| Objective:1. Mainly to study the short-term curative effects of radiotherapy combined with a cox-2 selective inhibitor celecoxib and cisplatin jointly or separately in advanced cervical carcinoma.2. Next to compare with the adverse reactions of three different treatments.3. Besides to investigate the influence on biological parameters of cervical tumor including proliferation, apopotosis and microvessel density caused by treatments.Methods:1. Patients and grouping46 cases of local advanced cervical carcinomal(in stageⅡb-Ⅳa )with gynecologic examination and pathologic diagnosis were randomly divided into 3 groups. Group A: Radical radiation therapy + cisplatin (18 patients): cisplatin 20mg/m2 was applied once a week during radiotherapy since the first fraction of external radiation and the total use number was 5-6.Group B: Radical radiation therapy + celecoxib (9 patients): celecoxib was administered peros(at dose of 200mg each time, twice a day) on a daily basis 3 days before and throughout the course of radiotherapy.GroupC: Radical radiation therapy + cisplatin + celecoxib (19 patients): Both cisplatin and celecoxib were applied with identical usages of group A and B.2. Biopsy and specimens obtaining: tissue specimens from cervical tumor were collected before treatment and within 24 hours after external radiation 10Gy/5F. 3. Study and assessing index: Systematic observations and records of the patients were made thoroughly during the treatments. Follow-up were taken to assess the short-term curative effects within 3 months after the treatments. Gynecologic examination and cervix Doppler ultrasound evaluation were used to measure the tumor partial remission time (T0.5) and partial remission dose(PRD). These were used to calculate reponse enhancement ratio of celecoxib and to analyze the difference of effects and adverse reaction amongst the 3 groups.Cox-2, ki67 and MVD expression of the cervical tumor tissue were measured by immunohistochemistry. Apoptosis ratio of cervical carcinoma cell was detected with flow cytometer. The indices were analyzed before and after the treatments and compared among groups A, B and C.Results:1. Cervical tumor complete remission rate after treatment: 94.44% for group A, 88.89% for group B and 94.74% for group C. No significant difference ( P=0.797 ) was detected by Fisher's exact statistical method.2. Cervical tumor partial remission time: T0.5 for group C (13.79±3.15 days) was significantly lower than those of group A(16.33±1.91 days) and group B(17.33±2.5 days). The P-values were 0.018 and 0.007 respectively. The difference between group A and B was not significant with a P-value of 0.647.3.Cervical tumor partial remission dose: PRD for group C(2252.63±520.01cGy ) was lower than those of group A (2711.11±344.52cGy) and B (2911.11±413.66cGy ). Sheffe method showed that group C was significantly different from A and B.The reponse enhancement ratio for celecoxib was 1.20 by further calculation.4. Adverse reaction: the rate of nausea and vomiting of group B (22.22%) was significant lower than those of group A (66.67%) and C (68.42%) (P<0.05). There was no statistical significance between the rates of blood adverse reaction and radiation reaction (P>0.05). None of the patients had damages to the functions of liver and kidney or cardiovascular systems.5. Variation of biological indices of the tumor tissue:Cox-2: Before treatment, the positive expression rates for group A, B and C were 66.67%,66.67%,63.16%, respectively(P>0.05 ). After 10Gy radiation the rate were reduced for group B(11.11%) and group C (15.79%), P-values were 0.025 and 0.003 respectively. But the expression rate for group A showed no significant difference.Ki67: The levels of Ki67 for all groups were lower after 10Gy radiation(the average reduction were 9.89, 10.12 and 16.23). Among them the reduction for group C was more significant than those of group A and B(P-values were 0.009 and 0.047). MVD: The levels of MVD for all groups were lower after 10Gy radiation. Among them, the average reduction of group C (14.03) was greater than those of group A(12.06) and B(10.74) (P-values were 0.03 and 0.002 respectively).Apoptosis ratio: With flow cytometer, apoptosis ratio for all groups increased after 10Gy radiation (the average is 12.89, 10.79, 21.55). Comparing with group A and B, respectively, the increase for group C was significant (P<0.05). 6. Correlation between T0.5 and tumor tissue biological indices'variation For group B, T0.5 is negatively correlated with the decrease of Ki67 and MVD, r=-0.9160,r=-0.8347,P<0.01.For group C, T0.5 is negatively correlated with the decrease of Ki67 and MVD, rs=-0.9454,rs=-0.9201,P<0.01.Conclusion:The clinical effect of radiotherapy combined with cisplatin on advanced cervical carcinoma has been demonstrated. To the objective of possible improvement, this work shows that the enhanced clinical effect can be achieved by using cox-2 selective inhibitor celecoxib capsules, at dose of 200mg each time, twice a day.Cervical tumor partial remission time T0.5 is reduced and less partial remission dose is needed. The safety of this treatment can be revealed since no significant enhancement of severe adverse reaction in gastrointestinal tract or marrow inhibition is observed.Otherwise, this approach can lead to both decline in the proliferation and formation of cervical tumor tissue blood vessels and rise in the apoptosis ratio.In conclusion, this approach may be superior to the other two means (radiotherapy + cisplatin and radiotherapy+ celecoxib), an encouraging outcome that warrants further assessment in the follow-up and other multicenter trials including more samples.
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