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Objective To compare the efficacy and toxicity of nedaplatin and cispaltin chemotherapy combined with intensity modulated radiotherpy ( IMRT) in the treatment of locally advanced nasopharygeal carcinoma (NPC) patients in unendemic area. Methods From January 2014 to July 2016, sixty-two pairs of patients with stageⅢ-ⅣB NPC patients who underwent radical radiotherapy were selected for pair analysis (nedaplatin group and cisplatin group, 62 cases for each group). The nedaplatin group was treated with IMRT concurrent with nedaplatin at a dose of 100 mg/m2 every three-weeks for 2 -3 cycles, and sequential adjuvant chemotherapy of nedaplatin + fluorouracil regimen for 2 to 3 courses. The cisplatin group was treated with IMRT concurrent with cisplatin at a dose of 80 mg/m2 every three-weeks for 2-3 cycles, and sequential adjuvant chemotherapy of cisplatin + fluorouracil regimen for 2 to 3 courses. Results The 2-year overall survival ( OS ) of nedaplatin group and cisplatin group was 89. 9％ and 91. 1％, local recurrence free survival ( LRFS ) 90. 5％ and 93. 5％, regional recurrence free survival ( RRFS ) 96. 4％ and 96. 0％, and distant metastasis free survival ( DMFS ) 85. 9％ and 90. 3％, respectively. There were no significant differences between nedaplatin group and cisplatin group ( P >0. 05 ) . In the occurrence of acute toxicity, during concurrent chemoradiotherapy and adjuvant chemotherapy, the incidence of grade 3-4 vomiting in nedaplatin group was significantly lower than that in cisplatin group. During adjuvant chemotherapy, the incidence of grade 3 - 4 thrombocytopenia in nedaplatin group was significantly higher than that in cisplatin group. Conclusions For NPC patients with stage Ⅲ-ⅣB in unendemic area, the 2-year survival rates of nedaplatin group was silimiar to cisplatin group, while the incidence of grade 3 -4 vomiting was significantly lower than that in cisplatin group. Nedaplatin maybe an alternative chemotherapy for patients who cannot tolerate cisplatin chemotherapy.
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Objective To investigate the maximum-tolerated dose (MTD) of cisplatin in docetaxel,cisplatin,and fluorouracil (TPF) induction chemotherapy followed by intensity-modulated radiotherapy (IMRT) and concomitant chemotherapy as well as the safety and short-term efficacy of TPF induction chemotherapy in the treatment of locally advanced nasopharyngeal carcinoma (NPC).Methods Thirtythree patients with locally advanced NPC were enrolled in this trial.The MTD of cisplatin was determined by dose escalation study,and the short-term efficacy and toxicities were evaluated.Results When the doses of docetaxel and fluorouracil were 60 mg/m2 d1 and 550 mg/m2 d1-5,respectively,the MTD of cisplatin was 65 mg/m2 d1.In this regimen (repeated every 3 weeks),grade 3-4 toxicities included neutropenia (67％),febrile neutropenia (9％),diarrhea (21％),and oral mucositis (6％).Except those who experienced dose-limited toxicity,other patients completed the whole treatment schedule.After TPF induction chemotherapy,the overall response rate was 97％,and the complete response rate was 21％.Conclusions In the endemic areas of NPC,induction chemotherapy with docetaxel (60 mg/m2 d1),cisplatin (65 mg/m2 d1),and fluorouracil (550 mg/m2 d1-5),which is repeated every 3 weeks,is proved safe and effective for Asian patients with locally advanced NPC.
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Objective:To study the inhibitory effect of E1A gene on the growth of tumors in nude mice implanted with nasopharygeal carcinoma CNE2 cells and its promotion effect on the racliosensitivity of CNE2-implanted tumors, and to investigate the related mechanism. Methods: E1A gene was transfected into CNE2 cells using adenovirus system, and sta-ble E1A positive clones were established. The inhibitory effect of E1A on tumor formation-ability of CNE2 cells was ob-served in nude mice. The efficacy of E1A gene therapy with or without radiotherapy against CNE2 cell-implanted tumors was evaluated. The effect of E1A gene therapy on the expression of P53 was detected by RT-PCR. Results: CNE2 cells stably transfected with E1A gene (CNE2-Ad-E1A) were successfully established. The tumor formation time was later and tumor size was smaller in CNE2-Ad-E1A cell-implanted mice compared with those in CNE2 cell- and CNE2-Ad-β-gal cell-implanted mice (CNE2 cells stably transfected with Ad-β-gal). Radiotherapy, E1A gene therapy and E1A gene + radio-therapy all suppressed the growth of implanted tumors, with the tumor suppression rates being (60.32±5.34) %, (70.53±6.12) %, and (97.15±4.87) % , respectively. E1A gene therapy significantly increased the expression of P53 gene in tumor tissues. Conclusion: E1A can inhibit the growth of tumors in mice implanted with nasopharygeal carcinoma cells, and enhance its sensitivity to radiotherapy, which may be related to the increased expression of P53 gene in tumor tissues.
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Objective:To study the inhibitory effect of E1A gene on the growth of tumors in nude mice implanted with nasopharygeal carcinoma CNE2 cells and its promotion effect on the radiosensitivity of CNE2-implanted tumors,and to investigate the related mechanism.Methods: E1A gene was transfected into CNE2 cells using adenovirus system,and stable E1A positive clones were established.The inhibitory effect of E1A on tumor formation-ability of CNE2 cells was observed in nude mice.The efficacy of E1A gene therapy with or without radiotherapy against CNE2 cell-implanted tumors was evaluated.The effect of E1A gene therapy on the expression of P53 was detected by RT-PCR.Results: CNE2 cells stably transfected with E1A gene(CNE2-Ad-E1A)were successfully established.The tumor formation time was later and tumor size was smaller in CNE2-Ad-E1A cell-implanted mice compared with those in CNE2 cell-and CNE2-Ad-?-gal cell-implanted mice(CNE2 cells stably transfected with Ad-?-gal).Radiotherapy,E1A gene therapy and E1A gene+radiotherapy all suppressed the growth of implanted tumors,with the tumor suppression rates being(60.32?5.34)%,(70.53?6.12)%,and(97.15?4.87)%,respectively.E1A gene therapy significantly increased the expression of P53 gene in tumor tissues.Conclusion: E1A can inhibit the growth of tumors in mice implanted with nasopharygeal carcinoma cells,and enhance its sensitivity to radiotherapy,which may be related to the increased expression of P53 gene in tumor tissues.
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Objective To compare the therapeutic effects,toxic side effects of late-course three dimensional conformal radiotherapy plus chrono-chemotherapy(DDP+5-FU/CF) and conventional radiotherapy plus chemotherapy for nasopharyngeal carcinoma (NPC). Methods Eighty-six NPC patients admitted from Feb. 2001 to Jan. 2002 were divided randomly into two groups:1.Chrono-chemotherapy + late course three dimensional conformal radiotherapy(CCR) group—44 patients were treated by late course three dimensional conformal radiotherapy plus chrono-chemotherapy, and 2.Routine-chemotherapy-radiotherapy (RCR) group—42 patients were treated by routine chemotherapy plus radiotherapy. The patients in CCR and RCR group were comparable in age, KPS, stage and pathology. All patients were treated by combined chemotherapy and radiotherapy, with chemotherapy stared 2 weeks ahead of radiotherapy. Chemotherapy: Braun pump was used in all drug infusions;1.CCR group—DDP 80?mg/m2 starting from 10:00 until 22:00,5-Fu 750?mg/d/m2 starting from 22:00 until 10:00 next day, CF 200?mg/d/m2 starting from 10:00 every day, infused at normal speed. These drugs were given for 3 days, 14 days as one cycle, totally 2 cycle, and 2.RCR group—with the same drugs at the same total dose, only with the difference being DDP and CF given QD, starting from 10:00 but at the normal speed. 5-Fu was given throughout the day and continuously for 3 days, totally for 2 cycles. Radiotherapy: linear accelerator irradiation was given to either group. Composite facio-cervical field + anterior cervical tangential field to D_T 40?Gy/4w, followed by the coned down per-auricular field plus anterior tangential field or ?beam irradiation. In CCR group, after D_T 40gy/4w, late course 3-dimensional conformal radiotherapy(3DCRT) was used to add D_T 30?Gy/3w. In RCR group, routine radiotherapy of 40?Gy/w was supplemented with 30?Gy/3w. The total dose in either group was 70?Gy/7w at the nasopharynx, D_T60-70?Gy/6-7w at the neck, as cure while 50?Gy/5w for prophylaxis. Results The CR and PR of the CCR group was 45.5% and 95.5%, while the CR and PR of RCR group was 23.8% and 71.4% respectively. There was significant difference between the two groups in CR and PR (P
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Objective To analyze the local control rate and the desimetric patterns of local recurrence in nasopharyngeal carcinoma(NPC)patients having been treated with standardized conventional radiotherapy and to evaluate the delineation of rational target volume.Methods From Jan.2000 to Dec.2000,476 patients with untreated NPC were treated by standardized conventional radiotherapy alone at the Sun Yat-sen University Cancer Center.The radiation ports were designed on a X-ray simulator.The nasopharyngeal lesion demonstrated by CT scan and the subclinical spread regions adjacent to the nasopharynx were defined as the target volume.Kaplan- Meier method was used to calculate the cumulative local recurrence rate.For patients with locad recurrence,the primary and recurrent local tumor volumes(V_(nx),V_(recur))were delineated with three-dimensional treatment planning system(3DTPS),and the dataset of radiation ports and delivered prescription dose to the 3DTPS were transferred according to the first treatment.The dose of radiation received by V_(recur)was calculated and analyzed with dose- volume histogram(DVH).Local recurrence was classified as:1.“in-port”with 95% or mere of the recurrence volume((recur)_V_(95))was within the 95% isedase;2.“marginal”with 20% to95% of _(recur)V_(95)within the 95% isedese; 3.“outside”with only less than 20% of _(recur)_V_(95)within the 95% isodose curve.Results With the median follow- up of 42.5 months(range 8～54 months),52 patients developed local recurrence.The 1-,2-,3 and 4-year cumulative local failure rate was 0.6%,3.9%,8.7% and 11.5%,respectively.Among the 42 local recurrent patients who could be analyzed by 3DTPS,52% were in-port,40% were marginal and 7% were outside.For most of the marginal recurrence and all the outside recurrence patients,the main reason of recurrence were related to the unreasonable design of the radiation port and inaccuracy in the interpretation image findings.Conclusions The outcome of better local control rate and the dosimetric pattern of local recurrence show that the target volume is reasonable for NPC in Sun Yat-sen University Cancer Center.Enhancing the capability of correct interpretation of images,accurate design of the radiation pouts and making most useful molecular or functional imaging techniques to escalate the local radiation dose are promising ways to improve the local control further and better.