Neoadjuvant chemotherapy for advanced ovarian cancer: long-term survival. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. Complete cytoreductive surgery is feasible and maximizes survival in patients with advanced epithelial ovarian cancer: a prospective study. Neoadjuvant chemotherapy with carboplatin and docetaxel in advanced ovarian cancer--a prospective multicenter phase II trial (PRIMOVAR). Preliminary results of neoadjuvant chemotherapy with paclitaxel and cisplatin in patients with advanced epithelial ovarian cancer who are inadequate for optimum primary surgery. Sorafenib in combination with carboplatin and paclitaxel as neoadjuvant chemotherapy in patients with advanced ovarian cancer Neoadjuvant chemotherapy in advanced ovarian cancer: On what do we agree and disagree? Clinical outcomes of neoadjuvant chemotherapy and primary debulking surgery in advanced ovarian carcinoma. Which patients benefit most from primary surgery or neoadjuvant chemotherapy in stage IIIC or IV ovarian cancer? An exploratory analysis of the European Organisation for Research and Treatment of Cancer 55971 randomised trial. Phase II evaluation of neoadjuvant chemotherapy and debulking followed by intraperitoneal chemotherapy in women with stage III and IV epithelial ovarian, fallopian tube or primary peritoneal cancer: Southwest Oncology Group Study S0009. A randomized multicenter phase II study on neoadjuvant chemotherapy with carboplatin and docetaxel in advanced ovarian carcinomas (PRIMOVAR). Neoadjuvant (Cytoreductive) Chemotherapy Combined With Intervention Debulking Surgery in Advanced, Unresected Epithelial Ovarian Cancer Neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy in patients with primarily unresectable, advanced-stage ovarian cancer. Erlotinib added to carboplatin and paclitaxel as first-line treatment of ovarian cancer: a phase II study based on surgical reassessment. Five-year results of cyclic semi-high dose neoadjuvant chemotherapy supported by autologous peripheral blood stem-cell transplantation in patients with advanced ovarian cancer Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy as upfront therapy for advanced epithelial ovarian cancer: multi-institutional phase-II trial. Intraperitoneal cisplatin-based chemotherapy vs. intravenous cisplatin-based chemotherapy for stage III optimally cytoreduced epithelial ovarian cancer. Neoadjuvant chemotherapy in advanced ovarian cancer: a case‐control study Differences in Regional Diagnostic Strategies and in Intended Versus Actual First-Line Treatment of Patients With Advanced Ovarian Cancer in Denmark Quality of life in women treated with neoadjuvant chemotherapy for advanced ovarian cancer: a prospective longitudinal study. Evaluation of new platinum-based treatment regimens in advanced-stage ovarian cancer: a Phase III Trial of the Gynecologic Cancer Intergroup. Cost-effective treatment of women with advanced ovarian cancer by cytoreductive surgery and chemotherapy directed by an in vitro assay for drug resistance. Clinically occult recurrent ovarian cancer: patient selection for secondary cytoreductive surgery using combined PET/CT.
PURPOSE The aim of this study was to compare the progression-free and overall survivals of women with advanced ovarian cancer treated with neoadjuvant chemotherapy followed by surgery  with those treated conventionally with cytoreductive surgery followed by cytotoxic chemotherapy . MATERIAL S AND METHODS Fifty-nine consecutive women with advanced malignancies compatible with ovarian cancer based on ( 1 ) physical examinations , ( 2 ) computerized tomography scans , and ( 3 ) cytologic or histologic specimens and treated with platinum-based combination chemotherapy , i.e. , neoadjuvant chemotherapy , were retrospectively review ed . Forty-one subsequently underwent cytoreductive surgery . Their overall and progression-free survivals were compared to those of 206 consecutive women with Stage IIIC and IV epithelial ovarian cancers treated with conventional cytoreductive surgery followed by platinum-based combination chemotherapy during the same era . RESULTS No statistical difference was observed in overall survival ( P = 0.1578 ) or in progression-free survival between the group treated with neoadjuvant chemotherapy and the conventionally treated group ( P = 0.5327 ) despite the neoadjuvant chemotherapy patients being statistically older ( median age 67 years [ range 44 to 85 years ] vs a median age of 60 years [ range 19 to 79 years ] for conventionally treated patients ; P < 0 . 001 ) and having a statistically poorer performance status ( P < 0 . 001 ) than the conventionally treated group . Women undergoing cytoreductive surgery following neoadjuvant chemotherapy had a statistically improved overall survival ( P < 0.0001 ) compared to those who did not undergo surgery . CONCLUSIONS Neoadjuvant chemotherapy does not compromise the survival of women treated for advanced ovarian cancer . Prospect i ve r and omized trials comparing neoadjuvant chemotherapy to conventional therapy to determine quality of life experiences and cost/benefit outcomes are now appropriate for women presenting with advanced ovarian cancer BACKGROUND Primary debulking surgery before initiation of chemotherapy has been the st and ard of care for patients with advanced ovarian cancer . METHODS We r and omly assigned patients with stage IIIC or IV epithelial ovarian carcinoma , fallopian-tube carcinoma , or primary peritoneal carcinoma to primary debulking surgery followed by platinum-based chemotherapy or to neoadjuvant platinum-based chemotherapy followed by debulking surgery ( so-called interval debulking surgery ) . RESULTS Of the 670 patients r and omly assigned to a study treatment , 632 ( 94.3 % ) were eligible and started the treatment . The majority of these patients had extensive stage IIIC or IV disease at primary debulking surgery ( metastatic lesions that were larger than 5 cm in diameter in 74.5 % of patients and larger than 10 cm in 61.6 % ) . The largest residual tumor was 1 cm or less in diameter in 41.6 % of patients after primary debulking and in 80.6 % of patients after interval debulking . Postoperative rates of adverse effects and mortality tended to be higher after primary debulking than after interval debulking . The hazard ratio for death ( intention-to-treat analysis ) in the group assigned to neoadjuvant chemotherapy followed by interval debulking , as compared with the group assigned to primary debulking surgery followed by chemotherapy , was 0.98 ( 90 % confidence interval [ CI ] , 0.84 to 1.13 ; P=0.01 for noninferiority ) , and the hazard ratio for progressive disease was 1.01 ( 90 % CI , 0.89 to 1.15 ) . Complete resection of all macroscopic disease ( at primary or interval surgery ) was the strongest independent variable in predicting overall survival . CONCLUSIONS Neoadjuvant chemotherapy followed by interval debulking surgery was not inferior to primary debulking surgery followed by chemotherapy as a treatment option for patients with bulky stage IIIC or IV ovarian carcinoma in this study . Complete resection of all macroscopic disease , whether performed as primary treatment or after neoadjuvant chemotherapy , remains the objective whenever cytoreductive surgery is performed . ( Funded by the National Cancer Institute ; Clinical Trials.gov number , NCT00003636 . OBJECTIVE Despite correlation between the completeness of surgical cytoreduction and survival for patients with advanced ovarian cancer , relatively few undergo complete cytoreduction . This study was initiated to prospect ively determine the ability to surgically eliminate all visible disease in patients with stage IIIC and IV epithelial ovarian cancer and the associated impact on survival . METHODS Between 1990 and 1996 , 163 consecutive patients underwent primary cytoreduction .  The goal was the excision or ablation of all visible disease prior to initiation of systemic platinum-based combination chemotherapy . A multivariate analysis determined which clinical and pathologic variables influenced the probability of achieving complete cytoreduction ( logistic regression ) and survival ( Cox proportional hazards model ) . RESULTS One hundred thirty-nine patients ( 85.3 % ) underwent removal of all visible tumor , 22 ( 13.5 % ) had cytoreduction to < /=1 cm residual disease , and 2 ( 1.2 % ) had unresected bulky disease . The median and estimated 5-year survival for the entire cohort was 54 months and 48 % , respectively . The probability of achieving complete cytoreduction was influenced independently by the preoperative Gynecologic Oncology Group performance status ( 0 - 1 vs 2 - 3 , P = 0.04 ) , the number of mesenteric and intestinal serosal implants ( < /=75 vs > 75 implants , P = 0.005 ) , and stage ( IIIC vs IV , P = 0.006 ) . The probability of survival was independently influenced by age ( < /=61 vs > 61 years , P = 0.003 ) , volume of ascites ( < /=1 vs > 1 liter , P = 0.01 ) , stage ( IIIC vs IV , P = 0.04 ) , histology ( clear cell and mucinous vs all other , P = 0.03 ) , and the completeness of cytoreductive operation ( complete vs incomplete cytoreduction , P = 0.02 ) . CONCLUSIONS Complete cytoreduction is possible for the majority of patients and improves survival , even compared to operations with minimal ( < /=1 cm ) residual disease . Unless their medical condition prohibits anesthesia and surgery , patients with advanced epithelial ovarian cancer should undergo primary cytoreductive surgery with the intention of complete tumor removal Early response criteria and surgical outcome were evaluated in patients with advanced epithelial ovarian cancer treated with neoadjuvant chemotherapy . Patients with FIGO stage IIIC or IV ovarian cancer and an ascites volume of > or=500 ml were r and omly assigned to receive preoperatively 3 ( A1 ) or 2 ( A2 ) of 6 cycles of carboplatin and docetaxel intravenously . Response was monitored by measuring target lesions , ascites volumes and serum CA 125 levels . The primary outcome measure was the preoperative reduction of ascites volume . Secondary outcome measures were the evaluation of residual tumor and perioperative morbidity and mortality .  Eighty-three patients underwent cytoreductive surgery , 40 after 3 cycles and 43 patients after 2 cycles of neoadjuvant chemotherapy .  ' Optimal debulking ' ( < or=1 cm ) was achieved in 30 ( A1 ) and 32 patients ( A2 ) . Eight ( A1 ) and 6 patients ( A2 ) had a persistent ascites volume > or=500 ml . A decrease of the CA 125 level from baseline of less than 50 % was observed in 7 ( A1 ) and 9 patients ( A2 ) . Computed tomography scan results showed progressive disease in 6 patients ( 3 A1 ; 3 A2 ) . Any amount of residual disease after cytoreductive surgery , persistent ascites , and a less pronounced decrease of CA 125 were associated with poor progression-free survival rates . In conclusion , ascites volume reduction and CA 125 decline appear to be appropriate response criteria . A treatment schedule with two preoperative cycles is a reasonable option for neoadjuvant chemotherapy in advanced ovarian cancer . High surgical st and ards are m and atory , even after neoadjuvant chemotherapy AIM This study was performed to evaluate the efficacy of neoadjuvant chemotherapy ( NAC ) with paclitaxel and cisplatin in patients with advanced epithelial ovarian cancer who were inadequate for primary optimal surgery . METHODS Patients with histologically confirmed epithelial ovarian cancer at International Federation of Gynecology and Obstetrics stages IIIc/IV that was unresectable according to computed tomography findings were eligible for this study . Three cycles of paclitaxel plus cisplatin NAC were administered and the response was evaluated . Patients were then selected for interval debulking surgery or three cycles of additional chemotherapy with the same regimen according to the resectability and response . Interval debulking surgery followed by second-line chemotherapy was applied to patients with no response to NAC . During the same period , patients who did not agree to the protocol were treated by the conventional method of tumor debulking surgery followed by adjuvant chemotherapy , and served as the control group . A comparison of both groups of patients was carried out . RESULTS A total of 40 patients were involved in the study . All patients were evaluable . Eighteen patients underwent NAC and 22 patients were treated by conventional therapy .  Optimal debulking was possible in 14 patients ( 77.8 % ) in the NAC group and in 10 patients ( 45.5 % ) in the conventional therapy group ( P = 0.04 ) . The mean estimated blood loss was 620 cc ( range : 300 - 1500 cc ) in the NAC group and 1061 cc ( range : 300 - 3500 cc ) in the conventional therapy group ( P = 0.04 ) . However , no significant differences were found in the disease-free and overall survival rates between the two groups ( P = 0.48 and P = 0.61 , respectively ) . CONCLUSION NAC provided a higher rate of optimum cytoreduction and equivalent survival with less invasive surgery and reduced morbidity compared with conventional therapy in patients with advanced epithelial ovarian cancer inadequate for primary optimum surgery . Therefore , NAC may be a valuable alternative treatment for these patients Purpose Sorafenib is a novel oral anticancer agent targeting signal transduction and angiogenic pathways through inhibitory effects against MAP kinases and vascular endothelial growth factor receptor-2 . The objectives of this neoadjuvant phase II-trial in patients with advanced epithelial ovarian cancer were to assess the activity and tolerability of the combination therapy of carboplatin/paclitaxel with multi-target tyrosine kinase inhibitor sorafenib . Material s and methods Patients with histologically proven stage IIIC or IV disease and large volume ascites were eligible . Enrolled patients received 2 of 6 cycles carboplatin ( area under the curve 5 ) and paclitaxel ( 175 mg/m2 ) preoperatively and concomitant sorafenib 400 mg twice daily . After four cycles of postoperative chemotherapy , a maintenance phase of single agent oral sorafenib through 1 year was planned . This phase II- study was planned with a sample size of 102 patients and progression-free survival as primary study endpoint . Results Four patients were enrolled . After preoperative treatment and cytoreductive surgery , all patients were excluded from protocol due to severe toxicities . Three patients had life threatening events ( cardiac output failure , myocardial infa rct ion , anastomotic leak ) ; two patients had primary progressive disease . The study was terminated on the basis of the recommendation of an independent data safety monitoring board . Conclusion The addition of sorafenib to carboplatin/paclitaxel chemotherapy was not feasible within this neoadjuvant regimen in primary advanced ovarian cancer . Although the occurrence of serious adverse events might have emerged at r and om , a detrimental effect of preoperative study medication could not be denied . Further evaluations of sorafenib in ovarian cancer are warranted Following the recent publication of the r and omized study in stages IIIC and IV ovarian cancer of the European Organisation for Treatment and Research —Gynaecological Cancer Group ( EORTC-GCG ) and the National Cancer Institute of Canada ( NCIC ) Clinical Trials Group [ 1 ] , a lot of controversy on the role of neoadjuvant chemotherapy and primary debulking in advanced ovarian cancer emerged [ 2–5 ] . At the recent Gynecologic Cancer InterGroup ( GCIG ) consensus conference a majority of 21 out of 23 member groups supported the statement : “ Delayed primary surgery after neoadjuvant chemotherapy is an option for selected patients with stage IIIC or IV ovarian cancer as included in the EORTC55971 ” [ 6 ] . However , two member groups ( the Arbeitsgemeinschaft Gynaekologische Onkologie [ AGO ] Study Group Germany and the AGO-Austria ) voted for the minority statement “ Neoadjuvant chemotherapy can not be regarded as adequate routine therapy of advanced ovarian cancer and should be limited to selected patients with very advanced International Federation ofGynecology and Obstetrics stage IIIC or IV disease and contraindications against upfront debulking surgery or tumor dissemination , implying no chance for complete resection . ” The latter was also the official statement of the German Society of Gynecologic Oncology [ 7 ] . The authors discussed the role of neoadjuvant chemotherapy in advanced ovarian cancer on many conferences . However , the authors believe it is important to summarize in this paper in which groups of patients we agree that primary debulking should be the preferred treatment strategy and in which patients will probably not benefit from upfront surgery and alternative strategies as neoadjuvant chemotherapy followed by interval debulking should be preferred . Furthermore , we summarize in which groups of patients with advanced ovarian cancer we disagree on the preferred treatment policy . The opinions expressed in this paper are solely the opinion of the authors and not of the Cooperative groups or Societies the authors are member of BACKGROUND Primary debulking surgery ( PDS ) and paclitaxel-platinum chemotherapy remains the mainstay of treatment for advanced ovarian cancer . However , there is considerable morbidity and even mortality associated with this approach . The concept of primary chemotherapy followed by interval debulking surgery ( IDS ) has emerged for advanced stage disease with the aim of improving sensitivity to chemotherapy and improving survival . The purpose of our study was to examine the impact of IDS on clinical outcomes of patients considered unsuitable for PDS  and compare them with outcomes of women that had conventional PDS  followed by chemotherapy . PATIENTS AND METHODS A non-r and omised prospect i ve cohort study of 35 patients who underwent IDS and 29 patients treated with PDS were included . All patients had Stage IIIC or IV disease . The IDS patients were considered unresectable based on an initial laparoscopy or preoperative computed tomography findings . All patients were treated by the same lead surgeons and received the same regimen of chemotherapy . RESULTS The median intraoperative blood loss , the incidence of pelvic lymphadenectomies , the median hospital stay and the possibility of admission to the Intensive Care Unit were significantly less in the IDS group . Optimal cytoreduction was higher in the IDS compared to the PDS group , but did not reach statistical significance . CONCLUSIONS IDS for advanced ovarian cancer may be associated with less morbidity compared to PDS and appears to require less use of hospital re sources . If the ongoing r and omised studies confirm that IDS does not adversely affect the long-term survival of these patients , morbidity related to ovarian cancer surgery may evolve as a crucial factor for choosing treatment options BACKGROUND To investigate whether biomarkers consisting of baseline characteristics of advanced stage ovarian cancer patients can help in identifying subgroups of patients who would benefit more  from primary surgery or neoadjuvant chemotherapy . METHODS We used data of the European Organisation for Research and Treatment of Cancer ( EORTC ) 55971 trial in which 670 patients were r and omly assigned to primary surgery or neoadjuvant chemotherapy .  The primary outcome was overall survival . Ten baseline clinical and pathological characteristics were selected as potential biomarkers . Using Sub population Treatment Effect Pattern Plots ( STEPP ) , biomarkers with a statistically significant qualitative additive interaction with treatment were considered as potentially informative for treatment selection . We also combined selected biomarkers to form a multimarker treatment selection rule . FINDINGS The size of the largest metastatic tumour and clinical stage were significantly associated with the magnitude of the benefit from treatment , in terms of five-year survival ( p for interaction : 0.008 and 0.016 , respectively ) . Stage IIIC patients with metastatic tumours ⩽45 mm benefited more from primary surgery while stage IV patients with metastatic tumours > 45 mm benefited more from neoadjuvant chemotherapy . In stage IIIC patients with larger metastatic tumours and in stage IV patients with less extensive metastatic tumours both treatments were equally effective . We estimated that by selecting treatments for patients based on largest metastatic tumour and clinical stage , the potential five-year survival rate in the population of treated patients would be 27.3 % ( 95 % confidence interval ( CI ) 21.9 - 33.0 ) , 7.8 % higher than if all were treated with primary surgery , and 5.6 % higher if all were treated with neoadjuvant chemotherapy . INTERPRETATION Although survival was comparable after primary surgery and neoadjuvant chemotherapy in the overall group of patients with ovarian cancer in the EORTC 55971 trial , we found in this exploratory analysis that patients with stage IIIC and less extensive metastatic tumours had higher survival with primary surgery , while patients with stage IV disease and large metastatic tumours had higher  survival with neoadjuvant chemotherapy . For patients who did not meet these criteria , both treatment options led to comparable survival rates OBJECTIVE Intraperitoneal ( IP ) chemotherapy prolongs survival in optimally reduced ovarian cancer patients . For patients in whom optimal debulking can not be achieved , one could incorporate IP therapy post-operatively if the cancer was optimally debulked following neoadjuvant chemotherapy . We sought to evaluate overall survival ( OS ) , progression-free survival ( PFS ) , percent of patients optimally debulked and toxicity in patients treated with this strategy . METHODS Women with adenocarcinoma by biopsy or cytology with stage III/IV ( pleural effusions only ) epithelial ovarian , fallopian tube or primary peritoneal carcinoma that presented with bulky disease were treated with neoadjuvant intravenous ( IV ) paclitaxel 175 mg/m2 and carboplatin AUC 6 q 21 daysx3 cycles followed by surgery ( if > /=50 % decrease in CA125 ) . If optimally debulked they received IV paclitaxel 175 mg/m2 and IP carboplatin AUC 5 ( day 1 ) and IP paclitaxel 60 mg/m2 ( day 8) q 28 daysx6 cycles . RESULTS Sixty-two patients were registered . Four were ineligible . Fifty-six were evaluated for neoadjuvant chemotherapy toxicities . One patient died of pneumonia . Five patients had grade 4 toxicity , including neutropenia ( 3 ) , anemia , leukopenia , anorexia , fatigue , muscle weakness , respiratory infection , and cardiac ischemia . Thirty-six patients had debulking surgery . Two had grade 4 hemorrhage . Twenty-six patients received post-cytoreduction chemotherapy . Four had grade 4 neutropenia . At a median follow-up of 21 months , median PFS is 21 months and median OS is 32 months for all 58 patients . PFS and OS for the 26 patients who received IV/IP chemotherapy is 29 and 34 months respectively . CONCLUSIONS These results compare favorably with other studies of sub-optimally debulked patients 15025 Background : In the past years the concept of neoadjuvant chemotherapy and interval laparotomy has emerged for patients with advanced ovarian cancer and unfavorable prognosis ( e.g. diffuse peritoneal carcinosis ) . In a recent study on neoadjuvant chemotherapy higher tumor resection rates and longer median survival were demonstrated in patients with advanced ovarian carcinoma and ascites > 500ml . Most studies use three cycles of preoperative chemotherapy . However , chemoresistant tumorclones may be induced by increasing number of preoperative chemotherapy cycles . The purpose of this study is to evaluate the optimal number of cycles prior to interval laparotomy . METHODS 67/73 patients with advanced serous ovarian carcinoma ( FIGO IIIc n = 48 , FIGO IV n = 19 ) and ascites > 500ml were r and omized into two arms , receiving either 2 ( n = 33 ) or 3 ( n = 34 ) cycles of Carboplatin ( AUC5 ) and Docetaxel ( 75mg/m2 ) before interval laparotomy . Postoperatively , they received either 4 or 3 additional cycles . Response rate and postoperative residual tumor were evaluated . RESULTS Surgical response was assessed during interval laparotomy . At present 32 patients underwent tumordebulking . Partial remission was observed in 28/32 patients irrespective of the number of preoperative chemotherapy cycles . Two patients in each arm showed stable disease . Optimal cytoreduction was achieved in 25/32 patients . No severe adverse events were reported . Six of 73 patients were not eligible . Two patients were excluded due to therapy-unrelated events . In 4 patients ovarian cancer was excluded by laparoscopy prior to neoadjuvant chemotherapy . CONCLUSIONS Neoadjuvant chemotherapy followed by interval laparotomy was safe and well tolerated . Diagnostic laparoscopy prior to neoadjuvant chemotherapy allowed differentiation of primary ovarian cancers from tumors of other origin . In these cases laparotomy could be circumvented . Optimal tumor reduction was achieved in a significant number of patients . Response rate and postoperative residual tumor were essentially the same in both arms . Our data indicate that two cycles of preoperative chemotherapy may be the preferential choice of therapy for future studies . No significant financial relationships to disclose Thirty-six patients with epithelial ovarian cancer , incompletely resected at primary laparotomy , were treated with one of two intensive cis-platinum-based combination chemotherapy regimens . The intention was to perform further surgical debulking ( intervention debulking surgery ) after three cycles in patients responding to treatment . Intervention debulking surgery was carried Out in 28 of 36 patients ( 78 % ) at a median interval of 12.7 weeks from primary diagnosis .  Omentectomy and total abdominal hysterectomy were the most commonly performed procedures at intervention debulking . As a result of such surgery , 16 of the 28 women ( 57 % ) were left with no macroscopic residual disease , five ( 18 % ) had less than 1 cm , four ( 14 % ) less than 2 cm residuum , and three ( 11 % ) remained with more extensive disease . Post-intervention debulking surgical complications were few , with a median postoperative hospital stay of 10 days and a median interval of 21 days from debulking surgery to resumption of chemotherapy . Neoadjuvant ( cytoreductive ) chemotherapy combined with early secondary surgical debulking is feasible , with little severe morbidity , and can leave a high proportion of patients free of macroscopic disease . The effect of such a program on patient survival is now being tested in a r and omized OBJECTIVE The aim of this review is to report our experience and the feasibility of neoadjuvant chemotherapy in patients with advanced-stage ovarian cancer . METHODS Forty-five patients with primarily unresectable advanced-stage epithelial ovarian cancer were treated in our center between 1995 and 2002 by platinum-based neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy . Their files were review ed retrospectively . RESULTS At the end of neoadjuvant chemotherapy , according to RECIST criteria , 1 patient ( 2.2 % ) had achieved a clinical complete response ( CR ) , 33 ( 73.4 % ) a partial response ( PR ) , and 8 ( 17.8 % ) had stable disease ( SD ) . Only 3 ( 6.6 % ) patients showed disease progression ( PD ) . Surgery was performed in patients with objective response or SD after a median number of 4 courses ( range : 2 - 6 ) of induction chemotherapy . A complete macroscopic debulking was achieved in 24 ( 53.3 % ) out of 39 patients in whom cytoreductive surgery was performed . For the entire group , median overall survival was 29 months . Survival was significantly improved in patients with optimal debulking compared to patients with persistent tumor after surgery : 41 months versus 23 months ( P = 0.0062 ) . Median survival for patients responding to neoadjuvant chemotherapy ( CR and PR ) was 44 months compared to 27 months for patients with SD or PD after initial chemotherapy ( P = 0.01 ) . Neither treatment-related deaths nor significant toxicities were observed . CONCLUSION Neoadjuvant chemotherapy followed by optimal debulking may be a safe and valuable treatment alternative in patients with primarily unresectable advanced-stage bulky ovarian cancer . Patients with an objective response to chemotherapy or absence of macroscopic residual tumor after surgery have a better outcome . This approach is currently being tested in large , prospect i ve r and omized clinical trials BACKGROUND The purpose of this study was to determine whether adding the anti-epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor erlotinib to carboplatin/paclitaxel  improved pathologic complete response ( pCR ) at re assessment surgery in epithelial ovarian , fallopian tube , or primary peritoneal cancers ( OFPC ) . METHODS Patients with stage III-IV OFPC initiated treatment within 12 weeks of initial cytoreductive surgery or , after histologic confirmation of diagnosis , neoadjuvantly . Treatment included paclitaxel ( 175 mg/m² ) and carboplatin ( AUC 6 ) every 3 weeks for up to 6 cycles , plus oral erlotinib 150 mg daily . The primary objective was to determine whether the pCR rate at re assessment surgery was at least 60 % after optimal cytoreduction at initial surgery ( < 1 cm residual disease ) , or at least 40 % after suboptimal cytoreduction ( at least 1 cm residual disease ) using a two-stage design ( alpha=0.10 , beta=0.10 ) . RESULTS The study population included 56 patients with stage III-IV OFPC . EGFR gene amplification was present in 15 % of the 20 tumors evaluated . Twenty-eight patients had protocol therapy after optimal cytoreduction ( stratum I ) , 23 had protocol therapy either after suboptimal cytoreduction ( stratum II ) , and 5 received neoadjuvant therapy prior to cytoreduction ( stratum III ) . Pathologic CR was confirmed in 8 patients ( 29 % ; 95 % confidence intervals 13 % , 49 % ) in stratum I and 3 patients ( 11 % , 95 % C.I. 2 % , 28 % ) in stratum II , which did not meet the prespecified efficacy endpoint in either stratum . CONCLUSIONS Among unselected patients , erlotinib plus carboplatin-paclitaxel did not improve pCR rates compared with historical experience with carboplatin-paclitaxel alone in patients with stage III-IV OFPC Background To achieve anti-ovarian tumor responses similar to those obtained with high-dose chemotherapy but with milder side effects , we developed a treatment protocol in which semi-high dose multi-cycle neoadjuvant chemotherapy was supported by autologous peripheral blood stem-cell transplantation ( auto-PBSCT ) . Methods Seventeen patients with advanced ovarian cancer were enrolled in this study . Two cycles of semi-high dose neoadjuvant chemotherapy , using carboplatin ( AUC , 8.75 ; average dose , 621 mg/m2 ) and etoposide ( average dose , 960 mg/m2 ) were supported by auto-PBSCT and followed by cytoreductive surgery and further chemotherapy . Each patient was followed for at least 5 years . Results This treatment schedule achieved an overall response rate of 70.6 % in 17 patients with stage III or stage IV ovarian cancer .  The 5-year disease-free survival rate was 52.9 % ( 95 % confidence interval , 29.2%–76.6 % ) and the median survival time was 63 months ( 95 % confidence interval , 16–79 months ) . Thus , we obtained superior treatment outcomes in these 17 patients in comparison with published conventional protocol s. Conclusion Cyclic semi-high dose neoadjuvant chemotherapy supported by auto-PBSCT may be tolerable and favorable for patients with advanced ovarian cancer OBJECTIVE The primary end-point of this multi-institutional phase-II trial was to assess results in terms of overall survival after cytoreductive surgery ( CRS ) and hyperthermic intraperitoneal chemotherapy ( HIPEC ) in treatment-naive epithelial ovarian cancer ( EOC ) with advanced peritoneal involvement . Secondary end-points were treatment morbi-mortality and outcome effects of time to subsequent adjuvant systemic chemotherapy ( TTC ) . METHODS Twenty-six women with stage III-IV EOC were prospect ively enrolled in 4 Italian centers to undergo CRS and closed-abdomen HIPEC with cisplatin and doxorubicin . Then they received systemic chemotherapy with carboplatin ( AUC 6 ) and paclitaxel ( 175 mg/m(2 ) ) for 6 cycles . RESULTS Macroscopically complete cytoreduction was achieved in 15 patients ; only minimal residual disease ( ≤2.5 mm ) remained in 11 . Major complications occurred in four patients and postoperative death in one . After a median follow-up of 25 months , 5-year overall survival was 60.7 % and 5-year progression-free survival 15.2 % ( median 30 months ) . Excluding operative death , all the patients underwent systemic chemotherapy at a median of 46 days from combined treatment ( range : 29 - 75 ) . The median number of cycles per patient was 6 ( range : 1 - 8 ) . The time to chemotherapy did not affect the OS or PFS . CONCLUSIONS In selected patients with advanced stage EOC , upfront CRS and HIPEC provided promising results in terms of outcome . Morbidity was comparable to aggressive cytoreduction without HIPEC  . Postoperative recovery delayed the initiation of adjuvant systemic chemotherapy but not sufficiently to impact negatively on survival . These data warrant further evaluation in a r and omized clinical trial OBJECTIVE To compare the survival between intraperitoneal cisplatin-based chemotherapy ( IPCT ) and intravenous cisplatin-based chemotherapy ( IVCT ) in stage III epithelial ovarian cancer with minimal residual disease ( < 1 cm ) after primary debulking surgery . METHOD One hundred and thirty-two patients with stage III epithelial ovarian cancer after optimal primary debulking surgery with minimal residual disease between April 1990 and March 1995 were entered into a r and omized clinical trial in which IPCT or IVCT was administered at 3-week intervals . Patients in the IPCT arm received cisplatin-based ( 100 mg/m(2 ) ) intraperitoneal chemotherapy . Patients in the IVCT arm received cisplatin-based ( 50 mg/m(2 ) ) intravenous chemotherapy . The tumor response was assessed every 3 months . The hematological toxicity using the South West Oncology Group ( SWOG ) toxicity criteria was assessed . Catheter complications associated with intraperitoneal chemotherapy were also analyzed . RESULT The estimated median survival in the IPCT group was 43 months ( 95 % confidence interval , 34 - 54 ) and IVCT group was 48 months ( 95 % confidence interval , 37 - 59 ) . The hazard ratio of death was not statistically significant between IPCT and IVCT ( hazard ratio , 1.13 ; 95 % CI , 0.69 - 1.86 ; P=0.317 ) . The frequencies of hematological toxic effects were significantly lower in the IPCT group than in the IVCT group . CONCLUSION Intravenous and intraperitoneal chemotherapy are associated with equivalent survival in patients with minimal residual stage III epithelial ovarian cancer after optimal cytoreductive surgery The aim of this study was to compare the outcome of patients with advanced ovarian carcinoma treated with neoadjuvant chemotherapy ( NACT )  with those treated conventionally with primary debulking surgery . From 1994 to 2003 , all consecutive cases of advanced-stage epithelial ovarian carcinoma treated with NACT at the University of Bari were identified . A well-balanced group of women who underwent primary debulking surgery followed by platinum-based chemotherapy was selected as controls .  Kaplan – Meier and Cox proportional hazards analyses were used to determine the predictors for survival . Thirty women with advanced-stage epithelial ovarian carcinoma were treated with NACT and compared to 30 patients who underwent primary debulking surgery .  Patients in the NACT were significantly older and had a poorer performance status compared to the controls . However , no statistical difference was observed in overall disease-specific survival ( P = 0.66 ) and disease-free survival ( P = 0.25 ) between the two groups . Although patients in the NACT group are significantly older and have a poorer performance status , this treatment modality does not compromise survival . Prospect i ve r and omized trials comparing NACT to conventional treatment to determine the quality of life and cost/benefit outcomes are now appropriate for women presenting advanced epithelial ovarian cancer Background Triage of patients with ovarian cancer to primary debulking surgery ( PDS ) or neoadjuvant chemotherapy ( NACT )  is challenging . In Denmark , the use of NACT has increased , but substantial differences in the use of NACT or PDS exist among centers . We aim ed to characterize the differences between intended and actual first-line treatments in addition to the differences in the triage process among the centers and to evaluate the different diagnostic modalities and the clinical aspects ’ influence in the triage process . Material s and Methods From 4 centers , forms containing data about the diagnostic process and intended treatment were prospect ively collected and merged with data from the Danish Gynecological Cancer Data base and medical records . Results Of the 671 completed forms , 540 patients had stage IIIC or IV epithelial ovarian cancer . Of the 238 ( 44 % ) referred to PDS  , 91 % received PDS and 4 % never had debulking surgery . Of the 288 patients ( 53 % ) referred to NACT  , 44 % were never debulked . Fourteen patients ( 3 % ) were referred to palliative treatment . The use of different imaging modalities , diagnostic laparoscopy , and laparotomy varied significantly among the centers . Diagnostic surgical procedures were considered to be most influential in the triage process . Regardless of the intended first-line treatment or center , the tumor size and dissemination was the most influential clinical aspect . Conclusions In Denmark , substantial differences exist between intended and actual first-line treatments as well as in the diagnostic process and use of NACT , calling for further discussion on diagnostic strategy and therapeutically approach for patients with advanced ovarian cancer OBJECTIVE The purpose was to examine the outcomes of patients with advanced ovarian cancer treated with neoadjuvant chemotherapy  , with a special emphasis on the patients '  quality of life ( QOL ) . METHODS Seventeen patients with advanced ovarian cancer were treated with neoadjuvant chemotherapy based on the extent of disease on computer tomography . All patients received combined platinum/paclitaxel chemotherapy . Debulking surgery was performed after three cycles or six cycles of chemotherapy , depending on the response to the chemotherapy . Patients ' QOL was studied over time using European Organization for Research and Treatment of Cancer Quality of Life Question naire C30 and was then compared with that of patients treated with conventional treatment in the previous cohort . RESULTS The response rate to chemotherapy assessed at three cycles was 82.4 % . The rate of optimum debulking to residual disease less than 2 cm after chemotherapy was 76.9 % , and 38.5 % had no gross residual disease after surgery . The median overall survival was 22.9 months . The median disease-free interval was 13.3 months . The overall QOL improved after chemotherapy and this continued to improve up to 12 months . The other functional scales also showed improvements over time , apart from the initial transient deterioration in the role functioning and cognitive functioning at 3 months after chemotherapy . Patients treated with neoadjuvant chemotherapy seem to have better but statistically insignificant difference in QOL parameters than patients treated conventionally . CONCLUSION Neoadjuvant chemotherapy is an alternative treatment for patients with advanced ovarian cancer in whom the chance of optimal cytoreduction is low . The patients ' overall quality of life and functional status improve after neoadjuvant chemotherapy PURPOSE To determine if incorporation of an additional cytotoxic agent improves overall survival ( OS ) and progression-free survival ( PFS ) for women with advanced-stage epithelial ovarian carcinoma ( EOC ) and primary peritoneal carcinoma who receive carboplatin and paclitaxel .  PATIENTS AND METHODS Women with stages III to IV disease were stratified by coordinating center , maximal diameter of residual tumor , and intent for interval cytoreduction and were then r and omly assigned among five arms that incorporated gemcitabine , methoxypolyethylene glycosylated liposomal doxorubicin , or topotecan compared with carboplatin and paclitaxel . The primary end point was OS and was determined by pairwise comparison to the reference arm , with a 90 % chance of detecting a true hazard ratio of 1.33 that limited type I error to 5 % ( two-tail ) for the four comparisons . RESULTS Accrual exceeded 1,200 patients per year . An event-triggered interim analysis occurred after 272 events on the reference arm , and the study closed with 4,312 women enrolled . Arms were well balanced for demographic and prognostic factors , and 79 % of patients completed eight cycles of therapy . There were no improvements in either PFS or OS associated with any experimental regimen . Survival analyses of groups defined by size of residual disease also failed to show experimental benefit in any subgroup . CONCLUSION Compared with st and ard paclitaxel and carboplatin , addition of a third cytotoxic agent provided no benefit in PFS or OS after optimal or suboptimal cytoreduction . Dual-stage , multiarm , phase III trials can efficiently evaluate multiple experimental regimens against a single reference arm . The development of new interventions beyond surgery and conventional platinum-based chemotherapy is required to additionally improve outcomes for women with advanced EOC PURPOSE Epithelial ovarian cancer is the fourth leading cause of cancer-related death in women .  Five-year survival is about 25 % , and new approaches to the treatment of this disease are dearly warranted . This study was design ed to determine the feasibility of using an in vitro assay for drug resistance to guide treatment after cytoreductive surgery . We present preliminary results of this study after a median follow-up of 24 months . MATERIAL S AND METHODS We treated 66 patients with advanced ovarian cancer by use of a combination of cytoreductive surgery and chemotherapy . Patient inclusion criteria included histologic confirmation of epithelial ovarian cancer , International Federation of Gynecology and Obstectrics ( FIGO ) stage III , no prior chemotherapy or radiation therapy , no coexisting neoplasm , and optimal residual disease ( < 2 cm ) . Malignant tissue from the involved ovary of each patient was tested in vitro for drug resistance , and chemotherapy was directed individually by assay results . On the basis of the assay we treated 19 patients with platinum/paclitaxel ( TP ) and 47 with platinum/cyclophosphamide ( CP ) .  RESULTS Three-year survival ( Kaplan-Meier estimate ) was 69 % ; the 95 % confidence interval was 58 % to 80 % . There was no difference in 3-year survival between the 19 patients treated with TP ( 66 % ) and the 47 patients treated with CP ( 74 % ) . The cost-effectiveness of each treatment option was determined . It cost $ 4615 to achieve 3-year survival for patients receiving CP and $ 17,988 to obtain a similar survival with TP . The cost-effectiveness of assay-directed therapy was $ 9768 . DISCUSSION Because of the high recurrence rate and the poor long-term survival of women with advanced ovarian cancer , improved therapies for this disease are needed . After surgical debulking , we used results of an in vitro assay for drug resistance to individually select chemotherapy for the patients in this study . Although the 3-year survival of 69 % obtained in the present study appears good compared with previously published studies of optimally debulked patients , the results must be viewed with caution . Patients were not r and omized , and differences in prognostic factors , such as tumor grade , patient age , and performance status , could account in part for the higher survival found in the current study compared with previously published studies . Treatment with either CP or TP result ed in equivalent 3-year survival . The cost to achieve 3-year survival with this protocol , including the cost of the drug resistance assay , was $ 9768 . We believe that consideration of costs avoided by the elimination of ineffective treatments , needless toxicity , and loss of quality of life would likely increase the cost-effectiveness of assay-directed therapy compared with conventional therapy . This study demonstrates that it is feasible to use an in vitro assay in routine clinical practice to eliminate ineffective chemotherapeutic agents OBJECTIVE The aim of this study was to evaluate the utility of combined positron emission tomography/computed tomography ( PET/CT ) for identifying ovarian cancer tumor masses > or = 1 cm in patients with clinical ly occult recurrent disease by conventional CT imaging .  METHODS Twenty-two patients with epithelial ovarian cancer , rising serum CA125 levels , and negative or equivocal conventional CT imaging > or = 6 months after primary therapy underwent combined PET/CT imaging followed by surgical re assessment .  Fisher 's exact test was used to measure the ability of PET/CT to predict macroscopic disease > or = 1 cm . RESULTS The median patient age was 55 years , and 91 % of patients had FIGO Stage IIIC/IV disease . The median increase in serum CA125 was 24 U/ml ( range 10 to 330 U/ml ) . Conventional CT was reported as negative ( n = 15 ) or equivocal ( n = 7 ) in all cases . Eighteen patients were ultimately found to harbor recurrent ovarian cancer measuring > or = 1 cm at the time of surgery , with a median maximal tumor diameter of 2.3 cm ( range 1.5 to 3.2 cm ) . The overall patient-based accuracy of PET/CT  in detecting recurrent disease > or = 1 cm was 81.8 % , with a sensitivity of 83.3 % and positive predictive value of 93.8 % ( P = 0.046 ) . Of patients with recurrent ovarian cancer > or = 1 cm , complete cytoreduction to no gross residual tumor was accomplished in 72.2 % . CONCLUSION PET/CT imaging demonstrates high sensitivity and positive predictive value in identifying potentially resectable , macroscopic recurrent ovarian cancer among patients with biochemical evidence of recurrence and negative or equivocal conventional CT findings . In appropriately selected patients , early identification of macroscopic recurrent disease may facilitate complete surgical cytoreduction
The published studies suggest that for selected women with stage IIIC or IV epithelial ovarian cancer , neoadjuvant chemotherapy and interval cytoreduction are non-inferior to primary cytoreduction and adjuvant chemotherapy with respect to overall and progression-free survival and are associated with less perioperative morbidity and mortality .
PURPOSE To provide guidance to clinicians regarding the use of neoadjuvant chemotherapy and interval cytoreduction among women with stage IIIC or IV epithelial ovarian cancer .