Treatment Of Nasopharyngeal Carcinoma Patients Research Articles

PLUNC inhibits invasion and metastasis in nasopharyngeal carcinoma by inhibiting NLRP3 inflammasome activation

Nasopharyngeal carcinoma (NPC) is a malignant tumor that occurs in the nasopharynx. Palate, lung, and nasal epithelium clone (PLUNC) has been identified as an early secreted protein that is specifically expressed in the nasopharynx. The aim of this study was to determine the role and mechanism of PLUNC in NPC. We used mRNA sequencing (seq) combined with ribosome-nascent chain complex (RNC)-seq to determine the biological role of PLUNC. The expression of epithelial-to-mesenchymal transition (EMT)-related molecules was detected by western blotting. Then, cell migration and invasion were detected by wound healing and Transwell chamber assays. NPC cells were injected into the tail vein of nude mice to explore the biological role of PLUNC in vivo. The sequencing results showed that PLUNC inhibited the progression of NPC and its expression was correlated with that of NOD-like receptors. Experiments confirmed that PLUNC inhibited the invasion and metastasis of NPC cells by promoting the ubiquitination degradation of NLRP3. PLUNC overexpression in combination with the treatment by MCC950, an inhibitor of NLRP3 inflammasome activation, was most effective in inhibiting NPC invasion and metastasis. In vivo experiments also confirmed that the combination of PLUNC overexpression and MCC950 treatment effectively inhibited the lung metastasis of NPC cells. In summary, our research suggested that PLUNC inhibited the invasion and metastasis of NPC by inhibiting NLRP3 inflammasome activation, and targeting the PLUNC-NLRP3 inflammasome axis could provide a new strategy for the diagnosis and treatment of NPC patients.

KIF23, under regulation by androgen receptor, contributes to nasopharyngeal carcinoma deterioration by activating the Wnt/β-catenin signaling pathway.

Our study aimed to explore the potential mechanisms of KIF23 regulating function in the progression of nasopharyngeal carcinoma and pinpoint novel therapeutic targets for the clinical treatment of nasopharyngeal carcinoma patients. Firstly, the mRNA and protein level of KIF23 in nasopharyngeal carcinoma was measured using quantitative real-time PCR and western blot. Then, the influence of KIF23 on tumor metastasis and growth in nasopharyngeal carcinoma was determined through the in vivo and in vitro experiments. Lastly, the regulatory mechanisms of KIF23 in nasopharyngeal carcinoma were illustrated in the chromatin immunoprecipitation assay. KIF23 was first found to be overexpressed in nasopharyngeal carcinoma samples, and its expression was associated with poor prognosis. Then, the nasopharyngeal carcinoma cell's proliferation, migration, and invasion potential could be improved by inducing KIF23 expression both in vivo and in vitro. Furthermore, androgen receptor (AR) was found to bind to the KIF23 promoter region directly and enhance KIF23 transcription. At last, KIF23 could accelerate nasopharyngeal carcinoma deterioration via activating the Wnt/β-catenin signaling pathway. AR/KIF23/Wnt/β-catenin pathway promotes nasopharyngeal carcinoma deterioration. Our findings could serve as a new therapeutic strategy for nasopharyngeal carcinoma in the clinical practice.

Efficacy and safety of low concentration hydrogen peroxide as nasopharyngeal lavage fluid in the treatment for nasopharyngeal carcinoma radiotherapy: a pilot cohort study.

Purpose: This study aimed to evaluate and analyze the efficacy and safety of low concentration (0.15%) hydrogen peroxide as nasopharyngeal lavage fluid in the treatment for nasopharyngeal carcinoma radiotherapy. Methods: Patients with nasopharyngeal carcinoma from Jiangxi cancer hospital were randomly divided into two cohorts. The training cohort (n= 50) received low concentration (0.15%) hydrogen peroxide as nasopharyngeal lavage fluid in the treatment for nasopharyngeal carcinoma radiotherapy, and the control cohort (n= 50) received 0.02% nitrofurazone lavage fluid. The primary endpoint of the study was result of short-term efficacy. Second endpoints were assessment of the linear visual analogue scale score and the incidences rate of nasopharyngeal radiation related toxicity. Results: All patients had completed the scheduled nasopharyngeal radiotherapy except two patients in control cohort. The complete response, partial response, stable disease and disease objective response of nasopharyngeal primary tumor observed in the training cohort included 18 cases, 23 cases, 9 cases and 41 cases respectively, while in the control cohort 20 cases, 25 cases, 5 cases and 45 cases were recorded, respectively. The study showed a significant discrepancy in the incidence rate of radiation-related mucosa damage between the two. Specifically, Grade 1 and 2 included 37 cases (74.0%) in the training cohort, while in the control cohort the cases were 20 (40.0%). Grade 3 and 4 damage however reported an incidence of 26.0% and 60%, respectively, which clearly constitutes a significant statistical difference (P = 0.002). The assessment of linear visual analogue scale showed that the patients self-conscious comfortable feeling in the training cohort were significantly higher than in the control cohort (P = 0.003). Conclusions: low concentration (0.15%) hydrogen peroxide as nasopharyngeal lavage fluid in the treatment for nasopharyngeal carcinoma patients is effective and safe, and can reduce nasopharyngeal local mucosa radiation related toxicity after radiotherapy.

Identification of a five-miRNA signature as a novel potential prognostic biomarker in patients with nasopharyngeal carcinoma

BackgroundMicroRNAs (miRNAs) are involved in the prognosis of nasopharyngeal carcinoma (NPC). This study used clinical data and expression data of miRNAs to develop a prognostic survival signature for NPC patients to detect high-risk subject.ResultsWe identified 160 differentially expressed miRNAs using RNA-Seq data from the GEO database. Cox regression model consisting of hsa-miR-26a, hsa-let-7e, hsa-miR-647, hsa-miR-30e, and hsa-miR-93 was constructed by the least absolute contraction and selection operator (LASSO) in the training set. All the patients were classified into high-risk or low-risk groups by the optimal cutoff value of the 5-miRNA signature risk score, and the two risk groups demonstrated significant different survival. The 5-miRNA signature showed high predictive and prognostic accuracies. The results were further confirmed in validation and external validation set. Results from multivariate Cox regression analysis validated 5-miRNA signature as an independent prognostic factor. A total of 13 target genes were predicted to be the target genes of miRNA target genes. Both PPI analysis and KEGG analysis networks were closely related to tumor signaling pathways. The prognostic model of mRNAs constructed using data from the dataset GSE102349 had higher AUCs of the target genes and higher immune infiltration scores of the low-risk groups. The mRNA prognostic model also performed well on the independent immunotherapy dataset Imvigor210.ConclusionsThis study constructed a novel 5-miRNA signature for prognostic prediction of the survival of NPC patients and may be useful for individualized treatment of NPC patients.

A Nomogram to Predict Critical Weight Loss in Patients with Nasopharyngeal Carcinoma During (Chemo) Radiotherapy.

Background:Weight loss is an important side effect of long-term anticancer treatment for nasopharyngeal carcinoma patients. The decline in body function will cause many adverse effects, such as local recurrence and distant metastasis, and reduce the patient’s quality of life. Therefore, this study developed a predictive model for the probability of critical weight loss to provide timely appropriate nutritional interventions and prevent serious side effects.Methods:A 20-week prospective follow-up study of 137 nasopharyngeal carcinoma patients in West China Hospital of Sichuan University undergoing radiotherapy and chemotherapy from February 2018 to March 2020 was conducted to collect relevant clinical data. The clinical usefulness and calibration of the prediction model were assessed using the C-index, calibration plot, receiver operating curve, and decision curve analysis. Internal validation was assessed using bootstrapping validation.Results:The nomogram consisted of sex, smoking status, physical status, chemotherapy regimen, and body mass index. Good calibration was observed for the cohort, with an area under the curve of 0.924. Five independent prognostic factors were included in the nomogram, which showed a high C-index value of 0.815 in the interval validation. Decision curve analysis showed that the nomogram was clinically useful when the intervention was decided at the critical weight loss possibility threshold in the 0% to 97% range.Conclusions:We constructed and validated a nomogram for predicting the incidence of critical weight loss in nasopharyngeal cancer patients undergoing chemotherapy and radiotherapy.

Prognostic Value of Tumor Infiltrating Lymphocytes in Nasopharyngeal Carcinoma Patients: Meta-Analysis.

Objective:To evaluate the prognostic value of tumor infiltrating lymphocytes (TILs) in nasopharyngeal carcinoma (NPC) patients.Method:Meta-analysis was performed on eligible studies that was identified by systematic searching of Google scholar, MEDLINE, CNKI, Scopus, PubMed, PMC, Embase and Web of Science databases. The study protocol was registered in International Platform of Registered Systematic Review and Meta-Analysis Protocols-INPLASY (registration number: INPLASY202160014). Databases were searched from inception to January 20, 2020 to identify eligible studies. Those studies that evaluated survival in the form of hazard ratio (HR) in TILs of NPC patients was analyzed. All statistical analysis was performed by using STATA version 16.0 software.Result:Fourteen studies with a total of 3025 patients was analyzed. The pooled result showed that high TILs was significantly associated with favorable overall survival (OS) (HR = 0.55; 95%CI = 0.39-0.77; P = 0.001) and disease free survival (DFS) (HR = 0.60; 95%CI = 0.44-0.81; P = 0.04). Interestingly, high intratumoral TILs had relatively better OS (HR = 0.45; 95%CI = 0.35-0.58; P = 0.006) than stromal TILs (HR = 0.59; 95%CI = 0.36-0.97; P = 0.03). Moreover, an increased level of CD4+ cells infiltration was correlated with favorable OS (HR = 0.4; 95%CI = 0.18-0.85; P = 0.01). CD3+, CD8+ and FoxP3+ lymphocyte’s better prognosis was not statistically significant for OS (P = 0.09; P = 0.07; P = 0.52) and for DFS (P = 0.13; P = 0.29) respectively. However, subgroup analysis of intratumoral CD3+ (HR = 0.48; 95%CI = 0.33-0.70; P = 0.05) and intratumoral CD8+ (HR = 0.32; 95%CI = 0.16-0.62; P = 0.001) was significantly associated with improved OS, but not significant in stromal CD3+ (HR = 0.66; 95%CI = 0.20-2.20; P = 0.62).Conclusion:TILs were variably correlated with better prognosis depending on their microanatomic location and subset of TILs in NPC patients. CD4+, intratumoral CD3+ and intratumoral CD8+ lymphocytes could predict favorable patient outcome which suggest that their role in mediating antitumor immune response could potentially be exploited in the treatment of NPC patients. Future large study on the prognostic value of microanatomic location of TILs is needed for confirmation.

Transoral Robotic Retropharyngeal Lymph Node Dissection in Nasopharyngeal Carcinoma With Retropharyngeal Lymph Node Recurrence.

Nasopharyngeal carcinoma (NPC) patients with retropharyngeal lymph node (RPLN) recurrence typically undergo reirradiation and experience severe radiotoxicity. Salvage open surgery is challenging because gaining access to the retropharyngeal space is complex and risky. Thus, only several centers can perform this procedure, and complications are common. We applied transoral robotic surgery RPLN dissection (TORS-RPLND) to NPC patients with RPLN recurrence to address the problem with open surgery. From March 2017 to October 2020, 10 NPC patients with RPLN recurrence underwent TORS-RPLND using the da Vinci Si/Xi Surgical System. We applied the balloon occlusion test to protect the internal carotid artery, induction chemotherapy to shrink large tumors preoperatively, and ultrasound positioning to effectively locate unrecognizable RPLNs during surgery. Clinical characteristics, complications, and survival outcome data were retrospectively collected. Of 10 patients, 8 underwent en bloc resection via TORS-RPLND, and the remaining 2 patients were converted to open surgery because we failed to identify the RPLN during TORS. After introducing intraoperative ultrasound positioning, no such failure occurred. The mean operative time and intraoperative blood loss were 297 ± 120 min and 40 ± 43 ml, respectively. All surgical margins were negative. TORS-related complications were mild, and the most severe one was grade 3 dysphagia in one patient who underwent conversion to open surgery (10%). With a median follow-up of 19 months, only 1 (10%) patient developed cervical recurrence. TORS-RPLND is feasible, safe, and effective in the treatment of NPC patients with RPLN recurrence, especially with the help of intraoperative ultrasound positioning. 4 Laryngoscope, 131:E1895-E1902, 2021.

Observation of efficacy of paclitaxel with concurrent radiotherapy in the treatment for nasopharyngeal carcinoma patients with liver metastasis

Objective To investigate the efficacy, prognosis and safety of weekly paclitaxel with concurrent radiotherapy in nasopharyngeal carcinoma (NPC) patients with multiple liver metastases. Methods A total of 64 NPC patients with multiple liver metastases in First Affiliated Hospital of Hainan Medical University between January 2016 and January 2018 were recruited and randomly divided into experimental group (n=32) and control group (n=32) by the method of random number table. The patients in the two groups were given palliative radiotherapy with a median dose of 30 Gy. The experimental group used weekly paclitaxel (40 mg/m2) concurrent chemotherapy, cisplatin (40 mg/m2) in the control group. Paclitaxel and cisplatin were used weekly until the end of radiotherapy. The clinical efficacy and adverse effects between the two groups were compared. Results During the follow-up, 1 patient was lost to follow-up in the experimental group, complete remission (CR) in 6 cases (19.4%), partial remission (PR) in 9 cases (29.0%), stable disease (SD) in 7 cases (22.6%) and progressive disease (PD) in 9 cases (29.0%); 2 patients were lost to follow-up in the control group, CR in 4 cases (13.4%), PR in 10 cases (33.3%), SD in 9 cases (30.0%) and PD in 7 cases (23.3%). There was no significant difference between the two groups (Z=-0.060, P=0.952). The effective rates of the experimental group and the control group were 48.4% (15/31) and 46.7% (14/30) respectively, and the difference was not statistically significant (χ2=0.018, P=0.893); the tumor control rates were 71.0% (22/31) and 76.7% (23/30), with no statistically significant difference (χ2=0.256, P=0.613). The median survival time of the experimental group and the control group were 9.4 months and 8.9 months respectively, and the 1-year survival rates were 14.5% and 10.0%, with no significant difference (χ2=1.136, P=0.286). Among the adverse effects, the incidence rates of allergic reaction, neurotoxicity and cardiovascular toxicity in the experimental group were higher than those in the control group [18.8% (6/32) vs. 3.1% (1/32), 28.1% (9/32) vs. 15.6% (5/32), 31.3% (10/32) vs. 15.6% (5/32)], with no significant differences (χ2=2.566, P=0.109; χ2=1.463, P=0.226; χ2=2.177, P=0.140). The incidence rates of granulocyte decline, platelet decline, red blood cell decline, and impaired liver and kidney function in the experimental group were lower than those in the control group [56.3% (18/32) vs. 68.8% (22/32), 12.5% (4/32) vs. 21.9% (7/32), 15.6% (5/32) vs. 25.0% (8/32), 21.9% (7/32) vs. 28.1% (9/32)], with no significant differences (χ2=1.067, P=0.302; χ2=0.988, P=0.320; χ2=0.868, P=0.351; χ2=0.333, P=0.564). The incidence rates of nausea and vomiting was lower than that in the control group [(40.6% (13/32) vs. 78.1% (25/32)], with a significant difference (χ2=9.328, P=0.002). Conclusion Weekly paclitaxel with concurrent radiotherapy has equivalent efficacy to cisplatin and the adverse effects can be tolerated. Key words: Nasopharyngeal neoplasms; Neoplasm metastasis; Radiotherapy; Paclitaxel

Berberine Hydrochloride-Loaded Chitosan Nanoparticles Effectively Targets and Suppresses Human Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is a common epithelial malignancy that occurs in the nasopharynx and it is one of the high incidences of malignant tumors in China. As previous reports, berberine hydrochloride (BH) possesses a repressive effect on the proliferation of various cancer types. But the application of BH was hampered for a long time due to its hydrophobic properties, along with poor stability and bioavailability. In this study, folate acid modified chitosan nanoparticles loaded berberine hydrochloride (BH/FA-CTS NPs) were prepared by the ionic cross-linking technique, the physicochemical properties and the influence of BH/FA-CTS NPs on proliferation, migration and apoptosis in human nasopharyngeal carcinoma CNE-1 cells were studied in vitro and in vivo. Results of scanning electron microscopy (SEM) images showed that BH/FA-CTS NPs were sphere and the diameter was 258.2±9.1 nm. The drug loading and encapsulation efficiency were 8.17±1.12% and 87.73±4.21%, respectively. The drug release kinetics exhibited a slower and sustained release over a period of 48 h. Moreover, results of MTT assay and scratch assay displayed that BH/FA-CTS NPs inhibited proliferation and migration of CNE-1 cells remarkably. BH/FA-CTS NPs promoted apoptosis and necrosis of CNE-1 cells. And BH/FA-CTS NPs displayed distinguished higher tumor inhibition than control group, free BH and BH/CTS NPs in vivo. Therefore, as a nanocomposite, BH/FA-CTS NPs provide a new method and option for the treatment of nasopharyngeal carcinoma patients.

Joint quantitative measurement of hTERT mRNA in both peripheral blood and circulating tumor cells of patients with nasopharyngeal carcinoma and its clinical significance

BackgroundThe study was aimed to quantitatively detect mRNA levels of the catalytic subunit of telomerase (hTERT) in both peripheral blood and circulating tumor cells (CTCs) of patients with nasopharyngeal carcinoma (NPC) and explore its significance in early diagnosis and treatment of NPC.MethodshTERT mRNA levels in peripheral blood and CTCs of 33 NPC patients before and after treatment with intensity-modulated radiation therapy (IMRT) or/and chemotherapy and 24 healthy controls were measured using real-time quantitative PCR (qPCR) and their correlations to clinic pathological factors of NPC were analyzed.ResultsPeripheral hTERT mRNA content was 10.75 ± 4.29 in NPC patients and 0.95 ± 0.37 in control subjects (P < 0.05), and had a significant correlation with patients’ clinical stage, T stage, and N stage (P < 0.05). Treatment of NPC patients at stages I and II with simple IMRT significantly reduced hTERT mRNA level from 5.60 ± 2.33 to 3.43 ± 1.42 (P < 0.05) and treatment of patients at advanced stage (III and IV) with induction chemotherapy followed by IMRT significantly reduced hTERT mRNA levels from 12.68 ± 3.08 to 10.68 ± 2.48 to 3.13 ± 1.69 (P < 0.05), respectively. In addition, the study also showed that hTERT mRNA content in CTCs of NPC patients was 10.65 ± 4.28, evidently higher than that of 1.09 ± 0.40 in control subjects (P < 0.05) and hTERT mRNA level in CTCs of NPC patients was obviously correlated to patients’ clinical stage, T stage and N stage (P < 0.05). After treatment, hTERT mRNA level in CTCs of NPC patients lowered from 10.65 ± 4.28 to 5.59 ± 2.32 (P < 0.05). The correlation analysis found that hTERT mRNA level in peripheral blood and CTCs of NPC patients were highly correlated with a correlation coefficient of 0.981.ConclusionshTERT mRNA levels in peripheral blood and CTCs of NPC patients were significantly enhanced compared to that in healthy controls and highly correlated. Changes in hTERT mRNA level was closely correlated to patients’ clinical stage and T stage. Radiochemotherapy could effectively reduce hTERT mRNA level in peripheral blood and CTCs. Thus, it is possible using the joint detection of hTERT mRNA level in peripheral blood and CTCs as a new biomarker for early diagnosis, treatment efficacy and prognosis of NPC.

Quantitative Assessment of Skull-Base Invasion in Nasopharyngeal Carcinoma Patients with Signal Intensity Index Based on Magnetic Resonance Imaging

Purpose: To evaluate the use of signal intensity index (SII) of skull-base invasion in nasopharyngeal carcinoma (NPC) using magnetic resonance imaging (MRI), select a best cut-off SII value to predict the outcome of NPC. Materials and Methods: One hundred and twenty-two NPC patients (92 men, 30 women) with skull-base invasion were included. All patients underwent MRI, signal intensities on T1-weighted imaging (T1WI) were measured for each invaded site and its contralateral normal counterpart. The SIIs were calculated, receiver operating characteristic curves were constructed. The optimal cut-off values were extracted. The overall survival (OS) rates of 5-year follow-up were performed. Results: Sensitivities for differentiating skull-base invasion from normal contralateral anatomy were 98.9%, 88.5% and 70.0%, and specificities were 98.9%, 96.0% and 74.4%, respectively. There were three cut-off values for differentiating invasion from normal anatomy of skull-base, 49%, 98%, and 60%. Significant difference in OS rates (84.2% vs. 57.1%, p=0.007) was seen for SII threshold values > 60% and those ≤ 60%. Conclusions: The SII might be a useful means of differentiating invasion from normal tissue at the skull-base in NPC. The cut-off value of quantitative SII at the skull-base may aid in monitoring the response to treatment of NPC patients.

Co-treatment with arsenic trioxide and ganciclovir reduces tumor volume in a murine xenograft model of nasopharyngeal carcinoma

We have previously shown that disruption of promyelocytic leukemia nuclear bodies (PML NBs) is sufficient to activate the EBV lytic cycle thus making infected cells susceptible to ganciclovir (GCV) mediated killing in vitro. Here we show that co-administration of GCV and arsenic trioxide (ATO), a PML NB disruptor, reduces tumor volume in a xenograft model of nasopharyngeal carcinoma utilizing CNE1 cells. When administered at pharmacologic levels, both GCV and ATO reduced tumor growth while co-treatment with GCV + ATO resulted in a diminution of tumor volume. Treatment with GCV or ATO individually resulted in an increased number of apoptotic cells while co-treatment with GCV + ATO synergistically induced apoptosis. Treatment with ATO or co-treatment with GCV + ATO resulted in expression of EBV lytic proteins. These data suggest that co-treatment with GCV + ATO may provide an effective treatment for nasopharyngeal carcinoma patients.

Quantitative measurement of optical attenuation coefficients of cell lines CNE1, CNE2, and NP69 using optical coherence tomography

The radiotherapy-related types of nasopharyngeal carcinoma (NPC) have been established, which give the most effective treatment for NPC patients using the individual therapy. To diagnose the types of NPC, we assess the general NPC cell lines CNE1, CNE2 and normal nasopharyngeal cell line NP69 using optical coherence tomography (OCT) in two steps: firstly, the OCT images of the three different types of cell pellets are captured. Secondly, by fitting Beer's law to the averaged A-scans in these OCT datasets, the attenuation coefficients (μ t ) of the cells can be extracted. The median attenuation coefficients (interquartile range) of CNE1, CNE2, and NP69 are 5.58mm(-1) (IQR 5.55 to 5.65mm(-1)), 5.91mm(-1) (IQR 5.82 to 5.88mm(-1)), and 8.96mm(-1) (IQR 8.80 to 9.47mm(-1)), respectively. The distinguishable quantitative OCT analysis (by μ t ) shows that the types of NPC could potentially be differentiated in real time and noninvasive.

Advances in nasopharyngeal carcinoma

Nasopharyngeal carcinoma prognosis is related to its potential locoregional invasion and metastatic spread. Among prognostic factors, initial tumor-node-metastasis stage is the main one, besides other biological parameters. Worldwide development of positron emission tomography imaging is changing modalities of staging. Concomitant chemoradiotherapy represents one of the most recent advances in the treatment of nasopharyngeal carcinoma patients, besides intensity-modulated radiation therapy. This review updates these recent advances in diagnosis and treatment of nasopharyngeal carcinoma. Recent publications have shown the superiority of fused positron emission tomography/computed tomography over positron emission tomography alone and conventional imaging to do an accurate staging and to impact on patient management. Circulating Epstein-Barr virus DNA load may be a useful prognostic marker in endemic regions. Recent meta-analysis confirmed the superiority of concurrent chemoradiotherapy to radiotherapy alone. Previous publications have shown that induction chemotherapy with new agents might be promising. Data demonstrating targeted therapies efficacy in metastatic nasopharyngeal carcinoma are limited to date. Positron emission tomography-computed tomography is replacing conventional imaging in the initial M staging of nasopharyngeal carcinoma. Its usefulness in response evaluation after therapy and its place in the follow-up need to be prospectively evaluated. Cisplatin-based concomitant chemoradiotherapy is now the standard treatment for locally advanced patients. However, incidence of relapses remains high, and new multimodal therapy is needed.

Phase II Trial of Systemic Recombinant Interleukin-2 in the Treatment of Refractory Nasopharyngeal Carcinoma

Background: Interleukin-2 (IL-2) is a cytokine produced by activated T cells, which has shown powerful immunostimulatory and antineoplastic properties. Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus-associated cancer with abundant lymphocyte infiltration histologically. The activity of IL-2 in the treatment of NPC patients is currently unknown. A phase II study was, therefore, initiated to evaluate the efficacy, toxicity and immunological consequences of intravenous bolus IL-2 in patients with recurrent/metastatic NPC. Methods: Between November 1996 and April 1997, 14 patients with recurrent/metastatic NPC were entered into the study. Recombinant IL-2 (Proleukin, Chiron) was injected by intravenous bolus every 8 h at 72,000 IU/kg for a maximum of 15 doses. After 7 days, patients were retreated with a second identical cycle of therapy. Those patients who were stable or responding to treatment 5–6 weeks later went on to receive another course (two cycles) of therapy. All patients received prophylactic antibiotics and antipyretic medicine. Response and toxicities were evaluated. Serial plasma level of TNF-α, IL-6, soluble IL-2 receptor, IL-10 and soluble CD8 were determined. Results: Fourteen patients received a total of 34 cycles of therapy. No response was observed. Fifty percent had stable disease, 50% had progressive disease after a median of two cycles of therapy. There was one treatment-related death from acute myocardial infarction. Body weight increase (>5%) occurred in 80% of cycles, and hypotension (BP <80 mm Hg systolic) occurred in 53%. Serum creatinine increase (>2 mg%) occurred in 24% of cycles, and SGOT/SGPT increase (>3×) in 10% of cycles. Symptoms of somnolence, general malaise, nausea and vomiting, pruritus, xerostomia, desquamation were generally mild to moderate but rapidly reversible. Conclusion: The single modality of intravenous bolus IL-2 at the dose level of 72,000 IU/kg is clinically ineffective in NPC patients. Potential mechanisms of the ineffectiveness of IL-2 therapy on NPC patients are discussed.