A phase II study of weekly neoadjuvant chemotherapy followed by radical chemoradiation for locally advanced cervical cancer Phase 2 trial of erlotinib combined with cisplatin and radiotherapy in patients with locally advanced cervical cancer 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. Long-term survival following neoadjuvant chemotherapy and radical surgery in locally advanced cervical cancer. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. 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.
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 % ) Cisplatin‐based chemoradiation ( CRT ) is the st and ard treatment for patients with locally advanced cervical cancer . Epidermal growth factor receptor ( EGFR ) is frequently overexpressed in cervical cancer , and EGFR inhibition itself has antitumor effects and potentiates CRT . Results of a previous phase 1 trial of the EGFR inhibitor erlotinib combined with cisplatin‐based CRT ( E + CRT ) recommended a phase 2 erlotinib dose of 150 mg/day 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 The aim of this study was to analyse the long-term survival and the relationships between prognostic factors at presentation , chemoresponsiveness and disease outcome in patients with locally advanced cervical cancer treated by neoadjuvant chemotherapy and radical surgery ( RS ) . Two consecutive studies of neoadjuvant chemotherapy containing cisplatin , bleomycin plus/minus methotrexate followed by radical hysterectomy and systematic aortic and pelvic lymphadenectomy were carried out between January 1986 and September 1990 on 130 patients with > or = 4 cm stage IB2-III cervical cancer .  Survival analysis was performed using the Kaplan and Meier test and Cox 's multivariate regression analysis . 128 ( 98 % ) of the patients enrolled were evaluable for clinical response and survival , 83 % ( 106 ) of the patients responded to chemotherapy , with a 15 % complete response rate . Logistic regression analysis demonstrated that International Federation of Gynecology and Obstetrics ( FIGO ) stage , cervical tumour size , parametrial involvement and histotype are highly predictive of response . Responding patients underwent laparotomy , but 8 % were not amenable for radical surgery . The 10-year survival estimates were 91 % , 80 % and 34.5 % for stage IB2-IIA bulky , IIB and III , respectively ( P < 0.001 ) . After Cox 's regression analysis , the parameters significantly associated with survival were the same factors predicting response to neoadjuvant chemotherapy . No stage IB2-IIA bulky patient has so far relapsed , while 12 % stage IIB and 56 % stage III patients recurred . The 10-year disease-free survival estimates are 91 % and 44 % for stage IB2-IIB and III , respectively ( P < 0.001 ) . Metastatic nodes and persistent tumour in the parametria were the only two independent factors for disease-free survival after multiple regression analysis . After a long-term follow-up ( median follow-up 98 months ( 20 - 129 + ) ) , our results give new evidence of the prognostic value of response to neoadjuvant chemotherapy  and of a possible therapeutic benefit of the sequential treatment adopted which , however , must be verified in a r and omised setting PURPOSE In 1986 , a protocol comparing primary radiation therapy ( RT ) plus hydroxyurea ( HU ) to irradiation plus fluorouracil ( 5-FU ) and cisplatin ( CF ) was activated by the Gynecologic Oncology Group ( GOG ) for the treatment of patients with locally advanced cervical carcinoma . The goals were to determine the superior chemoradiation regimen and to quantitate the relative toxicities . METHODS All patients had biopsy-proven invasive squamous cell carcinoma , adenocarcinoma , or adenosquamous carcinoma of the uterine cervix . Patients underwent st and ard clinical staging studies and their tumors were found to be International Federation of Gynaecology and Obstetrics stages IIB , III , or IVA . Negative cytologic washings and para-aortic lymph nodes were required for entry . Patients were r and omized to receive either st and ard whole pelvic RT with concurrent 5-FU infusion and bolus CF or the same RT plus oral HU . RESULTS Of 388 r and omized patients , 368 were eligible ; 177 were r and omized to CF and 191 to HU .  Adverse effects were predominantly hematologic or gastrointestinal in both regimens . Severe or life-threatening leukopenia was more common in the HU group ( 24 % ) than in the CF group ( 4 % ) . The difference in progression-free survival ( PFS ) was statistically significant in favor of the CF group ( P = .033 ) . The sites of progression in the two treatment groups were not substantially different . Survival was significantly better for the patients r and omized to CF ( P = .018 ) . CONCLUSION This study demonstrates that for patients with locally advanced carcinoma of the cervix , the combination of 5-FU and CF with RT offers patients better PFS and overall survival than HU , and with manageable toxicity BACKGROUND AND METHODS We compared the effect of radiotherapy to a pelvic and para-aortic field with that of pelvic radiation and concurrent chemotherapy with fluorouracil and cisplatin in women with advanced cervical cancer . Between 1990 and 1997 , 403 women with advanced cervical cancer confined to the pelvis ( stages IIB through IVA or stage IB or IIa with a tumor diameter of at least 5 cm or involvement of pelvic lymph nodes ) were r and omly assigned to receive either 45 Gy of radiation to the pelvis and para-aortic lymph nodes or 45 Gy of radiation to the pelvis alone plus two cycles of fluorouracil and cisplatin ( days 1 through 5 and days 22 through 26 of radiation ) . Patients were then to receive one or two applications of low-dose-rate intracavitary radiation , with a third cycle of chemotherapy planned for the second intracavitary procedure in the combined-therapy group . RESULTS Of the 403 eligible patients , 193 in each group could be evaluated . The median duration of follow-up was 43 months . Estimated cumulative rates of survival at five years were 73 percent among patients treated with radiotherapy and chemotherapy and 58 percent among patients treated with radiotherapy alone ( P=0.004 ) . Cumulative rates of disease-free survival at five years were 67 percent among patients in the combined-therapy group and 40 percent among patients in the radiotherapy group ( P<0.001 ) . The rates of both distant metastases ( P<0.001 ) and locoregional recurrences ( P<0.001 ) were significantly higher among patients treated with radiotherapy alone . The seriousness of side effects was similar in the two groups , with a higher rate of reversible hematologic effects in the combined-therapy group . CONCLUSIONS The addition of chemotherapy with fluorouracil and cisplatin to treatment with external-beam and intracavitary radiation significantly improved survival among women with locally advanced cervical cancer 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
OBJECTIVE Cervical cancer is a public health problem .
A large proportion of patients have locally advanced ( LA ) disease at presentation and for this group , neoadjuvant chemotherapy ( NACT ) has an undefined role in the era of chemoradiotherapy .
In countries with restricted access to radiotherapy , NACT may precipitate patients ' access to an effective treatment approach .
We carried out a systematic review to evaluate available data about NACT followed by chemoradiation .