Intraperitoneal radioactive phosphorus (32P) versus observation after negative second-look laparotomy for stage III ovarian carcinoma: a randomized trial of the Gynecologic Oncology Group. Phase III randomized trial of high-dose chemotherapy (HDC) and peripheral blood stem cell (PBSC) support as consolidation in patients (pts) with advanced ovarian cancer (AOC): 5-year follow-up of a GINECO/FNCLCC/SFGM-TC study. A checklist designed to aid consistency and reproducibility of GRADE assessments: development and pilot validation Incorporation of pazopanib in maintenance therapy of ovarian cancer. A pilot study of three‐cycle consolidation chemotherapy with paclitaxel and platinum in epithelial ovarian cancer patients with clinical complete response after paclitaxel and platinum chemotherapy Phase III randomized trial of 12 versus 3 months of maintenance paclitaxel in patients with advanced ovarian cancer after complete response to platinum and paclitaxel-based chemotherapy: a Southwest Oncology Group and Gynecologic Oncology Group trial. Randomized prospective trial of 5 versus 10 cycles of cyclophosphamide, doxorubicin, and cisplatin in advanced ovarian carcinoma. Consolidation paclitaxel is more cost-effective than bevacizumab following upfront treatment of advanced epithelial ovarian cancer. A prospective randomized comparison of 6 and 12 cycles of cyclophosphamide, adriamycin, and cisplatin in advanced epithelial ovarian cancer: a Danish Ovarian Study Group trial (DACOVA). A randomized trial of five versus eight courses of cisplatin or carboplatin in advanced epithelial ovarian carcinoma. A North Thames Ovary Group Study. A Randomized Study of Epithelial Ovarian Cancer: Is Chemotherapy Useful after Complete Remission? Topotecan compared with no therapy after response to surgery and carboplatin/paclitaxel in patients with ovarian cancer: Multicenter Italian Trials in Ovarian Cancer (MITO-1) randomized study. Phase III trial of induction gemcitabine or paclitaxel plus carboplatin followed by paclitaxel consolidation in ovarian cancer. Consolidation treatment of advanced (FIGO stage III) ovarian carcinoma in complete surgical remission after induction chemotherapy: A randomized, controlled, clinical trial comparing whole abdominal radiotherapy, chemotherapy, and no further treatment Intraperitoneal cisplatin versus no further treatment: 8‐year results of EORTC 55875, a randomized phase III study in ovarian cancer patients with a pathologically complete remission after platinum‐based intravenous chemotherapy Phase III trial of observation versus six courses of paclitaxel in patients with advanced epithelial ovarian cancer in complete response after six courses of paclitaxel/platinum-based chemotherapy: final results of the After-6 protocol 1. A randomized phase III trial of IV carboplatin and paclitaxel × 3 courses followed by observation versus weekly maintenance low-dose paclitaxel in patients with early-stage ovarian carcinoma: a Gynecologic Oncology Group Study. Epidoxorubicin versus no treatment as consolidation therapy in advanced ovarian cancer: results from a phase II study
PURPOSE The objectives of this prospect i ve r and omized study of consolidation therapy were to evaluate recurrence-free survival ( RFS ) , overall survival ( OS ) , and the morbidity of intraperitoneal ( IP ) chromic phosphate suspension ( 32P ) therapy in patients with stage III epithelial ovarian carcinoma who have no detectable evidence of disease at the second-look laparotomy ( SLL ) procedure after primary chemotherapy . PATIENTS AND METHODS In a multi-institution clinical cooperative trial , 202 eligible patients with a negative SLL were r and omly selected to receive either 15 mCi IP 32P ( n = 104 ) or no further therapy ( NFT ; n = 98 ) . RESULTS With a median follow-up of 63 months in living patients , 68 patients in the IP 32P group ( 65 % ) and 63 patients in the NFT group ( 64 % ) have developed tumor recurrence . The relative risk of recurrence is 0.90 ( IP 32P to NFT ) ( 90 % confidence interval [ CI ] , 0.68 to 1.19 ) . The 5-year RFS rate is 42 % and 36 % for the IP 32P and NFT groups , respectively ; the difference is not statistically significant ( log-rank test , P = .27 ) . There was no statistically significant difference in OS ( P = .19 ) . The relative risk of death is 0.85 ( IP 32P to NFT ) ( 90 % CI , 0.62 to 1.16 ) . Sixteen patients ( 8 % ) experienced grade 3 or 4 adverse effects , with eight in each respective group . CONCLUSION Intraperitoneal chromic phosphate did not decrease the risk of relapse or improve survival for patients with stage III epithelial ovarian cancer after a negative SLL . Despite complete pathologic remission at SLL after initial surgery and platinum-based chemotherapy , 61 % of stage III ovarian cancer patients had tumor recurrence within 5 years of negative SLL . This indicates a need for more effective initial therapy and further studies of consolidation therapy 5006 Background : Phase II studies have suggested that HDC is most effective in chemosensitive AOC pts with low tumor burden . METHODS We compared the disease free-survival ( DFS ) , overall survival ( OS ) and toxicity of women with AOC r and omized after second-look surgery ( SLS ) to receive either HDC Carboplatin-Cyclophosphamide and PBSC support ( Cb 400 mg/m2/d and Cy 1500 mg/m2/d x 4 days ) or 3 cycles of conventional-dose maintenance ( CDM ) ( q4w , Cb 300 mg/m2 , Cy 500 mg/m2 ) . Eligibility criteria were : age < 60 yrs , FIGO stage III-IV , disease responsive to 4 - 6 cycles of a platinum-based first-line chemotherapy , tumor size < 2 cm at the end of the SLS or a pathological complete response ( pCR ) but high-risk factors . RESULTS Between 07/1995 to 10/2000 , 110 pts were enrolled , 57 in the HDC and 53 in the CDM arm . Pts characteristics were well balanced between the 2 arms . Half of the pts received paclitaxel in first-line . Nine pts had Stage IV and 101 pts stage III with at SLS : pCR ( 39 % ) , microscopic ( 20 % ) and macroscopic ( 41 % ) disease . In the HDC arm , 1 pt was ineligible and 11 ( 20 % ) did not receive the HDC because of poor PBSC mobilization ( n= 7 ) , pt refusal ( n=3 ) or early relapse ( n=1 ) . Median time to neutrophil and platelet recovery was 11 days . Two pts died from toxic myocarditis and renal insufficiency respectively . Median follow-up is 60 months . At time of analysis , 94 pts have relapsed and 63 have died . DFS and OS were not significantly different between the 2 arms . Median DFS and OS from r and omization were 12.2 ( 95 % CI : 7.3 - 17.1 ) and 42.5 ( 95 % CI : 28.8 - 56.6 ) months in the CDM arm , and were 17.5 ( 95 % CI : 5.2 - 29.9 ) ( p=.22 ) and 49.7 ( 95 % CI : 29.9 - 69.4 ) ( p=.43 ) months in the HDC arm , respectively . CONCLUSIONS These data do not support high-dose consolidation chemotherapy in AOC . [ Table : see text ] Background The grading of recommendation , assessment , development and evaluation ( GRADE ) approach is widely implemented in health technology assessment and guideline development organisations throughout the world . GRADE provides a transparent approach to reaching judgements about the quality of evidence on the effects of a health care intervention , but is complex and therefore challenging to apply in a consistent manner . Methods We developed a checklist to guide the research er to extract the data required to make a GRADE assessment . We applied the checklist to 29 meta-analyses of r and omised controlled trials on the effectiveness of health care interventions . Two review ers used the checklist for each paper and used these data to rate the quality of evidence for a particular outcome . Results For most ( 70 % ) checklist items , there was good agreement between review ers . The main problems were for items relating to indirectness where considerable judgement is required . Conclusions There was consistent agreement between review ers on most items in the checklist . The use of this checklist may be an aid to improving the consistency and reproducibility of GRADE assessment s , particularly for inexperienced users or in rapid review s without the re sources to conduct assessment s by two research ers independently PURPOSE Pazopanib is an oral , multikinase inhibitor of vascular endothelial growth factor receptor ( VEGFR ) -1/-2/-3 , platelet-derived growth factor receptor ( PDGFR ) -α/-β , and c-Kit . Pre clinical and clinical studies support VEGFR and PDGFR as targets for advanced ovarian cancer treatment . This study evaluated the role of pazopanib maintenance therapy in patients with ovarian cancer whose disease did not progress during first-line chemotherapy . PATIENTS AND METHODS Nine hundred forty patients with histologically confirmed cancer of the ovary , fallopian tube , or peritoneum , International Federation Gynecology Obstetrics ( FIGO ) stages II-IV , no evidence of progression after primary therapy consisting of surgery and at least five cycles of platinum-taxane chemotherapy  were r and omized 1:1 to receive pazopanib 800 mg once per day or placebo for up to 24 months . The primary end point was progression-free survival by RECIST 1.0 assessed by the investigators . RESULTS Maintenance pazopanib  prolonged progression-free survival  compared with placebo ( hazard ratio [ HR ] , 0.77 ; 95 % CI , 0.64 to 0.91 ; P = .0021 ; median , 17.9 v 12.3 months , respectively ) . Interim survival analysis based on events in 35.6 % of the population did not show any significant difference . Grade 3 or 4 adverse events of hypertension ( 30.8 % ) , neutropenia ( 9.9 % ) , liver-related toxicity ( 9.4 % ) , diarrhea ( 8.2 % ) , fatigue ( 2.7 % ) , thrombocytopenia ( 2.5 % ) , and palmar-plantar erythrodysesthesia ( 1.9 % ) were significantly higher in the pazopanib arm . Treatment discontinuation related to adverse events was higher among patients treated with pazopanib ( 33.3 % ) compared with placebo ( 5.6 % ) . CONCLUSION Pazopanib maintenance therapy provided a median improvement of 5.6 months ( HR , 0.77 ) in progression-free survival in patients with advanced ovarian cancer who have not progressed after first-line chemotherapy . Overall survival data to this point did not suggest any benefit . Additional analysis should help to identify subgroups of patients in whom improved efficacy may balance toxicity ( NCT00866697 ) The aim of this study is to evaluate the efficacy of three additional cycles of paclitaxel and platinum chemotherapy in epithelial ovarian cancer patients with clinical complete response ( CR ) . Patients with histologically confirmed epithelial ovarian cancer stages II – IV with clinical CR after primary surgery and six cycles of chemotherapy with paclitaxel/platinum entered into the study . Three cycles of paclitaxel/platinum ( cisplatin , carboplatin ) were administered as a consolidation chemotherapy only in patients who agreed to the informed consent . Patients without further treatment served as controls . A total of 81 patients entered into the study . According to the informed consent , 42 patients were treated by the consolidation chemotherapy , and 39 patients were followed up without further treatment .  The median actuarial disease-free survival for the patients with and without consolidation chemotherapy was 25.0 months and 26.0 months , respectively ( P = 0.80 ) . The median overall survival is not reached . World Health Organization grade 3–4 toxicities in the consolidation arm were increased but showed no significant differences statistically . Although the sample size is small and not r and omized , these results suggest that three cycles of consolidation chemotherapy with paclitaxel/platinum might not provide a favorable outcome in patients with a clinical CR PURPOSE To determine whether continuing paclitaxel for an extended time period in women with advanced ovarian cancer who had achieved a clinical ly defined complete response to a platinum/paclitaxel-based chemotherapy  could prolong subsequent progression-free survival ( PFS ) and affect ultimate survival . PATIENTS AND METHODS Patients were r and omly assigned to either three or 12 cycles of single-agent paclitaxel administered every 28 days and were then followed up for progression-free and overall survival . RESULTS As of September 6 , 2001 , 277 patients ( 262 assessable ) had entered the trial , with a total of 54 PFS events having developed among 222 patients with follow-up data . With the exception of peripheral neuropathy , there were no major differences in toxicity between the regimens . The median PFS was 21 and 28 months in the three-cycle and 12-cycle paclitaxel arms , respectively . One-sided P values from an unadjusted log-rank test and an adjusted Cox model analysis ( for stratification factors ) were.0035 and .0023 , respectively , both in favor of the 12-cycle arm . The Cox model-adjusted three-cycle versus the 12-cycle progression hazard ratio was estimated to be 2.31 ( 99 % confidence interval , 1.08 to 4.94 ) . With a protocol -specified early termination boundary of P = .005 , these findings led the Southwest Oncology Group Data Safety Monitoring Committee to discontinue the trial . As of the date of study closure , there was no difference in overall survival between the treatment arms . CONCLUSION Twelve cycles of single-agent paclitaxel administered to women with advanced ovarian cancer who attain a clinical ly defined complete response to initial platinum/paclitaxel-based chemotherapy significantly prolongs the duration of PFS Five versus ten cycles of cyclophosphamide , doxorubicin , and cisplatin ( CAP ) were compared in advanced ovarian carcinoma by a prospect i ve r and omized study of 78 patients , 41 receiving 5 cycles ( CAP5 ) and 37 receiving 10 cycles ( CAP10 ) of chemotherapy .  Patients were stratified by histologic grade and size of residual disease . Cyclophosphamide , 600 mg/m2 , doxorubicin , 40 mg/m2 , and cisplatin , 100 mg/m2 , were administered every 4 weeks for 5 or 10 cycles . Second-look laparotomy was performed to evaluate response and plan further therapy . CAP5 patients found a second-look laparotomy to have partially responded to chemotherapy were treated with 5 additional cycles of CAP . CAP10 was more toxic than CAP5 with respect to myelosuppression , hospital admissions for nadir fever , median elevation of creatinine , and degree of peripheral neuropathy . Median follow-up is 64 months . CAP5 and CAP10 were equivalent in surgically documented complete responses ( 34 versus 35 % ) and survival ( P = 0.41 ) . Twelve partial responders to CAP5 received additional CAP chemotherapy ; one complete response result ed . We conclude that CAP5 is preferable to CAP10 in treatment of advanced ovarian cancer as it is equally effective and less toxic INTRODUCTION R and omized trials have demonstrated significant improvements in progression-free survival ( PFS ) with consolidation paclitaxel ( P ) and bevacizumab ( B )  following cytoreduction and adjuvant carboplatin/paclitaxel ( CP ) for advanced epithelial ovarian cancer ( EOC ) . We sought to evaluate the cost-effectiveness ( C/E ) of these consolidation strategies . METHODS A decision model was developed based on Gynecologic Oncology Group ( GOG ) protocol s # 178 and # 218 . Arm 1 is 6 cycles of CP . Arm 2 is 6 cycles of CP followed by 12 cycles of P ( CP+P ) . Arm 3 is 1 cycle of CP , 5 cycles of CPB , and 16 cycles of B ( CPB+B ) . Parameters include PFS , overall survival ( OS ) , cost , complications ( neuropathy for P and bowel perforation for B ) , and quality -of-life utility values . Sensitivity analyses were performed . RESULTS The incremental cost-effectiveness ratio ( ICER ) for CT+T is $ 13,402/ quality adjusted life year ( QALY ) gained compared to CP . For CPB+B compared to CP , the ICER is $ 326,530/QALY . When compared simultaneously , CPB+B is dominated , i.e. is more costly and less effective than CP+P. Results were robust to parameter variation . At a willingness to pay threshold of $ 100,000/QALY , CP+P was the preferred option throughout most of the decision space . Sensitivity analyses suggest that CPB+B would become the preferred option if it were to improve OS by 6.1 years over CP+P. CONCLUSIONS In this model , B consolidation for advanced EOC was associated with a modest improvement in effectiveness that is less than that with P consolidation and more costly . A statistically significant improvement in survival may improve the value of B consolidation Two hundred-two patients with FIGO stages III and IV epithelial ovarian cancer were r and omized to 6 or 12 cycles of cyclophosphamide , Adriamycin , and cisplatin ( CAP ) . Patients in complete clinical response underwent a second-look laparotomy , 1 month after cessation of chemotherapy . Patients r and omized to 6 cycles and found to be in partial remission at second-look were to receive a further 6 cycles of CAP .  Rate of complete pathological response was 23 % for 6 cycles of CAP and 25 % for 12 cycles ; the median survival was 23 months for 6 cycles and 27 months for 12 cycles , and 3-year survival was 29 % for 6 cycles and 35 % for 12 cycles . None of these differences were statistically significant . Fifty-four patients r and omized to 6 cycles were found to be in partial surgical remission at second-look laparotomy , and 24 of these patients agreed to a further 6 cycles and a third-look laparotomy . Six of these 24 patients had a complete pathological response at third-look , improving the complete response rate to 28 % in those originally r and omized to 6 cycles . However , 3 of these patients all had macroscopic tumors removed at second-look , and two had microscopic disease at second-look . Among patients achieving complete response mean cumulative doses in the CAP 6 cycle group were approximately 50 % of those in the CAP 12 cycle group . However , when all patients were considered , this difference was only approximately 15 % owing the continuation of chemotherapy in the partial responders of the 6 cycle group and early stopping for chemotherapy in the CAP 12 cycle group due to toxicity or progression . Patients in complete pathological response also showed similar survivals for 6 and 12 cycles . In conclusion , the study did not show a correlation between mean cumulative doses and complete pathological response and survival BACKGROUND There is no clear data on the optimum number of courses of platinum chemotherapy required for treating advanced ovarian cancer . A prospect i ve r and omised trial was performed to compare five with eight courses of either carboplatin 400 mg/m2 or cisplatin 75 mg/m2 given four-weekly to patients with stage IC-IV ovarian cancer . PATIENTS AND METHODS 225 patients were entered into the study and 233 were eligible for r and omisation : 118 to five courses and 115 to eight courses . In each r and omisation , half the patients received carboplatin and half received cisplatin . RESULTS The mean number of courses received on the five arm was 4.74 and on the eight arm , 6.42 , an increase of 35 % . The median survival for all patients was 24 months with the median survival for the 156 patients with stage 3 disease being 21 months . No difference was detected in survival ( P = 0.53 ) or time to progression from initial surgery ( P = 0.29 ) between the two arms of the trial . False-negative calculations based on a multivariate analysis show that the trial currently has 95 % power for excluding a difference of 10 % in favour of the eight course arm at three years . CONCLUSION There is insufficient evidence at the present time to justify more than five courses of first-line single agent platinum chemotherapy in the management of advanced ovarian cancer Objective . The aim of this study is to verify whether consolidation chemotherapy with Cisplatin improves disease-free survival and /or overall survival in patients affected by epithelial ovarian cancer . Methods . A multicenter study examined 122 r and omized patients in complete remission as judged by laparoscopy or laparotomy following first-line chemotherapy consisting of ACy ( Adriamycin + Cyclophosphamide ) , PCy ( Cisplatin + Cyclophosphamide ) , or Mitoxantrone + Carboplatin . Sixty-one of these patients were treated with 3 cycles of 5-Fluorouracil ( FU ) 500 mg/m2 for 5 days followed by Cisplatin at 100 mg/m2 on the 6th or 7th day every 28 days ; the other 61 received no further treatment ( nihil group ) . Results . Sixty patients in the Cisplatin arm were evaluable . There were 36 relapses in the FU+Cisplatin arm and 30 in the nihil arm . Peritoneal relapses were 25 % for Cisplatin treatment vs. 16.4 % for nihil . There were 29 deaths in the Cisplatin arm vs. 27 for nihil . Median overall survival time ( 95 months with Cisplatin vs. 96 months in the nihil group ) and median disease-free survival ( 66 months with Cisplatin vs. 73 in the nihil group ) were similar in both arms ( p=0.66 and p=0.41 , respectively ) . There were no significant differences in tumor stage and grade between the two arms . Seven patients presented a second neoplasm during follow-up : six in the nihil arm , but only one patient in the Cisplatin arm . Death in these patients was due to the second neoplasm and not to progression of ovarian cancer . Conclusion . Three courses of additional platinum+FU treatment after five cycles of first-line chemotherapy without FU produced no increase in overall survival or disease-free survival PURPOSE Topotecan is an active second-line treatment for advanced ovarian cancer . Its efficacy as consolidation treatment after first-line st and ard chemotherapy is unknown . PATIENTS AND METHODS To investigate whether topotecan ( 1.5 mg/m(2 ) on days 1 through 5 , four cycles , every 3 weeks ) prolonged progression-free survival ( PFS ) for patients responding to st and ard carboplatin  ( area under the curve 5 ) and paclitaxel ( 175 mg/m(2 ) administered as a 3-hour infusion in six cycles ; CP ) , a multicenter phase III study was performed with an 80 % power to detect a 50 % prolongation of median PFS . Patients were registered at diagnosis and r and omized after the end of CP . RESULTS Two hundred seventy-three patients were r and omly assigned ( topotecan , n = 137 ; observation , n = 136 ) , with a median age of 56 years . Stage at diagnosis was advanced in three fourths of patients ( stage III in 65 % of patients ; stage IV in 10 % ) ; after primary surgery , 46 % had no residual disease and 20 % were optimally debulked . After CP , 87 % reached a clinical complete response , and 13 % achieved a partial response . Neutropenia ( grade 3/4 in 58 % of the patients ) and thrombocytopenia ( grade 3 in 21 % ; grade 4 in 3 % ) were the most frequent toxicities attributed to topotecan . There was no statistically significant difference in PFS between the arms ( P = .83 ; log-rank test ) : median PFS was 18.2 months in the topotecan arm and 28.4 in the control arm . Hazard ratio of progression for patients receiving topotecan was 1.18 ( 95 % CI , 0.86 to 1.63 ) after adjustment for residual disease , interval debulking surgery , and response to CP . CONCLUSION The present analysis indicates that consolidation with topotecan does not improve PFS for patients with advanced ovarian cancer who respond to initial chemotherapy with carboplatin and paclitaxel OBJECTIVE The safety and efficacy of gemcitabine plus carboplatin ( GC ) or paclitaxel plus carboplatin ( TC ) induction regimens with or without paclitaxel consolidation therapy were assessed in ovarian cancer ( OC ) . METHODS Patients with stage IC-IV OC were r and omized to either GC ( gemcitabine 1,000 mg/m(2 ) , days 1 and 8 , plus carboplatin area under the curve [ AUC ] 5 , day 1 ) or TC ( paclitaxel 175 mg/m(2 ) plus carboplatin AUC 6 , day 1 ) every 21 days for up to six cycles . Patients with complete response ( CR )  were allowed optional consolidation with paclitaxel 135 mg/m(2 ) every 28 days for ≤ 12 months . Patients without CR received single-agent crossover therapy at induction doses/schedules until CR , disease progression ( PD ) , or unacceptable toxicity . PD or death in 636 patients was required to compare induction arms with 80 % statistical power for progression-free survival ( PFS ) , the primary endpoint . RESULTS R and omized induction therapy was received by 820 of 919 patients enrolled ; 352 patients with CR received paclitaxel consolidation whereas 155 patients without CR received single-agent crossover therapy . PFS was similar for GC and TC ( median , 20.0 and 22.2 months , respectively ; P=.199 ) . Despite high censoring rates ( > 52 % ) , overall survival was longer for TC ( median , 57.3 versus 43.8 months for GC ; P=.013 ) . Controlling for patient characteristics including performance status , residual tumor size , and tumor stage , there was no statistical difference in a multivariate analysis ( HR=1.22 ; 95 % CI=0.99 - 1.52 ; P=.067 ) . CONCLUSIONS GC does not improve PFS  over TC as first-line induction chemotherapy in OC . Although  favoring TC , overall survival analyses were limited by the study design and high censoring rates In a prospect i ve r and omized trial , consolidation treatment with radiotherapy or chemotherapy was compared with no treatment in a series of 172 patients with epithelial ovarian carcinoma , FIGO stage III , with complete surgical remission after primary cytoreductive surgery and induction chemotherapy .  In the subgroup with complete surgical and pathologic remission , progression-free survival was significantly ( P = 0.032 ) better in the radiotherapy group ( 56 % at 5 years ) than in the chemotherapy group ( 36 % at 5 years ) and the untreated control group ( 35 % at 5 years ) . Overall survival was also most favorable in the radiotherapy group ( 69 % at 5 years ) . The number of recurrences was lowest in the radiotherapy group . In the subgroup with microscopic residual carcinoma there were no significant differences in survival between the radiotherapy and the chemotherapy-treated patients . Early and late radiation reactions were recorded . Treatment-related side effects were seen most frequently in the radiotherapy group . Late intestinal radiation reactions of a severe type were recorded in 10 % First-line intravenous chemotherapy ( CT ) following debulking surgery is associated with prolonged survival , in particular in patients who achieve a pathological complete remission ( pCR ) at second-look surgery but in whom a high rate of relapses still occurs . Between 1988 and 1997 , 153 patients in pCR following platinum-based intravenous CT were r and omized between four courses of intraperitoneal cisplatin ( P ) ( 90 mg/m2 every 3 weeks ) or observation .  Overall survival ( OS ) was the primary endpoint , while progression-free survival ( PFS ) was a secondary endpoint . This intent-to-treat analysis includes 16 patients who were not eligible and 17 patients who had protocol violations . The two groups were well balanced in terms of age ( median = 55 years ) , performance status ( 78 % P.S. O ) , FIGO stage ( 96 % stage III ) , histology ( serous in 66 % ) , grade ( 2 or 3 in 80 % ) , and residuum before intravenous CT ( > 1 cm in 40 % ) . Intraperitoneal CT was delivered mainly through intraperitoneal catheters ( Port-a-Cath 61 % and Tenckhoff 25 % ) . Side effects of intraperitoneal cisplatin  included vomiting [ ≥ grade 2 ( 82 % ) ] , rise in serum creatinine [ ≥ grade 2 ( 14 % ) ] , abdominal pain [ grade 1–2 ( 38 % ) ] , and neurotoxicity [ grade 2–3 (15%)].After a median follow-up of 8 years , 80 patients ( 52 % ) have progressed with no difference in the pattern of relapse between the two groups and 75 patients ( 49 % ) have died ; the respective hazard ratios for PFS and OS with 95 % CI are 0.89 ( 0.59–1.33 ) and 0.82 ( 0.52–1.29 ) . These results are suggestive of a treatment benefit but do not support a change in clinical practice . Other r and omized clinical trials of intraperitoneal CT are review ed and briefly discussed PURPOSE To assess whether six courses of paclitaxel are effective as consolidation treatment in patients with advanced epithelial ovarian cancer who are in complete response after first-line paclitaxel/platinum-based chemotherapy .  PATIENTS AND METHODS Patients with stages IIb to IV disease in clinical or pathologic complete response after six courses of paclitaxel/platinum-based chemotherapy  were r and omly allocated to either observation ( ie , control ) or six courses of paclitaxel 175 mg/m(2 ) every 3 weeks ( ie , maintenance ) . RESULTS Two hundred patients were r and omly assigned from March 1999 to July 2006 . Because of the low accrual rate , an unplanned interim analysis of futility according to the Bayesian approach was performed . Grade 2 or greater motor neurotoxicity and sensory neurotoxicity were reported in 11.3 % and 28.0 % of the paclitaxel-arm patients , respectively . After a median follow-up of 43.5 months , 107 patients ( 53 % ) had experienced relapse , and 48 patients ( 24 % ) had died . Two-year progression-free survival rates were 54 % ( 95 % CI , 43 % to 64 % ) and 59 % ( 95 % CI , 49 % to 69 % ; P = not significant ) in the control and maintenance arms , respectively . Corresponding 2-year overall survival rates were 90 % ( 95 % CI , 84 % to 97 % ) and 87 % ( 95 % CI , 80 % to 94 % ; P = not significant ) , respectively . The Cox model showed that residual disease after initial surgery ( macroscopic v no macroscopic residuum ; hazard ratio [ HR ] , 1.91 ; 95%CI , 1.21 to 3.03 ) and stage ( IIIc to IV v others ; HR , 3.10 ; 95 % CI , 1.13 to 8.48 ) were independent prognostic factors for progression-free survival , whereas the treatment arm ( maintenance v control ) had no prognostic relevance . CONCLUSION A consolidation treatment with six cycles of paclitaxel does not prolong progression-free survival or overall survival in patients in complete response after first-line paclitaxel/platinum-based regimens OBJECTIVE To compare the recurrence-free interval ( RFI ) and safety profile in patients with completely resected high-risk early-stage ovarian cancer treated with intravenous ( IV ) carboplatin and paclitaxel with or without maintenance low-dose paclitaxel for 24 weeks . METHODS Eligibility was limited to patients with stage IA/B ( grade 3 or clear cell ) , all IC or II epithelial ovarian cancer . All patients were to receive carboplatin AUC 6 and paclitaxel 175 mg/m² q3 weeks × 3 courses with r and om assignment to either observation or maintenance paclitaxel 40 mg/m²/week × 24 weeks . Recurrence required clinical or radiological evidence of new tumor . RESULTS There were 571 patients enrolled onto this study , of whom 29 were deemed ineligible due to inappropriate stage or pathology , leaving 542 patients . At least 3 cycles of treatment were administered to 524/542 ( 97 % ) of patients , and among those assigned to maintenance paclitaxel , 80 % completed the regimen . The incidence of grade 2 or worse peripheral neuropathy ( 15.5 % vs. 6 % ) , infection/fever ( 19.9 % vs. 8.7 % ) , and dermatologic events ( 70.8 % vs. 52.1 % ) was higher on the maintenance regimen ( p<0.001 ) . The cumulative probability of recurring within 5 years for the maintenance paclitaxel regimen is 20 % vs. 23 % for surveillance ( hazard ratio 0.807 ; 95 % CI : 0.565 - 1.15 ) . The probability of surviving 5 years was 85.4 % and 86.2 % , respectively . CONCLUSION Maintenance paclitaxel at 40 mg/m²/week × 24 weeks added to st and ard dose AUC6 and paclitaxel 175 mg/m² × 3 doses provides no significant increase in RFI To compare the effect of epidoxorubicin given for 4 months versus no treatment in the survival of patients with advanced ovarian cancer and complete pathologic response after first-line surgery and chemotherapy with platinum-based schedules , we conducted a multicenter r and omized clinical trial . Patients with histologic diagnosis of epithelial ovarian cancer FIGO stage III or IV at first diagnosis ; complete pathologic response at second-look laparotomy/laparoscopy or complete clinic response ; and those who have had first-line therapy including surgery and one regimen containing cisplatin or carboplatinum were eligible for the study and were r and omly allocated to epidoxorubicin 120 mg/sqm or no treatment . A total of 64 women were allocated to epidoxorubicin and 74 to no treatment . There were 20 and 19 deaths , respectively , in the epidoxorubicin and no-treatment groups . The 3-year percent overall survival was 79.0 % and 78.7 % , respectively , in the no-treatment and epidoxorubicin groups ( log-rank test , P= 0.93 )
BACKGROUND Epithelial ovarian cancer accounts for about 90 % of all cases of ovarian cancer .
Debulking surgery and six courses of platinum-based chemotherapy results in complete clinical remission ( CCR ) in up to 75 % of cases .
However , 75 % of the responders will relapse within a median time of 18 to 28 months and only 20 % to 40 % of women will survive beyond five years .
It has been suggested that maintenance chemotherapy could assist in prolonging remission .
To date , there has not been a systematic review on the impact of maintenance chemotherapy for epithelial ovarian cancer .
OBJECTIVES To assess the effectiveness and toxicity of maintenance chemotherapy for epithelial ovarian cancer and to evaluate the impact on quality of life ( QoL ) .