| Purpose: To study the clinical effect of neoadjuvant chemotherapy by carboplatin-based regime in patients with locally advanced cervical carcinoma followed by radical surgery;the factors affecting outcome of chemotherapy. The expression of cell proliferation, apoptosis associated-proteins, such as Ki67 and Bax protein were evaluated in tumor samples before and after chemotherapy, its correlation with clinical effect and prognosis.Methods: 1. In the present study, between May 2000 and Dec. 2005 in PLA general hospital, 46 patients with locally advanced cervical cancer were treated with neoadjuvant intraarterial chemotherapy using carboplatin (400mg/m2), mitomycin-C (10mg/m2) and vincristin (1.4mg/m2). Age ranged from 33~74, mean age was 47.7, according to FIGO stage, Stage was â… b in 1, â…¡ a in 6, â…¡ b in 30, â…¢a in 2, â…¢b in 6, â…£a in 1. All patients' pathological diagnosis were definite before chemoembolization as 41 cases in squamous carcinoma, 5 cases in adenocarcinoma. After 1-2 cycles of chemotherapy, it was decided whether radical surgery was possible compared with 44 patients who received radical surgery alone at the same time. Age ranged from 24-73, mean age was 47.8. Stage was â… b in 12, â…¡a in 25, â…¡b in 7. 40 cases in squamous carcinoma, 3 cases in adenocarcinoma, 1 case in squamoadenocarcinoma. To observe the clinical effect of neoadjuvant chemotherapy, side effects and factors affecting outcome of the treatment;compare intra-operative and postoperative complications of two groups. 2. 23 patients who underwent biopsy were brought into experimental group. The expression of Ki67 and Bax protein were evaluated in tumor samples by immunohistochemistry before and after NAIC, its correlation with clinical effect and its effect on prognosis.Results: 1. In investigative group, overall clinical response was noted inthirty-eight patients (82.61%) including two complete response (4.35%) and thirty-six partial response (78.26%). Eight patients had stable disease and none had progression disease. The effective rate was associated with tumor volume (P <0.05), but not with FIGO stage, histology, lymph node metastasis status and grade of differentiation. All patients underwent radical hysterectomy and pelvic lymphadenectomy four weeks following neoadjuvant chemotherapy. The median blood loss, operating time, the length of postoperative hospital stay and bladder rehabilitation time in investigative group were similar to those patients in control group. The lymph node metastasis rate of control group was 36.36%, higher than 26.09% in investigative group (P>0.05). The mean disease-free survival of investigative group was 42.7 months, in control group was 52.6 months (P>0.05). The mean disease-free survival of patients who responded to chemotherapy was significantly longer than that of those who did not response (48.9months vs. 13.7 months, P<0.05). 2. Of 23 patients, 19 patients responded to NAIC and 4 did not, overall clinical response was 82.61%. The expression of Bax protein and Ki67 did not differ between responders and non-responders before chemotherapy. After chemotherapy, the expression of Ki67 decreased in both groups, and was significantly lower for responders than for non-responders;while Bax increased in both groups, and was significantly higher for responders than for non-responders. Ki67 discrepancy before and after chemotherapy was not associated with histological subtype, stage and grade of differentiation;Bax discrepancy before and after NACT was associated with grade of differentiation, but not with the others. The mean disease-free survival of patients with Ki67 LI>33% before chemotherapy was signifantly longer than that of patients with Ki67 LI< 33%(48.6 months vs. 19 months, P<0.05).Conclusion: NAIC was a safe and effective treatment for locally advanced cervical cancer. PVM regime yielded a high response rate with acceptable toxicity. It was able to diminish the primary tumor effectively, decrease staging, which made radical surgery feasible in cases previously considered inoperable. NAICdecreased lymph node metastasis rate.The effective rate was associated with tumor volume, but not with other factors. Responders' disease-free survival was significantly longer than non-responders. Neoadjuvant intraarterial chemotherapy decreased cell proliferation and increased cell apoptosis in tissues of cervical cancer significantly. The disease-free survival of patients with Ki67 LI>33% before chemotherapy was longer than that of patients with Ki67 LI<33%. Chemosensitivity may be related to Ki67 and Bax protein, which may be reference marker of clinical effect and prognosis. |
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