A randomized multicenter phase II study on neoadjuvant chemotherapy with carboplatin and docetaxel in advanced ovarian carcinomas (PRIMOVAR). Neoadjuvant chemotherapy with carboplatin and docetaxel in advanced ovarian cancer--a prospective multicenter phase II trial (PRIMOVAR). 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. Operative morbidity following primary and interval debulking surgery for advanced ovarian cancer. Five-year results of cyclic semi-high dose neoadjuvant chemotherapy supported by autologous peripheral blood stem-cell transplantation in patients with advanced ovarian cancer Phase II prospective study of paclitaxel and carboplatin in older patients with newly diagnosed Müllerian tumors. Preliminary results of neoadjuvant chemotherapy with paclitaxel and cisplatin in patients with advanced epithelial ovarian cancer who are inadequate for optimum primary surgery. Neoadjuvant chemotherapy for epithelial ovarian cancer—role of apoptosis Neoadjuvant chemotherapy or primary debulking surgery in advanced ovarian carcinoma: a retrospective analysis of 285 patients. Quality-of-life comparisons in a randomized trial of interval secondary cytoreduction in advanced ovarian carcinoma: a Gynecologic Oncology Group study. Gemcitabine–carboplatin–paclitaxel combination as first‐line therapy in advanced ovarian carcinoma: a single institution phase II study in 24 patients Feasibility study of neoadjuvant chemotherapy followed by interval debulking surgery for stage III/IV ovarian, tubal, and peritoneal cancers: Japan Clinical Oncology Group Study JCOG0206. Clinical outcomes of neoadjuvant chemotherapy and primary debulking surgery in advanced ovarian carcinoma. The Role of Surgical Reexploration Following Chemotherapy in Ovarian Cancer Intervention debulking surgery in advanced epithelial ovarian cancer Primary chemotherapy in stage IV ovarian cancer. A prospective phase II study. Neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy in patients with primarily unresectable, advanced-stage ovarian cancer. Neo-adjuvant chemotherapy in advanced epithelial ovarian cancer (EOC): A prospective, randomized study. Secondary surgical cytoreduction for advanced ovarian carcinoma. Quality of life in women treated with neoadjuvant chemotherapy for advanced ovarian cancer: a prospective longitudinal study. The effect of debulking surgery after induction chemotherapy on the prognosis in advanced epithelial ovarian cancer. Gynecological Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer. Neoadjuvant chemotherapy for advanced ovarian cancer: long-term survival. The effect of diameter of largest residual disease on survival after primary cytoreductive surgery in patients with suboptimal residual epithelial ovarian carcinoma. Neoadjuvant chemotherapy in advanced ovarian cancer: a case‐control study Neoadjuvant (Cytoreductive) Chemotherapy Combined With Intervention Debulking Surgery in Advanced, Unresected Epithelial Ovarian Cancer Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer.
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 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 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 5010 Background : To compare the operative morbidity of  primary ( PDS ) and interval debulking surgery ( IDS )  for advanced stage ovarian cancer . METHODS A large multi-institutional cooperative group study ( GOG 152 ) was conducted to evaluate the impact of IDS on progression-free and overall survival . Operative records were review ed to determine operative data and morbidity . The first three quartiles ( 1st q , median and 3rd q ) of the distribution is reported . A sign test is used to compare the characteristics and morbidities between PDS and IDS . RESULTS Two hundred and one patients underwent IDS  following r and omization to this procedure and three cycles of chemotherapy . All but nine cases had PDS and all but one had IDS performed by a board certified GYN surgeon . The surgeon estimated a similar percentage of the initial tumor volume was debulked during PDS and IDS . However , significantly less ascites , blood loss and duration of hospitalization were reported with IDS . [ Figure : see text ] Conclusion : There is less operative morbidity with IDS than with primary debulking surgery . This is consistent with previous retrospective studies . A r and omized trial evaluating the efficacy and morbidity of primary surgery vs neoadjuvant chemotherapy followed by IDS ( EORTC 55971 ) is ongoing . No significant financial relationships to disclose 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 OBJECTIVES The primary objective was to determine the completion rate of 6 cycles of paclitaxel and carboplatin chemotherapy with no dose reductions in patients > or = 70 years of age . METHODS Phase II study of intravenous ( IV ) carboplatin Area Under the Curve ( AUC ) of 5 and paclitaxel 175 mg/m(2 ) given to patients > or = 70 years of age , had any stage Müllerian cancer , and an ECOG performance status ( PS ) of 0 - 2 . RESULTS Twelve patients were enrolled ( median age of 82 years , range 75 to 86 years ) . Six of 12 completed 6 cycles of chemotherapy with no dose reductions . Three patients died on study precipitating study closure ; one with refractory cancer following cycle 1 , one of aspiration pneumonia after cycle 1 , and one with sudden death on day 5 of cycle 6 . Patients undergoing upfront debulking surgery tolerated chemotherapy better compared to patients receiving neoadjuvant chemotherapy .  Grade 3 or higher hematologic toxicities included 2 patients with febile neutropenia ( 17 % ) . > or = Grade 3 non-hematologic toxicities included fatigue ( 8 % ) , nausea ( 8 % ) , constipation ( 8 % ) , obstipation ( 8 % ) , vomiting ( 8 % ) , and hypoxia ( 8 % ) . CONCLUSIONS In this prospect i ve trial of st and ard carboplatin and paclitaxel chemotherapy in a heterogeneous population of elderly patients , chemotherapy was well tolerated by patients who underwent upfront debulking surgery , had a PS of 0 - 1 , and had few comorbidities . Patients not undergoing upfront debulking surgery because of either advanced cancer or poor surgical risk had excess morbidity/mortality . Prospect i ve studies to identify risk factors for toxicity prediction are needed 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 Background Ovarian cancer is one of the most frequently fatal gynecological cancers because most cases are diagnosed at an advanced stage . Loss of growth control and a marked resistance to apoptosis are considered major mechanisms driving tumor progression . Little is known about the effect of various treatment regimens on the distribution of molecular markers of apoptosis in epithelial ovarian cancer . The objective of this study was to compare the expression levels of both proapoptotic and antiapoptotic proteins p53 , p73 , Bcl-2 , Bcl-XL and survivin in the ascitic cells and tumor sample s of patients undergoing treatment with two different regimens . Methods A total of 24 patients with untreated epithelial ovarian cancer were r and omized into two groups of 12 each . Group 1 patients received three cycles of chemotherapy prior to surgery and three cycles after surgery and group 2 patients received six cycles of chemotherapy prior to surgery . The expression of apoptosis-related proteins was analyzed in ascitic fluid and tumor sample s by Western blotting and immunohistochemistry . The apoptotic index was also determined in these sample s by the TUNEL assay . Results Significant decreases in antiapoptotic bcl-2 and survivin were seen , accompanied by increases in apoptotic index in tumors that had undergone chemotherapy as compared to the baseline ascites sample s. No significant change in bcl-XL was observed . A significant decrease in proapoptotic p53 was also seen . No expression of p73 was observed in tumors or ascites . The findings were similar in groups 1 and 2 patients and were not statistically significantly different , perhaps due to the small sample size ( n=12 ) of each group . Conclusions The above findings indicate that chemotherapy in ovarian carcinoma leads to an increase in apoptosis by a p53-independent pathway , which involves the downregulation of antiapoptotic Bcl-2 and survivin but not Bcl-XL . Furthermore , administering neoadjuvant chemotherapy ( six cycles ) as an alternative form of therapy for advanced epithelial ovarian cancer is more effective in inducing apoptosis than three cycles . However , the findings of this study need to be corroborated using a larger sample OBJECTIVE This study was aim ed at comparison of neoadjuvant chemotherapy with primary debulking surgery in advanced ovarian carcinoma . METHODS Retrospective analysis of 285 patients with advanced ovarian carcinoma treated between 1980 and 1997 was performed . RESULTS In the period 1980 - 1988 all patients underwent primary debulking surgery and 82 % were cytoreduced to less than 0.5 cm largest residual tumor mass ( n = 112 ) . Analysis of this group of patients showed that some subgroups of patients ( e.g. , Stage IV disease or a total metastatic tumor load of more than 1000 g prior to debulking surgery ) had a poor survival despite cytoreduction to no or less than 1 g of total residual tumor load . The complication rate was high especially in the group with unfavorable prognosis ( postoperative mortality , 6 % ) . In the period 1989 - 1997 ( n = 173 ) the patients were surgically evaluated to receive primary chemotherapy ( 43 % ) or primary debulking surgery ( 57 % ) . Prognostic variables were similar for both treatment periods . The actuarial crude survival was higher in the second time period ( 3-year crude survival of 26 % + /- 4 . 3 and 42 % + /- 4.6 for the first and second time periods , respectively ; P = 0.0001 ) . The postoperative mortality was 0 % during the second time period . From 1993 on , the decision to give neoadjuvant chemotherapy or to perform primary debulking surgery in patients with clinical ly obvious metastatic disease was made with the help of an open laparoscopy ( n = 77 ) . Median duration of the laparoscopy , blood loss , and hospital stay due to this procedure were 25 min , 10 ml , and 2 days . Primary and interval debulking surgery was performed in 36 and 63 % of this subgroup of patients , respectively . CONCLUSION In this retrospective analysis over two different time periods , crude survival was higher when treating about half of the patients with advanced ovarian carcinoma with primary chemotherapy instead of primary debulking surgery . The role of neoadjuvant chemotherapy should be evaluated in a prospect i ve r and omized study PURPOSE To compare self-reported quality of life ( QOL ) in patients who did versus did not undergo interval secondary cytoreduction after initial surgery and combination chemotherapy for advanced ovarian cancer and to assess the association between baseline QOL scores and survival . PATIENTS AND METHODS Consenting patients participating in a Gynecologic Oncology Group ( GOG ) phase III treatment trial ( GOG 152 ) completed the Functional Assessment of Cancer Therapy-Ovarian ( FACT-O ) question naire and treatment-specific supplemental questions at the third and sixth chemotherapy cycles and at 6 and 12 months after starting treatment . RESULTS For all patients , QOL decreased approximately 1 unit from the first to second assessment . Significant improvement observed at 6 months ( P < .001 ) was sustained at 12 months , with no appreciable between-group difference . The baseline FACT-O score was associated with overall survival ( P = .048 ) but not progression-free survival . Less neurotoxicity was reported among patients who did ( 38.4 % ) versus did not ( 54.0 % ) undergo interval secondary cytoreduction at the third assessment ( P = .005 ) , and older patients experienced more long-term effects . CONCLUSION This is the first multicenter r and omized trial in ovarian cancer to longitudinally examine self-reported QOL and establish a predictive value of baseline QOL on survival , attributed primarily to the lowest-scoring quartile . Although interval secondary cytoreduction result ed in no notable long-term difference , a clinical ly significant improvement was seen in both arms at 6 and 12 months after starting therapy . Interestingly , there were fewer complaints of neurotoxicity at 6 months among patients who did versus did not undergo interval secondary cytoreduction Single-agent gemcitabine demonstrated response rates of 11–60 % in platinum/paclitaxel-resistant ovarian cancer . Twenty-four patients with epithelial ovarian cancer were treated with gemcitabine 800 mg/m2 on days 1 and 8 , carboplatin area under the curve 5 on day 1 , and paclitaxel 175 mg/m2 over 3 h on day 1 every 3 weeks for six cycles . Median age was 54 years , and FIGO stage distribution was IIC , 1 patient , III , 18 , and IV , 5 . A total of 22 ( 92 % ) patients completed all the six planned courses of chemotherapy . Doses were reduced in 8 out of 24 ( 33 % ) patients . Of the 17 patients with measurable disease , 15 underwent an interval debulking surgery . Prior to interval debulking surgery , all 15 patients had a partial response according to the response evaluation criteria in solid tumors criteria . Overall in the 17 patients with measurable disease , the response rate at the end of the first-line chemotherapy ( including interval debulking ) was 94 % ( 14 [ 82 % ] complete response and 2 [ 12 % ] , partial response ) . One patient ( 6 % ) received only one cycle due to early progression . Using the CA125 criteria as defined by the Gynecologic Cancer Intergroup , all patients had at least a partial response prior to interval debulking , and the overall response rate of the whole first-line chemotherapy and interval debulking ( n= 15 ) was observed in 21 out of 23 patients ( 91 % ) . The dose-limiting toxicity was bone marrow toxicity . Median overall survival was 28 months , and the 2-year actuarial survival was 73 % . The gemcitabine , carboplatin , paclitaxel triplet has an acceptable toxicity with high response rates as first-line therapy in advanced ovarian cancer BACKGROUND To assess the safety and efficacy of neoadjuvant chemotherapy ( NAC ) followed by interval debulking surgery ( IDS ) for müllerian carcinomas , such as ovarian , tubal , and peritoneal cancers , and to determine whether we can omit diagnostic laparoscopy before treatment initiation , a feasibility study was performed . METHODS Eligible patients had presumed stage III/IV müllerian carcinomas clinical ly diagnosed by imaging studies , cytology , and tumor markers . All patients underwent diagnostic laparoscopy to confirm the clinical diagnosis . Four cycles of paclitaxel and carboplatin were administered as NAC , followed by interval debulking surgery and an additional 4 cycles of chemotherapy . The primary end point was the proportion of patients achieving clinical complete remission ( cCR ) among all stage III/IV müllerian carcinomas confirmed by diagnostic laparoscopy . The major secondary end point was the positive predictive value ( PPV ) of clinical diagnosis . RESULTS Fifty-six patients were enrolled into the study . The PPV of overall clinical diagnosis for the tumor origin , histology , and stage was 95 % ( 53/56 ) . Fifty-three patients received the protocol treatment starting with NAC . IDS was performed in 89 % ( 47/53 ) of patients . Complete resection without residual tumors was achieved in 55 % ( 29/53 ) and residual tumors became < 1 cm in 17 % ( 9/53 ) of patients . Twenty-two patients ( 42 % ) achieved cCR after completion of the treatment . The median overall and progression-free survival was 45 and 14 months , respectively . CONCLUSION NAC without diagnostic laparoscopy for advanced müllerian carcinomas holds sufficient promise to be compared with direct surgery in a phase III trial 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 Summary : Two hundred and eighty three patients with FIGO Stages III‐IV ovarian epithelial cancer were entered on a r and omized trial of chlorambucil with or without cisplatin . Eighty two of these patients have subsequently undergone surgical reexploration . Ten of these were for surgical indications ( intestinal obstruction , etc . ) , and 7 were interval reexplorations at about 6 months on patients who had not been adequately debulked at primary surgery . The remaining 65 patients had elective operations after 12 months chemotherapy , and in 52 of these there was no pre‐operative clinical evidence of residual disease . Complete Surgical Response rate ( CRS ) was similar in the 2 treatment arms ( 8 % v 9.7 % ) ; 42.3 % of patients in apparent remission at 12 months had negative reexploration and 57.5 % of these were alive after 4 years ( post‐reexploration median survival > 4!/2 years ) . The remaining 57.7 % of patients had residual disease at reexploration and their 4‐year survival was 15 % ( median survival 73 weeks ) Objective To study whether intervention debulking surgery improves survival in patients with advanced ovarian cancer who have bulky ( > 2 cm ) residual disease after primary surgery BACKGROUND AND RATIONALE Non-curative surgical cytoreduction of advanced tumors is associated with increased proliferation of the remaining tumor cells . Thus , appropriate preoperative chemotherapy should prevent both cell proliferation and the increase of resistant cells . The aim of the present study was to evaluate the efficacy and toxicity of primary chemotherapy ( P-CT ) in previously untreated patients with stage IV ovarian cancer ( OC ) . PATIENTS AND METHODS Thirty-four patients with stage IV OC were treated from January 1993 to April 2000 with P-CT . Eligibility criteria included : histologically or cytologically confirmed , unresectable stage IV OC and performance status < or = 3 .  P-CT consisted of four courses of carboplatin , cyclophosphamide and epirubicin until October 1996 , and paclitaxel , carboplatin thereafter . Surgery followed P-CT . After the operation patients received two further courses of chemotherapy that were tailored according to their individual response . Median ( M ) age was 61 years , range 32 - 73 ; median performance status was 2 . A total number of 197 courses of CT were administered , median 5.7 per patient . RESULTS Complete or partial response ( CR , PR ) was observed in 28 patients ( response rate 82 % , 95 % CI : 65.4 % to 93.2 % ) , disease stability and progression ( SD , PD ) was observed in three and three patients , respectively . Median time to progression was 16.45 months ( range 4.8 - 90.4 + ) , median survival time was 28 months ( range 4.5 - 90.4 + ) : 1-year survival rate was 94 % . Toxicity according to WHO : nausea and vomiting grade ( G ) 2 , 30 % of patients ; gastrointestinal G 2 - 3 , 20 % of patients ; alopecia G 3 , 88 % of patients ; hematological G 3 - 4 , 73 % of patients ; neurologic G 2 , 12 % of patients . Nine pathological CRs were observed . CONCLUSION Neoadjuvant treatment with CBDCA with either CTX and EPI or Taxol is feasible and shows activity in OC 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 5123 Background : To determine the impact of NACT on surgical debulking rate , overall and disease-free survival and quality of life . METHODS Between Oct 2001 and Dec 2003 , 43 previously untreated patients ( median age- 50 years , range 30 - 65 ) with FIGO stage III C & IV were r and omized into two arms ; Arm A ( n=22 ) upfront debulking Sx followed by 6 cycles of paclitaxel & carboplatin ( TC ) . In Arm B ( n=21 ) patients received upfront 3 cycles of TC followed by debulking Sx followed by 3 more cycles . Eligibility criteria included -age 18 to 65 years , biopsy / cytological proven diagnosis of EOC , adequate hematological , renal , liver & cardiac functions , normal upper & lower GI endoscopy & CEA levels . Both groups were compared with respect to tumor debulking rate , duration of Sx , blood loss , intra & postoperative morbidity & mortality , overall response to treatment and quality of life , using FACT-O question naire . RESULTS A total of 174 CT cycles were administered with grade III-IV GI toxicity ( 3 % vs 4 % ) & myelosuppression ( 10 % Vs 8 % , p = ns ) in arm A & B , respectively . Patients receiving NACT had higher optimum debulking rate , 78 % Vs 9 % , p<. 001 . There was good correlation between CAT scan findings and sub-optimal debulking ( p<.001 ) . Mean operative time ( 69.5 vs 79.2 minutes , p=0.5 ) , mean blood loss ( 461 vs 327 ml , p=0.430 ) , PO infection rate 29.4 % vs 10 % , p=0.35 and hospital stay ( 14.2 Vs 11 days , p=0.52 ) ) were not significantly different . Mean survival is similar in both arms ( 22.3 vs 18.6 months ) . The physical & functional wellbeing were similar in both groups . 23 have completed treatment ; of these 16 are alive & disease-free ( arm A-9 , arm B-7 ) , 7 relapsed , 3 in arm A & 4 in B. 8 patients are currently on treatment . 11 patients have died ; 4 of PO complications ( 3 in arm A ) , CT toxicity-2 , 5 of progressive disease , 1 lost to follow up . CONCLUSION Primary NACT followed by debulking surgery is associated with higher resection rates & lower morbidity with outcome similar to st and ard approach . [ Table : see text ] BACKGROUND We evaluated the effect of adding secondary cytoreductive surgery to postoperative chemotherapy on progression-free survival and overall survival among patients who had advanced ovarian cancer and residual tumor exceeding 1 cm in diameter after primary surgery . METHODS Women were enrolled within six weeks after primary surgery . If , after three cycles of postoperative paclitaxel plus cisplatin , a patient had no evidence of progressive disease , she was r and omly assigned to undergo secondary cytoreductive surgery followed by three more cycles of chemotherapy or three more cycles of chemotherapy alone . RESULTS We enrolled 550 women . After completing three cycles of postoperative chemotherapy , 216 eligible patients were r and omly assigned to receive secondary surgical cytoreduction followed by chemotherapy and 208 to receive chemotherapy alone . Surgery was declined by or medically contraindicated in 15 patients who were assigned to secondary surgery ( 7 percent ) . As of March 2003 , 296 patients had died and 82 had progressive disease . The likelihood of progression-free survival in the group assigned to secondary surgery plus chemotherapy , as compared with the chemotherapy-alone group , was 1.07 ( 95 percent confidence interval , 0.87 to 1.31 ; P=0.54 ) , and the relative risk of death was 0.99 ( 95 percent confidence interval , 0.79 to 1.24 ; P=0.92 ) . CONCLUSIONS For patients with advanced ovarian carcinoma in whom primary cytoreductive surgery was considered to be maximal , the addition of secondary cytoreductive surgery to postoperative chemotherapy with paclitaxel plus cisplatin does not improve progression-free survival or overall survival 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 BACKGROUND Although the value of primary cytoreductive surgery for epithelial ovarian cancer is beyond doubt , the value of debulking surgery after induction chemotherapy has not yet been defined . In this r and omized study we investigated the effect on survival of debulking surgery . METHODS Eligible patients had residual lesions measuring more than 1 cm in diameter after primary surgery . After three cycles of cyclophosphamide and cisplatin , these patients were r and omly assigned to undergo either debulking surgery or no surgery , followed by further cycles of cyclophosphamide and cisplatin . The study end points were progression-free and overall survival . At surgery 65 percent of the patients had lesions measuring more than 1 cm . In 45 percent of this group , the lesions were reduced surgically to less than 1 cm . RESULTS Of the 319 patients who underwent r and omization , 278 could be evaluated ( 140 patients who underwent surgery and 138 patients who did not ) .  Progression-free and overall survival were both significantly longer in the group that underwent surgery ( P = 0.01 ) . The difference in median survival was six months . The survival rate at two years was 56 percent for the group that underwent surgery and 46 percent for the group that did not . In the multivariate analysis , debulking surgery was an independent prognostic factor ( P = 0.012 ) . Overall , after adjustment for all other prognostic factors , surgery reduced the risk of death by 33 percent ( 95 percent confidence interval , 10 to 50 percent ; P = 0.008 ) . Surgery was not associated with death or severe morbidity . CONCLUSIONS Debulking surgery significantly lengthened progression-free and overall survival . The risk of death was reduced by one third , after adjustment for a variety of prognostic factors 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 OBJECTIVE The Gynecologic Oncology Group has divided patients with advanced epithelial ovarian cancer into those with optimal residual cancer , in which the maximum diameter of residual is < or = 1 cm , and suboptimal residual cancer , in which the residual disease is > 1 cm . Within the optimal group of patients there is a survival difference between patients with microscopic residual disease and those with any macroscopic disease < or = 1 cm . No analysis of the effect of various residual disease diameters in patients with residual disease > or = 1 cm has been performed . This study evaluates the effect of residual disease diameter in patients with suboptimal disease entered on a r and omized trial of intense versus st and ard chemotherapy .  STUDY DESIGN Gynecologic Oncology Group protocol 97 compared cisplatin 50 mg/m2 and cyclophosphamide 500 mg/m2 for eight courses with the same drugs at 100 mg/m2 and 1000 mg/m2 for four courses , respectively . There was no difference in progression-free interval or survival between the two arms . Of the 458 stage III ( with residual disease > 1 cm ) and stage IV patients entered in this study , 294 stage III patients comprise the current analysis . Surgical reporting forms , operation reports , and pathology reports were review ed to determine initial greatest tumor diameter and residual tumor diameter . Patients were grouped by residual diameter . Multivariate analysis considered residual diameter of disease , age , histologic characteristics , performance status , and ascites . An adjusted relative hazard of dying of ovarian cancer was calculated for each residual disease group . RESULTS Patients ranged in age from 20 to 80 years , with a median of 60 years . All patients were Gynecologic Oncology Group performance status 0 to 2 . Fifty-two percent had grade 3 tumors , and 39 % and 9 % , respectively , had grade 2 or 1 tumors . All patients had stage III disease . Ninety percent had serous , endometrioid , or mixed epithelial cell type tumors . Multivariate analysis revealed a relative risk of dying as follows : residual disease < 2 cm , relative risk 1.00 ; 2 to 2.9 cm , relative risk 1.90 ; 3 to 3.9 cm , relative risk 1.91 ; 4 to 5.9 cm , relative risk 1.74 ; 6 to 7.9 cm , relative risk 1.85 ; 8 to 9.9 cm , relative risk 2.16 ; > or = 10 cm , relative risk 1.82 . The difference in survival between those with < 2 cm residual disease and those with > or = 2 cm residual disease was significant ( p < 0.01 ) . There is no significant difference in the risk of dying between groups with residual disease > or = 2 cm . CONCLUSIONS Among patients with suboptimal ( > 1 cm residual disease ) epithelial ovarian cancer , those who have small diameter residual disease ( < 2 cm ) tend to survive longer than those who have larger residual disease . Among those with larger residual disease , size does not affect prognosis appreciably 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 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 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 .
BACKGROUND Interval debulking surgery ( IDS ) , following induction or neoadjuvant chemotherapy , may have a role in treating advanced epithelial ovarian cancer ( stage III to IV ) where primary debulking surgery is not an option .
OBJECTIVES To assess the effectiveness and complications of IDS for women with advanced stage epithelial ovarian cancer .