Randomized phase III trial of standard timed doxorubicin plus cisplatin versus circadian timed doxorubicin plus cisplatin in stage III and IV or recurrent endometrial carcinoma: a Gynecologic Oncology Group Study. Adjuvant sequential chemoradiation therapy in high-risk endometrial cancer: results of a prospective, multicenter phase-II study of the NOGGO (North-Eastern German Society of Gynaecological Oncology) Randomized phase II study comparing docetaxel plus cisplatin, docetaxel plus carboplatin, and paclitaxel plus carboplatin in patients with advanced or recurrent endometrial carcinoma: a Japanese Gynecologic Oncology Group study (JGOG2041). Doxorubicin versus doxorubicin and cisplatin in endometrial carcinoma: definitive results of a randomised study (55872) by the EORTC Gynaecological Cancer Group. A gynecologic oncology group randomized phase III trial of whole abdominal irradiation (WAI) vs. cisplatin-ifosfamide and mesna (CIM) as post-surgical therapy in stage I-IV carcinosarcoma (CS) of the uterus. Randomized trial results of quality of life comparing whole abdominal
irradiation and combination chemotherapy in advanced endometrial carcinoma: A gynecologic oncology group study Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. Association of number of positive nodes and cervical stroma invasion with outcome of advanced endometrial cancer treated with chemotherapy or whole abdominal irradiation: a Gynecologic Oncology Group study. Randomized phase III trial of pelvic radiotherapy versus cisplatin-based combined chemotherapy in patients with intermediate- and high-risk endometrial cancer: a Japanese Gynecologic Oncology Group study. Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer--results from two randomised studies. Phase III randomized trial of doxorubicin + cisplatin versus doxorubicin + 24-h paclitaxel + filgrastim in endometrial carcinoma: a Gynecologic Oncology Group study. Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. Surgically staged high-risk endometrial cancer: randomized study of adjuvant radiotherapy alone vs. sequential chemo-radiotherapy. A randomized phase III trial in advanced endometrial carcinoma of surgery and volume directed radiation followed by cisplatin and doxorubicin with or without paclitaxel: A Gynecologic Oncology Group study.
PURPOSE To determine if circadian timed ( CT ) chemotherapy results in improved response , progression-free survival ( PFS ) , overall survival ( OS ) , and lower toxicity , when compared with st and ard timed ( ST ) chemotherapy . MATERIAL S AND METHODS Eligibility criteria were stage III , IV , or recurrent endometrial cancer with poor potential for cure by radiation therapy or surgery ; measurable disease ; and no prior chemotherapy . Therapy was r and omized to schedules of ST doxorubicin 60 mg/m2 plus cisplatin 60 mg/m2 , or CT doxorubicin 60 mg/m2 at 6:00 am plus cisplatin 60 mg/m2 at 6:00 pm . Cycles were repeated every 3 weeks to a maximum of eight cycles . RESULTS The ST arm included 169 patients , and the CT arm included 173 patients . The objective response rate ( complete responses plus partial responses ) was 46 % in the ST group compared with 49 % in the CT group ( P = .26 , one tail ) . Median PFS and OS were 6.5 and 11.2 months , respectively , in the ST group ; and 5.9 and 13.2 months , respectively , in the CT group ( PFS : P = .31 ; OS : P = .21 , one tail ) . Median total doses were 209 mg/m2 doxorubicin and 349 mg/m2 cisplatin in the ST group , versus 246 mg/m2 doxorubicin and 354 mg/m2 cisplatin in the CT group . Grade 3 or 4 leukopenia occurred in 73 % of patients in the ST arm and in 63 % of patients in the CT arm . There were eight treatment-related deaths . CONCLUSION In this trial , no significant benefit in terms of response rate , PFS or OS , or toxicity profile was observed with CT doxorubicin plus cisplatin in patients with advanced or recurrent endometrial carcinoma Purpose The management of high-risk endometrial cancer ( HREC ) remains controversial . We conducted a prospect i ve multicenter phase-II clinical trial to evaluate an adjuvant chemotherapy ( CT ) with sequential radiotherapy ( RT ) in patients with HREC . Methods Patients with HREC from 8 institutions in Germany were enrolled . After surgery , patients received four cycles of paclitaxel 175 mg/m² ( P ) and carboplatin AUC5 ( C ) ( d1 , q21d ) and subsequent external pelvic radiation therapy ( 1.8 Gy/d , d1 - 5 ) at a total dose of 45 Gy with vaginal brachytherapy ( 3 × 5 Gy  ) . Quality of life ( QoL ) was assessed using the EORTC-QLQ-C30 question naire . Primary endpoints were tolerability , toxicity and QoL. Progression-free survival ( PFS ) was defined as secondary endpoint . Results Thirty-five patients were enrolled from 2004 through 2008 . Median follow-up was 24 months ( range 3–24 months ) . All patients received 4 cycles of P and C and completed RT . Overall , grade 3/4 haematological toxicity was 25.6 % . Three cycles were delayed because of leukopenia . Grade 3/4 non-haematologic toxicities were rare ( ≤3 % ) . No overall change in QoL occurred during treatment . Two-year median PFS and OS rates were both 75.8 % . Conclusions Adjuvant combination CT with P + C and sequential RT is well tolerated and a feasible regimen in patients with HREC . Subsequent phase-III trials are warranted BACKGROUND The purpose of this study is to assess the efficacy and safety of treatment with taxane plus platinum in combination therapies for advanced or recurrent endometrial carcinoma . PATIENTS AND METHODS Patients with measurable disease derived from histologically confirmed stage III/IV or recurrent endometrial carcinoma were r and omly assigned to receive docetaxel plus cisplatin ( DP ) , docetaxel plus carboplatin ( DC ) , or paclitaxel plus carboplatin ( TC ) every 3 weeks until disease progression or adverse events prohibited further therapy . Among these regimens , the study evaluated the tumor response rate as the primary end point as well as toxicity . RESULTS Ninety patients were enrolled . Of them , 88 were eligible and consequently 29 , 29 , and 30 patients were r and omly assigned to DP , DC , and TC , respectively . Tumor response rates were 51.7 % , 48.3 % , and 60.0 % in DP , DC , and TC , respectively ( P = 0.65 ) . The following toxic effects were observed : grade 3/4 neutropenia in 83.3 % , 90.0 % , and 76.6 % ; febrile neutropenia in 10.0 % , 6.7 % , and 3.3 % ; grade 3/4 thrombocytopenia in 6.7 % , 10.0 % , and 10.0 % ; grade 3/4 diarrhea in 13.3 % , 3.3 % , and 0 % , respectively ; and grade 3 neurotoxicity in 10.0 % of TC . These toxicity profiles were not significantly different . CONCLUSION The taxane plus platinum combination therapies could be c and i date s in further phase III trials for endometrial carcinoma BACKGROUND Combination chemotherapy yields better response rates which do not always lead to a survival advantage . The aim of this study was to investigate whether the reported differences in the efficacy and toxicity of monotherapy with doxorubicin ( DOX ) versus combination therapy with cisplatin ( CDDP ) in endometrial adenocarcinoma lead to significant advantage in favour of the combination . PATIENTS AND METHODS Eligible patients had histologically-proven advanced and /or recurrent endometrial adenocarcinoma and were chemo-naïve . Treatment consisted of either DOX 60 mg/m(2 ) alone or CDDP 50 mg/m2 added to DOX 60 mg/m2 , every 4 weeks . RESULTS A total of 177 patients were entered and median follow-up is 7.1 years . The combination DOX-CDDP was more toxic than DOX alone . Haematological toxicity consisted mainly of white blood cell toxicity grade 3 and 4 ( 55 % versus 30 % ) . Non-haematological toxicity consisted mainly of grade 3 and 4 alopecia ( 72 % versus 65 % ) and nausea/vomiting ( 36 % versus 12 % ) . The combination DOX-CDDP provided a significantly higher response rate than single agent DOX ( P < 0.001 ) . Thirty-nine patients ( 43 % ) responded on DOX-CDDP [ 13 complete responses ( CRs ) and 26 partial responses ( PRs ) ] , versus 15 patients ( 17 % ) on DOX alone ( 8 CR and 7 PR ) . The median overall survival ( OS ) was 9 months in the DOX-CDDP arm versus 7 months in the DOX alone arm ( Wilcoxon P = 0.0654 ) . Regression analysis showed that WHO performance status was statistically significant as a prognostic factor for survival , and stratifying for this factor , treatment effect reaches significance ( hazard ratio = 1.46 , 95 % confidence interval 1.05 - 2.03 , P = 0.024 ) . CONCLUSIONS In comparison to single agent DOX , the combination of DOX-CDDP results in higher but acceptable toxicity . The response rate produced is significantly higher , and a modest survival benefit is achieved with this combination regimen , especially in patients with a good performance status PURPOSE After initial surgery , there has been no established consensus regarding adjunctive therapy for patients with uterine carcinosarcoma ( CS ) . This study was design ed to compare patient outcome following treatment with adjuvant whole abdominal irradiation ( WAI ) versus ( vs. ) chemotherapy for patients with this rare group of female pelvic malignancies . PATIENTS AND METHODS Eligible , consenting women with stage I-IV uterine CS , no more than 1 cm postsurgical residuum and /or no extra-abdominal spread had their treatments r and omly assigned as either WAI or three cycles of cisplatin ( C ) , ifosfamide ( I ) , and mesna ( M ) . RESULTS 232 patients were enrolled , of whom 206 ( WAI=105 ; CIM=101 ) were deemed eligible . Patient demographics and characteristics were similar between arms . FIGO stage ( both arms ) was : I=64 ( 31 % ) ; II=26 ( 13 % ) ; III=92 ( 45 % ) ; IV=24 ( 12 % ) . The estimated crude probability of recurring within 5 years was 58 % ( WAI ) and 52 % ( CIM ) . Adjusting for stage and age , the recurrence rate was 21 % lower for CIM patients than for WAI patients ( relative hazard [RH]=0.789 , 95 % confidence interval [ CI ] : ( 0.530 - 1.176 ) , p=0.245 , 2-tail test ) . The estimated death rate was 29 % lower among the CIM group ( RH=0.712 , 95 % CI : 0.484 - 1.048 , p=0.085 , two-tail test ) . CONCLUSION We did not find a statistically significant advantage in recurrence rate or survival for adjuvant CIM over WAI in patients with uterine CS . However , the observed differences favor the use of combination chemotherapy in future trials Objective To prospect ively compare quality of life ( QOL ) outcomes in patients with advanced endometrial cancer treated with whole abdominal irradiation ( WAI ) or doxorubicin-cisplatin ( AP ) chemotherapy .  Methods Using the Fatigue Scale ( FS ) , Assessment of Peripheral Neuropathy ( APN ) , Functional Alterations due to Changes in Elimination ( FACE ) , and Functional Assessment of Cancer Therapy-General ( FACT-G ) , QOL was measured at : pre-treatment , end of treatment ( EOT ) , and 3 and 6 months post-treatment . Results 317 of 396 eligible patients provided a baseline QOL assessment .  The AP arm produced a statistically significant survival benefit along with greater toxicities , including peripheral neuropathy persisting up to 6 months . WAI patients reported worse FS ( p<0.001 ) and FACE ( p<0.001 ) scores at EOT and poorer FACE scores 3 months post-treatment ( p = 0.004 ) compared to AP patients . APN scores were significantly worse among AP patients at EOT , and 3 and 6 months post-treatment ( p<0.001 for all ) . There is no indication that FACT-G scores differed between the two arms at any assessment point . Conclusions The trade-off for increased survival with AP is its potential for clinical ly significant peripheral neuropathy . This should be discussed with patients , particularly those who work with their h and s or on their feet , in weighing therapeutic choices . Further research is needed to manage side effects having an enduring impact on QOL PURPOSE To determine whether the addition of paclitaxel to doxorubicin plus cisplatin improves overall survival ( OS ) in women with advanced or recurrent endometrial carcinoma . Secondary comparisons included progression-free survival ( PFS ) , response rate ( RR ) , and toxicities . PATIENTS AND METHODS Eligible , consenting patients received doxorubicin 60 mg/m(2 ) and cisplatin 50 mg/m(2 ) ( AP ) , or doxorubicin 45 mg/m(2 ) and cisplatin 50 mg/m(2 ) ( day 1 ) , followed by paclitaxel 160 mg/m(2 ) ( day 2 ) with filgrastim support ( TAP ) . The initial doxorubicin dose in the AP arm was reduced to 45 mg/m(2 ) in patients with prior pelvic radiotherapy and those older than 65 years . Both regimens were repeated every 3 weeks to a maximum of seven cycles . Patients completed a neurotoxicity question naire before each cycle . RESULTS Two hundred seventy-three women ( 10 ineligible ) were registered .  Objective response ( 57 % v 34 % ; P < .01 ) , PFS ( median , 8.3 v 5.3 months ; P < .01 ) , and OS ( median , 15.3 v 12.3 months ; P = .037 ) were improved with TAP . Treatment was hematologically well tolerated , with only 2 % of patients receiving AP , and 3 % of patients receiving TAP experiencing neutropenic fever . Neurologic toxicity was worse for those receiving TAP , with 12 % grade 3 , and 27 % grade 2 peripheral neuropathy , compared with 1 % and 4 % , respectively , in those receiving AP .  Patient-reported neurotoxicity was significantly higher in the TAP arm following two cycles of therapy . CONCLUSION TAP significantly improves RR , PFS , and OS compared with AP . Evaluation of this regimen in the high-risk adjuvant setting is warranted , but close attention should be paid to the increased risk of peripheral neuropathy OBJECTIVE To determine whether the number of positive pelvic nodes ( PPN ) , cervical stromal involvement ( CSI ) , and /or lymphovascular space involvement ( LVSI ) were prognostic factors among women with advanced endometrial carcinoma treated with adriamycin plus cisplatin ( AP ) or whole abdominal irradiation ( WAI ) .  METHODS Data were abstract ed from records of patients treated with adjuvant WAI or AP in a GOG r and omized trial . Cox proportional hazards models were used to estimate the association of CSI and PPN with differences in PFS and OS while adjusting for treatment and previously studied factors . RESULTS  WAI was r and omly allocated to 202 and AP to 194 eligible patients . CSI ( n=93 total ) was associated with a 44 % increase in risk of progression and a 33 % increase in risk of death . There was a trend for increasing number PPN being associated with a 7 % per positive node increase in risk of progression/death . For CSI , the estimated unadjusted treatment hazard ratios ( HRs ) were : PFS 0.85 ( 0.53 , 1.38 ) ; OS 0.81 ( 0.50 , 1.33 ) . For metastatic disease limited to a single PPN ( n=25 ) , the unadjusted HRs were : PFS 0.96 ( 0.34 , 2.74 ) ; OS 0.73 ( 0.24 , 2.18 ) . The test of homogeneity of treatment effect ( ie . , AP vs WAI ) across subgroups ( CSI , number of positive pelvic nodes ) was not statistically significant for either endpoint , thus supporting the superiority of chemotherapy as reported in the original manuscript . CONCLUSIONS The presence of CSI and increasing number of PPN were associated with poor prognosis . On average , patients with CSI experienced improved PFS and OS when treated with AP relative to WAI OBJECTIVE To establish an optimal adjuvant therapy for intermediate- and high-risk endometrial cancer patients , we conducted a multi-center r and omized phase III trial of adjuvant pelvic radiation therapy ( PRT ) versus cyclophosphamide-doxorubicin-cisplatin ( CAP ) chemotherapy in women with endometrioid adenocarcinoma with deeper than 50 % myometrial invasion . METHODS Among 385 evaluated patients , 193 patients received PRT and 192 received CAP .  The PRT group received at least 40 Gy . The CAP group received cyclophosphamide ( 333 mg/m2 ) , doxorubicin ( 40 mg/m2 ) and cisplatin ( 50 mg/m2 ) every 4 weeks for 3 or more courses . RESULTS No statistically significant differences in progression-free survival ( PFS ) and overall survival ( OS ) were observed . The 5-year PFS rates in the PRT and CAP groups were 83.5 % and 81.8 % respectively , while the 5-year OS rates were 85.3 % and 86.7 % respectively . These rates were also not significantly different in a low- to intermediate-risk group defined as stage IC patients under 70 years old with G1/2 endometrioid adenocarcinoma . However , among 120 patients in a high- to intermediate-risk group defined as ( 1 ) stage IC in patients over 70 years old or with G3 endometrioid adenocarcinoma or ( 2 ) stage II or IIIA ( positive cytology ) , the CAP group had a significantly higher PFS rate ( 83.8 % vs. 66.2 % , log-rank test P=0.024 , hazard ratio 0.44 ) and higher OS rate ( 89.7 % vs. 73.6 % , log-rank test P=0.006 , hazard ratio 0.24 ) . Adverse effects were not significantly increased in the CAP group versus the PRT group . CONCLUSION Adjuvant chemotherapy may be a useful alternative to radiotherapy for intermediate-risk endometrial cancer INTRODUCTION Endometrial cancer patients with high grade tumours , deep myometrial invasion or advanced stage disease have a poor prognosis . R and omised studies have demonstrated the prevention of loco-regional relapses with radiotherapy ( RT ) with no effect on overall survival ( OS ) . The possible additive effect of chemotherapy ( CT ) remains unclear . Two r and omised clinical trials ( NSGO-EC-9501/EORTC-55991 and MaNGO ILIADE-III ) were undertaken to clarify if sequential combination of chemotherapy and radiotherapy improves progression-free survival ( PFS ) in high-risk endometrial cancer . The two studies were pooled . METHODS Patients ( n=540 ; 534 evaluable ) with operated endometrial cancer International Federation of Obstetrics and Gynaecology ( FIGO ) stage I-III with no residual tumour and prognostic factors implying high-risk were r and omly allocated to adjuvant radiotherapy with or without sequential chemotherapy . RESULTS In the NSGO/EORTC study , the combined modality treatment was associated with 36 % reduction in the risk for relapse or death ( hazard ratio ( HR ) 0.64 , 95%confidence interval ( CI ) 0.41 - 0.99 ; P=0.04 ) ; two-sided tests were used . The result from the Gynaecologic Oncology group at the Mario Negri Institute (MaNGO)- study pointed in the same direction ( HR 0.61 ) , but was not significant . In the combined analysis , the estimate of risk for relapse or death was similar but with narrower confidence limits ( HR 0.63 , CI 0.44 - 0.89 ; P=0.009 ) . Neither study showed significant differences in the overall survival . In the combined analysis , overall survival approached statistical significance ( HR 0.69 , CI 0.46 - 1.03 ; P=0.07 ) and cancer-specific survival ( CSS ) was significant ( HR 0.55 , CI 0.35 - 0.88 ; P=0.01 ) . CONCLUSION Addition of adjuvant chemotherapy to radiation improves progression-free survival in operated endometrial cancer patients with no residual tumour and a high-risk profile . A remaining question for future studies is if addition of radiotherapy to chemotherapy improves the results BACKGROUND This study was performed to determine whether 24-h paclitaxel plus doxorubicin and filgrastim was superior to cisplatin plus doxorubicin in patients with endometrial cancer with respect to response , progression-free survival ( PFS ) and overall survival ( OS ) . PATIENTS AND METHODS Eligible chemotherapy-naïve patients were r and omly assigned to doxorubicin 60 mg/m2 intravenously ( i.v . ) followed by cisplatin 50 mg/m2 i.v . ( arm 1 , n=157 ) or doxorubicin 50 mg/m2 i.v . followed 4 h later by paclitaxel 150 mg/m2 i.v . over 24 h plus filgrastim 5 microg/kg on days 3 - 12 ( arm 2 , n=160 ) . Starting doses were reduced for prior pelvic radiotherapy and age > 65 years . Both regimens were to be repeated every 3 weeks for a maximum of seven cycles . RESULTS There was no significant difference in response rate ( 40 % versus 43 % ) , PFS ( median 7.2 versus 6 months ) or OS ( median 12.6 versus 13.6 months ) for arm 1 and arm 2 , respectively . Toxicities were primarily hematological , with 54 % ( arm 1 ) and 50 % ( arm 2 ) of patients experiencing grade 4 granulocytopenia . Gastrointestinal toxicities were similar in both arms . CONCLUSIONS Doxorubicin and 24-h paclitaxel plus filgrastim was not superior to doxorubicin and cisplatin in terms of response , PFS or survival in advanced endometrial cancer PURPOSE To compare whole-abdominal irradiation ( WAI ) and doxorubicin-cisplatin ( AP ) chemotherapy in women with stage III or IV endometrial carcinoma having a maximum of 2 cm of postoperative residual disease . PATIENTS AND METHODS Four hundred twenty-two patients were entered onto this trial . Of 396 assessable patients , 202 were r and omly allocated to receive WAI , and 194 were allocated to receive AP .  Irradiation dosage was 30 Gy in 20 fractions , with a 15-Gy boost . Chemotherapy consisted of doxorubicin 60 mg/m2 and cisplatin 50 mg/m2 every 3 weeks for seven cycles , followed by one cycle of cisplatin . RESULTS Most patient and tumor characteristics were well balanced . The median patient age was 63 years ; 50 % had endometrioid tumors . Median follow-up time was 74 months . The hazard ratio for progression adjusted for stage was 0.71 favoring AP ( 95 % CI , 0.55 to 0.91 ; P < .01 ) . At 60 months , 50 % of patients receiving AP were predicted to be alive and disease free when adjusting for stage compared with 38 % of patients receiving WAI . The stage-adjusted death hazard ratio was 0.68 ( 95 % CI , 0.52 to 0.89 ; P < .01 ) favoring AP . Moreover , at 60 months and adjusting for stage , 55 % of AP patients were predicted to be alive compared with 42 % of WAI patients . Greater acute toxicity was seen with AP . Treatment probably contributed to the deaths of eight patients ( 4 % ) on the AP arm and five patients ( 2 % ) on the WAI arm . CONCLUSION Chemotherapy with AP significantly improved progression-free and overall survival compared with WAI . Nevertheless , further advances in efficacy and reduction in toxicity are clearly needed OBJECTIVE Our purpose was to establish whether platinum-based chemotherapy combined with st and ard surgery and radiotherapy will improve overall and disease-free survival and lower the recurrence rate in patients with high-risk endometrial cancer . STUDY DESIGN A total of 156 patients with Stage IA-B Grade 3 ( n=28 ) , or Stage IC-IIIA Grade 1 - 3 ( n=128 ) were postoperatively r and omized to receive radiotherapy ( 56 Gy ) only  ( Group A , n=72 ) or  radiotherapy combined with three courses of cisplatin ( 50 mg/m(2 ) ) , epirubicin ( 60 mg/m(2 ) ) and cyclophosphamide ( 500 mg/m(2 ) ) ( Group B , n=84 ) . RESULTS The disease-specific overall five-year survival was in Group A 84.7 % vs. 82.1 % in Group B ( p=0.148 ) . The median disease-free survival in A was 18 ( range 9 - 36 ) months and 25 ( range 12 - 49 ) months in B ( p=0.134 ) , respectively . During a five-year follow-up 32 patients relapsed . Of the recurrences 5 were local and 20 distant , while 7 were combined . As calculated from the operation , the median time to recurrence was 15 ( range 6 - 37 ) months in Group A , and 20 ( range 8 - 60 ) months in Group B , respectively ( p=0.170 ) . Twenty-six patients died of the disease during the five-year follow-up , 11 in A and 15 in B. The patients succumbing in A lived a median 23 ( range 15 - 44 ) months as compared to 37 ( range 13 - 50 ) months in B ( p=0.148 ) . Chemotherapy was associated with an acceptable rate of acute toxicity . Less than 8 % of the patients complained of Grade 3/4 nausea . The rate of Grade 3/4 leucopenia was at the highest at 16.6 % during the third cycle but only 6.2 % of the patients had Grade 3 infection . A total of 10 patients developed intestinal complications dem and ing surgery , 2 in Group A ( 2.7 % ) and 8 ( 9.5 % ) in Group B , respectively . CONCLUSION Adjuvant chemotherapy with cisplatin , epirubicin and cyclophosphamide failed to improve overall survival or lower the recurrence rate in patients operated on and radiated for high-risk endometrial carcinoma . Chemotherapy was associated with a low rate of acute toxicity but appeared to increase the risk of bowel complications OBJECTIVES After surgical debulking and volume-directed irradiation of the pelvis/para-aortic lymph nodes , treatment was r and omized to compare recurrence-free survival ( RFS ) and toxicity between two chemotherapy regimens for the treatment of women with advanced stage endometrial carcinoma . METHODS Treatment was r and omized between 6 cycles of cisplatin [ C ] ( 50 mg/m(2 ) ) and doxorubicin [ D ] ( 45 mg/m(2 ) ) with or without paclitaxel [ P ] ( 160 mg/m(2 ) ) . Initially in paclitaxel treated patients and , after May 2002 , all patients received granulocyte growth factor with each cycle . RESULTS Of 659 patients enrolled following surgery , 552 eligible patients were r and omized to chemotherapy after irradiation . Accrual closed to Stage IV patients in June , 2003 . Approximately 80 % completed six cycles of chemotherapy . Three deaths result ed from bowel complications and one death was due to renal failure . Hematologic adverse events , sensory neuropathy and myalgia , were more frequent and severe in the paclitaxel arm ( p<0.01 ) which was confirmed by Quality of Life assessment s. Percentage of patients alive and recurrence-free at 36 months was 62 % for CD vs. 64 % for CDP . The hazard of recurrence or death relative to the CD arm stratified by stage is 0.90 ( 95 % CI is 0.69 to 1.17 , p=0.21 , one-tail ) . However , in subgroup analysis , CDP was associated with a 50 % reduction in the risk of recurrence or death among patients with gross residual disease ( 95 % CI : 0.26 to 0.92 ) . Stage , residual disease , histology/ grade , positive para-aortic node and cytology , pelvic metastases and age were significantly associated with RFS . CONCLUSION The addition of paclitaxel to cisplatin and doxorubicin following surgery and radiation was not associated with a significant improvement in RFS but was associated with increased toxicity
BACKGROUND Approximately 13 % of women diagnosed with endometrial cancer present with advanced stage disease ( International Federation of Gynecology and Obstetrics ( FIGO ) stage III/IV ) .
The st and ard treatment of advanced endometrial cancer consists of cytoreductive surgery followed by radiation therapy , or chemotherapy , or both .
There is currently little agreement about which adjuvant treatment is the safest and most effective .
OBJECTIVES To evaluate the effectiveness and safety of adjuvant chemotherapy compared with radiotherapy or chemoradiation , and to determine which chemotherapy agents are most effective in women presenting with advanced endometrial cancer ( FIGO stage III/IV ) .