ABSTRACT
We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.
Subject(s)
Female , Humans , Uterine Cervical Neoplasms/drug therapy , Prospective Studies , Quality of Life , Neoplasm Staging , Chemoradiotherapy , Chemotherapy, Adjuvant/adverse effects , Adjuvants, Immunologic , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Retrospective StudiesABSTRACT
We aimed to evaluate the effectiveness and safety of single-course initial regimens in patients with low-risk gestational trophoblastic neoplasia (GTN). In this trial (NCT01823315), 276 patients were analyzed. Patients were allocated to three initiated regimens: single-course methotrexate (MTX), single-course MTX + dactinomycin (ACTD), and multi-course MTX (control arm). The primary endpoint was the complete remission (CR) rate by initial drug(s). The primary CR rate was 64.4% with multi-course MTX in the control arm. For the single-course MTX arm, the CR rate was 35.8% by one course; it increased to 59.3% after subsequent multi-course MTX, with non-inferiority to the control (difference -5.1%,95% confidence interval (CI) -19.4% to 9.2%, P = 0.014). After further treatment with multi-course ACTD, the CR rate (93.3%) was similar to that of the control (95.2%, P = 0.577). For the single-course MTX + ACTD arm, the CR rate was 46.7% by one course, which increased to 89.1% after subsequent multi-course, with non-inferiority (difference 24.7%, 95% CI 12.8%-36.6%, P < 0.001) to the control. It was similar to the CR rate by MTX and further ACTD in the control arm (89.1% vs. 95.2%, P =0.135). Four patients experienced recurrence, with no death, during the 2-year follow-up. We demonstrated that chemotherapy initiation with single-course MTX may be an alternative regimen for patients with low-risk GTN.
Subject(s)
Female , Humans , Pregnancy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Dactinomycin/adverse effects , Gestational Trophoblastic Disease/drug therapy , Methotrexate/therapeutic use , Retrospective StudiesABSTRACT
Objective To assess the high risk factors associated with the positive margin of conization in patients with cervical intraepithelial neoplasia (CIN). Methods From January 2000 to February 2008, 1699 consecutive patients with CIN undergoing conization was reviewed retrospectively in order to analyze the relationship between the positive margin of conization with clinical prognostic factors,such as patients age, disease grade, size of lesion, the procedure of excision and menopause. X<'2> tests was used to compare the different frequencies of factors in groups of positive and negative margin conization, then seven factors with positive margin were processed into unconditional logistic regression analysis. Results The rate of the positive margin in 1699 patients was 14.01% (238/1699). The mean age of patients with positive margins was (39±9 ) years old, while patients with negative margins was ( 39±8 ) years old, which didn't reach statistical difference(P>0.05). The rate of the positive margin was 8.63% in cold knife cone (CKC) and 18.66% in loop electrosurgical excision procedure (LEEP), which showed significant difference( P<0.01 ). Among 1699 patients, 90 patients were with CIN Ⅰ ,339 patients were with CIN Ⅱ ,1113 patients were with CIN Ⅲ [ including 972 with severe dysplasia and 141 with cancer in situ(CIS) ],87 patients were with cervical cancer stage Ⅰ al, 70 patients were with stage Ⅰ a2 or advanced stages. The rate of positive margin was 1.11% ( 1/90), 3.83% ( 13/339), 10.70% (104/972), 26.24% (37/141),35. 63% (31/87) and 74.29% (52/70),respectively. There was statistic difference among them, except CIN Ⅰ and CIN Ⅱ . When combined CIN Ⅰ with CIN Ⅱ , then compared with CIN Ⅲ, cervical cancer withⅠ al and Ⅰ a2, it also showed statistical difference (P<0.05 ) . The rate of positive margin in postmenopausal women was 21.54% (28/130), which was significantly higher than 13.38% (210/1569)in premenopausal women (P=0.010 ). The logistic regression analysis showed that the procedure of excision, grade of disease, size of lesion, surface of cervix, and menopause were high risk factors associated with the positive margin, the risk ratio were 5.147, 3.048, 1.271, 1.905 and 1.860, respectively.Conclusions High grade, the extent of CIN disease, LEEP and postmenopausal age are high-risk factors associated with positive margin in patients treated by conization. It should be warranted in those patients when designing conization treatment.
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Objective To identify the molecular components involved in acquired methotrexate-resistance of human choriocarcinoma. Methods Methotrexate-resistant cell line(JAR/MTX) was derived from JAR cell line by exposed to intervally and progressively increasing higher concentration of MTX. cDNA microarray analyses of JAR/MTX and its parental cell line JAR were performed. Results JAR/MTX was established after one year with stable resistance. Its resistant index to MTX was 7.3. Nine genes were differential expressed between JAR/MTX and JAR cells. INSR,SLC1A3,SAT,HBB,and FLJ12443 were underexpressed and HS1,TXNRD1,TAGLN2,and EEF2 were overexpressed in JAR/MTX cells. Conclusion The cDNA microarray system showed that several alterations of gene expression were present in acquired methotrexate-resistance of human choriocarcinoma.
ABSTRACT
Objective To study the efficacy and side effects of methotrexate with different protocols in the treatment of ectopic pregnancy (EP). Methods Total of 648 patients who had EP and were treated only with MTX were analysed.Patients were divided into six groups according to protocol: Group 1,100 mg intravenously( IV); Group 2,100 mg, IV, followed by citrovorum factor; Group 3, 20 mg, IV every day for five days; Group 4, 20 mg intramusculary (IM) every day for five days; Group 5, 75 mg,IV; Group 6, 75 mg, IM.Results The rates of repeated MTX injection in group1～6 because of inadequate decrease of hCG were 23.3%,25.0%,21.4%,20.6%,24.4% and 22.4% respectively .Success rates were 87.4%,85.4%,90.5%,92.6%,86.3% and 91.4% respectively.Rates of liver dysfunction were 10.3%,8.3%,64.3%,69.1%,8.7% and 31.0%.Conclusion Single-dose of 75mg MTX IV injection may be the best regimen in the treatment of EP because of the same efficacy but the least side effects.