[Show abstract][Hide abstract] ABSTRACT: Radiation and cisplatin-based chemotherapy are major treatments for nasopharyngeal carcinoma (NPC). However, a major impediment for further improving the cure rate is the development of treatment resistance with an undetermined molecular mechanism in metastatic NPC cells. Our established, highly metastatic NPC cells have been reported to be more resistant to cisplatin chemotherapy. In the present study, we found that Ras association domain family member 6 (RASSF6) was downregulated in highly metastatic cells but upregulated in low metastatic cells in comparison to their parental cell line. Ectopic-expression of RASSF6 enhanced the sensitivity of highly metastatic NPC cells to cisplatin or radiation by enhancing apoptosis. RASSF6 depletion conversely reduced treatment sensitivity by decreasing the apoptosis rate. Over-expression of RASSF6 in highly metastatic NPC cells could enhance the phosphorylation of JNK when exposed to cisplatin or radiation treatment, while knocking down RASSF6 in low metastatic NPC cells could reduce the level of phospho-JNK when exposed to the same treatments. The activation of JNK signaling by RASSF6 and its subsequent sensitivity to apoptosis in NPC cells could be inhibited by applying the JNK inhibitor SP600125. In conclusion, the downregulation of RASSF6 in highly metastatic NPC cells contributed to their treatment resistance, and over-expression of RASSF6 conferred treatment sensitivity to highly metastatic NPC cells by activating JNK signaling. RASSF6 could be a valuable molecular marker for identifying sensitive metastatic NPC tumors during cisplatin treatment or radiotherapy.
PLoS ONE 07/2014; 9(7):e100843. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in southern China and Southeast Asia, with the highest metastasis rate among head and neck cancers. The mechanisms underlying NPC progression remain poorly understood. Genome-wide expression profiling on 18 NPC vs. 18 noncancerous nasopharyngeal tissues together with GeneGo pathway analysis and expression verification in NPC cells and tissues revealed a potential role of urokinase-type plasminogen activator receptor (uPAR) in NPC progression, which has not been investigated in NPC. We then observed that uPAR expression is increased in poorly differentiated, highly metastatic NPC cells compared with lowly metastatic cells or differentiated NPC cells. In vitro studies demonstrated that uPAR regulates NPC cell growth, colony formation, migration, and invasion and promotes the epithelial-mesenchymal transition (EMT). Additional tumor xenograft and spontaneous metastasis experiments revealed that uPAR promotes NPC cell growth and metastasis in vivo. The JAK-STAT pathway is involved in uPAR-regulated signaling in NPC cells as determined by immunoblotting. Moreover, uPAR-mediated growth and motility is partially abolished upon treatment with the Jak1/Jak2 inhibitor INCB018424. We suppressed uPA expression in uPAR-overexpressing NPC cells and found that uPAR-mediated cellular growth and motility is not exclusively dependent on uPA. In summary, uPAR is a significant regulator of NPC progression and could serve as a promising therapeutic target.
[Show abstract][Hide abstract] ABSTRACT: Treatment outcomes vary greatly in patients with nasopharyngeal carcinoma (NPC). The purpose of this study is to evaluate the influence of radiation and chemotherapy drug action pathway gene polymorphisms on the survival of patients with locoregionally advanced NPC treated with cisplatin- and fluorouracil-based chemoradiotherapy.
Four hundred twenty-one consecutive patients with locoregionally advanced NPC were prospectively recruited. We utilized a pathway approach and examined 18 polymorphisms in 13 major genes. Polymorphisms were detected using the LDR-PCR technique. Multifactor dimensionality reduction (MDR) analysis was performed to detect potential gene-gene interaction.
After adjustment for clinicopathological characteristics, overall survival was significantly decreased in patients with the MPO rs2243828 CT/CC genotype (HR=2.453, 95% CI, 1.687-3.566, P<0.001). The ERCC1 rs3212986 CC (HR=1.711, 95% CI, 1.135-2.579, P=0.010), MDM2 rs2279744 GT/GG (HR=1.743, 95% CI, 1.086-2.798, P=0.021), MPO rs2243828 CT/CC (HR=3.184, 95% CI, 2.261-4.483, P<0.001) and ABCB1 rs2032582 AT/AA (HR=1.997, 95% CI, 1.086-3.670, P=0.026) genotypes were associated with poor progression-free survival. Prognostic score models based on independent prognostic factors successfully classified patients into low-, intermediate-, and high-risk groups. Furthermore, MDR analysis showed no significant interaction between polymorphisms.
Four single nucleotide polymorphisms were associated with survival in patients with locoregionally advanced NPC treated with cisplatin- and fluorouracil-based chemoradiotherapy. Combining clinical prognostic factors with genetic information was valuable in identifying patients with different risk.
PLoS ONE 12/2013; 8(12):e82750. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the prognostic role of major matrix metalloproteinase (MMP) gene polymorphisms in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated with chemoradiotherapy. Four hundred twenty-one consecutive NPC patients were prospectively recruited. Two hundred patients were randomly selected as the training cohort, and the remaining 221 patients were the validation cohort. Twelve polymorphisms in the MMP-1, 2, 3, 7, 8, and 9 genes were genotyped by ligase detection reaction-PCR. MMP-9 rs2250889 PR/RR (HR = 2.287, 95 % CI 1.400-3.735) and rs17576 RQ/QQ (HR = 2.347, 95 % CI 1.431-3.849) genotypes were significantly related with increased death risk in the training cohort. Analysis of the validation cohort confirmed these results (rs2250889: HR = 2.231, 95 % CI 1.281-3.886; rs17576: HR = 2.987, 95 % CI 1.674-5.330). Multivariate analysis showed that rs17576 (HR = 2.284, 95 % CI 1.123-4.643, P = 0.023) was still an independent prognostic factor. The MMP-9 rs17576 is a novel independent prognostic marker in patients with locoregionally advanced NPC treated with chemoradiotherapy.
Medical Oncology 12/2013; 30(4):685. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine whether baseline C-reactive protein (CRP) levels and CRP kinetics predict the overall survival in metastatic nasopharyngeal carcinoma (mNPC) patients.
A total of 116 mNPC patients from January 2006 to July 2011 were retrospectively reviewed. Serum CRP level was measured at baseline and thereafter at the start of each palliative chemotherapy cycle for all patients.
Patients with higher values of baseline CRP (≥ 3.4 mg/L) had significantly worse survival than those with lower baseline CRP values (< 3.4 mg/L). Patients were divided into four groups according to baseline CRP and CRP kinetics: (1) patients whose CRP < 3.4 mg/L and never elevated during treatment; (2) patients whose CRP < 3.4 mg/L and elevated at least one time during treatment; (3) patients whose CRP ≥ 3.4 mg/L and normalized at least one time during treatment; and (4) patients whose CRP ≥ 3.4 mg/L and never normalized during treatment. The patients were further assigned to non-elevated, elevated, normalized, and non-normalized CRP groups. Overall survival rates were significantly different among the four groups, with three-year survival rates of 68%, 41%, 33%, and 0.03% for non-elevated, elevated, normalized, and non-normalized CRP groups respectively. When compared with the non-elevated group, hazard ratios of death were 1.69, 2.57, and 10.34 in the normalized, elevated, and non-normalized groups (P < 0.001).
Baseline CRP and CRP kinetics may be useful to predict the prognosis of metastatic NPC patients treated with palliative chemotherapy and facilitate individualized treatment. A prospective study to validate this prognostic model is still needed however.
PLoS ONE 10/2013; 8(10):e76958. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PURPOSETo evaluate which patients with nasopharyngeal carcinoma (NPC) obtained the greatest benefits from the detection of distant metastasis with [(18)F]fluorodeoxyglucose positron emission tomography and computed tomography (PET/CT) combined with plasma Epstein-Barr virus (EBV) DNA levels. PATIENTS AND METHODS
Consecutive patients with NPC were prospectively enrolled. PET/CT, conventional work-up (CWU), and quantification of plasma EBV DNA were performed before treatment. The accuracy of these strategies for distant metastases was assessed. The costs of the diagnostic strategies were compared.ResultsEighty-six (14.8%) of the 583 eligible patients were found to have distant metastases; 71 patients (82.6%) by PET/CT and 31 patients (36.0%) by CWU. In the multivariable analysis, advanced N stage (odds ratio, 2.689; 95% CI, 1.894 to 3.818) and pretreatment EBV DNA level (odds ratio, 3.344; 95% CI, 1.825 to 6.126) were significant risk factors for distant metastases. PET/CT was not superior to CWU for detecting distant metastases in very low-risk patients (N0-1 with EBV DNA < 4,000 copies/mL; P = .062), but was superior for the low-risk patients (N0-1 with EBV DNA ≥ 4,000 copies/mL and N2-3 with EBV DNA < 4,000 copies/mL; P = .039) and intermediate-risk patients (N2-3 disease with EBV DNA ≥ 4,000 copies/mL; P < .001). The corresponding patient management changes based on PET/CT were 2.9%, 6.3%, and 16.5%, respectively. The costs per true-positive case detected by PET/CT among these groups were ¥324,138 (≈$47,458), ¥96,907 (≈$14,188), and ¥34,182 (≈$5,005), respectively. CONCLUSIONPET/CT detects more distant metastases than conventional staging in patients with NPC. The largest benefit in terms of cost and patient management was observed in the subgroup with N2-3 disease and EBV DNA ≥ 4,000 copies/mL.
Journal of Clinical Oncology 07/2013; · 17.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: Chronic inflammation plays an important role in nasopharyngeal carcinoma (NPC) development and progression. Aim of this study is to determine whether inflammation-related parameters predict distant metastasis in NPC patients. MATERIALS AND METHODS: 335 newly diagnosed non-metastatic NPC patients were recruited. The values of the C-reactive protein (CRP), lactate dehydrogenase, albumin, globulin, white blood cell and neutrophil at baseline were measured. RESULTS: Among the above six parameters, only CRP was independently associated with distant metastasis-free survival (DMFS). CRP concentration of advanced T-/TNM-classification patients was higher than those with early classification (P=0.001). Higher-CRP (CRP⩾2.46mg/L) predicted shorter overall survival, disease-free survival and DMFS than lower-CRP (CRP<2.46mg/L). In a multivariable model, higher-CRP and advanced N-classification were independent predictors of distant metastasis. On the basis of these two parameters, a prognostic NC-model was developed as following: (1) low-risk (early N-classification and lower-CRP); (2) intermediate-risk (advanced N-classification or higher-CRP) and (3) the high-risk distant metastasis (advanced N-classification and higher-CRP). When compared with the low-risk group, the hazard ratios (HRs) for distant metastasis and death for the intermediate-/high-risk patients were 3.6/16.1 and 2.26/7.61, respectively (both P<0.001). CONCLUSION: We developed a new prognostic model based on CRP and N-classification for predicting distant metastasis and death of NPC patients, which may facilitate patient counselling and individualised treatment.
European journal of cancer (Oxford, England: 1990) 04/2013; · 4.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The female sex is traditionally considered a favorable prognostic factor for nasopharyngeal carcinoma (NPC). However, no particular study has reported this difference. To explore the prognostic impact of gender in patients with NPC after definitive radiotherapy, we reviewed the clinical data of 2063 consecutive patients treated between 1st January 2000 and 31st December 2003 in the Sun Yat-sen University Cancer Center. The median follow-up for the whole series was 81 months. The female and male patients with early stage disease comprised 49.4% and 28.1% of the patient population, respectively. Both the 5-year overall survival (OS) and disease-specific survival (DSS) rates of the female patients were significantly higher than those of the male patients (OS: 79% vs. 69%, P < 0.001; DSS: 81% vs. 70%, P < 0.001). For patients with locoregionally advanced NPC, the 5-year OS and DSS rates of female vs. male patients were 74% vs. 63% (P < 0.001) and 76% vs. 64%, respectively (P < 0.001). A multivariate analysis showed that gender, age, and the TNM staging system were the independent prognostic factors for the 5-year OS and DSS of NPC patients. The favorable survival of female patients is not only attributed to the early diagnosis and treatment but might also be attributed to some intrinsic feature of female patients.
[Show abstract][Hide abstract] ABSTRACT: Nasopharyngeal carcinoma (NPC) has the highest metastatic potential among head and neck cancers. Distant metastasis is the major cause of treatment failure. The role of interleukin-8 (IL-8) in NPC progression remains unknown. Our multivariate survival analyses of 255 patients with NPC revealed that higher IL-8 expression in primary NPC tissue was an independent prognostic factor for overall survival, disease-free survival, and distant metastasis-free survival of the patients. In vitro study revealed that IL-8 was highly expressed in the established high-metastasis NPC clone S18 relative to the low-metastasis cells. Suppression of IL-8 by short-hairpin RNA reduced the expression of IL-8 in S18 cells and subsequently inhibited migration, invasion, and hepatic metastasis of the cells without influencing cellular growth. Overexpression of IL-8 in S26 cells resulted in increased migration, invasion, and metastasis capabilities of the cells without affecting cellular growth. Exogenous IL-8 enhanced the migration and invasion of low-metastasis CNE-2 cells in a dose-dependent manner. An epithelial-mesenchymal transition (EMT) could be induced by IL-8 in various NPC cell lines. The high level of phosphorylated AKT in S18 cells could be suppressed by knocking down IL-8 expression. Further, IL-8-promoted migration and invasion could be abolished by either the application of the phosphoinositide-3-kinase inhibitor LY294002 or the knock down of AKT expression by using small-interfering RNA. In summary, IL-8 serves as an independent prognostic indicator of overall survival, disease-free survival, and metastasis-free survival for patients with NPC. IL-8 promotes NPC metastasis via autocrine and paracrine means, involving activation of AKT signaling and inducing EMT in NPC cells.
[Show abstract][Hide abstract] ABSTRACT: The aim of this randomized study was to compare the efficacy of induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) versus induction chemotherapy plus radiotherapy (IC+RT) for patients with locoregionally advanced nasopharyngeal carcinoma. From August 2002 to April 2005, 408 patients were randomly divided into two groups: an IC+CCRT group and an IC+RT group. Patients in both groups received the same induction chemotherapy: two cycles of floxuridine (FuDR)+carboplatin (FuDR, 750mg/m(2), d1-5; carboplatin, area under the curve [AUC]=6). The patients received radiotherapy 1week after they finished the induction chemotherapy. The patients in the IC+CCRT group also received carboplatin (AUC=6) on days 7, 28, and 49 of radiotherapy. Eight patients did not meet the inclusion criteria, and the remaining 400 cases were analyzed. Grade III or IV toxicity was found in 28.4% of the patients in the IC+CCRT group and 13.1% of those in the IC+RT group (P<.001). Five-year overall survival rates were 70.3% and 71.7% (P=0.734) in the IC+CCRT and IC+RT groups, respectively. No significant differences in failure-free survival, locoregional control, and distant control were found between the two groups. Compared with the IC+RT program, the IC+CCRT program used in the present study did not improve the overall survival and failure-free survival in patients with locoregionally advanced nasopharyngeal carcinoma. Using carboplatin in the concurrent chemoradiotherapy was not suitable for nasopharyngeal carcinoma.
[Show abstract][Hide abstract] ABSTRACT: Concurrent chemoradiotherapy (CCRT) has been shown to improve outcomes for stage III-IV nasopharyngeal carcinoma (NPC) patients compared with radiotherapy (RT) alone, but the effectiveness of the combined therapy for stage II NPC patients is unknown.
Patients with Chinese 1992 stage II NPC were randomly assigned to receive either RT alone (n = 114) or CCRT (n = 116). The CCRT patients were given concurrent cisplatin (30 mg/m(2) on day 1) weekly during RT. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), distant metastasis-free survival, and locoregional relapse-free survival. All patients were analyzed by the intent-to-treat principle. The Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) and in multivariable analyses to test the independent statistical significance of treatment intervention. Toxic effects and the response to treatment were analyzed using the χ(2) test. All statistical tests were two-sided.
With a median follow-up of 60 months, adding chemotherapy statistically significantly improved the 5-year OS rate (94.5% vs 85.8%; HR of death = 0.30, 95% CI = 0.12 to 0.76; P = .007), PFS (87.9% vs 77.8%; HR of progression = 0.45, 95% CI = 0.23 to 0.88; P = .017), and distant metastasis-free survival (94.8% vs 83.9%; HR of distant relapse = 0.27, 95% CI = 0.10 to 0.74; P = .007); however, there was no statistically significant difference in the 5-year locoregional relapse-free survival rate (93.0% vs 91.1%; HR of locoregional relapse = 0.61, 95% CI = 0.25 to 1.51; P = .29). Multivariable analysis showed that the number of chemotherapy cycles was the only independent factor that was associated with OS, PFS, and distant control in stage II NPC. The CCRT arm experienced statistically significantly more acute toxic effects (P = .001), although the rate of late toxic effects did not increase statistically significantly.
Concurrent chemotherapy and radiotherapy is associated with a considerable survival benefit for patients with stage II NPC.
[Show abstract][Hide abstract] ABSTRACT: Nasopharyngeal carcinoma (NPC) is known for its high-metastatic potential. Here we report the identification of the proteoglycan serglycin as a functionally significant regulator of metastasis in this setting. Comparative genomic expression profiling of NPC cell line clones with high- and low-metastatic potential revealed the serglycin gene (SRGN) as one of the most upregulated genes in highly metastatic cells. RNAi-mediated inhibition of serglycin expression blocked serglycin secretion and the invasive motility of highly metastatic cells, reducing metastatic capacity in vivo. Conversely, serglycin overexpression in poorly metastatic cells increased their motile behavior and metastatic capacity in vivo. Growth rate was not influenced by serglycin in either highly or poorly metastatic cells. Secreted but not bacterial recombinant serglycin promoted motile behavior, suggesting a critical role for glycosylation in serglycin activity. Serglycin inhibition was associated with reduced expression of vimentin but not other epithelial-mesenchymal transition proteins. In clinical specimens, serglycin expression was elevated significantly in liver metastases from NPC relative to primary NPC tumors. We evaluated the prognostic value of serglycin by immunohistochemical staining of tissue microarrays from 263 NPC patients followed by multivariate analyses. High serglycin expression in primary NPC was found to be an unfavorable independent indicator of distant metastasis-free and disease-free survival. Our findings establish that glycosylated serglycin regulates NPC metastasis via autocrine and paracrine routes, and that it serves as an independent prognostic indicator of metastasis-free survival and disease-free survival in NPC patients.
Cancer Research 02/2011; 71(8):3162-72. · 9.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this prospective study was to investigate the prognostic value of serum vascular endothelial growth factor (sVEGF) in patients with nasopharyngeal carcinoma (NPC).
sVEGF was prospectively detected in 306 patients with NPC with enzyme-linked immunosorbent assay before treatment. The correlations between sVEGF and the survival of these patients were evaluated.
Patients were followed for at least 36 months. The mean sVEGF was 387.0 ng/L. sVEGF showed no difference in sex, age, and local recurrence. However, sVEGF was positively associated with histology, TNM classification, distant metastasis, and overall survival (OS; p < .05). The 4-year OS and distant metastasis-free survival (DMFS) of the high-sVEGF versus low-sVEGF groups were 68% versus 86% and 70% versus 89%, respectively (p < .05). Stratified analysis showed that patients with stage IV(a,b) , T(4) , N(1) , or N(positive) disease with high VEGF levels had worse 4-year OS and 4-year DMFS than those with low VEGF levels (p < .05). Multifactorial Cox regression confirmed sVEGF was among the independent prognostic factors.
Elevation of sVEGF in patients with NPC predicts more posttreatment distant metastases and shorter OS and can be used as an independent poor prognostic indicator.
Head & Neck 10/2010; 33(6):780-5. · 2.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the prognostic potential of serum CCL2 (sCCL2) and serum TNF-α (sTNF-α) in nasopharyngeal carcinoma (NPC) before treatment by analysing the expression of these two markers.
Both sCCL2 and sTNF-α were prospectively detected in 297 NPC patients with enzyme-linked immunosorbent assay (ELISA) before treatment. The correlations between sCCL2 level or sTNF-α level and patient's survival were evaluated.
For sCCL2, the 5-year overall survival (OS) and 5-year distant metastasis-free survival (DMFS) of high expression group and low expression group were 64% versus 81% and 67% versus 84% (P < 0.05), respectively. For sTNF-α, the 5-year OS and 5-year DMFS of high expression group and low expression group were 62% versus 79% and 66% versus 82% (P < 0.05), respectively. The 5-year OS and 5-year DMFS for both positive patients, one marker positive patient and both negative patients were 53% versus 77% versus 85% and 58% versus 80% versus 86% (P < 0.05), respectively. Concentrations of sCCL2 and sTNF-α in patients with large skull base invasion were higher than those without or with small skull invasion (P < 0.05). Patients who developed bone metastasis alone after radical treatment had higher pre-treatment concentrations of sCCL2 and sTNF-α than those without metastasis (P < 0.001). Multifactorial Cox regression analyses demonstrated that T/N/M classification, chemotherapy, sCCL2 level and sTNF-α level were independent predictors of OS and DMFS of NPC patients.
High expression levels of sCCL2 and sTNF-α predict bone invasion, post-treatment distant metastasis and poor overall survival in NPC patients.
European journal of cancer (Oxford, England: 1990) 10/2010; 47(3):339-46. · 4.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Early diagnosis of nasopharyngeal carcinoma (NPC) is difficult due to the insufficient specificity of the conventional examination method. This study was to investigate potential and consistent biomarkers for NPC, particularly for early detection of NPC.
A proteomic pattern was identified in a training set (134 NPC patients and 73 control individuals) using the surface-enhanced laser desorption and ionization-mass spectrometry (SELDI-MS), and used to screen the test set (44 NPC patients and 25 control individuals) to determine the screening accuracy. To confirm the accuracy, it was used to test another group of 52 NPC patients and 32 healthy individuals at 6 months later.
Eight proteomic biomarkers with top-scored peak mass/charge ratios (m/z) of 8605 Da, 5320 Da, 5355 Da, 5380 Da, 5336 Da, 2791 Da, 7154 Da, and 9366 Da were selected as the potential biomarkers of NPC with a sensitivity of 90.9% (40/44) and a specificity of 92.0% (23/25). The performance was better than the current diagnostic method by using the Epstein-Barr virus (EBV) capsid antigen IgA antibodies (VCA/IgA). Similar sensitivity (88.5%) and specificity (90.6%) were achieved in another group of 84 samples.
SELDI-MS profiling might be a potential tool to identify patients with NPC, particularly at early clinical stages.
[Show abstract][Hide abstract] ABSTRACT: The platinum-based chemotherapy combined with 5-fluorouracil (5-FU) is most frequently used for nasopharyngeal carcinoma (NPC), but the efficacy has been maintained at 50%-60%. Docetaxel is an effective drug for head and neck tumors, its administration is simple, and the administration time is short. This study was to compare the short-term efficacy and toxicity between TC regimen (inductive chemotherapy with docetaxol plus carboplatin) and FC regimen (5-FU plus carboplatin) in local advanced NPC so as to provide a new chemotherapeutic regimen for NPC.
Fifty-eight local advanced NPC patients without previous treatment in Sun Yat-sen University Cancer Center were randomly assigned to receive either TC or FC regimen inductive chemotherapy, followed by concurrent chemoradiotherapy with two cycles of carboplatin (AUC=6) plus radiotherapy of 60-78 Gy to the nasopharynx and 60-70 Gy to the neck. The short-term efficacy and adverse events were observed.
More chemotherapy cycles were finished in TC group than in FC group (3.31 vs. 2.83, P = 0.043). There was no significant difference in short-term efficacy and 1-year survival rate between the two groups (P > 0.05). More grades 3-4 neutropenia appeared in TC group than in FC group (72.4% vs. 37.9%, P < 0.05) , whereas less thrombocytopenia and emesis occurred in TC than in FC group (P = 0.013 and 0.018, respectively).
The short-term efficacy of TC regimen in local advanced NPC is similar to that of FC regimen with tolerable adverse events. But the long-term outcomes and toxicities need to be further investigated.
[Show abstract][Hide abstract] ABSTRACT: Induction chemotherapy and radiotherapy or concurrent chemoradiotherapy are the most two effective treatments for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). This study was to compare the efficacy of induction-concurrent chemoradiotherapy versus induction chemotherapy and radiotherapy for patients with locoregionally advanced NPC.
From August 2002 to April 2005, 408 patients were randomly divided into the induction-concurrent chemoradiotherapy (IC/CCRT) group and the induction chemotherapy and radiotherapy (IC/RT) group. Patients in both groups received the same induction chemotherapy, including two cycles of floxuridine (FuDR) plus carboplatin (FuDR750 mg/m2, d1-5; carboplatin AUC=6). All the patients underwent radiotherapy one week after completing the induction chemotherapy. The patients in the IC/CCRT group also received carboplatin (AUC=6) on day 7, 28, and 49 during radiotherapy. Eight patients did not meet the inclusion criteria and were excluded. The remaining 400 cases were analyzed.
Grade III/IV toxicity was found in 28.4% of the patients in the IC/CCRT group and 13.1% in the IC/RT group (P < 0.001). After a median follow up time of 3.9 years, the three-year overall survival was 75.9% and 83.4% (P = 0.12) in the IC/CCRT and IC/RT groups, respectively. No significant differences in the failure-free survival rate, the locoregional control rate, and the distant control rate were found between the two groups.
The IC/CCRT program does not improve the overall survival rate in patients with locoregionally advanced NPC compared with the IC/RT program.
Ai zheng = Aizheng = Chinese journal of cancer 10/2009; 28(10):1033-42.