Adjuvant oral 5-fluorouracil for cervical cancer: Japanese Gynecologic Oncology Group report. The potential for adjuvant therapy in early-stage cervical cancer Chemotherapy versus radiotherapy versus observation for high-risk cervical carcinoma after radical hysterectomy: A randomized, prospective, multicenter trial. Radiation therapy with concomitant and adjuvant cisplatin and paclitaxel in high-risk cervical cancer: long-term follow-up. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. Prospective phase I-II trial of helical tomotherapy with or without chemotherapy for postoperative cervical cancer patients. Neoadjuvant and Adjuvant Chemotherapy of Cervical Cancer: Mature Results of the Phase 2 PBM-PFU Protocol [A multicenter cooperative study on supplementary chemotherapy of uterocervical cancer. The Kyushu UFT Study Group of Uterocervical Cancer]. Adjuvant chemotherapy versus chemotherapy plus pelvic irradiation for high-risk cervical cancer patients after radical hysterectomy and pelvic lymphadenectomy (RH-PLND): a randomized phase III trial. Long‐term results of sequential postoperative treatment with vincristine, bleomycin, mitomycin c, cis‐platin and radiotherapy after surgery for high‐risk patients with cervical carcinoma stage IB–IIA [Long-term administration of carmofur as a post-operative adjuvant chemotherapy for cervical adenocarcinoma. Cervical Adenocarcinoma Cooperative Research Association]. Feasibility of concurrent cisplatin use during primary and adjuvant chemoradiation therapy: a phase I study in Japanese patients with cancer of the uterine cervix Chemoradiation in Cervical Cancer with Cisplatin and High-Dose Rate Brachytherapy Combined with External Beam Radiotherapy
Results of a Phase-II Study A pilot study of adjuvant therapy in patients with cervical cancer at high risk of recurrence after radical hysterectomy and pelvic lymphadenectomy. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. [About the value of adjuvant chemotherapy in advanced cervical cancer. First results of a prospective randomised study (author's transl)]. Adjuvant chemotherapy in "high risk" patients after Wertheim hysterectomy--10-year survivals. [Intention-to-treat].
Japanese women with low-stage cervical cancer receiving radical hysterectomy and radiotherapy  have a good 5-year survival rate . However , women with risk factors such as nodal metastasis may benefit from adjuvant chemotherapy , which was studied in women having surgery alone or surgery plus radiotherapy .  Patients having surgery alone ( S ) ( n=623 ) or surgery and radiotherapy ( SR ) ( n=919 ) were r and omly assigned to receive or not receive oral 5-fluorouracil ( 5-FU ) for 1 year . The effect of various factors on survival was studied by multivariate analysis . Patients who received S obtained no benefit from 5-FU , whereas 5-FU-treated SR patients had significantly better 5-year survival than those not receiving chemotherapy ( P=0.043 ) . The SR patients without nodal metastases had a better survival rate if they received 5-FU ( P<0.001 ) , whereas those with nodal metastases did not . Oral 5-FU after radical hysterectomy with radiotherapy appears useful for patients with low-stage cervical cancer who have some risk factors but not for those with pelvic lymph node metastases Summary Adjuvant therapy may potentially improve prognosis in women with early-stage cervical cancer who are at high risk of relapse after primary therapy . Patients with lymph node involvement at surgery are at high risk of recurrence and may benefit from adjuvant therapy , but many patients are treated with radical radiotherapy . At present there is no method of accurately identifying patients at high risk of recurrence in the latter group . A retrospective analysis of 141 surgically managed cases with state I/IIa cervical cancer is presented . The study aims were to characterize patients at high risk of relapse , identify independent prognostic variables predicting for relapse and , using these variables , develop a model , that would accurately predict high-risk patients . Univariate analysis identified depht of invasion , substage , lymph node involvement , lymphatic and blood vessel invasion and tumour differentiation as significant prognostic variables . After stratification for depth of invasion , which did not conform to the proportional hazards assumption implicit in the Cox model , Cox regression analysis showed substage , lymphatic and vascular invasion and histological tumour type to be independent prognostic variables . Using these variables , classification models were constructed that would be applicable to patients treated with either surgery or radiotherapy . Applying the models to 110 cases with > 18 months follow-up , 11/18 ( 61 % ) and 11/19 cases ( 58 % ) predicted as being at high risk of relapse have developed recurrence . Highly active chemotherapy is now available for this disease . We have demonstrated that combined bleomycin , ifosfamide and cisplatin ( BIP ) is one of the most active regimens in this disease . BIP produces cytoreduction in around 70 % of patients with recurrent and primary advanced disease . Responses are achieved rapidly and acute radiotherapy toxicity is not enhanced by giving chemotherapy prior to radical local radiotherapy . A multicentre , prospect i ve r and omized trial testing the role of BIP as adjuvant therapy in patients with positive nodes at radical hysterectomy is now in progress . A complementary study testing the role of adjuvant chemotherapy in high-risk patients treated with radical radiotherapy  is in preparation BACKGROUND Adjuvant treatment modalities after radical hysterectomy have long been used in an attempt to eradicate microscopic tumor residuals in patients at high risk for recurrence . However , it has not been clearly demonstrated that adjuvant radiation , adjuvant chemotherapy , or both improve the outcome . To evaluate the effect of adjuvant treatment in patients with high-risk cervical cancer after radical hysterectomy , the Austrian Gynecologic Oncology Group conducted a prospect i ve , r and omized , multicenter clinical trial between 1989 and 1995 . MATERIAL AND METHODS Seventy-six patients with stage IB-IIB cervical cancer treated with radical hysterectomy with pelvic lymph node metastases and /or vascular invasion r and omly received adjuvant chemotherapy ( 400 mg/m2 carboplatin , and 30 mg bleomycin ) , st and ardized external pelvic radiation therapy , or no further treatment . RESULTS After a median follow-up of 4.1 years ( range , 2 - 7 ) there were no statistically significant differences ( P = 0.9530 ) in disease-free survival among the three treatment arms . CONCLUSION The data suggest that adjuvant chemotherapy or radiation do not improve survival or recurrence rates in high-risk cervical cancer patients after radical hysterectomy . The most important treatment for these patients seems to be radical abdominal hysterectomy with systematic pelvic lymphadenectomy INTRODUCTION Chemo-potentiation of radiation improves survival in women with cervical cancer . Our group has previously demonstrated the tolerability of weekly paclitaxel combined with cisplatin during radiation therapy . We sought to determine the efficacy of this regimen in patients with " high risk " cervical cancer , and to determine the short- and long-term toxicity of this approach . METHODS We prospect ively enrolled surgically staged patients with positive peritoneal cytology , resectable nodal metastases , or primary tumor > 6 cm . Patients were treated using external beam radiation with concomitant cisplatin ( 50 mg/m2 ) during weeks 1 , 4 , and 7 , and weekly paclitaxel ( 50 mg/m2 ) , followed by four courses of adjuvant cisplatin ( 50 mg/m2 ) and paclitaxel ( 135 mg/m2 ) . Toxicity , overall , and disease-free survival were evaluated . RESULTS Twenty-three patients were enrolled , and 21 were evaluable . Patient allotment by FIGO stage was : IB1 - seven , IB2 - five , IIA - two , IIB - four , IIIB - two , IV - three . Twenty patients ( 95 % ) completed radiation treatment ( median dose to point A was 8278 cGy ) . Seventeen patients ( 81 % ) completed all chemotherapy . At a median follow-up of 58 months the overall survival was 68 % . Overall survival for patients with clinical Stage I and II disease was 82 % at a median of 64 months . Hematologic toxicity was common but rarely result ed in treatment delays . Late complications requiring intervention ( obstruction , fistula , significant lymphocyst ) occurred in 11 patients ( 52 % ) . CONCLUSION The combination of paclitaxel and cisplatin appears efficacious in " high-risk " cervical cancer patients .  Hematologic toxicity was common but tolerable . Long-term survival was common in these patients , however late toxicity was significant . This regimen should be investigated in collaborative phase III trials PURPOSE To determine whether the addition of cisplatin-based chemotherapy ( CT ) to pelvic radiation therapy ( RT ) will improve the survival of early-stage , high-risk patients with cervical carcinoma . PATIENTS AND METHODS Patients with clinical stage IA(2 ) , IB , and IIA carcinoma of the cervix , initially treated with radical hysterectomy and pelvic lymphadenectomy , and who had positive pelvic lymph nodes and /or positive margins and /or microscopic involvement of the parametrium were eligible for this study . Patients were r and omized to receive RT or RT + CT . Patients in each group received 49.3 GY RT in 29 fractions to a st and ard pelvic field . Chemotherapy consisted of bolus cisplatin 70 mg/m(2 ) and a 96-hour infusion of fluorouracil 1,000 mg/m(2)/d every 3 weeks for four cycles , with the first and second cycles given concurrent to RT . RESULTS Between 1991 and 1996 , 268 patients were entered onto the study . Two hundred forty-three patients were assessable ( 127 RT + CT patients and 116 RT patients ) .  Progression-free and overall survival are significantly improved in the patients receiving CT . The hazard ratios for progression-free survival and overall survival in the RT only arm versus the RT + CT arm are 2.01 ( P = .003 ) and 1.96 ( P = . 007 ) , respectively . The projected progression-free survivals at 4 years is 63 % with RT and 80 % with RT + CT . The projected overall survival rate at 4 years is 71 % with RT and 81 % with RT + CT . Grade s 3 and 4 hematologic and gastrointestinal toxicity were more frequent in the RT + CT group . CONCLUSION The addition of concurrent cisplatin-based CT to RT significantly improves progression-free and overall survival for high-risk , early-stage patients who undergo radical hysterectomy and pelvic lymphadenectomy for carcinoma of the cervix PURPOSE To investigate , in a prospect i ve trial , the acute and chronic toxicity of patients with cervical cancer treated with surgery and postoperative intensity-modulated radiotherapy ( RT ) delivered using helical tomotherapy , with or without the administration of concurrent chemotherapy . PATIENTS AND METHODS A total of 24 evaluable patients entered the study between March 2006 and August 2009 . The indications for postoperative RT were tumor size , lymphovascular space invasion , and the depth of cervical stromal invasion in 15 patients ; 9 patients underwent postoperative RT because of surgically positive lymph nodes . All patients underwent pelvic RT delivered with helical tomotherapy and intracavitary high-dose-rate brachytherapy . Treatment consisted of concurrent weekly platinum in 17 , sequential carboplatin/Taxol in 1 , and RT alone in 6 . The patients were monitored for acute and chronic toxicity using the  Common Toxicity Criteria  , version 3.0 . RESULTS The median follow-up was 24 months ( range , 4 - 49 ) . At the last follow-up visit , 23 patients were alive and disease free . Of the 24 patients , 12 ( 50 % ) experienced acute Grade 3 gastrointestinal toxicity ( anorexia in 5 , diarrhea in 4 , and nausea in 3 ) . One patient developed acute Grade 4 genitourinary toxicity ( vesicovaginal fistula ) . For patients treated with concurrent chemotherapy , the incidence of acute Grade 3 and 4 hematologic toxicity was 71 % and 24 % , respectively . For patients treated without concurrent chemotherapy , the incidence of acute Grade 3 and 4 hematologic toxicity was 29 % and 14 % , respectively . Two long-term toxicities occurred ( vesicovaginal fistula at 25 months and small bowel obstruction at 30 months ) . The overall and progression-free survival rate at 3 years for all patients was 100 % and 89 % , respectively . CONCLUSION The results of our study have shown that postoperative external RT for cervical cancer delivered with helical tomotherapy and high-dose-rate brachytherapy and with or without chemotherapy is feasible , with acceptable acute and chronic toxicity 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 A r and omized study was carried out by means of multicentered cooperation in respect to 5-FU and UFT administration , which was used as the supplementary chemotherapy after treatment of uterocervical cancer . Five years later , the improvement in prognosis was examined . Out of all the cases with radical operation + supplementary chemotherapy as well as with radical operation + postoperative radiotherapy + supplementary chemotherapy , 98 cases were ratable . The analysis of 98 cases led to no significant difference in the survival rate between the 5-FU administration group and the UFT administration group . As to the cases with supplementary chemotherapy + postoperative radiotherapy only , the survival rate was significantly higher in the UFT administration group than in the 5-FU administration group . During the administration , severe adverse side effects developed neither in the 5-FU administration group nor in the UFT administration group . These results suggest that UFT may be useful as a factor in supplementary chemotherapy of uterocervical cancer in combination with radiotherapy OBJECTIVE To compare the clinical efficacy of adjuvant chemotherapy a lone vs chemotherapy plus whole pelvic radiation therapy ( RT ) on recurrence rates , patterns of recurrence , and survival of patients post-RH-PLND for cervical cancer at high risk for recurrence . METHODS Prospect i ve multicenter r and omized Phase III trial . Patients with Stage IB-IIA cervical cancer undergoing RH-PLND were eligible . Risk factors include deep cervical invasion , tumor > or = 4 cm , parametrial involvement , nonsquamous histology , and /or pelvic lymph node metastasis .  Chemotherapy consisted of cisplatin and bleomycin , alone or in combination with whole pelvic RT .  Survival was determined by Kaplan-Meier estimate . RESULTS Eighty-nine patients were entered from 1987 to 1994 . Seventy-five patients had a Stage IB cancer and 14 patients had Stage IIA . Twenty-five patients had > or = 3 risk factors . Forty-four patients received chemotherapy alone vs 45 patients treated with chemotherapy and RT . Nineteen patients had recurrences and 16 patients have died . Nine of 44 ( 20 % ) patients receiving chemo alone recurred compared to 10/45 ( 22 % ) patients receiving chemo and RT ( P = ns ) . Patterns of recurrence were statistically similar between the two treatment arms , even among the subgroup of patients with > or = 3 risk factors . Both regimens were well tolerated . CONCLUSION CT + RT did not prove a superior adjuvant therapy for patients at high risk of recurrence after RH-PLND for early cervical cancer in this limited trial . Recurrence rates and patterns of recurrences ( local , regional , or distant ) were not influenced by the addition of RT & NA ; Adjuvant treatment of patients with risk factors after surgery for cervical carcinoma remains unsatisfactory . A combination of radiotherapy and chemotherapy might improve the control of microscopic metastases . In this prospect i ve study , 28 patients with risk factors after surgery for cervical carcinoma underwent a sequential treatment consisting of two courses of chemotherapy with vincristine , bleomycin , mitomycin c and cis‐platin ( VBMP ) , followed by radiotherapy with 54 Gy to the pelvis and the aortic nodes . Risk factors mainly consisted of nodes metastases ( 25 patients ) , but patients with parametrial invasion or histologic evidence of neoplastic vascular permeation outside the tumor were also included in the study . The treatment was well tolerated and all patients received the planned dose of chemotherapy and radiotherapy ; in the follow‐up one patient died of ileal necrosis and one died of pulmonary embolism after being medically treated for subocclusion . With a minimal follow‐up of 70 months , 15 patients are alive and free of disease , two have died of complications ( one with local recurrence ) , one has died of intercurrent disease and 10 have died of disease ( six distant , four local ) . The site of recurrence was outside the field of irradiation in six cases ( lungs in two cases , liver and para‐aortic nodes in one and distant nodes in three ) . This treatment is feasible but control of distant metastases in high‐risk patients after surgical treatment remains unsatisfactory Cervical adenocarcinoma and adenosquamous cell carcinoma are low in radiation sensitivity , and the prognosis is said to be inferior to that of squamous cell carcinoma . Eleven facilities nationwide participated in the historical control study on the recurrence prevention effect of carmofur ( HCFU ) administered at 300 mg/day for more than two years postoperatively as an adjuvant chemotherapy to patients with cervical adenocarcinoma or adenosquamous cell carcinoma for which radical operation is possible . Registered for the study was a total of 252 patients : 77 patients for whom administration of carmofur was begun during the period from January 1987 and March 1989 , 71 patients ( control 1 ) who were treated for the cancer after January 1982 but did not receive adjuvant chemotherapy , and 104 patients who received adjuvant chemotherapies with other than carmofur ( control 2 ) . In analyses with the Kaplan-Meier method , the carmofur administration group demonstrated a better cumulative survival rate and disease free rate than control 1 ( no adjuvant chemotherapy ) , suggesting carmofur was effective in preventing the recurrence of cervical adenocarcinoma and adenosquamous cell carcinoma Background Although the prognostic advantages of concurrent cisplatin ( CDDP ) chemoradiation therapy ( CCRT ) , for uterine cervical cancer ( UCC ) has been demonstrated , the feasibility of concurrent CDDP administration has not yet been evaluated . We determined the optimal CDDP dose for both weekly and monthly schedules during primary and adjuvant CCRT in patients with UCC . Methods The study was conducted as a phase I , dose-escalation trial . Concurrent CDDP was started at the dose of 30 mg/m2 for the weekly schedule and at 50 mg/m2 for the monthly schedule , and the doses were steadily escalated to the maximum tolerated dose ( MTD ) . Results A total of 45 patients with UCC ( 25 receiving primary CCRT and 20 receiving adjuvant CCRT ) were entered in the study . In both the primary and adjuvant CCRT patients , the MTD was observed to be 40 mg/m2 for the weekly schedule and 80 mg/m2 for the monthly schedule . Dose-limiting toxicity was observed in 10 patients ( granulocytopenia in 9 patients and diarrhea in 1 patient ) . Disease recurrence was confirmed in 6 patients in the primary CCRT group during a mean follow-up period of 22.4 ± 13.2 months , and in patients 3 in the adjuvant CCRT group during a mean follow-up period of 17.7 ± 6.8 months . Conclusion For Japanese patients with UCC receiving primary or adjuvant CCRT therapy , the recommended CDDP dose was determined to be 30 mg/m2 for the weekly schedule and 75 mg/m2 for the monthly schedule Background : In 1999 , five r and omized studies demonstrated that chemoradiation with cisplatin and low-dose rate ( LDR ) brachytherapy has a benefit in locally advanced cervical cancer and for surgically treated patients in high-risk situations . We evaluated the safety and efficacy of concomitant chemoradiation with cisplatin and high-dose rate ( HDR ) brachytherapy in patients with cervical cancer . Patients and Method : 27 patients were included in our phase-II trial : 13 locally advanced cases ( group A ) and 14 adjuvant-therapy patients in high-risk situations ( group B ) . A definitive radiotherapy was performed with 25 fractions of external beam therapy ( 1.8 Gy per fraction/middle shielded after eleven fractions ) . Brachytherapy was delivered at HDR schedules with 7 Gy in point A per fraction ( total dose 35 Gy ) in FIGO Stages IIB – IIIB . The total dose of external and brachytherapy was 70 Gy in point A and 52–54 Gy in point B. All patients in stage IVA were treated without brachytherapy . Adjuvant radiotherapy was performed with external beam radiotherapy of the pelvis with 1.8 Gy single-dose up to 50.4 Gy . Brachytherapy was delivered at HDR schedules with two fractions of 5 Gy only in patients with tumor-positive margins or tumor involvement of the upper vagina . The chemotherapeutic treatment schedule provided six courses of cisplatin 40 mg/m2 weekly recommended in the r and omized studies GOG-120 and -123 . Results : A total of 18/27 patients ( 66.7 % ) completed all six courses of chemotherapy . Discontinuation of radiotherapy due to therapy- result ed morbidity was not necessary in the whole study group . G3 leukopenia ( 29.6 % ) was the only relevant acute toxicity . There were no differences in toxicity between group A and B. Serious late morbidity occurred in 2/27 patients ( 7.4 % ) . 12/13 patients ( 92.3 % ) with IIB – IVA cervical cancer showed a complete response ( CR ) . 13/14 adjuvant cases ( 92.8 % ) are free of recurrence ( median follow up : 19.1 months ) . Conclusion : Concomitant chemoradiation with cisplatin 40 mg/m2 weekly × 6 using HDR brachytherapy represents a promising treatment of cervical cancer with an acceptable toxicity . Hintergrund : 1999 zeigten fünf r and omisierte Studien , dass die simultane Radiochemotherapie mit Cisplatin und einer Low-Dose-Rate-Brachytherapie für Patientinnen mit einem lokal fortgeschrittenen Zervixkarzinom und in der adjuvanten Hochrisikosituation einen Überlebensvorteil bringt . Wir untersuchten die Sicherheit und Effektivität der simultanen Radiochemotherapie mit Cisplatin und High-Dose-Rate-Brachytherapie bei diesen Patientinnen . Patientinnen und Method e : 27 Patientinnen wurden in unsere Phase-II-Studie eingeschlossen : 13 mit lokal fortgeschrittenen Zervixkarzinomen ( Gruppe A ) und 14 adjuvante Hochrisikopatientinnen ( Gruppe B ) . Die primär radiochemotherapierten Fälle erhielten 25 Fraktionen einer perkutanen Hochvolttherapie des Beckens ( 1.8 Gy pro Fraktion/Einbringen eines Mittelblocks nach elf Fraktionen ) . Die Brachytherapie wurde bei den FIGO-Stadien IIB – IIIB nach dem High-Dose-Rate-Afterloading-Prinzip mit 7 Gy pro Fraktion in Punkt A ( Gesamtdosis 35 Gy ) appliziert . Die Gesamtdosis der kombinierten Therapie war 70 Gy in Punkt A und 52–54 Gy in Punkt B. Bei den FIGO-Stadien IVA erfolgte keine Brachytherapie . Bei der adjuvanten Strahlentherapie wurde die perkutane  Hochvolttherapie  des Beckens mit Fraktionen von 1,8 Gy bis zu einer Gesamtdosis von 50,4 Gy appliziert . Die  High-Dose-Rate-Afterloading-Brachytherapie  mit zwei Fraktionen von 5 Gy erfolgte nur bei Patientinnen , bei denen sich i m Operationspräparat tumorbefallene Resektionsränder oder ein Befall der Scheide f and en . Das Chemotherapieregime mit 6 wöchentlichenGaben von 40 mg/m2 Cisplatin entsprach dem der Studien 120 und 123 der GOG . Ergebnisse : 18 von 27 Patientinnen ( 66,7 % ) erhielten alle sechs Cisplatingaben . Eine Unterbrechung der Strahlentherapie aufgrund von Nebenwirkungen war in keinem Fall erforderlich . Die G3-Leukozytopenie ( 29,6 % ) war die einzige relevante Akuttoxizität ; Toxizitätsunterschiede zwischen Gruppe A und B konnten nicht gesehen werden . Erhebliche späte Nebenwirkungen traten bei zwei der 27 Patientinnen ( 7,4 % ) auf . Zwölf von 13 Patientinnen ( 92,3 % ) mit einem Zervixkarzinom FIGO IIB – IVA zeigten eine Komplettremission ( CR ) . 13 von 14 adjuvanten Fällen ( 92,8 % ) sind nach einer medianen Nachbeobachtungszeit von 19,1Monaten rezidivfrei . Schlussfolgerung : Die simultane Radiochemotherapie des Zervixkarzinoms mit 6 wöchentlichen Cisplatingaben 40 mg/m2 und High-Dose-Rate-Afterloading-Brachytherapie stellt eine sichere und effektive Therapieform dar The prognosis after surgical therapy ( radical hysterectomy and pelvic lymphadenectomy ) of stages IB and IIA carcinoma of the cervix is affected by several histopathologic findings within the resected specimen . Patients at high risk of recurrence include those with involved pelvic lymph nodes , lymphatic or vascular invasion in the cervix , tumor size greater than 4 cm , grade 3 lesions , adenosquamous histology , parametrial invasion , and evidence of locally metastatic ( noncontiguous ) disease . We report the results of adjuvant chemotherapy ( cisplatin and bleomycin ) and pelvic radiotherapy in 32 patients with cervix cancer deemed to be at high risk of recurrence after radical hysterectomy and pelvic lymphadenectomy .  The continuous disease-free survival rate for the 32 evaluable patients in 84 % at a mean and median follow-up time of 28 months . Three patients are dead of disease and two patients are alive after treatment of local recurrences giving a survival rate of 91 % . The two patients who are alive after disease recurrence demonstrated only locally recurrent disease while the three patients who have died with recurrent disease relapsed both locally and systemically . Complications of this treatment program were not significantly greater than those observed in prior studies using the combination of surgery and adjuvant radiotherapy without chemotherapy . When compared with the results from historical controls in a large series of similar patients at the same institution , the results in this pilot study are encouraging and would seem to justify a r and omized prospect i ve clinical trial 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 It was reported on a prospect i ve r and omised study of cervical cancer with lymphonodus involvement . After operation and radiotherapy twenty three women were treated with an additional adjuvant chemotherapy by using cyclophosphamide , methotrexate and vincristine for a period of 30 weeks . According to the first results obtained there is no significant difference as against the control group . In this publication the generally unsatisfactory results of the chemotherapy of cervical cancer have been outlined Although the primary operative mortality following radical hysterectomy for stage IB and early stage IIA cervical carcinoma is less than 1 % , survival is poor in those patients with histological evidence of " risk " features -- lymph node metastases , lymphatic vascular tumour permeation and clinical ly undetected parametrial metastases . In the 7-year period 1983 to 1989 , 239 patients with stage IB and early IIA disease had radical hysterectomy and pelvic lymphadenectomy . One hundred and eight patients ( 45.2 % ) had various poor prognostic histological features and received adjuvant chemotherapy--70  had cisplatin , vinblastine , bleomycin ( PVB ) , 16 had mitomycin C ( MMC ) and 22 others received mitomycin C + 5-fluorouracil ( 5-FU ) . Although not r and omised , the risk factors present in each group were identical . These patients have now been followed up for periods ranging from 8 to 14 years . All recurrences , except one , occurred within 23 months of surgery ; in the remaining this occurred 8 years later . This suggests that very close long-term follow-up is needed . Recurrences were markedly higher in the group who refused adjuvant chemotherapy ( 31.6 % ) . The 10-year survival in patients without risk factors was 97.2 % . In those patients with risk factors refusing adjuvant therapy it was 73.7 % . The adjuvant chemotherapy group had a better survival of 86.1 % ( P = 0.001 ) . The 10-year survivals in patients with positive nodes were similar--66.7 % in the MMC group and 71.4 % in the PVB group . The 10-year survival in patients with squamous cell carcinoma was significantly better ( 90.3 % ) in the mitomycin C ( and MMC + 5-FU ) group compared to the PVB group ( 80.1 % ) ( P = 0.005 ) . The 10-year survival in patients with adenocarcinoma and adenosquamous carcinoma was significantly better ( 96.3 % ) in the PVB group compared to those receiving MMC ( and MMC + 5-FU ) ( 57.1 % ) ( P = 0.01 ) . It would , thus , appear that the adjuvant chemotherapy of choice for patients with squamous cell carcinoma would be MMC ( and MMC + 5-FU ) and for those with adenocarcinoma , the PVB regime What is meant by intention-to-treat ? Why should data be analyzed in controlled trials in a way that all participants are included in the group to which they were r and omly assigned , regardless of whether they completed the intervention given to the group ? In this Tutorial , the logic of the intention-to-treat principle is outlined . It is shown that study results may be biased by excluding patients post hoc thus producing spurious effects that do not exist in the population under study . The intention-to-treat strategy avoids this bias
BACKGROUND Patients with early stage cervical cancer ( stages IA2 , IB1 or IIA ) with risk factors such as lymph node metastasis , lympho vascular space invasion , depth invasion of more than 10 mm , microscopic parametrial invasion , non-squamous histology and positive surgical margins have a high risk of recurrence when compared to patients with early stage cervical cancer with no risk factors for recurrence .
OBJECTIVES To evaluate the effectiveness and safety of platinum-based adjuvant chemotherapy after radical hysterectomy , radiotherapy , or both in the treatment of early stage cervical cancer ( stages IA2 , IB1 or IIA ) .