGFR and non-smoker status in patients with wild-type EGFR were associated with better overall survival after TK inhibitor treatment. In both patient groups with mutant EGFR or wild-type EGFR, the effectiveness of gefitinib and erlotinib, including drug response or overall survival, were not different.Conclusions
Our study revealed the obvious disparity in drug selection between erlotinib and gefitinib in clinical practice. Type of TK inhibitors did not influence treatment outcomes in patients with EGFR mutation or wild-type EGFR. 相似文献3.
George PentheroudakisAikaterini Stoyianni Nicholas Pavlidis 《Cancer treatment reviews》2011,37(2):120-126
Background
Midline nodal cancer of unknown primary (CUP) has varying definitions and an unclear natural history compared to that of extragonadal germ cell cancer (EGCC) and neuroendocrine tumors.Methods
We systematically reviewed all published series of patients with midline nodal CUP using three distinct definitions and presented our own retrospective cohort.Results
Sixty four fit patients (median age 64) with poorly differentiated carcinoma or adenocarcinoma in midline nodal areas were treated from 1998 to 2008 at our center. Only two patients had elevated serum germ cell markers. Forty-eight percentage of patients responded to platinum-based chemotherapy (CR 11%). The median survival was 12 months (2-year survival 18%). Good PS (Hazard Ratio HR 0.287, p = 0.058) and administration of platinum (HR 0.340, p = 0.08) predicted for more favourable outcome. A subgroup of 15 male patients selected with stricter criteria had a CR rate of 33% and median survival of 18 months (2-year survival 24%). We identified 10 series of midline nodal CUP patients defined with discordant criteria. Despite high response rates (35-65%) to platinum chemotherapy, the median survival clustered around 12 months. Predictive factors for superior survival were low tumor bulk, patient fitness, female gender, carcinomatous histology, and absence of visceral metastases. There were differences between midline nodal CUP patients and EGCC as well as neuroendocrine tumors (age, tumor markers, response to therapy, long-term survival).Conclusions
Midline nodal CUP patients are poorly defined, fare less well than EGCC or neuroendocrine cancer and probably constitute a heterogeneous entity with a minority harbouring atypical germ cell cancer. 相似文献4.
Hata A Katakami N Yoshioka H Fujita S Kunimasa K Nanjo S Otsuka K Kaji R Tomii K Iwasaku M Nishiyama A Hayashi H Morita S Ishida T 《Lung cancer (Amsterdam, Netherlands)》2011,74(2):268-273
Background
Recent reports have suggested that erlotinib therapy after gefitinib failure requires optimal patient selection to obtain clinical benefits in relapsed non-small cell lung cancer (NSCLC). However, insufficient evidence exists to determine which clinical factors best identify patients who benefit from erlotinib therapy.Methods
One hundred twenty-five patients with relapsed NSCLC who had received erlotinib therapy after gefitinib failure were retrospectively evaluated between January 2008 and May 2009.Results
The response rate (RR), disease control rate (DCR), and median progression-free survival (PFS) for all patients were 9% (95% confidence interval [CI], 5-15%), 44% (95% CI, 35-53%), and 2.0 months (95% CI, 1.4-2.5 months), respectively. The median survival time was estimated to be 11.8 months (95% CI, 6.4-16.0 months). Using multivariate analysis, good performance status (PS), EGFR mutation-positive status, and benefit from prior gefitinib therapy were identified as significant predictive factors for disease control. Using a proportional hazards model, benefit from prior gefitinib therapy, good PS, and insertion of cytotoxic chemotherapies between gefitinib and erlotinib therapies emerged as significant predictive factors for longer PFS. Thirty-two patients with concomitant PS 0/1, benefit from prior gefitinib therapy, and insertion of cytotoxic chemotherapies between gefitinib and erlotinib therapies benefitted more from erlotinib therapy: RR, 25% (95% CI, 12-43%); DCR, 72% (95% CI, 53-86%); and median PFS, 3.4 months (95% CI, 2.4-4.9 months).Conclusions
Higher efficacy of erlotinib after gefitinib failure can be achieved with proper patient selection criteria, including good PS, benefit from prior gefitinib therapy, and insertion of cytotoxic chemotherapies between gefitinib and erlotinib therapies. 相似文献5.
Jennifer L. Peterson Michael G. Heckman Stephen J. Ko Todd C. Igel Thomas M. Pisansky 《Radiotherapy and oncology》2009,93(2):203-206
Purpose
To evaluate late toxicity in patients who received salvage external beam radiotherapy (EBRT) for a detectable prostate-specific antigen (PSA) level after radical prostatectomy (RP).Methods
A cohort of 308 consecutive patients underwent salvage EBRT from July 1987 through June 2003 for a detectable PSA level after RP. All were treated with high-energy photons (6-20 MV) to a median dose of 64.8 Gy (range: 54.0-72.4 Gy) in 1.8- to 2.0-Gy fractions.Results
Median follow-up from the completion of EBRT was 60 months (range: 1 day-174 months). Late toxicity occurring more than 90 days after EBRT completion was identified in 41 patients (13%). Twelve patients (3.9%) had grade 2 urethral strictures and were treated with urethral dilation, 3 patients had grade 3 cystitis, and 1 had a grade 4 rectal complication. These numbers correspond to an estimated 0.7% (95% confidence interval, 0.0-1.6%) of patients experiencing a grade 3 or 4 complication by 5 years after the start of EBRT.Conclusions
Salvage EBRT for a detectable PSA level after RP is the only curative treatment in this setting. This treatment can be administered in a manner that results in a low likelihood of late complications. 相似文献6.
Purpose
It has been suggested that hepatocyte growth factor (HGF) and insulin-like growth factor binding protein (IGFBP)-3 are associated with gefitinib resistance in non-small cell lung cancer (NSCLC). We investigated the predictive and prognostic roles of these proteins in NSCLC patients treated with gefitinib.Patients and methods
Of 106 patients enrolled in a randomized phase II study of gefitinib, 97 had plasma samples available for ELISA testing. Of these samples, seven and eight, respectively, had HGF and IGFBP-3 values that could not be measured. Therefore, the correlations between clinical outcomes and plasma levels of HGF and IGFBP-3 were evaluated in 90 and 89 patients, respectively.Results
Plasma HGF levels were significantly higher in older patients, male patients, patients with squamous cell carcinoma, current smokers, and patients with epidermal growth factor receptor (EGFR) wild-type tumors. Low HGF levels were significantly associated with higher response rate, and longer progression-free survival (PFS) and overall survival (OS) irrespective of EGFR mutation status. In a multivariate analysis, the presence of EGFR mutations (P = 0.002) and low HGF levels (P = 0.031) were independently predictive of longer PFS, and an ECOG PS of 0 (P = 0.001) and low HGF levels (P = 0.002) were independently predictive of longer OS. No statistically significant differences were found for IGFBP-3.Conclusion
High HGF levels are significantly associated with resistance to gefitinib and can be used as a predictive marker for the differential outcome of gefitinib treatment in NSCLC irrespective of EGFR mutation status. 相似文献7.
Timothy M. Zagar Edward F. Miles Mark W. Dewhirst Leonard R. Prosnitz 《Radiotherapy and oncology》2010,97(3):535-540
Background and purpose
Chest wall recurrences of breast cancer are a therapeutic challenge and durable local control is difficult to achieve. Our objective was to determine the local progression free survival (LPFS) and toxicity of thermochemoradiotherapy (ThChRT) for chest wall recurrence.Methods
Twenty-seven patients received ThChRT for chest wall failure from 2/1995 to 6/2007 and make up this retrospective series. All received concurrent superficial hyperthermia twice weekly (median 8 sessions), chemotherapy (capecitabine in 21, vinorelbine in 2, and paclitaxel in 4), and radiation (median 45 Gy). Patients were followed up every 1.5-3 months and responses were graded with RECIST criteria and toxicities with the NCI CTC v4.0.Results
Twenty-three (85%) patients were previously irradiated (median 60.4 Gy) and 22 (81%) patients received prior chemotherapy. Median follow-up was 11 months. Complete response (CR) was achieved in 16/20 (80%) of patients with follow-up data, and 1 year LPFS was 76%. Overall survival was 23 months for patients with CR, and 5.4 months in patients achieving a partial response (PR) (p = 0.01). Twenty-two patients experienced acute grade 1/2 treatment related toxicities, primarily moist desquamation. Two patients experienced 3rd degree burns; all resolved with conservative measures.Conclusions
ThChRT offers durable palliation and prolonged LPFS with tolerable acute toxicity, especially if CR is achieved. 相似文献8.
Vergnenègre A Monnet I Chouaïd C Hureaux J Mazières J Quéré G Lombard JN Cumin I Abdiche S Ejnaini CN Bonnabau H Decroisette Ch;GFPC team 《Lung cancer (Amsterdam, Netherlands)》2011,74(2):264-267
Context
Erlotinib therapy for non small-cell lung cancer (NSCLC) has mainly been evaluated in randomized trials.Method
OBSTAR was a multicenter, retrospective, observational study involving all patients treated with erlotinib in 18 French centers between June 2005 and September 2007. The analyses focused on the patients’ characteristics, previous treatments, and treatment efficacy during a three-year follow-up period.Results
534 patients were included in this study. The median survival times were respectively 5.2 [3.7-7.4] and 4.7 [4.1-5.7] months, depending to whether erlotinib was used as second- (n = 190), or ≥third-line treatment (n = 305). The disease control rate were 39.1% [30.2-48.7] and 29.9% [29.6-36.9] according to the line of treatment. Factors predictive of an objective response were gender, age, and smoking status. Factors predictive of progression were age, sex, smoking status, the line of treatment, and the number of metastases. Treatment had to be interrupted for toxicity in 8.5% of cases.Conclusion
This study of erlotinib therapy in 2005-2007 confirms, in the general NSCLC patient population, the results of pivotal trials. 相似文献9.
O'Brien ME Myerson JS Coward JI Puglisi M Trani L Wotherspoon A Sharma B Cook G Ashley S Gunapala R Chua S Popat S 《European journal of cancer (Oxford, England : 1990)》2012,48(1):68-74
Background
The aim of this study was to assess if 18F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)-CT scanning could minimise the time non-responding patients were exposed to erlotinib (Tarceva®).Methods
Patients were selected for clinical factors that would predict response to erlotinib. A FDG PET-CT and diagnostic contrast-enhanced (traditional) CT scan were carried out at baseline, and then a FDG PET-CT at 6 weeks and a traditional CT at 12 weeks were repeated. The primary end-point was rate of early progression in patients after 6 weeks, of which a minimum 12 out of 35 were required to make the study worthwhile. The responses at 6 (PET-CT) and 12 weeks (traditional CT) were compared and correlated with symptomatic response at both these time points.Results
Forty seven patients were recruited with 38 and 33 patients assessable by FDG PET-CT at 6 weeks and traditional CT at 12 weeks, respectively. There was good correlation between Partial response (PR) at both time points and all 10 patients who had a PR at 12 weeks had a PR at 6 weeks. Of the 13 patients with progressive disease (PD) at 12 weeks, seven had PD at 6 weeks and could have had their treatment stopped early. No evaluable patient with stable disease (SD) (8/38) or PD (9/38) on FDG PET-CT at 6 weeks went on to have a later response. Symptomatic response at 6 or 12 weeks did not correlate well with objective response on scanning at either time point.Conclusions
The primary end-point of this study was met as >12 (15/38) patients could have stopped treatment early on the basis of the FDG PET-CT scan result. A FDG PET-CT evaluable response of SD or PD at 6 weeks does predict future lack of response. No correlation was found between response and symptomatic response at either 6 or 12 weeks. 相似文献10.
Shimokawa H Uramoto H Onitsuka T Iwata T Nakagawa M Ono K Hanagiri T 《Lung cancer (Amsterdam, Netherlands)》2011,72(3):360-364
Background
Not all patients with lung cancer require postoperative adjuvant chemotherapy after a complete resection. However, no useful markers for either selecting appropriate candidates or for predicting clinical recurrence exist.Methods
Tumor specimens were collected from 183 consecutive patients who underwent a complete resection for lung adenocarcinoma from 2003 to 2007 in our department. We analyzed the thymidylate synthase (TS) and dihydrofolate reductase (DHFR) expressions in the primary lung adenocarcinoma by immunohistochemisty.Results
The strong expression of TS and DHFR was identified in 39 (21.3%) and 120 (65.6%) patients, respectively. The strong TS expression was identified in 11 (39.3%) of 28 patients and 28 (18.1%) of 155 patients in patients with and without recurrence, respectively (p = 0.012). The strong DHFR expression was also identified in 23 (82.1%) and 97 (62.6%) of the patients with and without recurrence, respectively (p = 0.045). Logistic regression models indicated the strong TS expression to be an independent factor for tumor recurrence. The strong TS and DHFR expression was associated with a poorer disease-free survival (DFS) according to the survival analysis. A multivariate analysis demonstrated the strong TS expression to be independently associated with an increased risk for poor DFS.Conclusions
The strong TS expression may be a useful marker for predicting postoperative recurrence in patients with lung adenocarcinoma following surgery. 相似文献11.
Zheng-Fei ZhuMin Fan Kai-Liang WuKuai-Le Zhao Huan-Jun YangGui-Yuan Chen Guo-Liang JiangLi-Juan Wang Sen ZhaoXiao-Long Fu 《Radiotherapy and oncology》2011,98(3):304-308
Purpose
The aim of this study is to evaluate the safety and efficacy of accelerated hypofractionated radiotherapy (HypoRT) combined with sequential chemotherapy in locally advanced non-small cell lung cancer (NSCLC).Materials and methods
A total of 34 patients with stage III NSCLC were enrolled. All patients received accelerated HypoRT (initially 50 Gy/20 fractions, then a fraction dose of 3 Gy) using three-dimensional conformal radiation therapy (3D-CRT), omitting elective nodal irradiation (ENI), to a total dose of 65-68 Gy. All patients received two cycles of induction chemotherapy; 1-2 cycles of consolidation chemotherapy were given to 31 patients. The primary outcome measure was a profile of radiation toxicity. The secondary endpoints included overall survival (OS), progression-free survival (PFS), locoregional PFS (LR-PFS) and the pattern of initial failure.Results
Radiation toxicity was minimal. The median and 3-year OS, PFS were 19.0 months, 32.1%; 10.0 months, 29.8%, respectively. The 1-, 2-, and 3-year LR-PFS were 69.6%, 60.9% and 60.9%, respectively. No patient experienced isolated elective nodal failure as the first site of failure.Conclusion
This study suggests that accelerated HypoRT using 3D-CRT omitting ENI can be used in combination with sequential chemotherapy in locally advanced NSCLC. 相似文献12.
Seung-Gu Yeo Dae Yong Kim Tae Hyun Kim Yong Sang Hong Ji Won Park Jae Hwan Oh 《Radiotherapy and oncology》2010,97(2):307-311
Purpose
To investigate the efficacy of curative chemoradiotherapy for isolated retroperitoneal lymph node recurrence of colorectal cancer.Materials and methods
Twenty-two colorectal cancer patients who received three-dimensional conformal radiotherapy (n = 20) or helical tomotherapy (n = 2) for isolated retroperitoneal lymph node recurrence were analyzed retrospectively. Radiation dose was 55.8 Gy in 31 fractions or 63 Gy in 35 fractions, and 60 Gy in 20 fractions by helical tomotherapy. All patients received concurrent chemotherapy and 16 (72.7%) received adjuvant chemotherapy.Results
The treatment response was complete in 13 (59.1%), partial in 6 (27.3%), and stable in 3 (13.6%) patients. Median follow-up for 11 (50%) surviving patients was 32 months (range, 27-61). The 3- and 5-year overall survival rates were 64.7% and 36.4%, and median overall survival was 41 months. Recurrences developed in 15 (68.2%) patients; outside the retroperitoneum in 13. The 3- and 5-year recurrence-free survival rates were 34.1% and 25.6%, and median recurrence-free survival was 20 months. Response and adjuvant chemotherapy were significant prognostic factors for overall survival. Gastrointestinal toxicity ? Grade 3 was not observed.Conclusions
Definitive chemoradiotherapy is an effective salvage treatment for isolated retroperitoneal lymph node recurrence of colorectal cancer without severe complications. 相似文献13.
Stephanie E. Combs Adriana KalbeAnna Nikoghosyan Benjamin AckermannOliver Jäkel Thomas HabererJürgen Debus 《Radiotherapy and oncology》2011,98(1):63-67
Introduction
To asses carbon ion radiation therapy (RT) performed as re-irradiation in 28 patients with recurrent tumors.Materials and methods
Twenty-eight patients were treated with carbon ion RT as re-irradiation for recurrent chordoma and chondrosarcoma of the skull base (n = 16 and n = 2), one chordoma and one chondrosarcoma of the os sacrum, high-risk meningioma (n = 3), adenoid-cystic carcinoma (n = 4) as well as one SCCHN.All patients were treated using active raster scanning, and treatment planning was performed on CT- and MRI-basis.All patients were followed prospectively during follow-up.Results
In all patients re-irradiation could be applied safely without interruptions. For skull base tumors, local tumor control after re-irradiation was 92% at 24 months and 64% at 36 months. Survival after re-irradiation was 86% at 24 months, and 43% at 60 months. In all three meningiomas treated with C12 for re-irradiation, the tumor recurrence was located within the former RT-field. Two patients developed tumor progression at 6 months, and in one patient the tumor remained stable for 67 months. In patients with head-and-neck tumors, three patients developed local tumor progression at 12, 24 and 29 months after re-irradiation. Median local progression-free survival was 24 months.For sacral tumors, re-irradiation offered palliation with tumor control for 24 and 36 months.Conclusion
Due to the physical characteristics particle therapy offers a new treatment modality in cases with tumor recurrences. With carbon ions, the additional biological benefits may be exploited for long-term tumor control. Further evaluation in a larger patients’ cohort will be performed in the future. 相似文献14.
Neil Kopek Merete Paludan Anders Traberg Hansen Morten Høyer 《Radiotherapy and oncology》2009,93(3):402-407
Purpose
To determine the prognostic role of co-morbidity in medically inoperable early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT).Methods and materials
Between 2000 and 2007, 88 consecutive early-stage medically inoperable NSCLC patients were treated by linac-based SBRT. The dose was either 45 Gy or 67.5 Gy in three fractions prescribed to the isocenter. Baseline co-morbidities were retrospectively retrieved by consultation of a formal electronic registry of diagnoses as well as patients’ charts. The age-adjusted Charlson Co-morbidity Index (CCI) was scored for each patient and subjected to univariate and multivariate analysis.Results
With a median follow-up of 44 months, the actuarial local control rate at 4 years was 89% while the median overall survival was 22 months. The median age-adjusted CCI score was 5. The age-adjusted CCI was a significant predictor of overall survival on both univariate (p = 0.002) and multivariate analysis (p = 0.011). Patients with an age-adjusted CCI score of 3 or less had a median survival of 41 months versus only 11 months for those scoring 6 or more.Conclusion
The number and seriousness of co-morbidities predict overall survival in medically inoperable early-stage NSCLC treated with SBRT. Because the determination of medical operability is frequently based on both objective measures and subjective clinical judgment, it is recommended that co-morbidity be formally indexed in all studies examining the outcomes of SBRT. 相似文献15.
Kushner BH Kramer K Modak S Yataghene K Cheung NK 《European journal of cancer (Oxford, England : 1990)》2011,47(1):84-89
Background
We used a novel regimen for neuroblastoma (NB) that had responded inadequately to standard chemotherapy which now includes topotecan in induction or second-line therapy.Patients and methods
We retrospectively studied 38 patients who received one or two courses of high-dose cyclophosphamide (140 mg/kg)-irinotecan (CPT-11) (250 mg/m2)-vincristine (HD-CCV) as treatment for NB that had responded incompletely to induction but had never progressed. Treatment was outpatient and was preceded and followed by extent-of-disease and toxicity evaluations because the patients were being considered for enrolment on formal protocols. Progression-free survival (PFS) was calculated from day 1 of HD-CCV.Results
Common toxicities were grade 4 myelosuppression and grade 2 diarrhoea. Responses - 5 complete (CR), 3 partial (PR), 4 mixed (MR) - occurred in 12/28 (43%) patients treated ?9 months, and in 1/10 (10%) patients treated >10 months, from diagnosis. HD-CCV was the initial salvage regimen after topotecan-containing induction in 5 patients, achieving 1 CR, 1 MR and 3 stable disease (NR). HD-CCV produced responses (2 PR, 3 MR) in all 5 patients previously treated with CPT-11/ temozolomide. In contrast, all 6 patients treated post-HD-CCV with CPT-11/temozolomide had NR to the latter. Post-HD-CCV treatments included immunotherapy, targeted radiotherapy and/or chemotherapy. PFS was 64% (±8%) at 24 months, with 20 patients progression-free at 2+-to-36+ (median 16+) months and 10 in first CR at 9+-to-36+ (median 16+) months.Conclusions
HD-CCV offers a treatment option against topotecan-resistant NB. Results support the concept that combining CPT-11 with very high doses of alkylators can yield greater antitumour effect. 相似文献16.
Vincent Gregoire Marc HamoirChanghu Chen Madeleine KaneAndrzej Kawecki Pramod K. JulkaHung-Ming Wang Srihari PrasadAnil K. D’Cruz Ljiljana Radosevic-JelicRejnish R. Kumar Stanislaw KorzeniowskiJacek Fijuth Jean-Pascal MachielsMark V. Sellers Ilian TchakovDavid Raben 《Radiotherapy and oncology》2011,100(1):62-69
Background and purpose
To assess the efficacy and safety of gefitinib given concomitantly and/or as maintenance therapy to standard cisplatin/radiotherapy for previously untreated, unresected, stage III/IV non-metastatic SCCHN.Materials and methods
In this phase II, double-blind, study, 226 patients were randomized to gefitinib 250 mg/day, 500 mg/day or placebo in two phases: a concomitant phase (gefitinib or placebo with chemoradiotherapy), followed by a maintenance phase (gefitinib or placebo alone). Primary endpoint was local disease control rate (LDCR) at 2 years; secondary endpoints were LDCR at 1 year, objective response rate, progression-free survival, overall survival, and safety and tolerability.Results
Gefitinib (250 and 500 mg/day) did not improve 2-year LDCR compared with placebo either when given concomitantly with chemoradiotherapy (32.7% vs. 33.6%, respectively; OR 0.921, 95% CI 0.508, 1.670 [1-sided p = 0.607]) or as maintenance therapy (28.8% vs. 37.4%, respectively; OR 0.684, 95% CI 0.377, 1.241 [1-sided p = 0.894]). Secondary efficacy outcomes were broadly consistent with the 2-year LDCR results. In both doses, gefitinib was well-tolerated and did not adversely affect the safety and tolerability of concomitant chemoradiotherapy.Conclusion
Gefitinib was well-tolerated, but did not improve efficacy compared with placebo when given concomitantly with chemoradiotherapy, or as maintenance therapy alone. 相似文献17.
Fedele P Marino A Orlando L Schiavone P Nacci A Sponziello F Rizzo P Calvani N Mazzoni E Cinefra M Cinieri S 《European journal of cancer (Oxford, England : 1990)》2012,48(1):24-29
Aim
Registered dose capecitabine monotherapy is active against metastatic breast cancer (MBC), but retrospective analyses indicate that lower doses may be as effective and better tolerated. This study was conducted to assess the safety and efficacy of metronomic capecitabine in heavily pretreated patients with MBC.Patients and methods
In this phase II study 60 MBC patients received continuous metronomic capecitabine monotherapy (1500 mg once a day). Primary endpoint was clinical benefit rate, secondary end points were clinical benefit rates (CBRs), tumour response rates (RRs), overall survival (OS), time to progression (TTP), duration of response (DOR) and toxicity.Results
Fifty eight assessable patients received two or more 28-day cycles of metronomic capecitabine. The CBR was 62%. Median DOR was 7 months. Median TTP and OS were 7 and 17 months, respectively. Two partial responses and 7 cases of stable disease were recorded in 13 patients who had previously received capecitabine intermittently (2000 mg/m2/day on days 1-14 every 21 days) as first- or subsequent-line treatment for MBC. Grade 3-4 adverse events were uncommon; haematologic toxicity was infrequent (5%) and consistently mild.Conclusion
This regimen of metronomic capecitabine displayed good activity and excellent tolerability in MBC patients, including those who had previously received the drug at standard doses. 相似文献18.
Ada L.Y. Law Wai-Tong NgMichael C.H. Lee Augustine T.S. ChanKai-Hung Fung Francis LiWai-Cheung Lao Anne W.M. Lee 《Radiotherapy and oncology》2012,102(1):56-61
Purpose
To implement a reliable, practical and reproducible treatment procedure, based on in-room kV-image guidance and respiratory control, for liver cancer patients treated with high dose conformal radiotherapy using a commercially available treatment system.Materials and methods
CT stimulation was conducted under voluntary breath hold or gating using the Varian Real-time Position Management™ (RPM) System. Treatments were delivered daily under kV image guidance to verify the diaphragmatic or lipiodol-defined tumor position.Results
Thirty-three patients with liver confined hepatocellular carcinoma were treated between May 2006 and Dec 2009. After a median follow-up period of 16.5 months (range: 3.5-40.7), all but 2 patients demonstrated radiological tumor regression. Eight patients (24%) achieved complete remission. The median tumor shrinkage was 42% (27-100%). Subsequent in-field tumor progression was observed in only three patients (10%). For the 23 patients with abnormal alpha fetoprotein level, 22 of them showed biochemical response with a median AFP level drop of 78%. The treatment was well tolerated: Grade 3 toxicities occurred in 5 patients (1 leucopenia, 1 elevated liver enzyme and 3 elevated bilirubin level) but there was no grade 4 toxicity or treatment related death. The 1 year overall survival rate is 71.7% and median survival time is 17.2 months (3.5-40.7 months).Conclusions
Excellent treatment results with minimal toxicities could be achieved in a clinical environment with a commercially available highly sophisticated radiotherapy system. 相似文献19.
Rodriguez J Boni V Hernández A Bitarte N Zarate R Ponz-Sarvisé M Chopitea A Bandres E Garcia-Foncillas J 《European journal of cancer (Oxford, England : 1990)》2011,47(6):839-847
Background
To investigate whether single nucleotide polymorphisms (SNPs) in gemcitabine (GMB) metabolism genes were associated with clinical outcome in pre-treated metastatic colorectal cancer (mCRC) patients.Patients and methods
SNPs of hCNT1, hENT1, CDA, dCTD and RRM1 genes were evaluated in 95 mCRC patients and detected using TaqMan genotyping assays. Association of genotypes with overall response rate (ORR), time to progression (TTP) and overall survival (OS) was tested by univariate and multivariate analysis. RRM1 -37A>C polymorphism was correlated with GMB IC50 value and with the RRM1 gene expression level in CRC cell lines.Results
The ORR was 38.9%. The median TTP and OS were 4 and 14.3 months, respectively. By multivariate analysis, patients carrying the RRM1 -37CC genotype or the CDA A-76 C-containing allele had a significantly higher likelihood of achieving a tumour response. RRM1 -37A>C polymorphism remained associated with clinical efficacy (TTP). In vitro experiments, in CRC cell lines, showed that the RRM1 A-37C genotype was associated with the levels of RRM1 expression and with GMB IC50 values. Finally, the down-regulation of RRM1 with a specific siRNA strongly influenced GMB sensitivity.Conclusion
RRM1 -37A>C polymorphism may represent a useful biomarker to select mCRC patients most likely to benefit from GMB-based salvage therapy. 相似文献20.
T. Iuchi M. Shingyoji T. Sakaida K. Hatano O. Nagano M. Itakura H. Kageyama S. Yokoi Y. Hasegawa K. Kawasaki T. Iizasa 《Lung cancer (Amsterdam, Netherlands)》2013