Use of neoadjuvant chemotherapy prior to radical hysterectomy in cervical cancer: monitoring tumour shrinkage and molecular profile on magnetic resonance and assessment of 3-year outcome Prognostic value of age and histologic type in neoadjuvant chemotherapy plus radical surgery for bulky (≥4 cm) stage IB and IIA cervical carcinoma A phase II study of multimodality treatment for locally advanced cervical cancer: neoadjuvant carboplatin and paclitaxel followed by radical hysterectomy and adjuvant cisplatin chemoradiation. Locally Advanced Cervix Cancer: Chemotherapy Prior to Definitive Surgery or Radiotherapy. A Single Institutional Experience Phase II study of neoadjuvant chemotherapy with irinotecan hydrochloride and nedaplatin followed by radical hysterectomy for bulky stage Ib2 to IIb, cervical squamous cell carcinoma: Japanese Gynecologic Oncology Group study (JGOG 1065). Concomitant chemoradiation versus neoadjuvant chemotherapy in locally advanced cervical carcinoma: results from two consecutive phase II studies. Neoadjuvant treatment of locally advanced carcinoma of the uterine cervix with epirubicin, paclitaxel and cisplatin Neoadjuvant chemotherapy with cisplatin, ifosfamide and paclitaxel for locally advanced squamous-cell cervical cancer. Neoadjuvant chemotherapy and radical surgery in locally advanced cervical cancer. Prognostic factors for response and survival Randomized trial of neoadjuvant cisplatin, vincristine, bleomycin, and radical hysterectomy versus radiation therapy for bulky stage IB and IIA cervical cancer. Long-term follow-up of the first randomized trial using neoadjuvant chemotherapy in stage Ib squamous carcinoma of the cervix: the final results. Ten-year survival of patients with locally advanced, stage ib-iib cervical cancer after neoadjuvant chemotherapy and radical hysterectomy. Follow-up in a long-term randomized trial with neoadjuvant chemotherapy for squamous cell cervical carcinoma. Treatment of ("bulky") stage IB cervical cancer with or without neoadjuvant vincristine and cisplatin prior to radical hysterectomy and pelvic/para-aortic lymphadenectomy: a phase III trial of the gynecologic oncology group. The role of neoadjuvant chemotherapy for squamous cell cervical cancer (Ib-IIIb): a long-term randomized trial. Neoadjuvant gemcitabine and cisplatin followed by radical surgery in (bulky) squamous cell carcinoma of cervix stage IB2. Neoadjuvant chemotherapy for patients younger than 50 years with high-risk squamous cell carcinoma of the cervix. Randomized study of preoperative chemotherapy versus primary surgery for stage IB cervical cancer. Neoadjuvant chemotherapy and radical surgery versus exclusive radiotherapy in locally advanced squamous cell cervical cancer: results from the Italian multicenter randomized study. Vinorelbine as neoadjuvant chemotherapy in advanced cervical carcinoma. Total laparoscopic radical hysterectomy and pelvic lymphadenectomy in locally advanced stage IB2-IIB cervical cancer patients after neoadjuvant chemotherapy.
The objective of this study is to assess tumour response to neoadjuvant chemotherapy prior to radical hysterectomy in cervical cancer using magnetic resonance ( MR ) to monitor tumour volume and changes in molecular profile and to compare the survival to that of a control group . Eligibility included Stage Ib – IIb previously untreated cervical tumours > 10 cm3 .  Neoadjuvant chemotherapy in 22 patients ( methotrexate 300 mg m−2 ( with folinic acid rescue ) , bleomycin 30 mg m−2 , cisplatin 60 mg m−2 ) was repeated twice weekly for three courses and followed by radical hysterectomy . Post-operative radiotherapy was given in 14 cases . A total of 23 patients treated either with radical surgery or chemoradiotherapy over the same time period comprised the nonr and omised control group . MR scans before and after neoadjuvant chemotherapy and in the control group documented tumour volume on imaging and metabolites on in vivo spectroscopy . Changes were compared using a paired t-test . Survival was calculated using the Kaplan – Meier method . There were no significant differences between the neoadjuvant chemotherapy and control groups in age ( mean , s.d . 43.3±10 , 44.7±8.5 years , respectively , P=0.63 ) or tumour volume ( medians , quartiles 35.8 , 17.8 , 57.7 cm3 vs 23.0 , 15.0 , 37.0 cm3 , respectively , P=0.068 ) . The reduction in tumour volume post-chemotherapy ( median , quartiles 7.5 , 3.0 , 19.0 cm3 ) was significant ( P=0.002 ) . The reduction in –CH2 triglyceride approached significance ( P=0.05 ) , but other metabolites were unchanged . The 3-year survival in the chemotherapy group ( 49.1 % ) was not significantly different from the control group ( 46 % , P=0.94 ) . There is a significant reduction in tumour volume and –CH2 triglyceride levels  after neoadjuvant chemotherapy , but there is no survival advantage The purpose of this study was to investigate pretreatment variables related to prognosis and to evaluate long-term outcome in patients with bulky early-stage cervical carcinoma who were enrolled into a protocol treatment of neoadjuvant chemotherapy ( NAC ) followed by radical surgery . Between 1988 and 1999 , 162 women with previously untreated bulky ( ≥4 cm ) stage IB or IIA carcinoma of the uterine cervix registered to receive cisplatin , vincristine , and bleomycin for three cycles followed by radical hysterectomy and pelvic lymphadenectomy  , were enrolled into this study . The 5-year relapse-free ( RFS ) and overall survival ( OS ) rates of the whole series were 65 % and 69 % , respectively . In multivariate analyses , age ( < 35 vs. ≥ 35-year-old : relative risk [ RR ] , 2.06 ; 95 % confidence interval [ CI ] , 1.02–4.14 ; P = 0.043 ) and histologic type ( adeno-adenosquamous vs. squamous carcinoma : RR , 2.60 ; 95 % CI , 1.26–5.39 ; P = 0.010 ) were independent variables associated with RFS , and age ( < 35 vs. ≥ 35-year-old : RR , 2.53 ; 95 % CI , 1.24–5.14 ; P = 0.010 ) and pre-NAC tumor size ( > 5 vs. = 5 cm : RR , 2.06 ; 95 % CI , 1.09–3.90 ; P = 0.027 ) were significantly related to OS . Narrowing down patient selection to squamous carcinoma and age older than 35 years with stratification of tumor size ( break point of 5 cm ) is recommended in future trials involving cisplatin-based NAC plus radical surgery BACKGROUND Our aim was to evaluate the efficacy and safety of neoadjuvant chemotherapy followed by radical hysterectomy and adjuvant radiation concurrent with weekly cisplatin for locally advanced cervical carcinoma . PATIENTS AND METHODS Forty-three patients staged as IB2-IIIB were treated with three 21-day courses of carboplatin ( area under the time-concentration curve 6 mg.min/ml ) and paclitaxel at 175 mg/m(2 ) by 3-h infusion both on day 1 followed by radical type III hysterectomy and adjuvant radiation concurrent with 6-weekly doses of cisplatin at 40 mg/m(2 ) . Response rate , resectability , toxicity and survival were evaluated . RESULTS From December 2000 to June 2001 , 43 patients were recruited . All were evaluated for response and toxicity to neoadjuvant chemotherapy . A total of 129 courses were administered . Clinical responses were seen in 41 patients ( 95 % ) [ 95 % confidence interval ( CI ) 89.2 % to 100 % ] with four ( 9 % ) complete and 37 ( 86 % ) partial . Forty-one patients underwent surgery ( resectability 95 % ) ; pathologically complete or near-complete responses were seen in seven ( 17 % ) and eight ( 20 % ) , respectively , positive surgical margins in five ( 12 % ) , and positive pelvic lymph nodes in eight ( 20 % ) . Twenty-six patients were scheduled for adjuvant chemoradiation . External radiation was delivered for 42.8 days ( range 33 - 61 ) , with a mean dose of 49.3 Gy ( range 46 - 56 ) , and a median of five cisplatin courses ( two to six ) . The mean dose of brachytherapy was 32 Gy ( range 25.5 - 35.6 ) . Neoadjuvant therapy was well-tolerated with neutropenia grade 3 and 4 in 12 % and 3 % of the courses , respectively . Toxicity to adjuvant chemoradiation was mainly hematological and gastrointestinal , mostly grade s 1/2 . A total of 39 patients completed all scheduled treatment . At a median follow-up of 21 months ( range 3 - 26 ) , the projected overall survival in the intention-to-treat analysis was 79 % ( 95 % CI 62 % to 88 % ) . CONCLUSIONS The triple modality of neoadjuvant chemotherapy followed by radical hysterectomy and adjuvant radiation concurrent with cisplatin is a highly active treatment for locally advanced cervical carcinoma with acceptable toxicity Primary or neoadjuvant chemotherapy prior to definitive local therapy has potential advantages for locally advanced cervix cancer . It can downstage a cancer and allow definitive local therapy to be technically possible ( surgery ) , or potentially more effective ( radiotherapy ) . It can also eradicate sub clinical systemic metastases . This report review s a single institution 's experience of neoadjuvant chemotherapy prior to definitive local therapy for cervix cancer over a 13-year period . One hundred and six patients were treated with this intent . The patients were analysed for their response to chemotherapy , treatment received , survival , relapse and toxicity . The chemotherapy was feasible and the majority of patients had a complete or partial response ( 58.5 % ) . Eight patients did not proceed to local treatment . Forty-six patients had definitive surgery and 52 had definitive radiotherapy . The 5-year overall survival was 27 % and the majority of patients died with disease . The first site of relapse was usually in the pelvis ( 46.2 % ) . Late complications that required ongoing medical therapy ( n=6 ) or surgical intervention ( n=2 ) were recorded in eight patients ( 7.5 % ) . On univariate analysis stage ( P=0.04 ) , tumour size ( P=0.01 ) , lymph node status ( P=0.003 ) , response to chemotherapy ( P=0.045 ) and treatment ( P=0.003 ) were all significant predictors of survival . On multivariate analysis , tumour size ( P < 0.0001 ) and nodal status ( P=0.02 ) were significant predictors of survival . Despite the impressive responses to chemotherapy of advanced cervix cancer , there is evidence from r and omized trials that it does not improve or compromise survival prior to radiotherapy . As its role prior to surgery remains unclear , it should not be used in this setting outside a prospect i ve r and omized trial The efficacy and adverse events of neoadjuvant chemotherapy with irinotecan hydrochloride and nedaplatin were evaluated in patients with bulky stage Ib2 to IIb cervical squamous cell carcinoma . Eligibility included patients who received irinotecan ( 60 mg/m2 ) on days 1 and 8 and nedaplatin ( 80 mg/m2 ) on day 1 of a 21-day cycle . After 1 - 3 courses of chemotherapy , radical hysterectomy was performed . Sixty-eight patients were enrolled . Sixty-six were included in the full analysis set . Their median age was 47 years ( range 22 - 71 ) , the FIGO stage was Ib2 in 18 patients , IIa in 10 , and IIb in 38 .  Radical hysterectomy was performed after NAC in 63 patients ( 95.5 % ) . The number of administered courses of NAC was 1 in 13 patients , 2 in 43 , and 3 in 10 . The response rate , the primary endpoint of this study , was 75.8 % ( CR in 2 patients , PR in 48 , SD in 12 , PD in 0 , and NE in 4 ) . The mean number of treatment courses required for a response was 1.42 ( 1 course in 30 patients , 2 courses in 19 , and 3 courses in 1 ) . The incidences of grade 3 or 4 hematological toxicities were : neutropenia 72.2 % , leukopenia 16.7 % , anemia 13.6 % , thrombocytopenia 7.6 % , febrile neutropenia 1.5 % , and elevations of alanine aminotransferase and aspartate aminotransferase 1.5 % . Grade 3 or 4 non-hematologic toxicities were as follows : diarrhea 6.1 % , nausea 3 % , anorexia 1.5 % , vomiting 1.5 % , fever 1.5 % , allergic reactions 1.5 % , ileus 1.5 % and vesicovaginal fistula 1.5 % . Neoadjuvant chemotherapy with irinotecan and nedaplatin was an effective and well-tolerated treatment for patients with bulky stage Ib2 to IIb squamous cell carcinoma of the uterine cervix BACKGROUND R and omized studies comparing induction chemotherapy followed by surgical resection with radiation alone found that the neoadjuvant approach produces better results . So far , this latter modality has not been compared with st and ard concomitant chemoradiation . The objective of this report was to compare the results of two consecutive phase II studies : neoadjuvant chemotherapy followed by surgery or chemoradiation for the unresectable cases versus st and ard cisplatin-based chemoradiation . PATIENTS AND METHODS From February 1999 to July 1999 , 41 patients with cervical carcinoma , stages IB2-IIIB , were treated with neoadjuvant chemotherapy . Treatment consisted of three 21-day courses of cisplatin 100 mg/m(2 ) on day 1 and gemcitabine 1000 mg/m(2 ) on days 1 and 8 , followed by either surgery or concomitant chemoradiation for the non-operable cases . From August 1999 to December 1999 , an equal number of patients having comparable clinicopathological characteristics were treated with six weekly courses of cisplatin 40 mg/m(2 ) during st and ard pelvic radiation . RESULTS A total of 82 patients were analyzed . Both groups were similar with regard to age , histology , International Federation of Gynecology and Obstetrics ( FIGO ) stage , tumor size , pretreatment hemoglobin levels , parametrial infiltration and performance status . In the neoadjuvant arm the overall response rate to induction chemotherapy was 95 % ( 95 % confidence interval 88 % to 100 % ) . Twenty-three patients had surgery and 14 underwent chemoradiation . In the definitive chemoradiation study , 38 patients completed treatment , the median number of cisplatin courses was six for a dose intensity of 33 mg/m(2)/week . Doses to points A and B were 85 Gy ( range 68 - 95 ) and 55 Gy ( range 51 - 65 ) , respectively . Chemoradiation was delivered in 44.6 ( range 28 - 113 ) days . Complete response rates after all treatment were similar : 97 % and 87 % in the neoadjuvant and chemoradiation groups , respectively . At a median follow-up of 28 ( range 2 - 33 ) and 24 ( range 3 - 30 ) months , respectively , there were no differences in overall survival . To date , 15 and 13 patients in the neoadjuvant and chemoradiation groups , respectively , have died of disease ( P = 0.8567 ) . CONCLUSIONS The results of this non-r and omized comparison suggest that induction chemotherapy followed by surgery or chemoradiation is at least as effective in terms of response and survival as st and ard cisplatin-based chemoradiation . A r and omized study is needed to confirm these findings Abstract . Purpose : The present study was conducted to explore whether neoadjuvant chemotherapy with a combination of epirubicin , paclitaxel and cisplatin could improve the operability and pathological response rate in locally advanced cervical cancer patients . Methods : Between April 1996 and July 2000 , 42 patients with carcinoma of the uterine cervix , FIGO stage Ib2-IVa , were treated with two or three 21-day cycles of an epirubicin 100 mg/m2 , paclitaxel 175 mg/m2 , cisplatin 100 mg/m2 regimen . Results : All patients were eligible for evaluation of toxicity and response . A total of 92 courses of therapy were administered . Three patients had a 20 % reduction from the starting dose due to haematological toxicity . Grade 3–4 leukopenia was observed in 15 % of cycles , requiring G-CSF support in half of them . Major non-haematological toxicity consisted of grade 3 alopecia ( 100 % ) , and grade 3 nausea and vomiting ( 40 % ) . A total of 33 clinical responses ( 78.5 % , 95 % CI 63.8–93.2 ) were recorded , 8 complete responses ( CR ) and 25 partial responses ( PR ) . Of the 42 patients , 32 ( 76.2 % ) underwent radical surgery . At pathological examination 8 complete or microscopic pathological responses , 17 PRs , and 9 patients with stable disease were observed . The median follow-up time was 17 months for the 42 patients enrolled ( range 3–62 months ) . Among the patients su bmi tted to radical surgery , five recurrences were observed , with a median disease-free survival of 47 months . Median overall survival had not been reached at the time of this report . These results appear to be in the range reported for other neoadjuvant cisplatin-based regimens not including paclitaxel . Conclusions : Neoadjuvant chemotherapy with the epirubicin , paclitaxel and cisplatin combination followed by radical surgery proved to be a safe and effective approach to advanced cervical cancer BACKGROUND Neoadjuvant chemotherapy is increasingly being used for the treatment of bulky and locally-advanced cervical cancer .  Cisplatin and ifosfamide are known to be effective in cervical cancer , while paclitaxel is one of the promising new drugs for the treatment of this neoplasm . OBJECTIVE To assess the toxic effects and antitumor activity of a multidrug neoadjuvant regimen consisting of cisplatin , ifosfamide , and paclitaxel in bulky and locally advanced cervical cancer . PATIENTS AND METHODS Thirty-eight patients with pathology-confirmed squamous-cell cervical cancer ( 27 IB2-IIA , two IIB , eight IIIB , one IVA ) were prospect ively enrolled in the study . Their treatment consisted of paclitaxel 175 mg/m2 given over three hours on day 1 , cisplatin 50 mg/m2 ( 75 mg/m2 in 10 patients ) , ifosfamide 5 g/m2 in a 24-hour continuous infusion and mesna 5 g/m2 in a 24-hour continuous infusion on day 2 , and mesna 3 g/m2 in a 24-hour continuous infusion on day 3 . The course was repeated every three weeks for three courses and all of the patients , except those with disease progression or who were inoperable , were scheduled for radical hysterectomy and pelvic lymphadenectomy . RESULTS All patients are evaluable for response . Eleven achieved clinical complete responses , 21 had partial responses , five had stable disease and one had progression of disease . Of 34 patients who underwent surgery , six ( 16 % ) had pathology-documented complete responses , seven ( 18 % ) had partial responses with only microscopic residual disease in the cervix , 19 had sub-optimal partial responses , and two had stable disease , for an overall response rate of 84 % ( 95 % confidence intervals ( CI ) : 68.7%-94 % ) . Grade 3 - 4 neutropenia was recorded for 27 ( 71 % ) patients , grade 3 - 4 thrombocytopenia for four ( 10.5 % ) , and grade 2 peripheral neuropathy for two ( 2.5 % ) . At a median follow-up of 16 months ( range 7 - 22 ) , 29 ( 76 % ) women are alive without recurrence , seven are alive with persistent/recurrent disease and two have died of their disease . CONCLUSIONS According to pathology examination , this regimen yields a 34 % complete and optimal partial response rate with acceptable toxicity , and it should be prospect ively compared to other regimens Between January 1986 and September 1988 , 75 patients with locally advanced cervical carcinoma ( International Federation of Gynecology and Obstetrics [ FIGO ] Stages IB – III ) received three courses of neoadjuvant chemotherapy ( NAC ) , including cisplatin , bleomycin , and methotrexate ( PBM ) . Fifteen percent of patients achieved a complete response ( CR ) and 68 % a partial response ( PR ) . Pretreatment characteristics were analyzed for response to NAC . Significantly lower response rates were found in patients with tumor size more than 5 cm in diameter and bilateral parametrial involvement to the pelvic side wall . None of the biological parameters studied was related to chemoresponsiveness . Patients achieving CR or PR had a significantly improved 3‐year survival rate compared with those who did not respond . After NAC , radical surgery was possible in all responding patients . The median number of lymph nodes removed was 60 . A lower than expected incidence of lymph node metastases was detected . None of the clinical and pathologic features considered was significantly correlated with the lymph node status . Twelve of the 62 operated patients  had disease recurrence . Pathologic parametrial involvement and cervical infiltration equal to or deeper than 5 mm were found to be significant prognostic factors for recurrence . A 3‐year , disease‐free survival of 89 % , 73 % , and 43 % for Stage IB – IIA , IIB , and III , respectively , was found . Among the operated patients these rates increased to 100 % , 81 % , and 66 % for Stage IB – IIA , IIB , and III , respectively . A prospect i ve r and omized trial comparing NAC and surgery with radiotherapy alone is in progress PURPOSE To compare the efficacy of neoadjuvant chemotherapy ( NAC ) followed by radical hysterectomy with that of radiotherapy ( R/T ) for bulky early-stage cervical cancer . PATIENTS AND METHODS Women with previously untreated bulky ( primary tumor > /= 4 cm ) stage IB or IIA non-small-cell carcinoma of the uterine cervix were r and omly assigned to receive either cisplatin 50 mg/m(2 ) and vincristine 1 mg/m(2 ) for 1 day and bleomycin 25 mg/m(2 ) for 3 days for three cycles followed by radical hysterectomy ( NAC arm ) or receive primary pelvic radiotherapy only ( R/T arm ) . The ratio of patient allocation was 6:4 for the NAC and R/T arms . Women with enlarged para-aortic lymph nodes on image study were ineligible unless results of cytologic or histologic studies were negative . RESULTS Of the 124 eligible patients , 68 in the NAC arm and 52 in the R/T arm could be evaluated . The median duration of follow-up was 39 months . Thirty-one percent of patients in the NAC arm and 27 % in the R/T arm had relapse or persistent diseases after treatment , and 21 % in each group died of disease . Estimated cumulative survival rates at 2 years were 81 % for the NAC arm and 84 % for the R/T arm ; the 5-year rates were 70 % and 61 % , respectively . There were no significant differences in disease-free survival and overall survival . CONCLUSION NAC followed by radical hysterectomy and primary R/T showed similar efficacy for bulky stage IB or IIA cervical cancer . Further study to identify patient subgroups better suited for either treatment modality and to evaluate the concurrent use of cisplatin and radiation without routine hysterectomy is necessary OBJECTIVE To determine if three courses consisting of 50 mg/m2 cis-platinum , 1 mg/m2 vincristine , and 25 mg/m2 bleomycin ( day 1 - 3 ) at 10-day intervals can improve survival before Wertheim-Meigs + radiotherapy . MATERIAL Two hundred five unselected stage Ib patients ( having tumors > 2 cm in diameter ) were divided into two groups at r and om : ( 1 ) The group control consisted of 103 patients ( 56 bulky , > 4 cm diameter ) treated with Wertheim-Meigs ( if the tumor was resectable with free surgical margins ) + adjuvant radiotherapy to whole pelvis ( extended field radiation was used only in patients with paraaortic lymph node metastases ) . When the tumor was unresectable , a surgical staging was performed and radiotherapy was the chosen treatment . ( 2 ) Neoadjuvant ( 102 patients , 61 bulky ) had neoadjuvant chemotherapy and then the same treatment as the control patients . RESULTS After 67 ( 31 - 102 ) months of follow-up , no difference was seen in tumors > 2 and < 4 cm in both groups ( C = 77 % vs N = 82 % ) , but statistically significant differences were seen in survival and disease-free survival , in bulky tumors , and between patients with neoadjuvant chemotherapy + Wertheim-Meigs + radiotherapy ( 80 % ) and the control ( 61 % ) . This was due to an increased operability that was substantially improved in bulky tumors in the neoadjuvant chemotherapy group ( 61/61 , 100 % ) vs control ( 48/56 , 85 % ; P < 0.01 ) . After 7 years of follow-up , the outcome of the unresectable bulky control group of patients is significantly worse ( 14 % ) than that of the resectable group ( 69 % ; P < 0.001 ) . With regard to recurrences , a significant decrease in pelvic failures in the neoadjuvant chemotherapy group was observed ( P < 0.001 ) . Survival was improved in bulky resectable cases ( N = 81 % vs C = 69 % , P < 0.05 ) . Pathological findings for the surgical specimens revealed differences between both groups because all the risk factors such as parametrial and lymph node metastases , tumor bulk , and vascular embolism had been decreased ( P < 0.001 ) . CONCLUSION Neoadjuvant chemotherapy can improve survival because of increased operability with free survival margins and a decrease in pathologic risk factors in unselected , bulky ( > 4 cm diameter ) stage Ib patients OBJECTIVE ( S ) The aim of this study was to evaluate the effects of neoadjuvant chemotherapy and radical hysterectomy on long-term survival in stage IB-IIB locally advanced cervical cancer by conducting a 10-year follow-up . METHODS Between August 1983 and May 1990 , 80 locally advanced , stage IB-IIB cervical cancer patients with tumor diameter greater than or equal to 4 cm were treated with neoadjuvant VBP chemotherapy ( cisplatin , vinblastine , and bleomycin ) followed by radical hysterectomy with pelvic lymphadenectomy . After this therapeutic modality , patients were followed for more than 10 years . Ten-year survival rates and factors affecting recurrence after this therapy were evaluated . RESULTS Of 80 patients , 75 ( 93.7 % ) showed a reduction in tumor size after neoadjuvant chemotherapy . At pathologic examination , stage reduction was noted in 53 ( 66.2 % ) patients and 20 patients ( 25 % ) showed no residual or microinvasive cervical tumor . Pelvic lymph node metastases were found in 17 patients ( 21.3 % ) . During the 10-year follow up , 2 patients were lost and 16 patients recurred . Overall 5-year and 10-year disease-free actual survival rates were 82.0 ( 64/78 ) and 79.4 % ( 62/78 ) , respectively . Clinical stage , initial tumor size , clinical response , and residual tumor size were not risk factors for recurrence after this therapy . However , pelvic lymph node metastasis was a significant risk factor for recurrence . CONCLUSION ( S ) Neoadjuvant VBP chemotherapy followed by radical hysterectomy in locally advanced , stage IB-IIB cervical cancer patients seemed to improve the long-term survival rate for these patients compared to that of conventional therapy . However , r and omized controlled trials are needed to confirm this result OBJECTIVE To assess the role of neoadjuvant chemotherapy to achieve radical surgery in a larger number of patients with locally advanced/or bulky Stage IB cervical carcinoma . We conducted a trial to determine whether neoadjuvant chemotherapy would improve disease-free survival and overall survival in Stage IB-III cervical cancer . DESIGN Prospect i ve r and omized clinical study with long-term follow-up . SETTING Department of Gynecology , Perinatology and Child Health , II Faculty University of Rome " La Sapienza " . METHODS 288 patients with squamous cell carcinoma of the uterine cervix , FIGO Stage IB-IIIB were r and omized to one of the following treatments : three courses of neoadjuvant chemotherapy with cisplatin , vincristine , bleomycin ( NACT arm ; n = 159 ) ; conventional surgery or exclusive radiotherapy ( CONV arm ; n = 129 ) . There was no difference in age , FIGO stage , tumor size and lymph node involvement between the two groups ( p = ns ) . Two hundred and thirty-four patients in Stage IB-IIb ( n = 129 NACT arm and n = 105 CONV arm ) and 24 patients in Stage III ( NACT arm ) who proved to be chemosensitive underwent radical hysterectomy .  Six Stage III patients , non responders to chemotherapy , and 24 patients , Stage III of the CONV arm , underwent radiotherapy . Follow-up extended for seven years . RESULTS The study was performed on disease-free survival related to several prognostic factors : age , FIGO stage , tumor size , grading , parametrial involvement , lymph node status and surgical margins . Recurrence of disease occurred in 49 ( 32.1 % ) patients of the NACT arm ( n = 153 ) and in 39 ( 37.1 % ) . patients of the CONV arm ( n = 105 ) . Statistically significant differences in the recurrence of the disease were related to FIGO stage ( p < 003 ) , grading ( p < .05 ) , parametrial involvement ( p < .002 ) lymph node status ( p < .0001 ) and tumor size ( p < .002 ) . No statistical significance was related to age and surgical margins ( p = ns ) . Disease-free and overall survival in the two groups were , respectively , 65.4 % vs 53.5 % ( p = ns ) and 70.4 % 65.9 % ( p = ns ) OBJECTIVE A r and omized phase III trial was conducted to determine if neoadjuvant chemotherapy ( NACT ) prior to radical hysterectomy and pelvic/para-aortic lymphadenectomy ( RHPPL ) could improve progression-free survival ( PFS ) and overall survival ( OS ) , as well as operability , with acceptable levels of toxicity . Adjuvant radiation therapy was prescribed for specific surgical/pathological risk factors for both regimens . METHODS Eligible patients were required to have bulky FIGO Stage IB cervical cancer , tumor diameter > or = 4 cm , adequate bone marrow , renal and hepatic function , and performance status < or = 2 . Prospect i ve r and om allocation was to either NACT ( vincristine-cisplatin chemotherapy every 10 days for 3 cycles ) before exploratory laparotomy and planned RHPPL ( NACT+RHPPL ) , or RHPPL only . RESULTS The study was closed prematurely , because of slow accrual , after 291 patients were enrolled , three were ineligible ; thus 288 were eligible and r and omly allocated to RHPPL ( N=143 ) or NACT+RHPPL ( N=145 ) . There were no notable differences between regimens with regard to patient age , race , performance status , or tumor size . The median follow-up time is 62 months among living patients . The NACT+RHPPL group had very similar recurrence rates ( relative risk : 0.998 ) and death rates ( relative risk : 1.008 ) when compared to the RHPPL group . There were 79 % that had surgery in the RHPPL group compared to 78 % in the NACT RHPPL group . There were 52 % who received post op RT in the RHPPL group compared to 45 % in the NACT+RHPPL group ( not statistically significant ) . CONCLUSION There is no evidence from this trial that NACT offered any additional objective benefit to patients undergoing RHPPL for suboptimal Stage IB cervical cancer OBJECTIVE to verify whether a regimen of preventive chemotherapy in the treatment of cervical carcinoma allows surgical treatment in a larger number of patients and whether cases treated with this combined neoadjuvant polychemotherapy/surgery regimen improves overall and disease-free survival rates . DESIGN prospect i ve r and omized clinical study . SETTING Department of Gynaecology and Obstetrics , University of Rome " La Sapienza " . METHODS 192 patients suffering from squamous cell carcinoma of the uterine cervix in Stages Ib-IIb were r and omized to one of the following treatments : three courses of neoadjuvant chemotherapy with cisplatin , vincristine , bleomycin ( NACT arm ; n = 106 ) ; conventional surgery or radiotherapy alone ( CO arm ; n = 86 ) . One hundred and fifty-six patients in Stage Ib-IIb ( n = 86 , NACT arm and n = 70 , CO arm ) and 16 patients in Stage III ( NACT arm ) who proved to be sensitive to the neoadjuvant chemotherapy , underwent radical hysterectomy . Four Stage III patients not sensitive to chemotherapy and 16 patients , Stage III , of the CO arm underwent radiotherapy . RESULTS the 5-year overall survival rates for the NACT and CO arm , respectively , were 78.6 % and 73.2 % in Stages Ib-IIa ( p = NS ) , 68.7 % and 64.3 % in Stage IIb ( p = NS ) . A 5-year disease-free survival rate for the NACT arm and CO arm , respectively , of 77.1 % and 64.3 % in Stages Ib-IIa ( p < .05 ) , 56.2 % and 57.1 % in Stage IIb ( p = NS ) was found . CONCLUSIONS the responsiveness of cervical cancer to neoadjuvant chemotherapy allows surgical treatment in a larger number of patients and results in longer overall and disease-free survival OBJECTIVES This study aim ed to evaluate the efficacy and toxicity of gemcitabine in combination with cisplatin as neoadjuvant therapy in patients with cervical carcinoma stage IB2 . PATIENTS AND METHODS Chemotherapy-naive patients with histologic diagnosis of squamous cell cervical carcinoma staged as IB2 were treated with 2 cycles of cisplatin ( 70 mg/m(2 ) on day 1 ) and gemcitabine ( 1000 mg/m(2 ) on days 1 and 8) , given every 21 days . After chemotherapy , patients underwent radical hysterectomy and pelvic lymphadenectomy .  Patients judged to have a non-resectable disease were treated with st and ard pelvic radiation . RESULTS Between September 2000 to March 2004 , 28 patients were enrolled in the study , of which 27 were evaluable for efficacy and toxicity . The mean age was 39 years ( 30 - 55 ) . The overall clinical response rate was 88.9 % ( 24/27 ) , with complete response ( CR ) in 9/27 patients ( 33.3 % ) and partial response in 15/27 patients ( 55.5 % ) . Three patients ( 11.1 % ) did not respond and nobody progressed . A pathological CR was noted in 2 of 24 patients who underwent radical surgery . The 3 non-responding patients were subsequently treated with radiation and achieved CR . Grade s 3 or 4 neutropenia , anemia , or thrombocytopenia was observed in 18.5 % , 7.4 % , and 3.7 % patients respectively . Non-hematological toxicity was mild except grade 3 nausea/vomiting in 18.5 % patients . At median follow-up time of 36.7 months ( range 7 - 51 months ) , the 3-year survival was 88.9 % . CONCLUSION Neoadjuvant treatment with gemcitabine/cisplatin combination for patients with cervical cancer ( stage IB2 ) appears encouraging , with manageable and acceptable toxicity profile OBJECTIVE To evaluate the response rate and toxicity and to improve survival , neoadjuvant chemotherapy ( NAC ) was utilized in patients younger than 50 years with locally advanced cervical squamous cell carcinoma . METHODS Twenty-one patients were treated with preoperative NAC . Eligibility included patients with previously untreated stage IB or IIA with deep stromal invasion assessed by magnetic resonance imaging or bulky tumor or IIB squamous cell carcinoma who were younger than 50 years . The NAC consisted of cisplatin ( 60 mg/m(2 ) ) on day 1 , vinblastine ( 4 mg/m(2)/day ) on days 1 and 2 , and peplomycin ( 10 mg/day ) on days 1 , 8 , and 15 ( PVP ) . Treatment was repeated every 3 weeks for a total of two cycles . All 21 patients underwent radical hysterectomy following NAC . Postoperative radiotherapy was given to 18 patients . We used 21 patients who underwent radical hysterectomy and postoperative radiation therapy as a nonr and omized control group . RESULTS The response rate for NAC was 86 % ( 18/21 ) . Two patients required discontinuation of PVP treatment after one administration because of grade 4 neutropenia and thrombocytopenia , and decreased carbon monoxide diffusion capacity , respectively . In the NAC group , stromal invasion was significantly reduced ( P = 0.0103 ) , and the incidence of lymph node metastasis was decreased . No patients had positive parametrial and vaginal margins . The overall 5-year survival rate was 84.0 % in the NAC group , which was significantly better than that in the control group ( 58.9 % ) ( P = 0.0434 ) . CONCLUSIONS NAC for younger patients with locally advanced cervical carcinoma is thought to be safe , well tolerated , effective , and useful for increasing operability , decreasing pathological risk factors , and improving survival AIM To determine the most effective treatment and long-term outcome of patients with stage IB carcinoma of the cervix . METHODS From January 1999 to December 2001 , 106 women with cervical cancer stage IB received neoadjuvant chemotherapy ( n = 52 ) or primary surgery ( n = 54 ) . These were r and omly assigned . Clinical effects and pathological changes were simultaneously recorded . RESULTS The overall clinical response rate was 84.6 % and included a complete response ( CR ) in four patients ( 7.7 % ) , partial response ( PR ) in 40 patients ( 76.9 % ) , and stable disease ( SD ) in the remaining eight patients ( 15.4 % ) . Surgery revealed positive nodes in 9.6 % neoadjuvant chemotherapy group patients and in 29.6 % primary surgery group patients ( P = 0.014 ) . Similar results occurred with vascular space involvement : 27.8 % in the primary surgery group compared to 9.6 % in the neoadjuvant chemotherapy group ( P = 0.024 ) . However , parametrial infiltration was found in 7.4 % of the patients in the primary surgery group , while only 3.8 % showed it in the neoadjuvant chemotherapy group ( P = 0.679 ) . The overall 5-year survival rate was significantly higher for all patients who received neoadjuvant chemotherapy ( 84.6 % ) than for the control group ( 75.9 % ) ( P = 0.0112 ) . The median survival time in patients with complete response and partial response to chemotherapy ( 83.3 months ) was significantly higher than that of patients with stable disease to chemotherapy ( 55.2 months ) ( P = 0.0049 ) . 27.3 % of patients developed recurrent disease within 5 years of the primary treatment . The women with recurrence included partial response in six patients ( 60.0 % ) , and stable disease in four patients ( 40.0 % ) . For the other patients there was partial response and complete response in 38 patients ( 90.5 % ) , and stable disease in the remaining four patients ( 9.5 % ) ( P = 0.035 ) . CONCLUSION Neoadjuvant chemotherapy can effectively eliminate the pathological risk factors and improve long-term survival in patients with locally advanced cervical cancer PURPOSE Neoadjuvant chemotherapy ( NACT ) and radical surgery ( RS ) have emerged as a possible alternative to conventional radiation therapy ( RT ) in locally advanced cervical carcinoma . In 1990 , a phase III trial was undertaken to verify such a hypothesis in terms of survival and treatment-related morbidity . PATIENTS AND METHODS Patients with squamous cell , International Federation of Gynecology and Obstetrics stage IB2 to III cervical cancer were eligible for the study . They received cisplatin-based NACT followed by RS ( type III to V radical hysterectomy plus systematic pelvic lymphadenectomy ) ( arm A ) or external-beam RT ( 45 to 50 Gy ) followed by brachyradiotherapy ( 20 to 30 Gy ) ( arm B ) . RESULTS Of 441 patients r and omly assigned to NACT+RS or RT , eligibility was confirmed in 210 and 199 patients , respectively . Treatment was administered according to protocol in 76 % of arm A patients and 72 % of arm B patients . Adjuvant treatment was delivered in 48 operated patients ( 29 % ) . There was no evidence for any significant excess of severe morbidity in one of the two arms . The 5-year overall survival ( OS ) and progression-free survival ( PFS ) rates were 58.9 % and 55.4 % for arm A and 44.5 % and 41.3 % for arm B ( P = .007 and P = .02 ) , respectively . Subgroup survival analysis shows OS and PFS rates of 64.7 % and 59.7 % ( stage IB2-IIB , NACT+RS ) , 46.4 % and 46.7 % ( stage IB2-IIB , RT ) ( P = .005 and P = .02 ) , 41.6 % and 41.9 % ( stage III , NCAT+RS ) , 36.7 % and 36.4 % ( stage III , RT ) ( P = .36 and P = .29 ) , respectively . Treatment had a significant impact on OS and PFS . CONCLUSION Although significant only for the stage IB2 to IIB group , a survival benefit seems to be associated with the NACT+RS compared with conventional RT PURPOSE To evaluate the efficacy and toxicity of vinorelbine ( VNB ) as single-agent neoadjuvant chemotherapy in advanced cervical carcinoma ( ACC ) . PATIENTS AND METHODS Between December 1993 and October 1995 , 43 untreated patients with stages IIB to IVA squamous cell cervical cancer were entered onto this study . Forty-two patients are assessable for response and 43 for toxicity .  The median age was 46 years ( range , 28 to 65 ) . Distribution by stages ( International Federation of Gynecology and Obstetrics [ FIGO ] ) was as follows : IIB , 18 patients ; IIIA , one ; IIIB , 19 ; and IVA , five . Therapy consisted of VNB 30 mg/m2 by 20-minute intravenous ( IV ) infusion repeated weekly for 12 injections and followed by radical surgery if feasible or definitive radiotherapy . Both staging and response assessment were performed by a multidisciplinary team . RESULTS One patient was considered not assessable for response . A total of 493 cycles of therapy were administered and objective remissions were observed in 19 of 42 patients ( 45 % ; 95 % confidence interval , 30 % to 60 % ) . Two patients ( 5 % ) had a complete response ( CR ) and 17 ( 40 % ) a partial response ( PR ) ; no change ( NC ) was observed in 16 ( 38 % ) and progressive disease ( PD ) in seven ( 17 % ) . Six of 19 patients ( 32 % ) who achieved objective responses ( ORs ) underwent surgery . The median time to failure and median survival time have not been reached yet . There were no therapy-related deaths . The dose-limiting toxicity was myelosuppression . Leukopenia occurred in 35 patients ( 81 % ) and was grade 3 or 4 in seven ( 17 % ) . Twelve patients ( 28 % ) developed peripheral neuropathy , while myalgias occurred in 10 ( 23 % ) . Constipation was observed in nine patients ( 21 % ) , one with a prolonged ileum . Phlebitis was recorded in 18 patients ( 41 % ) . In contrast , emesis and mucositis were rarely observed . No patient developed alopecia grade 3 . By the end of the twelfth course of treatment , the average received dose-intensity was 85.4 % of that projected . CONCLUSION VNB is an active drug against ACC with moderate toxicity . Its activity is among the highest reported for single agents . Further evaluation in association with other agents is clearly justified OBJECTIVE To evaluate the feasibility and morbidity of total laparoscopic class C2 radical hysterectomy ( TLRH ) with pelvic lymphadenectomy in patients with locally advanced cervical cancer stage IB2 to IIB after neoadjuvant chemotherapy ( NACT ) . METHODS A prospect i ve study was conducted from October 2004 to September 2009 . Cervical cancer patients , stage IB2-IIB with complete clinical response after 3 courses of NACT with paclitaxel 175 mg/m(2 ) , ifosfamide 5 g/m(2 ) and cisplatin 75 mg/m(2 ) ( TIP ) underwent TLRH . RESULTS Forty patients were included , with a median age of 46 years ( range , 25 - 65 ) , BMI of 24 kg/m(2 ) ( range , 15 - 49 ) . FIGO staging was IB2 in 23 , IIA > 4 cm in 6 and IIB in 11 patients . Four patients required conversion to laparotomy . Pathological evaluation showed 9 complete response ( pCR ) , 9 partial response ( pPR1 ) with microscopic tumour , and 15 partial response ( pPR2 ) with macroscopic tumour . Three patients had no response . The median operative time was 305 min ( range , 215 - 430 ) ; the median estimated blood loss was 250 ml ( range , 100 - 400 ) , with four postoperative blood transfusion ; the median number of removed pelvic lymph nodes was 25 ( range , 11 - 64 ) . The median length of hospital stay was 6 days ( range , 3 - 12 ) . The median follow-up time was 37 months ( range , 10 - 69 ) , with three patients having a recurrence . One patient died of disease ( DOD ) after 12 months . CONCLUSIONS TLRH can be safely performed in patients with stage IB2-IIB carcinoma of cervix after NACT , with advantages of minimal blood loss and morbidity
Cervical cancer is the second most common cancer in women .
Neoadjuvant chemotherapy for patients with locally advanced cervix cancer has comparable benefits to concurrent chemoradiotherapy ( CCRT ) , but with fewer side effects .
This systematic review aims to provide a comprehensive summary of the benefits of neoadjuvant chemotherapy for the management of locally advanced cervix cancer from stage IB2 ( tumor > 4.0 cm ) to IIIB ( tumor extending to the pelvic wall and /or hydronephrosis ) .
Our primary objective was to assess benefits in terms of survival .