Concurrent mitomycin C, 5-fluorouracil, and radiotherapy in the treatment of locally advanced carcinoma of the cervix: a randomized trial. A phase II study of weekly neoadjuvant chemotherapy followed by radical chemoradiation for locally advanced cervical cancer Phase II study of consolidation chemotherapy after concurrent chemoradiation in cervical cancer: preliminary results. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Pelvic irradiation with concurrent chemotherapy versus pelvic and para-aortic irradiation for high-risk cervical cancer: an update of radiation therapy oncology group trial (RTOG) 90-01. Concomitant chemobrachyradiotherapy with ifosfamide and cisplatin followed by consolidation chemotherapy for women with locally advanced carcinoma of the uterine cervix--final results of a prospective phase II-study. Efficacy of concurrent chemoradiotherapy plus adjuvant chemotherapy on advanced cervical cancer. Efficacy in high burden locally advanced cervical cancer with concurrent gemcitabine and cisplatin chemoradiotherapy plus adjuvant gemcitabine and cisplatin: prognostic and predictive factors and the impact of disease stage on outcomes from a prospective randomized phase III trial. Neoadjuvant and Adjuvant Chemotherapy of Cervical Cancer: Mature Results of the Phase 2 PBM-PFU Protocol Chemoradiation and adjuvant chemotherapy in cervical cancer. Concurrent chemoradiotherapy with paclitaxel and nedaplatin followed by consolidation chemotherapy in locally advanced squamous cell carcinoma of the uterine cervix: preliminary results of a phase II study. Concomitant chemobrachyradiotherapy with ifosfamide and cisplatin followed by consolidation chemotherapy in locally advanced squamous cell carcinoma of the uterine cervix: results of a phase II study. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. A phase III study comparing concurrent gemcitabine (Gem) plus cisplatin (Cis) and radiation followed by adjuvant Gem plus Cis versus concurrent Cis and radiation in patients with stage IIB to IVA carcinoma of the cervix. Capecitabine-based chemoradiotherapy with adjuvant capecitabine for locally advanced squamous carcinoma of the uterine cervix: phase II results. Chemoradiation and adjuvant chemotherapy in advanced cervical adenocarcinoma.
PURPOSE This is a prospect i ve , Phase III multicenter r and omized trial to assess the effectiveness of concurrent intravenous mitomycin C , oral 5-fluorouracil ( 5-FU ) , and radiotherapy ( RT ) in locally advanced carcinoma of the cervix . METHODS AND MATERIAL S Between January 1988 and November 1994 , 926 patients with locally advanced carcinoma of the cervix , FIGO Stage IIB-IVA , were entered into this study . The patients were r and omized into four arms , as follows : Arm 1 : conventional RT ; Arm 2 : conventional RT and adjuvant chemotherapy ; Arm 3 : conventional RT plus concurrent chemotherapy ; Arm 4 : conventional RT plus concurrent chemotherapy and adjuvant chemotherapy . Concurrent chemotherapy consisting of intravenous mitomycin C at 10 mg/m(2 ) was given on Days 1 and 29 , and oral 5-FU at 300 mg/day was administered on Days 1 - 14 and 29 - 42 during RT . Adjuvant chemotherapy of 5-FU orally at 200 mg/day was given for three courses of 4 weeks , with a 2-week rest every 6 weeks . Six centers participated in the trial . RESULTS The median follow-up time was 89 months . Acute side effects were generally higher in concurrent arms , but most of the patients tolerated the treatment well . Bone marrow toxicity was also higher in concurrent arms . The 5-year actuarial disease-free survival ( DFS ) was 48.2 % , 54.1 % , 64.5 % , and 59.7 % for arms 1 , 2 , 3 , and 4 , respectively . The pattern of failure revealed a significant increase in locoregional recurrence in the nonconcurrent chemoradiotherapy arm . The local recurrence was 25.5 % , 20.6 % , 14.3 % , and 17.6 % for arms 1 , 2 , 3 , and 4 , respectively . The metastatic rates were not significantly different in all four arms . At the time of analysis , there were no increases in late side effects , especially in gastrointestinal and genitourinary systems . CONCLUSIONS Concurrent chemotherapy , mitomycin C , and 5-FU together with conventional RT showed an improved DFS rate when compared with conventional RT alone in patients with locally advanced carcinoma of the cervix Background : We investigated the feasibility of dose-dense neoadjuvant chemotherapy ( NACT ) with paclitaxel and carboplatin before radical chemoradiation ( CRT ) and assessed the response rate to such a regimen . Methods : CxII is a single-arm phase II trial of 46 patients , with locally advanced cervical cancer ( stage Ib2-IVa ) . Patients received dose-dense carboplatin ( AUC2 ) and paclitaxel ( 80 mg m−2 ) weekly for six cycles followed by CRT ( 40 mg m−2 of weekly cisplatin , 50.4 Gy , 28 fractions plus brachytherapy ) . The primary end point was response rate 12 weeks post-CRT . Results : Baseline characteristics were : median age at diagnosis 43 years ; 72 % squamous , 22 % adenocarcinoma and 7 % adenosquamous histologies ; FIGO stage IB2 ( 11 % ) , II ( 50 % ) , III ( 33 % ) , IV ( 7 % ) . Complete or partial response rate was 70 % ( 95 % CI : 54–82 ) post-NACT and 85 % ( 95 % CI : 71–94 ) post-CRT . The median follow-up was 39.1 months . Overall and progression-free survivals at 3 years were 67 % ( 95 % CI : 51–79 ) and 68 % ( 95 % CI : 51–79 ) , respectively . Grade 3/4 toxicities were 20 % during NACT ( 11 % haematological , 9 % non-haematological ) and 52 % during CRT ( haematological : 41 % , non-haematological : 22 % ) . Conclusion : A good response rate is achieved by dose-dense weekly NACT with carboplatin and paclitaxel followed by radical CRT . This treatment regimen is feasible as evidence d by the acceptable toxicity of NACT and by the high compliance to radiotherapy ( 98 % ) PURPOSE Our aim was to determine the efficacy of consolidation chemotherapy after concurrent chemoradiation ( CCRT ) using high-dose-rate brachytherapy in patients with locally advanced cervical carcinoma . METHODS AND MATERIAL S Patients with cervical carcinoma ( FIGO stage IB2-IVA ) were treated with external beam radiation therapy to the whole pelvis ( 50.4 Gy ) and high-dose-rate brachytherapy ( 24 Gy to point A ) . Cisplatin 60 mg/m(2 ) ( Day 1 ) and 5-fluorouracil 1000 mg/m(2 ) ( Days 1 - 5 ) were given every 3 weeks starting concurrently with the radiation and followed by 3 more cycles of consolidation for a total of 6 cycles . RESULTS Thirty patients ( 94 % ) received 3 more cycles of post-CCRT consolidation chemotherapy and were evaluable for the toxicity and efficacy of consolidation . The most common toxicities of Grade 2 or higher were nausea or vomiting ( 47 % ) and anemia ( 33 % ) . Late complications of the rectum and bladder occurred in 13 % and 6 % of the patients , respectively . The clinical complete response rate was 87 % ( 95 % CI , 75%-99 % ) . During a median follow-up of 27 months ( range , 6 - 58 months ) , 5 patients ( 17 % ) had recurrence ; the sites of failure were 3 ( 10 % ) inside the radiation field and 2 ( 7 % ) outside the radiation field . The estimated 3-year progression-free survival rate was 83 % ( 95 % CI , 67%-99 % ) and overall survival rate was 91 % ( 95 % CI , 79%-100 % ) . CONCLUSIONS Consolidation chemotherapy after CCRT is well tolerated and effective in patients with locally advanced cervical carcinoma . A prospect i ve r and omized trial to compare this treatment strategy with st and ard CCRT seems to be worthwhile BACKGROUND Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics : both tumour shrinkage ( objective response ) and disease progression are useful endpoints in clinical trials . Since RECIST was published in 2000 , many investigators , cooperative groups , industry and government authorities have adopted these criteria in the assessment of treatment outcomes . However , a number of questions and issues have arisen which have led to the development of a revised RECIST guideline ( version 1.1 ) . Evidence for changes , summarised in separate papers in this special issue , has come from assessment of a large data warehouse ( > 6500 patients ) , simulation studies and literature review s. HIGHLIGHTS OF REVISED RECIST 1.1 : Major changes include : Number of lesions to be assessed : based on evidence from numerous trial data bases merged into a data warehouse for analysis purpose s , the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total ( and from five to two per organ , maximum ) . Assessment of pathological lymph nodes is now incorporated : nodes with a short axis of 15 mm are considered measurable and assessable as target lesions . The short axis measurement should be included in the sum of lesions in calculation of tumour response . Nodes that shrink to < 10 mm short axis are considered normal . Confirmation of response is required for trials with response primary endpoint but is no longer required in r and omised studies since the control arm serves as appropriate means of interpretation of data . Disease progression is clarified in several aspects : in addition to the previous definition of progression in target disease of 20 % increase in sum , a 5 mm absolute increase is now required as well to guard against over calling PD when the total sum is very small . Furthermore , there is guidance offered on what constitutes ' unequivocal progression ' of non-measurable/non-target disease , a source of confusion in the original RECIST guideline . Finally , a section on detection of new lesions , including the interpretation of FDG-PET scan assessment is included . Imaging guidance : the revised RECIST includes a new imaging appendix with up date d recommendations on the optimal anatomical assessment of lesions . FUTURE WORK A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI . It was concluded that , at present , there is not sufficient st and ardisation or evidence to ab and on anatomical assessment of tumour burden . The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression . As is detailed in the final paper in this special issue , the use of these promising newer approaches requires appropriate clinical validation studies PURPOSE To report mature results of a r and omized trial that compared extended-field radiotherapy ( EFRT ) versus pelvic radiotherapy with concomitant fluorouracil and cisplatin ( CTRT ) in women with locoregionally advanced carcinomas of the uterine cervix . PATIENTS AND METHODS Four hundred three women with cervical cancer were r and omly assigned to receive either EFRT or CTRT .  Patients were eligible if they had stage IIB to IVA disease , stage IB to IIA disease with a tumor diameter > or = 5 cm , or positive pelvic lymph nodes . Patients were stratified by stage and by method of lymph node evaluation . RESULTS The median follow-up time for 228 surviving patients was 6.6 years . The overall survival rate for patients treated with CTRT was significantly greater than that for patients treated with EFRT ( 67 % v 41 % at 8 years ; P < .0001 ) . There was an overall reduction in the risk of disease recurrence of 51 % ( 95 % CI , 36 % to 66 % ) for patients who received CTRT . Patients with stage IB to IIB disease who received CTRT had better overall and disease-free survival than those treated with EFRT ( P < .0001 ) ; 116 patients with stage III to IVA disease had better disease-free survival ( P = .05 ) and a trend toward better overall survival ( P = .07 ) if they were r and omly assigned to CTRT . The rate of serious late complications of treatment was similar for the two treatment arms . CONCLUSION Mature analysis confirms that the addition of fluorouracil and cisplatin to radiotherapy significantly improved the survival rate of women with locally advanced cervical cancer without increasing the rate of late treatment-related side effects OBJECTIVES To evaluate the efficacy and toxicity of ifosfamide and cisplatin administered concomitantly with low-dose rate brachyradiotherapy followed by consolidation chemotherapy in the treatment of locally advanced squamous cell carcinoma ( LASCC ) or adeno/adenosquamous carcinoma of the uterine cervix . METHODS Sixty-two patients with primary uterine cervical cancer were enrolled between August 1999 and November 2004 . The patients had to have FIGO-stage IB2 bulky to IVA disease , biopsy-proven squamous cell or adeno/adenosquamous carcinoma of the uterine cervix . The patients were to receive external radiotherapy ( 50 Gy in 25 fractions ) ; ifosfamide 2 g/m2 plus cisplatin 75 mg/m2 was applied concomitantly during two low-dose rate brachyradiotherapy applications ; the planned dose to point A was 85 Gy in total . After the completion of radiotherapy , i.e. external and concomitant chemobrachyradiotherapy , four cycles of consolidation chemotherapy with the same drug combination were to be administered . RESULTS The clinical complete response rate according to WHO-classification ( assessed after the completion of the whole treatment procedures by gynecologic and radiologic evaluation and cervical biopsy ) was 100 % . After a median follow-up of 49 months ( range 11 - 74 months ) , the recurrence-free and overall survival rates were 88.7 % , respectively . The most frequent early toxicities were grade 3 and 4 leukopenias occurring in 25 % and 11 % of the cycles , respectively . Major delayed local complications occurred in 10 patients ( 16.1 % ) . CONCLUSION These results indicate that concomitant chemobrachyradiotherapy with ifosfamide and cisplatin followed by consolidation chemotherapy with the same drug combination is a highly efficacious and very promising treatment protocol for patients with locally advanced LASCC or adeno/adenosquamous carcinoma of the uterine cervix BACKGROUND AND OBJECTIVE Concurrent chemoradiotherapy for cervical carcinoma develops rapidly and has become a common and st and ard therapy in recent years . Both the local control rate and survival rate of patients were increased and the risk of death fell by 30%-50 % . This study aim ed to explore the efficacy of concurrent chemoradiotherapy plus adjuvant chemotherapy on and the treatment compliance of the patients with advanced cervical squamous cell carcinoma . METHODS A total of 156 patients with stage IIa-IIIb cervical squamous cell carcinoma were r and omly divided into the concurrent chemoradiotherapy group ( experimental group ) and radiotherapy group ( control group ) . Intracavity and external beam radiation therapy were administered . At point A , 40 - 48 Gy were given by 10 - 12 fractions ; at point B , 46 - 50 Gy were given by 23 - 25 fractions . In the same time , experimental group was treated by cisplatin ( DDP , 40 mg ) on day 1 , repeated every week . Ten days after radiation therapy , TP regimen was administered as adjuvant chemotherapy . RESULTS For the experimental and control groups , the objective response rates were 88.61 % and 75.32 % , 1-year survival rates were 88.57 % and 70.77 % , 1-year local control rates were 81.43 % and 64.62 % , 3-year survival rates were 82.14 % and 57.69 % , and 3-year local control rates were 75.00 % and 46.15 % , with significant differences ( P<0.05 ) . Quality of life of all patients were significantly improved after treatment ( P<0.05 ) . CONCLUSION Concurrent chemoradiotherapy plus adjuvant chemotherapy for advanced cervical cancer can improve short-term and long-term survival and local control rates of patients , improve the quality of life , and the toxicity can be tolerated OBJECTIVE We recently published results of a phase III trial demonstrating superior outcomes in patients with locally advanced cervical cancer ( LACC ) when concurrent cisplatin chemoradiotherapy is supplemented with concurrent gemcitabine and adjuvant gemcitabine/cisplatin . We present prognostic and predictive factors identified in that study , along with analyses of the effect of disease stage and post- study therapy . PATIENTS AND METHODS In that trial , 515 patients with stage IIB-IVA LACC were administered concurrent cisplatin chemoradiotherapy with or without gemcitabine and adjuvant gemcitabine/cisplatin . Cox models were used to identify prognostic and predictive factors . Survival was estimated using the Kaplan-Meier method . RESULTS Advanced ( stage III-IVA ) disease , squamous histology , low hemoglobin , the presence of ≥1 enlarged para-aortic lymph nodes , and large tumor size , were associated with poorer prognosis , regardless of treatment assigned . Tumor size and histology were predictive of treatment efficacy . Chemoradiotherapy supplemented with gemcitabine produced relatively greater benefit in patients with stage III/IVA disease . Post- study therapy did not appear to affect the overall survival outcome . CONCLUSION Prognostic factors identified in this study are consistent with other reports . The finding of relatively greater benefit in advanced-stage patients makes for an important factor in consideration of treatment for these patients and the design of future studies Objective The mature results of the neoadjuvant and adjuvant chemotherapy arms of the nonr and omized , phase 2 Yale University  cisplatin , bleomycin , methotrexate , and 5-FU protocol are presented . Methods Sixty-seven patients were prospect ively accrued with a median follow-up of 5.4 years , and st and ard parameters of toxicity and efficacy were studied . Both univariate and multivariate analyses were applied . Results The 5-year disease-free survival of 78 % for the 25 patients in the adjuvant group , of which 80 % had high-risk features including positive margins , parametria , and lymph nodes and 28 % had adenocarcinomas , was comparable to recent relevant literature . Only 64 % of patients in this group received consolidation radiation therapy , which did not impact on survival . Only 12 % of patients recurred distantly . Notably , those who received 4 months or more of chemotherapy had prolonged survival ( P = 0.012 ) . In the neoadjuvant group , chemotherapy response rate among 42 patients ( with stages 1B-IIIB cancer ) was 79 % ( 50 % partial response , 29 % complete response ) , and no patient progressed . In the subgroup of 22 patients who underwent surgery after chemotherapy  , 59 % had nonsquamous histology . Forty-five percent of patients with stage IIB cancer were deemed operable after chemotherapy . Ninety-five percent received postoperative radiation therapy . There was a 9 % pathologic complete response rate , with positive lymph nodes found in 27 % . Notably , those who received 3 months or less of chemotherapy had improved overall survival ( P = 0.030 ) . Survival rates of these 22 patients at 3 and 5 years were 73 % and 63 % , respectively . Although not r and omized , these survival rates were similar to those achieved with chemoradiation . Conclusions Although there are several logistical/ design features of the cisplatin , bleomycin , methotrexate , and 5-FU regimen that are not in line with the current chemotherapy era , our experience with this well-tolerated regimen can serve as a proof of principle . Our data suggests that both neoadjuvant and adjuvant cisplatin-based neoadjuvant chemotherapy may have their place . It also raises the possibility that the optimal duration of chemotherapy in adjuvant cases should be longer than in neoadjuvant cases PURPOSE Radiotherapy is the st and ard treatment for locally advanced cervical cancer , but treatment results remain disappointing , particularly for women with bulky central disease . We investigated the role of concurrent chemoradiation and adjuvant chemotherapy in a r and omized trial . PATIENTS AND METHODS Two hundred twenty patients with bulky stage I , II , and III cervical cancer were r and omized to receive either st and ard pelvic radiotherapy or chemoradiation ( epirubicin 60 mg/m(2 ) ) followed by adjuvant chemotherapy with epirubicin 90 mg/m(2 ) administered at 4-week intervals for five additional cycles . RESULTS Fifty-nine patients have relapsed , with a median follow-up duration of 77 months . Patients who received epirubicin radiation therapy showed a significantly longer disease-free ( P = .03 ) and cumulative survival ( P = .04 ) . Patients who received radiation alone had significantly more distant metastasis than those who received chemoradiation ( P = .012 ) . There was no difference in long-term local tumor control ( P = .99 ) . CONCLUSION Survival benefit has been demonstrated in patients treated with chemoradiation followed by adjuvant chemotherapy with epirubicin as compared with patients treated with st and ard pelvic radiotherapy alone PURPOSE To evaluate the efficacy and toxicities of concurrent chemoradiotherapy ( CCRT ) and consolidation chemotherapy in patients with locally advanced squamous cell cervical carcinoma . METHODS AND MATERIAL S Patients with LASCC ( FIGO Stage IIB-IIIB ) were treated with pelvic external beam radiotherapy ( 45 Gy for Stage IIB and 50 Gy for Stage III ) and high-dose-rate intracavitary brachytherapy ( 50 Gy for Stage IIB and 35 Gy for Stage III ) . The cumulative dose at point A was 50 Gy for Stage IIB and 65 Gy for Stage III . Concurrent chemotherapy with paclitaxel ( 35 mg/m(2 ) ) and nedaplatin ( 20 mg/m(2 ) ) was given every week for 6 weeks . Consolidation chemotherapy with paclitaxel ( 135 mg/m(2 ) ) and nedaplatin ( 60 mg/m(2 ) ) was administered every 3 weeks for 4 cycles . RESULTS All patients completed CCRT , and 28 of 34 patients completed consolidation chemotherapy . The complete response rate was 88 % ( 95 % CI , 73 - 96 % ) . The most common Grade 3 or higher toxicities were leukopenia/neutropenia ( 10.9 % of the cycles ) . During a median follow up of 23 months ( range , 14 - 30 months ) , 5 patients had locoregional failure and 1 patient had distant metastasis . The estimated 2-year progression-free survival and overall survival were 82 % ( 95 % CI , 68 - 95 % ) and 93 % ( 95 % CI , 83 - 100 % ) , respectively . Grade 3 late complications occurred in 3 patients ( 9 % ) . CONCLUSIONS CCRT with paclitaxel and nedaplatin followed by consolidation chemotherapy is well tolerated and effective in patients with locally advanced squamous cell cervical carcinoma . Further r and omized trials of comparing this regimen with the st and ard treatment are worth while PURPOSE To evaluate the efficacy and toxicity of ifosfamide and cisplatin administered concomitantly with low-dose-rate brachytherapy followed by consolidation chemotherapy in the treatment of locally advanced squamous cell cervical carcinoma ( LASCC ) . METHODS AND MATERIAL S Forty-four patients with biopsy-proven LASCC were enrolled . FIGO Stages IB2 bulky to IVA were entered into this study . Patients were assigned to receive external radiotherapy ( 50 Gy in 25 fractions ) ; then ifosfamide 2 g/m(2 ) plus cisplatin 75 mg/m(2 ) was applied during two low-dose-rate brachytherapy applications , and 4 cycles of consolidation chemotherapy with the same drug combination were given after completion of radiotherapy . The planned dose to point A was 85 Gy . RESULTS All patients received both courses of concomitant chemobrachytherapy and at least 1 cycle of consolidation chemotherapy . The average duration of radiation was 45.1 days . The clinical complete response rate was 100 % . Grade 3 and 4 leukopenia occurred in 25 % and 11 % of the cycles , respectively . After a median follow-up of 34 months ( range , 20 - 54 months ) , the recurrence-free and the overall survival rates were 84 % and 91 % , respectively . Major delayed local complications occurred in 7 cases ( 16 % ) . CONCLUSIONS These results indicate that concomitant chemobrachyradiotherapy with ifosfamide and cisplatin is a feasible combination for patients with LASCC of the cervix uteri . A r and omized trial is planned PURPOSE To determine whether addition of gemcitabine to concurrent cisplatin chemoradiotherapy and as adjuvant chemotherapy with cisplatin improves progression-free survival ( PFS ) at 3 years compared with current st and ard of care in locally advanced cervical cancer . PATIENTS AND METHODS Eligible chemotherapy- and radiotherapy-naive patients with stage IIB to IVA disease and Karnofsky performance score ≥ 70 were r and omly assigned to arm A ( cisplatin 40 mg/m(2 ) and gemcitabine 125 mg/m(2 ) weekly for 6 weeks with concurrent external-beam radiotherapy [ XRT ] 50.4 Gy in 28 fractions , followed by brachytherapy [ BCT ] 30 to 35 Gy in 96 hours , and then two adjuvant 21-day cycles of cisplatin , 50 mg/m(2 ) on day 1 , plus gemcitabine , 1,000 mg/m(2 ) on days 1 and 8) or to arm B ( cisplatin and concurrent XRT followed by BCT only ; dosing same as for arm A ) . RESULTS Between May 2002 and March 2004 , 515 patients were enrolled ( arm A , n = 259 ; arm B , n = 256 ) . PFS at 3 years was significantly improved in arm A versus arm B ( 74.4 % v 65.0 % , respectively ; P = .029 ) , as were overall PFS ( log-rank P = .0227 ; hazard ratio [ HR ] , 0.68 ; 95 % CI , 0.49 to 0.95 ) , overall survival ( log-rank P = .0224 ; HR , 0.68 ; 95 % CI , 0.49 to 0.95 ) , and time to progressive disease ( log-rank P = .0012 ; HR , 0.54 ; 95 % CI , 0.37 to 0.79 ) . Grade 3 and 4 toxicities were more frequent in arm A than in arm B ( 86.5 % v 46.3 % , respectively ; P < .001 ) , including two deaths possibly related to treatment toxicity in arm A. CONCLUSION Gemcitabine plus cisplatin chemoradiotherapy followed by BCT and adjuvant gemcitabine/cisplatin chemotherapy  improved survival outcomes with increased but clinical ly manageable toxicity when compared with st and ard treatment CRA5507 Background : Cervical cancer is the second-most common cancer among women worldwide , in both incidence and mortality . Current st and ard therapy for locally advanced disease consists of concurrent Cis and external-beam radiation ( XRT ) . This multicenter , open-label , r and omized , phase III trial aim ed to improve outcomes , capitalizing on the synergistic activity of Gem , Cis , XRT , and the potential value of adjuvant therapy . METHODS Eligible patients ( pts ) with bulky stage IIB to IVA , 18 - 70 years of age , chemotherapy- and radiotherapy-naive , with a Karnofsky Performance Status score ≥70 , were r and omized to Arm A : Cis 40 mg/m2 followed by Gem 125 mg/m2 weekly × 6 doses with concurrent XRT ( 50.4 Gy : in 28 fractions : 1.8 Gy/day , 5 days/week ) , followed by brachytherapy ( brachy ) ( 30 - 35 Gy ) and then 2 adjuvant 21-day cycles of Gem ( 1,000 mg/m2 on Days 1 and 8) plus Cis ( 50 mg/m2 on Day 1 ) ; or Arm B : Cis 40 mg/m2 weekly × 6 doses with concurrent XRT followed by brachy , given as in Arm A. Primary endpoint was progression-free survival ( PFS ) at 3 years , compared between arms using Kaplan-Meier methods and a Z-statistic . RESULTS 515 pts were enrolled between 5/02 and 3/04 ( 259 pts Arm A , 256 pts Arm B ) . Median age was 46 years ; stage IIB/IIIB/IVA in 61/37/2 % of pts .  Compliance in the concurrent and brachy phase was > 90 % for both arms ; adjuvant cycles were completed by > 75 % of pts in Arm A. PFS at 3 years was 74 % in Arm A compared to 65 % in Arm B , result ing in a statistically significant improvement ( p = 0.029 ) . Overall survival ( log-rank p = 0.0224 ) and time to progressive disease ( log-rank p = 0.0008 ) were also significantly improved . Significantly more pts in Arm A experienced grade 3/4 toxicities ( 86.5 % ) , compared to pts in Arm B ( 46.3 % ; Fisher 's p < 0.001 ) . In Arm A , 2 pts died due to causes probably related to treatment compared to 0 pts in Arm B. CONCLUSIONS This novel regimen of concurrent Gem plus Cis and XRT followed by brachy and adjuvant Gem plus Cis significantly improved outcomes in pts with locally advanced carcinoma of the cervix , at the expense of increased but acceptable toxicity , compared to the current st and ard of care . [ Table : see text ] OBJECTIVES Cisplatin-based chemoradiotherapy is the st and ard treatment for locally advanced cervical cancer but causes considerable toxicity .  Capecitabine and radiotherapy show pre clinical synergy and clinical activity . The activity , tolerability , and oral administration of capecitabine make it an attractive adjunctive therapy . METHODS In this phase II study , patients with untreated International Federation of Gynecology and Obstetrics stage IIB-IIIB cervical cancer received capecitabine , 825 mg/m(2 ) twice daily ( Monday-Friday ) , during radiation ( 45 Gy per 25 fractions external-beam radiotherapy and 26 Gy high-dose rate brachytherapy to point A , maximum 8 weeks ) , followed by six cycles of capecitabine , 1,000 mg/m(2 ) twice daily ( days 1 - 14 every 21 days ) . RESULTS The overall response rate in 60 patients was 88 % ( 95 % confidence interval [ CI ] , 77.4%-95.2 % ) , including complete responses ( CRs ) in 80 % of patients . The 1-year progression-free and overall survival rates were 86 % ( 95 % CI , 77%-95 % ) and 95 % ( 95 % CI , 89%-100 % ) , respectively . At 23 months , 76 % of patients were progression free ( 95 % CI , 65%-88 % ) and CR was maintained in 90 % ( 95 % CI , 81%-99 % ) of the 48 patients achieving a CR . There were three grade 3 or 4 treatment-related events : reversible grade 4 hypokalemia , grade 3 diarrhea , and grade 3 h and -foot syndrome . CONCLUSIONS Capecitabine-based chemoradiotherapy with adjuvant capecitabine is a well-tolerated option with an early signal of efficacy meriting further evaluation PURPOSE The optimal treatment of women with advanced adenocarcinoma of uterine cervix is still undefined . We compared concurrent chemoradiation ( CCRT ) and adjuvant cisplatin-based chemotherapy with CCRT alone for advanced cervical adenocarcinoma in a r and omized trial at the Hunan Provincial Tumor Hospital in China . METHODS From 1998 to 2007 , 880 patients with clinical FIGO stages IIB-IVA cervical adenocarcinoma were r and omized to receive either CCRT or chemoradiation with one cycle of neo-adjuvant chemotherapy with Paclitaxel ( 135 mg/m(2))+Cisplatin ( 75 mg/m(2 ) ) before receiving radiation and two cycles of consolidation chemotherapy with the same drugs after radiotherapy in 3-week intervals . The disease control and survival rates were calculated using the Kaplan-Meier method . RESULTS All patients completed the treatment plan . 340 patients have relapsed , with a median follow-up duration of 60 months . Patients who received chemoradiation with adjuvant chemotherapy showed a significantly longer disease-free ( P<.05 ) , cumulative survival ( P<.05 ) and long-term local tumor control ( P<.05 ) . Patients who received CCRT alone had significantly more distant metastasis and pelvic failure than those who received chemoradiation with adjuvant chemotherapy ( P<.05 ) . CONCLUSION Incorporating neo-adjuvant and consolidation chemotherapy with Paclitaxel and Cisplatin into concomitant chemoradiation is highly effective , safe and may be a very promising treatment protocol for advanced cervical adenocarcinoma
BACKGROUND Current st and ard treatment for patients with cervical cancer who have locally advanced stage disease ( International Federation of Gynecology and Obstetrics ( FIGO ) stage IIB to IVA ) is concurrent chemoradiation therapy ( CCRT ) .
However , less than two-thirds of patients in this group survive for longer than five years post treatment .
Adjuvant chemotherapy ( ACT ) can be given in an attempt to improve survival by eradicating residual disease in the pelvis and treating occult disease outside the pelvic radiation field .
However , inconsistency in trial design , inclusion criteria for participants , interventions and survival benefit has been noted among trials of ACT after CCRT for locally advanced cervical cancer ( LACC ) .
OBJECTIVES To evaluate the effect of adjuvant chemotherapy ( ACT ) after concurrent chemoradiation ( CCRT ) on survival of women with locally advanced cervical cancer compared with CCRT alone .