Selective Radiotherapy after Distant Metastasis of Nasopharyngeal Carcinoma Treated with Dose-Dense Cisplatin plus Fluorouracil.

PURPOSE: To investigate the efficacy and safety of selective radiotherapy after distant metastasis of nasopharyngeal carcinoma (NPC) treated with dose-dense cisplatin plus fluorouracil. MATERIALS AND METHODS: Eligible patients were randomly assigned to a study group treated with dose-dense cisplatin plus fluorouracil following selective radiotherapy and a control group receiving traditional cisplatin plus fluorouracil following selective radiotherapy according to a 1:1 distribution using a digital random table method. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response rate, relapse or progression rate in the radiation field and treatment toxicity. RESULTS: Of 52 patients in the study group, 20 cases underwent radiotherapy., while in the control group of 51 patients, 16 underwent radiotherapy. The median PFS, median OS, survival rates in 1, 2 and 3 years in study and control group were 20.9 vs 12.7months, 28.3 vs 18.8months, 85.2%vs 65.9%, 62.2% vs 18.3%, and 36.6%vs 5.2% (p values of 0.00, 0.00, 0.04, 0.00 and 0.00, respectively). Subgroup analysis showed that the median OS and survival rates of 1, 2, 3 years for patients undergoing radiotherapy in the study group better than that in control group( 43.2vs24.1 months, 94.1% vs 86.7%, 82.4% vs 43.3%, 64.7% vs 17.3%, (p=0.00, 0.57, 0.04 and 0.01, respectively). The complete response rate, objective response rate after chemotherapy and three months after radiotherapy, relapse or progression rate in radiation field in study group and in control group were 19.2% vs 3.9%, 86.5% vs 56.9%, 85% vs 50%, 95% vs 81.3% and 41.3% vs 66.7% (p =0.03, 0.00, 0.03,0.30, 0.01 respectively). The grade 3-4 acute adverse reactions in the study group were significantly higher than in the control group (53.8% vs 9.8%, p=0.00). CONCLUSIONS: The survival of patients benefits from selective radiotherapy after distant metastasis of NPC treated with dose-dense cisplatin plus fluorouracil.

[Effects of short hairpin RNA targeting epidermal growth factor receptor on the radiosensitivity of human nasopharyngeal carcinoma xenografts in nude mice].

OBJECTIVE: To investigate the effect of the vector carrying short hairpin RNA targeting epidermal growth factor receptor (shRNA-EGFR) on the radiosensitivity of human nasopharyngeal carcinoma xenografts in nude mice. METHODS: shRNA-EGFR was transfected into human nasopharyngeal carcinoma cell line CNE1 via Lipofectamine 2000. The transfected cells were collected for quantitative RT-PCR detection of the expression level of EGFR mRNA. Western blotting was used to examine the expression of EGFR protein. CNE1 cells were inoculated into nude mice and the tumor volume was measured every 2 days. shRNA-EGFR was intratumorally injected in the mice, and 16 days after radiotherapy, the mice were sacrificed and tumors examined for radiosensitivity. RESULTS: shRNA-EGFR was effectively delivered via Lipofectamine 2000 into CNE cells to result in a significant downregulation of EGFR mRNA and protein expressions (P<0.05). A significant difference was noted in the tumor volume and weight in the tumor-bearing nude mice between shRNA-EGFR plus radiotherapy group and the control, exclusive radiotherapy and shRNA-EGFR groups (P<0.05). CONCLUSION: shRNA-EGFR combined with radiotherapy can effectively inhibit the growth of nasopharyngeal carcinoma in nude mice. shRNA-EGFR can enhance sensitivity of nasopharyngeal carcinoma to radiotherapy.

[Radiosensitivity changes of nasopharyngeal carcinoma cells with different levels of differentiation after treatment with chemotherapeutic agents].

OBJECTIVE: To examine the changes of radiosensitivity of CNE1, a well differentiated squamous cell line of nasopharyngeal carcinoma (NPC), and CNE2, a poorly differentiated squamous cell line of NPC, after treatment with chemotherapeutic agents. METHODS: CNE1 and CNE2 cells with and without treated by adriamycin (ADM) were irradiated by X-ray and the radiosensitivity changes of ADM-treated cells were analyzed according to the cell survival curve generated by colony formation assay. RESULT AND CONCLUSION: Radiosensitivity of CNE1 cells increased after ADM treatment, but that of CNE2 cells decreased, suggesting that different treatment regimens should be planned for advanced squamous cell NPC of different pathological types.

[Expression of multidrug resistance gene in nasopharyngeal carcinoma cells after irradiation exposure].

OBJECTIVE: To examine the changes in the function and expression of multidrug resistance gene (mdr1) and P-gly-coprotein (P-gp) in nasopharyngeal carcinoma (NPC) CNE1 cell following irradiation for determining the sequential order of radiotherapy and chemotherapy in the treatment of NPC. METHODS: The expressions of mdr1 gene and its protein P-gp as well as the function of P-gp efflux were examined in CNE1 cells before and after irradiation exposure by reverse transcriptional polymerase chain reaction (RT-PCR), Western blotting and flow cytometry, respectively. RESULTS: Irradiation of CNE1 cells induced a long-term overexpression of mdr1 gene and P-gp and reduction in intracellular daunorubicin accumulation. CONCLUSION: Irradiation decreases the chemotherapy sensitivity of CNE1 cell, and induction chemotherapy should be therefore performed before radiotherapy in the treatment of advanced NPC.