Neoadjuvant chemotherapy in advanced ovarian cancer: On what do we agree and disagree? Phase ii/iii study of intraperitoneal chemotherapy after neoadjuvant chemotherapy for ovarian cancer: ncic ctg ov.21. Neoadjuvant chemotherapy for advanced ovarian cancer: long-term survival. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. 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). Neoadjuvant chemotherapy in advanced ovarian cancer: a case‐control study 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. Neoadjuvant (Cytoreductive) Chemotherapy Combined With Intervention Debulking Surgery in Advanced, Unresected Epithelial Ovarian Cancer Phase III randomised clinical trial comparing primary surgery versus neoadjuvant chemotherapy in advanced epithelial ovarian cancer with high tumour load (SCORPION trial): Final analysis of peri-operative outcome. Quality of life in women treated with neoadjuvant chemotherapy for advanced ovarian cancer: a prospective longitudinal study. Chemoradiation and adjuvant chemotherapy in cervical cancer. Clinical outcomes of neoadjuvant chemotherapy and primary debulking surgery in advanced ovarian carcinoma. Evaluation of new platinum-based treatment regimens in advanced-stage ovarian cancer: a Phase III Trial of the Gynecologic Cancer Intergroup. Ovarian protection with goserelin during adjuvant chemotherapy for pre-menopausal women with early breast cancer (EBC) Neoadjuvant chemotherapy for epithelial ovarian cancer—role of apoptosis
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 Three large r and omized clinical trials have shown a survival benefit in women with stage iii epithelial ovarian cancer ( eoc ) who receive intraperitoneal ( IP ) chemotherapy after optimal primary debulking surgery . The most recent Gynecologic Oncology Group study , gog 172 , showed an improvement in median overall survival of approximately 17 months . That result led to a U.S. National Cancer Institute ( nci ) clinical announcement recommending that IP chemotherapy be considered for this group of women with eoc . However , IP chemotherapy is associated with increased toxicity , and rates for completion of treatment are low ( 42 % in gog 172 ) . The optimal IP regimen and duration of treatment has yet to be defined . Women undergoing chemotherapy before optimal debulking surgery were not included in the studies or in the nci clinical announcement . The National Cancer Institute of Canada Clinical Trials Group has developed a protocol for a r and omized phase ii/iii study which will examine whether IP platinum-taxane-based chemotherapy benefits women who have received neoadjuvant chemotherapy before optimal surgical debulking . To address whether the less systemically toxic  carboplatin can be substituted for cisplatin IP , the first phase of the study will have 3 arms : 1 intravenous-only , and 2 IP-containing regimens . At the end of the first stage , and provided that IP therapy is feasible to administer in this patient population , one of the IP regimens , either IP carboplatin or IP cisplatin , will proceed into a phase iii comparison with the intravenous arm . This exciting new study has gathered international support 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 . 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 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 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 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 To establishing whether neoadjuvant chemotherapy ( NACT ) followed by interval debulking surgery ( IDS ) is superior primary debulking surgery ( PDS ) in terms of clinical outcome as well as peri-operative morbidity in advanced epithelial ovarian cancer ( AEOC ) endowed with high tumour load ( HTL ) . MATERIAL AND METHODS This is a single-Institution , superiority , r and omised phase III trial enrolling supposed AEOC women . Patients considered pre-operatively eligible were triaged to staging laparoscopy to assess the predictive index ( PI ) of tumour load . All AEOC women with PI≥8 or≤12 ( considered as HTL ) were included . They were r and omly assigned ( 1:1 ratio ) to undergo either PDS followed by systemic adjuvant chemotherapy ( arm A , st and ard ) , or NACT followed by IDS ( NACT/IDS ) ( arm B , experimental ) . Co- primary outcome measures were postoperative complications ( grade d according to the Memorial Sloan Kettering Cancer Center surgical secondary events grading system ) and progression free survival ( PFS ) ; secondary outcomes were overall survival , and quality of life ( QoL ) . QoL was assessed using the EORTC QoL question naires . A sample size of 110 patients was required for the analysis of the first co- primary end-point ( major peri-operative morbidity ) whereas recruitment is still on-going to achieve the statistical power on PFS . RESULTS Between October 2011 and November 2014 , we registered 280 AEOC . Of the 110 eligible women , 55 were assigned to arm A and 55 to arm B. Despite different extension of surgery , rates of complete residual disease ( residual tumour=0 cm ) were superimposable between the groups ( 45.5 % versus 57.7 % ; p=0.206 ) . Twenty-nine patients ( 52.7 % ) in arm A experienced early grade III-IV complications versus three patients ( 5.7 % ) in IDS ( p=0.0001 ) . The most common complication was grade III and consisted of symptomatic pleural effusion requiring thoracic drainage ( 17/55 women ( 30.9 % ) in arm A versus 1/52 ( 1.9 % ) in arm B , p=0.0001 ) . Three grade IV ( 5.4 % ) ( i.e. , two re-operations for postoperative haemorrhage and one septic multi-organ failure ) , and two grade V ( 3.6 % ) ( two deaths for acute cardiopulmonary failure ) early complications were observed in arm A only . Mean QoL scores of several scales/items were shown to ameliorate over time in both arms . Emotional functioning , cognitive functioning , nausea/vomiting , dyspnoea , insomnia and hair loss were statistically and clinical ly better in NACT/IDS compared to PDS arm . CONCLUSIONS Perioperative moderate/severe morbidity as well as QoL scores were shown to be more favourable in NACT/IDS arm than PDS in AEOC patients with very HTL . Completion of patient enrolment and analysis of survival data will clarify whether PDS with such a high rate of severe complications is an acceptable treatment in AEOC women with HTL 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 Radiotherapy is the st and ard treatment for locally advanced cervical cancer , but treatment results remain disappointing , particularly for women with bulky central disease . We investigated the role of concurrent chemoradiation and adjuvant chemotherapy in a r and omized trial . PATIENTS AND METHODS Two hundred twenty patients with bulky stage I , II , and III cervical cancer were r and omized to receive either st and ard pelvic radiotherapy or chemoradiation ( epirubicin 60 mg/m(2 ) ) followed by adjuvant chemotherapy with epirubicin 90 mg/m(2 ) administered at 4-week intervals for five additional cycles . RESULTS Fifty-nine patients have relapsed , with a median follow-up duration of 77 months . Patients who received epirubicin radiation therapy showed a significantly longer disease-free ( P = .03 ) and cumulative survival ( P = .04 ) . Patients who received radiation alone had significantly more distant metastasis than those who received chemoradiation ( P = .012 ) . There was no difference in long-term local tumor control ( P = .99 ) . CONCLUSION Survival benefit has been demonstrated in patients treated with chemoradiation followed by adjuvant chemotherapy with epirubicin as compared with patients treated with st and ard pelvic radiotherapy alone 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 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 : Ovarian failure and infertility following adjuvant chemotherapy for early breast cancer are major concerns for some young women . Techniques for oocyte harvesting are associated with delay in starting treatment , potentially undesirable estrogen stimulation and a relatively low success rate . We report an audit of our experience with the luteinising hormone-releasing hormone agonist , goserelin , to achieve transient ovarian suppression during chemotherapy as a means of preserving ovarian function . Patient and methods : Pre-menopausal women were offered goserelin 3.6 mg by subcutaneous injection every 28 days during chemotherapy , starting 0–14 days prior to treatment . The primary end-point was recovery of menstruation . Serum luteinising hormone , follicle stimulating hormone and oestradiol were measured at recovery of menstruation or at first year follow-up if amenorrhoea persisted . Subsequent pregnancies were recorded . Results : Fifty-one evaluable women were audited .  Amenorrhoea occurred in all but one . All received combination anthracycline-containing chemotherapy regimens with a mean cumulative cyclophosphamide dose of 3.9 g/m2 . Forty-five ( 90 % ) recovered menstruation during the first year of follow-up ; mean time to recovery 5 months . Eight pregnancies in 10 women attempting this so far . Conclusion : Using goserelin concurrently with chemotherapy is associated with a high rate of ovarian function preservation 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
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 .