Treatment Of Advanced Nasopharyngeal Carcinoma Research Articles

A systematic analysis in efficacy and safety of nimotuzumab combined with chemoradiotherapy in treatment of advanced nasopharyngeal carcinoma.

To analyze the clinical effect of nitorzumab injection combined with chemoradiotherapy in the treatment of advanced nasopharyngeal carcinoma. The databases, such as CNKI, Wanfang, VIP, China Biology Medicine (CBM), PubMed, Cochrane Library, Wiley Online Library, and Google Academic were searched. The randomized controlled trials (RCT) of nimotuzumab combined with concurrent chemoradiotherapy (experimental group) and concurrent chemoradiotherapy (control group) were searched. The between-group differences of objective remission rate (ORR), disease control rate (DCR), and drug-related adverse reactions were analyzed by RevMan5.3 software. Totally, 11 studies were included in meta-analysis, including 655 patients. All 11 articles mentioned random grouping and no blind method was used. The objective remission rate, disease control rate, and adverse drug reactions are given in 11 articles. In this study, 11 literatures were analyzed by fixed effect model after heterogeneity and sensitivity analysis. The meta analysis showed that in 10 literatures, the objective remission rate and disease control rate of patients in the experimental group were significantly higher than those in the control group (RR = 1.32, 95% CI: 1.2-1.45, Z = 5.72, P < 0.00001); (RR = 1.07, 95% CI: 1.02-1.11, Z = 3.04, P = 0.002 < 0.01. There was no significant difference in adverse reactions between the two groups (RR = 0.95, 95% CI: 0.79-1.15, Z = 0.52, P = 0.6 > 0.05). The efficacy and safety of nituozumab injection combined with concurrent chemoradiotherapy are reliable and definite.

Immunotherapy for the treatment of advanced nasopharyngeal carcinoma: a promising new era.

Nasopharyngeal carcinoma (NPC) is ranked the top otorhinolaryngology malignant tumors in the world. However, the general prognosis of recurrent and metastatic (R/M) nasopharyngeal carcinomas (NPCs) remains poor, and current surgery and chemoradiotherapy do not generate satisfactory outcomes. As a new therapeutic choice, immunotherapy, especially with regard to the development of checkpoint inhibitors including PD-1 and CTLA-4 inhibitors have made considerable progress in recent years. As Epstein-Barr virus (EBV) infection is associated with increased risk of NPC, EBV-related immunotherapy may lead to a breakthrough in advanced NPCs. In this review, we summarized the clinical characters of NPC, and several past and ongoing clinical trials of checkpoint inhibitors and EBV-CTLs (CTLs: cytotoxic T lymphocytes) in R/M NPC immunotherapy. We conclude that although the evaluated effects of new immunotherapy drugs have brought us hope on NPC treatment, further phase II-III trials with larger samples are still required to improve the proportion and scheme of drug collocation for better clinical outcomes and less drug-related safety.

Clinical Observation of Three Dimensional Conformal Intensity-modulated Radiotherapy Combined with Cisplatin Chemotherapy and Nituzumab in the Treatment of Locally Advanced Nasopharyngeal Carcinoma

Objective . To observe the clinical effect of three-dimensional conformal intensity-modulated radiotherapy combined with cisplatin chemotherapy and nituzumab in the treatment of locally advanced nasopharyngeal carcinoma. Selection method. From January 2016 - January 2019 in fujian province third hospital treated 62 cases of patients with locally advanced nasopharyngeal carcinoma were selected as the research objects, which randomly divided into observation group (31 cases) and control group (31 cases). Control group were treated by three-dimensional conformal intensity modulated radiation therapy synchronous paclitaxel and cisplatin chemotherapy, observers group on the basis of control group, this bead sheet were given, and the treatment. Clinical efficacy and adverse reactions of 2 groups were compared. Results . The CR rate of nasopharyngeal primary foci 2 months after radiotherapy, the CR rate of cervical lymph node, the control rate of primary foci 1 year after radiotherapy . The rate of no distant metastasis in observation group were all higher than those in control group (P 0.05). Conclusion. Three-dimensional conformal intensity-modulated radiotherapy combined with cisplatin chemotherapy and nituzumab in the treatment of advanced nasopharyngeal carcinoma can improve the short-term efficacy, but in terms of improving the long-term efficacy and survival rate of patients, further follow-up investigation is needed.

A network meta-analysis for efficacies and toxicities of different therapeutic regimens in the treatment of advanced nasopharyngeal carcinoma.

The current study set out to compare the efficacies and toxicities (grad 3 and 4) between concurrent chemoradiotherapy (CCRT), induction chemotherapy plus radiotherapy (IC + RT), IC + CCRT, RT and CCRT + adjuvant chemotherapy (CCRT + AC) in regard to advanced nasopharyngeal carcinoma (NPC) treatment using a network meta-analysis. Literature retrieval was conducted using PubMed, Cochrane Library and other English databases. Eligible randomized controlled trails (RCTs) of 5 different regimens were included. The network meta-analysis combined direct and indirect comparisons to measure pooled odd ratios (OR) and the surface under the cumulative ranking curves (SUCRA). A total of eight eligible RCTs were enrolled into this network meta-analysis after initial exclusion. With respect to hematologic toxicity, CCRT + AC exhibited higher toxicity in patients with advanced NPC in terms of anemia and leukopenia/neutropenia compared to RT. As for anemia, the toxicity of IC + CCRT was higher than those with advanced NPC. In addition, CCRT exhibited higher toxicity than RT in relation to leukopenia/neutropenia. Non-hematologic toxicity in regard to nausea/vomiting suggested that CCRT, IC + CCRT and CCRT + AC presented with higher levels of toxicity in patients with advanced NPC, in contrast to RT. Lastly, RT was found to be less toxic but with higher five-year overall survival (OS) rate in patients with advanced NPC, while CCRT, IC + CCRT and CCRT + AC were more toxic in patients with advanced NPC. Among the five therapeutic regimens, the survival rate of IC + RT was similar to that of CCRT, and the toxicity SUCRA value of IC + RT was lower than that of CCRT. Together, our findings indicate that IC + RT may be a potentially acceptable treatment alternative to CCRT for advanced NPC, and is worthy of further investigation.

Whole-body hyperthermia combined with chemotherapy and intensity-modulated radiotherapy for treatment of advanced nasopharyngeal carcinoma: a retrospective study with propensity score matching

Background Several studies have reported the combination of intracavity or cervical lymph node hyperthermia with chemoradiotherapy (CRT) to improve clinical outcomes in nasopharyngeal carcinoma (NPC), but the combination with whole-body hyperthermia (WBH) for treating NPC is unexplored. We aimed to assess the efficacy of the combination of radiotherapy, chemotherapy and WBH in patients with locoregionally advanced NPC. Methods Between July 2008 and November 2012, 239 newly diagnosed NPC patients were enrolled in a pre-propensity score-matched cohort, including 193 patients who received CRT (CRT group) and 46 who underwent CRT with WBH (HCRT group). The feasibility and clinical outcomes of both groups were evaluated and toxicities assessed. Survival rates were assessed using the Kaplan–Meier method, log-rank test and Cox regression. Results Following propensity score matching, 46 patients from each group were included. The 5-year overall survival (OS) rates were 65.2% in the CRT group and 80.3% in the HCRT group (p=.027). In contrast, the other survival outcomes at 5 years were similar between the groups: locoregional recurrence-free survival (LRRFS), 74.7% vs. 87.6% (p=.152); distant metastasis-free survival (DMFS), 67.4% vs. 77.9% (p=.125); and progression-free survival (PFS), 53.1% vs. 69.2% (p=.115). In the multivariate analyses, the only two independent predictors of OS were clinical stage and HCRT. Conclusions These results suggest that WBH, when combined with CRT, can improve the OS of patients with advanced NPC.

Analysis Of Follow-Up Results Of Chronotherapy And Conventional Chemotherapy Combined With IMRT For Locally Advanced Nasopharyngeal Carcinoma

To compare the long-term side effects and survival rates of Intensity modulated radiation therapy combined with chemotherapy in the treatment of advanced Nasopharyngeal carcinoma, and It is expected to reduce the long-term toxic response without reducing the survival, to find a more reasonable treatment for locally advanced Nasopharyngeal carcinoma. 160 patients with locally advanced nasopharyngeal carcinoma were randomly divided into a Time group and conventional group using a professional statistical randomized list (1:1) for treatment. Time group induced chronotherapy with TPF regimen, docetaxel 75 mg/m2 ivgtt, execution in d1 03:30-04:30. Cisplatin 75mg/m2 civ, completed in 5 days, every day from 10:00 to 22:00.5-FU 750mg/m2/d civ, completed in 5 days, every day from 22:00 to 10:00, 2 cycles/21 day. IMRT combined with cisplatin chemotherapy after 3 weeks of induction chemotherapy 100mg/m2 civ, completed at 10:00-22:00,3cycles/21day.In the conventional group, the conventional TPF regimen chemotherapy docetaxel 75mg/m2 ivgtt starts at 10:00.Cisplatin 75mg/m2 civ, begins after the end of docetaxel.5-FU 750mg/m2/d civ, completed in 5 days, executed 24 hours a day, 2cycles/21day.IMRT combined with cisplatin chemotherapy after 3 weeks of induction chemotherapy 100mg/m2 ivgtt starts at 10:00,3cycles/21day.Observation of long-term toxic and 1,3 years of survival situation. The incidence of hearing loss in the time group and the conventional group was 22.7% vs 39.1%, the incidence of dysphagia was 0% vs 8.6%, and the incidence of neck fibrosis was 4.5% vs 15%. The difference was statistically significant (P<0.05). Results of 1,3-year survival of patients in the two groups: The overall survival of time group and conventional group is 97.0% vs 92.8%、80.3% vs 81.2%,not statistically significant (P>0.05), the progression-free survival of time group and conventional group is 95.50% vs 87.0%、71.2% vs 73.9%,not statistically significant(P>0.05),the local recurrence-free survival of time group and conventional group is 97.0% vs 95.7%、92.4% vs 92.8%, not statistically significant(P>0.05) and the distant metastasis-free survival of time group and conventional group is 97.0% vs 98.6%、90.9% vs 91.3%, not statistically significant(P>0.05) When chronotherapy and intensity modulated radiation therapy were combined, the toxicity and side effects of patients were decreased without decreasing survival. Chronotherapy combined with intensity modulation radiotherapy is a recommended mode in the treatment of locally advanced nasopharyngeal carcinoma.

Loss of AKR1C1 is a good prognostic factor in advanced NPC cases and increases chemosensitivity to cisplatin in NPC cells.

Cisplatin resistance is one of the main obstacles in the treatment of advanced nasopharyngeal carcinoma (NPC). AKR1C1 is a member of the Aldo‐keto reductase superfamily (AKRs), which converts aldehydes and ketones to their corresponding alcohols and has been reported to be involved in chemotherapeutic resistance of multiple drugs. The expression and function of AKR1C1 in NPC have not been reported until now. The aim of this research was to investigate the expression of AKR1C1 and it is role in cisplatin resistance in NPC. AKR1C1 protein expression was detected by immunohistochemistry in human NPC tissues and by Western blot assays in NPC and immortalized nasopharyngeal epithelial cells. The effects of AKR1C1 knock‐down by siRNA on proliferation, migration and invasion in NPC cells were evaluated by CCK8, wound healing and transwell assays. To evaluate the effects of AKR1C1 silencing on cisplatin sensitivity in NPC cells, CCK8 assays were used to detect cell proliferation, flow cytometry was used to detect cell cycle distribution, and flow cytometry and DAPI staining were used to detect cell apoptosis. AKR1C1 down‐regulation was associated with advanced clinicopathological characters such as larger tumor size, more lymphatic nodes involvement, with metastasis and later clinical stages, while AKR1C1 down‐regulation was a good prognostic factor for overall survival (OS) in NPC patients. In vitro study showed that AKR1C1 was not directly involved in the malignant biological behaviours such as proliferation, cell cycle progression and migration of NPC cells, whereas AKR1C1 knock‐down could enhance cisplatin sensitivity of NPC cells. These results suggest that AKR1C1 is a potential marker for predicting cisplatin response and could serve as a molecular target to increase cisplatin sensitivity in NPC.

The role of Caspase-1/GSDMD-mediated pyroptosis in Taxol-induced cell death and a Taxol-resistant phenotype in nasopharyngeal carcinoma regulated by autophagy.

Taxol has been widely used as a first-line chemotherapeutic agent for the treatment of advanced nasopharyngeal carcinoma (NPC). However, acquired drug resistance has caused great difficulties in clinical treatment. Pyroptosis is a newly discovered programmed cell death pathway, and Caspase-1 and gasdermin D (GSDMD) play key roles in driving canonical pyroptosis. Increasing evidence suggests that pyroptosis is associated with the development of cancer; however, the function and mechanism of pyroptosis in NPC remain obscure. In this study, we observed that Taxol treatment caused pyroptotic cell death, along with activation of Caspase-1 and maturation of IL-1β, as well as cleavage of GSDMD, which is the canonical pyroptosis executor. Furthermore, Taxol-induced pyroptotic cell death could be suppressed by Caspase-1 inhibitor (Z-YVAD-FMK) and GSDMD knockout. Moreover, NPC parental cells demonstrated higher levels of pyroptosis than Taxol-resistant cells, and pyroptosis mediated by Caspase-1/GSDMD suppression induced by a Caspase-1 inhibitor and GSDMD knockout could induce a Taxol-resistant phenotype in vitro and in vivo. By transfecting an siRNA targeting Beclin-1 into NPC Taxol-resistant cells, we discovered that autophagy could negatively regulate pyroptosis by inhibiting Caspase-1/GSDMD activation. Taken together, our results indicated that Caspase-1/GSDMD mediated Taxol-induced pyroptosis and a Taxol-resistant phenotype in NPC cell lines, which may be regulated by autophagy. Thus, we provide novel insight into the mechanisms of Taxol-induced cell death and a promising approach to improve the therapeutic outcomes of patients with advanced NPC.

Gemcitabine and cisplatin regimen facilitates prognosis of advanced nasopharyngeal carcinoma.

This study was conducted to assess the efficacy and adverse effects of GP (gemcitabine + cisplatin) regimen and FP (fluouracil + cisplatin) regimen in treatment of advanced nasopharyngeal carcinoma. Systematic online searches were performed in PubMed, Web of Sciences, China Knowledge Infrastructure and Weipu from the inception to November 15, 2017. Potential studies were assessed using the Cochrane risk of bias scale. Statistical analyses were performed on Stata 14.0 and RevMan 5.3. Finally, twelve studies entered final qualitative synthesis and quantitative analysis. The GP regimen compared with the FP regimen had significantly higher 1‐year survival rate (relative risk (RR) = 1.07, 95% confidence interval (CI): 1.01‐1.13), significantly better performance in the fixed‐effect model (RR = 1.16, 95%CI: 1.04‐1.30) and significantly higher remission rate (RR = 1.17, 95%CI: 1.05‐1.29). Significant differences between regimens were found in gastrointestinal effects (RR = 0.58, 95%CI: 0.45‐0.74). No significant differences between regimens were found in reduced hemoglobin rate (RR = 0.55, 95%CI: 0.36‐1.21), neutropenia (RR = 1.84, 95%CI: 0.93‐5.02), or reduced platelet (RR = 1.25, 95%CI: 0.85‐1.75) and mucosal inflammation (RR = 0.81, 95%CI: 0.57‐1.16). Sensitivity analysis indicated the results remained stable. The funnel plot indicated some publication bias. In conclusion, the GP regimen outperforms the FP regimen in treatment of advanced nasopharyngeal carcinoma with no difference in adverse effects. We may consider the GP regimen a better choice, but this conclusion should be confirmed by high‐quality trials.

Induction gemcitabine cisplatin followed by chemoradiation in locally advanced nasopharyngeal cancer.

6027 Background: The current standard of treatment in locally advanced nasopharyngeal cancer is concurrent chemoradiation, however recent addition of induction chemotherapy in the already established regimen has presented an attractive alternative approach. We report on survival with induction Gemcitabine and Cisplatin (GC) followed by chemoradiation (CRT) in the treatment of advanced nasopharyngeal carcinoma. Methods: Between 2005 and 2015, 300 patients (M 70%: F 30%) with histologically confirmed nasopharyngeal carcinoma. Histological subtypes WHO I 4% (13) and WHO III 96% (287). AJCC (7th edition) stage was Stage III 28% (85) and Stage IV 72% (215) patients. IC included a 2 drug combination; intravenous gemcitabine 1000 mg/m2 on day 1 and 8 and cisplatin 75 mg/m2 on day 1 only. Radiotherapy was given as a phase treatment to a total dose of 70 Gy in 35 fractions. Concurrent three weekly cisplatin (75 mg/m2) was administered to all patients. Results: Median follow up time was 30 months. The 5-year overall survival (OS), loco regional control (LRC) and relapse free survival (RFS) rates were 70% (95% CI 6.43 – 7.52), 69% (95% CI 6.52 – 7.64) and 52% (95% CI 5.25 – 6.34) respectively. One hundred and seven patients failed treatment; local or loco-regional 39% (42), regional 16% (17) and distant 45% (48). Conclusions: We conclude that induction gemcitabine and cisplatin followed by chemo-radiation is an effective regimen in management of nasopharyngeal carcinoma, meriting further investigation in randomized clinical trials.

Clinical efficacy and safety of gemcitabine plus nedaplatin in the treatment of advanced nasopharyngeal carcinoma.

The purpose was to explore the clinical effects and safety of gemcitabine plus nedaplatin in the treatment of advanced nasopharyngeal carcinoma. From March 2014 to August 2015, we recruited 63 advanced nasopharyngeal carcinoma patients in our hospital. Moreover, the 62 cases were randomly divided into control group (n = 31) and treatment group (n = 32). Patients in the control groups were treated with 5-fluorouracil 500 mg/m 2 + 500 ml 0.9% sodium chloride injection intervenous drop infusion in day 1-5 plus cisplatin 20 mg/m 2 + 500 ml 0.9% sodium chloride injection intervenous drop infusion in day 1-5 with 21 days per cycle for 3 cycles; Moreover, patients in the treatment group were given gemcitabine 1000 mg/m 2 + 500 ml 0.9% sodium chloride injection intervenous drop infusion in day 1 and 8 plus nedaplatin 20 mg/m 2 + 500 ml 0.9% sodium chloride injection intervenous drop infusion in day 1 with 21 days per cycle for 3 cycles. The objective response rate (ORR) and chemotherapy-associated toxicities were compared between the two groups. After 3 cycle chemotherapy, the ORR was 41.9% and 78.1% in the control and treatment group, respectively, with statistical difference (P < 0.05); The main chemotherapy-related toxicity were hematological toxicity and gastrointestinal reaction with no statistical difference between the two groups (P > 0.05). The ORR was relative high for gemcitabine plus nedaplatin in the treatment of advanced nasopharyngeal carcinoma with main toxicity of hematological toxicity and gastrointestinal reaction.

Advanced nasopharyngeal carcinoma radiotherapy with volumetric modulated arcs and the potential role of flattening filter-free beams

PurposeThe purpose of this study is to investigate the dosimetric characteristics of volumetric modulated arc therapy (VMAT) with flattening filter-free (FFF) beams and assess the role of VMAT in the treatment of advanced nasopharyngeal carcinoma (NPC).MethodsTen cases of CT data were randomly selected from advanced NPC patients. Three treatment plans were optimized for each patient, RapidArc with FFF beams (RA-FFF), conventional beams (RA) and static gantry intensity-modulated radiation therapy (IMRT). The doses to the planning target volumes (PTVs), organs at risk (OARs), skin and normal tissue were compared. All the plans were delivered on a Varian TrueBeam linear accelerator and verified using the Delta4 phantom. Technical delivery parameters including the mean gamma score, treatment delivery time and monitor units (MUs) were also analyzed.ResultsAll the techniques delivered adequate doses to the PTVs. RA-FFF gave the highest D1% (dose received by 1% of the volume), but the poorest conformity index (CI) and homogeneity index (HI) among the PTVs except for the planning target volume of involved regional lymph nodes (PTV66) CI, which showed no significant difference among three techniques. For the planning target volume of the primary nasopharyngeal tumor (PTV70), RA-FFF provided for higher mean dose than other techniques. For the planning target volume receiving 60 Gy (PTV60) and PTV66, RA delivered the lowest mean doses whereas IMRT delivered the highest mean doses. IMRT demonstrated the highest percentage of target coverage and D99% for PTV60. RA-FFF provided for the highest doses to the brain stem, skin and oral cavity. RA gave the highest D1% to the right optic nerve among three techniques while no significant differences were found between each other. IMRT delivered the highest mean doses to the parotid glands and larynx while RA delivered the lowest mean doses. Gamma analysis showed an excellent agreement for all the techniques at 3%/3mm. Significant differences in the MUs were observed among the three techniques (p < 0.001). Delivery times for RA-FFF and RA were 152 ± 7s and 153 ± 7s, respectively, nearly 70% lower than the 493 ± 24s mean time for IMRT.ConclusionsAll treatment plans met the planning objectives. The dose measurements also showed good agreement with computed doses. RapidArc technique can treat patients with advanced NPC effectively, with good target coverage and sparing of critical structures. RA has a greater dosimetric superiority than RA-FFF.

Characterization of human Fab antibody fragments specific to LMP1 (HLEAFab) in nasopharyngeal carcinoma for potential molecular diagnosis and therapeutic applications

In view of the previously demonstrated clinical role of the anti-latent membrane protein 1 (LMP1) immunoconjugate HLEAFab-MMC in the treatment of advanced nasopharyngeal carcinoma (NPC), reliable detection of LMP1 expression is of key importance. The aim of this study was to investigate LMP1 status in NPC. Tissue samples from 36 cases were analyzed by immunohistochemistry (IHC) and in situ hybridization for LMP1 and BNLF1 (LMP1 gene) expression, respectively. The results showed LMP1 expression in 20/36 (55.6%) cases in the HLEAFab group compared with 22/36 (61.1%) cases in the S12 group (purified mouse anti-human latent membrane protein 1 monoclonal antibody). The positive staining for LMP1 in the tumor cell membranes exhibited uniformity between HLEAFab and S12. BNLF1 was observed to be amplified in 19/36 NPC patients (52.8%). The sensitivities of HLEAFab-IHC-positivity and S12-IHC-positivity for amplification were 84.2 and 89.5%, respectively. Positive expression of LMP1 was present in a significant proportion of the NPC samples. The present findings provide an important strategy for molecular therapy targeting LMP1 in NPC patients.

Recombinant adenoviral human p53 gene combined with radio- and chemotherapy in treatment of advanced nasopharyngeal carcinoma: A randomized clinical study.

5558 Background: Studies showed p53 gene therapy could enhance the anti-tumor effect of both chemo- and radiotherapy. The anti-tumor function of p53 gene is associated with up-regulated expression of p21 and Bax. Here, we investigate the beneficial role of recombinant adenoviral human p53 gene (rAd-p53) combined with chemoradiotherapy in treatment of advanced nasopharyngeal carcinoma (NPC), and p21 and Bax protein expression in pre- and post-treatment tumor tissues. Methods: Sixty-three patients with historically-diagnosed advanced NPC, with ECOG performance status less than 2, life expectancy greater than 3 months and adequate organ function tests, were randomly assigned into two groups: 32 in experimental group (EG) and 31 in control group (CG). EG received intratumoral injection of 1×1012 rAd-p53 viral particles (VP) per 3 days for 6-8 times, carboplatin 300 mg/m2 on day1 and continuous infusion of a total dose of 2000 mg/m2 of 5-Fu on day1-5 for 3 cycles, and radiotherapy at a dose of 2Gy/fraction for a total dose of 70-76 Gy/35-38f. CG received the same chemo- and radiotherapy. Pre- and post-treatment tissue samples were analyzed for Bax and p21 protein levels. Results: The median follow-up time was 28 months. EG achieved a complete response rate (CR) of 62.5% and overall response rate (RR) of 90.6%, both rates being statistically significantly higher than that of CG (CR=35.5%, RR=74.2%). One-year of overall survival (OS) was 100.0% for EG and 90.3% for CG, and one year of progress free survival (PFS) was 96.7% and 77.4% for EG and CG, respectively. Two-year OS was 95.7% and 86.4% for EG and CG, respectively, and two-year of PFS was 79.6% and 73.5% for EG and CG, respectively. After treatment, both Bax and p21 protein levels in EG increased significantly. In CG, both proteins levels also increased after treatment but not significantly. The main side effects of rAd-p53 were self-limited fever, occurring in all of EG patients. Conclusions: RAd-p53 as a component of the comprehensive therapy for advanced NPC contributes significant beneficial effects. Increased levels of Bax and p21proteins after treatment represent two mechanisms of p53 anti-tumor activities.

The best combination treatment of patients with advanced nasopharyngeal carcinoma.

e16018 Background: To evaluate Radiotherapy, Platinum, 5-FU and Nimotuzumab combine therapy in treatment of advanced nasopharyngeal carcinoma. Methods: From January 2010 until October 2010, 268 patients with pathologically diagnosed advanced Nasopharyngeal carcinoma, stage II to IV with partial metastases combine treated with Nimotuzumab, chemo-radiotherapy were collected. Among 268 patients 241 were qualified for analysis by SAS program. Generally, patients were receiving a total dose of 45Gy-72Gy radiotherapy, and mainly receiving combination of chemotherapy program of Platinum, and all patients were receiving 100-200mg of Nimotuzumab treatment over the same period, once a week. Results: There were 241 cases medical records can be analyzed. Patients aged 37-75 years-old with median age of 60.2. Male and female ratio was 3.46:1. Pathology diagnosed as squamous cell carcinoma. Cancer staged as IV, III and II were 38.2%, 53.7% and 9.1%, and with 64.73% of them with metastasis. Seven patients(2.91%) had adverse events which considering doubt as due to treatment, including chills, fever, rash, oral mucositis and allergy. No patient had significant fatigue, thrombocytopenia, decreased white blood cells count. No other sensory abnormalities, such as sepsis, herpes zoster, bilirubin and heart discomfort were observed. Conclusions: Nimotuzumab combined with chemo-radiotherapy for patients with advanced carcinoma is well tolerated and safe. Radiotherapy, Platinum, 5-FU and Nimotuzumab combine therapy can be considered as the best treatment regimen for patients with advanced nasopharyngeal carcinoma.

Phase I study of TPF neoadjuvant chemotherapy followed by radical radiotherapy in advanced nasopharyngeal carcinoma

PF regimen is the standard chemotherapy for advanced head and neck cancers including nasopharyngeal cancer. Recently PF has been found to enhance the tumor control by addition of Taxotere. The purpose of this study was to evaluate the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of TPF neoadjuvant regimen (taxotere, cisplatin (DDP) and 5-fluorouracil (5-FU)) followed by radical radiotherapy in advanced nasopharyngeal carcinoma (NPC). Between December 2006 and May 2008, 41 patients with newly diagnosed UICC stage III or IV advanced nasopharyngeal cancer were enrolled. There were 29 male and 12 female patients, with a median age of 47 years (range, 29-60 years), and ECOG performance status < or = 2. The initial dose was taxotere 40 mg/m(2) d1, DDP 40 mg/m(2) d1, and 5-FU 400 mg/m(2) d1-5. The treatment was repeated every 3 weeks for two cycles. Each dose of taxotere and DDP was increased by 5 mg/m(2) and 5-FU by 50 mg/m(2), respectively. The dose was escalated after six patients completed two cycles at the initial dose and DLT was assessed. Radiotherapy was started from the 5th week, with 68-72 Gy/34-36 fractions delivered to the nasopharynx and 60-66 Gy/30-33 fractions to the node-positive area. Forty patients (79 cycles) were evaluated for toxicity and efficacy of the therapy. No DLT occurred at the dose levels 1-4. At dose level 5, three of six patients experienced DLT including grade III/IV neutropenia lasting more than 1 week. Two of them also had grade III mucositis, leading to the interruption of radiotherapy for more than 1 week. Three more new patients were retreated with the same dose (at dose level 6) under the G-CSF support, and no DLT occurred. Dose escalation continued to level 7, and DLT was found in all of the four patients, including three grade IV neutropenia, one of them had fever and pneumonitis; three grade III diarrhea; and one grade III mucositis lasting 10 days. Dose escalation was stopped and three more new patients were treated again at dose level 5 and no DLT was found. Other severe toxicities included grade III anemia (1 patients), grade III vomiting (4 patients), and grade III weight loss (9 patients). No severe hepatic and renal toxicities were found. TPF neoadjuvant chemotherapy is a safe and effective regimen in the treatment of advanced NPC, with recommended doses of taxotere 60 mg/m(2) d1, DDP 60 mg/m(2) d1, and 5-FU 600 mg/m(2) d1-5.

Efficacy and adverse effects of gemcitabine plus cisplatin regimen and fluorouracil plus cisplatin regimen in treatment of advanced nasopharyngeal carcinoma:a meta-analysis

Objective:To compare the efficacy and adverse reactions between gemcitabine+cisplatin regimen and fluorouracil+cisplatin regimen in the treatment of advanced nasopharyngeal carcinoma(NPC).Methods:The Cochrane Library,MEDLINE,EMbase,CBM and CNKI were searched for related articles published before 2009.Manual searching and additional searching were also performed.The quality of each included studies was evaluated by 2 independent oncologists and analyses of homogeneous property of the studies were done by RevMan 5.0 software.Results:Four studies were enrolled in our study,including 283 patients with NPC.Meta-analyses showed that the 1-year-and 3-year-survival rates of gemcitabine+cisplatin regimen were similar to those of fluorouracil+cisplatin regimen(Z=0.89,P=0.37),(Z=1.70,P=0.09),but gemcitabine+cisplatin regimen had significantly higher remission rate(Z=2.34,P=0.02) and slighter myelosuppression and gastrointestinal reactions(Z=2.47,P=0.01),(Z=3.20,P=0.001),(Z=2.19,P=0.03).Conclusion:Gemcitabine+cisplatin regimen has equivalent efficacy and slighter adverse effects compared with fluorouracil+cisplatin regimen in treatment of advanced nasopharyngeal carcinoma.

Intensity modulated radiation therapy combined with cetuximab and cisplatin in treatment of advanced nasopharyngeal carcinoma

Intensity modulated radiation therapy combined with cetuximab and cisplatin in treatment of advanced nasopharyngeal carcinoma

Systemic treatment strategies and therapeutic monitoring for advanced nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is endemic in Asia and is etiologically associated with the Epstein–Barr virus. Although radiotherapy can cure most patients with early-stage disease, those with advanced disease often develop recurrences following radiotherapy. The past decade has witnessed significant advances in the systemic treatment of advanced NPC. This article reviews the latest literature regarding: combined modality therapy for locoregionally advanced NPC; clinical trials of novel biologic and cytotoxic therapies for metastatic NPC; and disease monitoring with the plasma Epstein–Barr virus DNA assay.

Clinical research on the combination of paclitaxel and cisplatin in the treatment of advanced nasopharyngeal carcinoma

目的 观察紫杉醇加顺铂联合化疗对晚期鼻咽癌的客观疗效及毒副作用.方法采用紫杉醇175 mg/m2/d1+顺铂30 mg/d1～5化疗,每3周重复,连续2个周期诱导化疗晚期(Ⅲ、Ⅳ期)鼻咽癌患者42例.结果鼻咽病灶无CR病例,PR 33例(78.57%),颈转移淋巴结CR 2例(4.76%),PR 36例(85.71%).Ⅲ、Ⅳ期有效率分别为87.50%(21/24)和88.88%(16/18),总有效率(CR+PR)88.09%(37/42),较紫杉醇单药或同类研究高,毒副作用仍以白细胞下降(88.07%)及恶心呕吐(95.23%)明显,但多为Ⅰ～Ⅱ度反应.结论紫杉醇加顺铂联合化疗治疗晚期鼻咽癌近期疗效明显,能迅速减轻局部肿瘤负荷,是晚期鼻咽癌诱导化疗较理想的方案。