Suboptimal Debulking Surgery Research Articles

Rapid progression of synchronous ovarian and endometrial cancers with massive omental carcinomatosis

We present a rare case of a 41-year-old woman with synchronous primary cancers of the endometrium and ovary, both in advanced stages. Palliative surgery with incomplete tumor debulking followed by the first trial of chemotherapy provided no treatment benefit to her prognosis and she died shortly thereafter. A 41-year-old woman, para 1, was referred to our department for prolonged and profuse menstrual bleeding, poor appetite and marked abdominal distension. Abdominal ultrasound and computed tomography showed a large left adnexal tumor accompanied by massive ascites and carcinomatosis (Fig. 1). The levels of tumormarkers, including cancer antigen (CA) 125, CA 19-9, and carcinoembryonic antigen (CEA), were 1588 U/ mL, 21 U/mL, and 1.4 ng/mL, respectively. During her operation, we noted a huge omental cake of about 35 cm (Fig. 2), a left ovarian tumorwith rectal serosa invasion, diffuse intraperitoneal (including bowels) tumor implantation, and massive ascites totaling about 6600 mL. The uterus, the contralateral ovary and tube, and the liver surface were not involved. Suboptimal debulking surgery was done (residual tumor size > 1 cm), and the estimated blood loss was 2000 mL. The microscopic findings included two synchronous tumors of the left ovary and endometrium. The histological types were mixed clear cell (moderately differentiated), endometrioid (well-differentiated) carcinoma of the left ovary (90% clear and 10% endometrioid), and mucinous (moderately differentiated) carcinoma of the endometrium, respectively. The contralateral ovary revealed a microscopic tumor implant. The final histopathological findings were synchronous ovarian clear celleendometrioid carcinoma and endometrial mucinous carcinoma, with massive omental carcinomatosis, without lymph nodes metastasis, FIGO IIIC (pT3cN1) (Figs. 3 and 4). She received adjuvant chemotherapy with carboplatin and taxol immediately after the operation. The levels of tumor

Primary gallbladder carcinoma presenting as advanced-stage ovarian cancer

Primary gallbladder carcinomas are rare and the prognosisis very poor. The incidence is 1e2% of all gastro-intestinal(GI) tract cancers [1]. Information on ovarian metastasis ofprimary gallbladder cancer is limited [2e13], partly becauseprimary gallbladder cancers are rare, and partly becausemetastases from primary gallbladder cancer are mediatedthrough either lymphatic or hematogenous routes. Sinceprimary gallbladder cancers are mucinous tumors, there areproblems with the differential diagnosis if mucinous ovariancarcinomas are found. Furthermore, primary or secondaryovarian mucinous tumors may present similar clinical symp-toms, for example, non-specific GI symptoms or signs, andsimilar findings on imaging studies or tumor marker surveys.Before and during an operation, an accurate diagnosis some-times cannot be made [14]. Herein, we present a case ofsecondary ovarian mucinous cancer emanating from primarygallbladder mucinous carcinoma.An 84-year-old woman was sent to the emergency roombecause of diffuse abdominal pain and poor appetite. Clinicalexamination showed an acutely ill-looking woman withapparent peritoneal signs (diffuse tenderness and reboundingpain) associated with a lower abdominal mass. Ultrasoundshowed a 15-cm complex cystic mass in the right adnexa, butthe uterus and the left ovary were normal. Computed tomog-raphy further identified this 15-cm ill-defined right adnexalheterogeneous mass with diffuse peritoneal seeding andcarcinomatosis. Serum tumor markers, including CA 125, CA153, CA 199, and CEA were 327.3 U/mL, 29.0 U/mL, 218.0U/mL, and 85.8 ng/mL, respectively. The other hematologicaland biochemical tests were normal. Upper and lower gastro-intestinal tract evaluations were negative.Under the diagnosis of ovarian cancer, an exploratorylaparotomy was done. A complex cystic right ovarian masswith a mucinous component was found, as well as diffusecarcinomatosis involving the entire lower and upper abdom-inal cavity, including the omentum, in which the inflamedgallbladder was embedded. Frozen section of the removedovarian tumor favored the diagnosis of primary ovariancarcinoma, mucinous type. The patient underwent a subop-timal debulking surgery, including total hysterectomy, bilateralsalpingo-oophorectomy, omentectomy, and retroperitoneallymph node sampling, and multiple biopsies. The finalpathology was primary gallbladder mucinous carcinoma.Microscopic features showed hyperchromatic dysplasia ofthe mucinous glandular cells of the gallbladder; the mucinoustumor occupied the entire cavity of the gallbladder. The tumorhad invaded whole layers of the gallbladder, and penetrated tothe outside serosa and the attachment of the omentum. Othersections of the right ovary, appendix, omentum, abdominalwall, mesentery, and right pelvic lymph nodes all showedtumor metastases with floating mucinous tumor cells within anextensive mucin pool.Using the American Joint Committee on Cancer (AJCC)staging for gallbladder cancer, the final diagnosis was gall-bladder cancer stage IVB (pT4NxM1). However the patientdied of disease 48 days after the operation.This case report raised the following interesting issues.First, since 15% of ovarian cancers are secondary and 7e15%

Primary Chemotherapy for Inoperable Ovarian, Fallopian Tube, or Primary Peritoneal Cancer With or Without Delayed Debulking Surgery

To describe the outcome of primary chemotherapy for women with advanced-stage epithelial ovarian or primary peritoneal cancer and delayed surgery when optimal debulking surgery cannot be achieved at diagnosis. Between 1998 and 2006, we retrospectively reviewed the overall survival and examined prognostic markers in consecutive patients who were not suitable for initial radical surgery because of the extent of disease and/or poor performance status. They were treated with a policy of primary platinum-based chemotherapy, followed whenever possible in responding patients by debulking surgery. A total of 171 patients received least one cycle of chemotherapy. Eighty-six patients proceeded to surgery and 53 (31% of 171 and 62% of 86) had optimal (<1 cm) residual disease. Eighty-five patients did not undergo surgery because they remained unfit or had not responded sufficiently to chemotherapy. The median overall survival was 18.7 months (95% confidence interval [CI], 16.5-24.2). The median OS in the surgical group for optimal and suboptimal surgery was 40.8 (95% CI, 32.5-50.0) and 22.5 (95% CI, 17.7-37.1) months (P = 0.005). On multivariate analysis, interval surgery and optimal surgery were the only independent prognostic factors (hazard ratios, 0.45 and 0.43, respectively; P = 0.009). In the nonsurgical group, CA125 response was an independent prognostic factor (hazard ratio, 0.34; P = 0.001) with an OS of 21.7 months (95% CI, 14.0-35.4) in women with a normal CA125 after treatment compared with 6.7 (95% CI, 4.5-7.8) months. In one third of the women, the tumor was optimally debulked after primary chemotherapy and their median survival was 40.8 months. Suboptimal debulking surgery after primary chemotherapy did not result in a better survival than that achieved after a chemotherapy response alone, suggesting that surgery may be avoided when imaging after chemotherapy demonstrates residual disease that cannot be optimally debulked.

Highlights of This Issue

The value of neoadjuvant hormone therapy (NHT) before radical prostatectomy, for the treatment of early-stage prostate cancer, is not clear. Here, Sorrentino and colleagues found that NHT boosted IL-7 and IFNγ-inducible protein (IP)-10/CXCL10 expression in the prostate and promoted cytotoxic-effector T cell influx. However, NHT also induced thymus and activation-regulated chemokine (TARC)/CCL17 production in the prostate and draining lymph nodes and increased their Foxp3+CD25+CD127- T regulatory cell content. The concomitant recruitment of cytotoxic-effector and regulatory cells left their intratumoral balance unchanged and did not improve disease-free survival. These findings may help guide treatment decision-making in prostate cancer.The last decade has seen exciting progress in multiple myeloma research, leading to changes in treatment paradigms for the disease. In this issue of CCR Focus, guest editor Kenneth Anderson discusses some of the recent advances in myeloma research and also addresses challenges in translating this progress into better patient care. Topics covered include the underlying molecular biology of multiple myeloma; premalignant forms of the disease and potential prevention strategies; complexities in selecting upfront therapies; myeloma drugs in the pipeline and suggestions for combination therapies; improving the personalization of treatment; and progress in treating bone-related complications.Chondroitin sulfate proteoglycans are a family of extracellular matrix glycoproteins highly upregulated in gliomas. These proteins form large complexes that facilitate tumor growth while limiting the local diffusion of therapeutic agents. In this issue, Dmitrieva and colleagues found that digestion of chondroitin sulfate by bacterial chondroitinase enhanced distribution and spread of oncolytic viruses within the tumor. Furthermore, they showed that an oncolytic virus armed with bacterial chondroitinase had enhanced spread and therapeutic efficacy against gliomas, without increasing tumor invasion or migration. This approach against the tumor microenvironment shows promise as a therapeutic strategy for glioma.Ovarian clear cell carcinomas (OCCC) are a drug-resistant and aggressive type of epithelial ovarian cancer. In this issue, Tan and colleagues revealed that OCCCs are heterogeneous at the genomic level by performing highresolution microarray-based comparative genomic hybridisation. Unsupervised hierarchical clustering analysis identified two distinct clusters of OCCCs with distinct clinical outcomes, independent of their histologic features. Multivariate analysis showed that suboptimal debulking surgery and genomic cluster were independent predictors of progression-free survival. These findings provide evidence that OCCCs are genomically heterogeneous despite having similar histologic features and that this genomic heterogeneity is clinically significant.

Genomic Analysis Reveals the Molecular Heterogeneity of Ovarian Clear Cell Carcinomas

Ovarian clear cell carcinomas (OCCC) are a drug-resistant and aggressive type of epithelial ovarian cancer. We analyzed the molecular genetic profiles of OCCCs to determine whether distinct genomic subgroups of OCCCs exist. Fifty pure primary OCCCs were subjected to high-resolution microarray-based comparative genomic hybridization (aCGH). Unsupervised hierarchical clustering using Ward's linkage analysis was performed to identify genomic subgroups of OCCCs. Survival analysis was performed using Kaplan-Meier method and log-rank test. Cox-regression analysis was used to identify independent predictors of outcome. Differentially amplified regions between genomic subgroups of OCCCs were identified using a multi-Fisher's exact test. Hierarchical cluster analysis revealed two distinct clusters of OCCCs with different clinical outcomes. Patients from cluster-1 had a significantly shorter median progression-free survival (PFS) than those from cluster-2 (11 vs. 65 months, P = 0.009), although estimates for ovarian cancer-specific survival (OCS) did not reach statistical significance (P = 0.065). In multivariate analysis, suboptimal debulking surgery and genomic cluster were independently prognostic for PFS. Recurrently amplified genomic regions with a significantly higher prevalence in cluster-1 than cluster-2 OCCCs were identified and validated. HER2 gene amplification and protein overexpression was observed in 14% of OCCCs, suggesting that this may constitute a potential therapeutic target for a subgroup of these tumors. OCCCs constitute a heterogeneous disease at the genomic level despite having similar histological features. The pattern of genomic aberrations in subgroups of OCCCs is of clinical significance. We have identified recurrently amplified regions that may harbor potential therapeutic targets for subgroups of OCCCs.

Use of microarray-based comparative genomic hybridization analysis to identify prognostic subgroups of ovarian clear cell carcinomas.

5020 Background: Advanced ovarian clear cell carcinomas (OCCCs) are notoriously drug resistant and aggressive tumours. We previously focused our research efforts on identifying novel therapeutic targets in these tumours (Clin Can Res. 2009;15:2269- 80). The aim of this study was to identify prognostically distinct genomic subgroups of OCCCs. Methods: 50 pure archival OCCCs were reviewed by at least two gynaecologic pathologists, and subjected to microarray-based comparative genomic hybridisation (aCGH) using a 32K tiling-path platform. Unsupervised hierarchical clustering using Ward's linkage analysis was performed to identify genomic groups of OCCCs. Survival analysis was performed using a Kaplan-Meier method and log-rank test. Cox-regression analysis was used to identify independent predictors of outcome. Differentially amplified regions between genomic subgroups of OCCCs were identified using a Multi- Fisher's exact test. Results: Patients (pts) were diagnosed between October 1988 and March 2007 with a median follow-up period of 24 mths and median age of 57.5 yrs. Unsupervised hierarchical clustering analysis revealed 2 clusters of OCCCs with distinct clinical outcomes. Cluster 1 pts had a significantly shorter median progression free survival (PFS) than Cluster 2 pts (median survival 11 vs. 65 mths, p = 0.009) following first-line treatment. A trend towards poorer median overall survival (OS) was also observed for Cluster 1 compared with Cluster 2 pts (median survival 19 vs. 66 mths, p = 0.065). In multivariate analysis, suboptimal debulking surgery (HR = 6.811, 95%CI 2.359-19.663, p = 0.014) and genomic cluster (Cluster 2 vs. 1 OCCCs HR = 0.389, 95% CI: 0.174-0.872; p = 0.022) were independently prognostic for PFS. We identified 29 genomic regions significantly differentially gained at high level/amplified between cluster 1 and 2 OCCCs, including 8q24.3, 17q21.2, and 19q13.3, which may harbour potential mediators of tumour aggressiveness and chemoresistance. These regions may also harbour novel therapeutic targets for further assessment in OCCCs. Conclusions: Our results demonstrate that genomic heterogeneity and genomic subgroups of clinical significance exist in OCCCs. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Chugai Pharma, GlaxoSmithKline, Schering-Plough Schering-Plough Schering-Plough

Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Advanced epithelial ovarian cancer (EOC): Is there a place for maintenance therapy in patients with sub-optimal debulking?

e14580 Background: Survival of patients with advanced epithelial ovarian cancer (EOC) with initial suboptimal debulking surgery (residual disease (&gt;1 cm) and those with recurrent EOC is poor. We used EGFR inhibitor gefitinib for maintenance and analyzed data on safety and toxicity. Methods: Between Nov. 2004 and Dec. 2008, Patients who achieved complete response (CR) following six cycles of paclitaxel and carboplatin received gefitinib as (Group I). Similarly, patients with recurrent EOC who achieved CR following six cycles of salvage CT received gefitinib (Group II). Both groups received gefitinib 250 mg once daily till evidence of relapse. Patients were examined every month and toxicity (CTC version II) was recorded. Serum CA-125 was done once in 2 months and CAT scan of abdomen &amp; pelvis every 6 month. The study was approved by Institute Ethics Committee and informed written consent was obtained from each patient. Results: A total of 48 patients (median age 47 years, range 23 to 63) have been recruited. Group I: 17 subjects and Group II 31 patients (1st relapse- 13, 2nd- 9, 3rd -6 &amp; 4th relapse in 3 patients). The mean duration of gefitinib treatment is 8.77 months (Gp-I: 14.4 months, Gp-II: 5.68 months). Toxicity was mainly in the form of skin rash &amp; diarrhea. Skin rash: 16 patients (33.3%); Group I - 8 (grade I-2, II-4, III-3,) &amp; Group II - 8 patients (grade I-3,II-4,III-1). Diarrhea: 12 patients (25%); Group I-3, group II- 9) all grade I. Two patients had both skin rashes and diarrhea. No pulmonary or hematological toxicity was observed. Currently, 13 patients are on gefitinib (mean duration of treatment 12.6 months); in 34 patients gefitinib has been discontinued due to relapse and in 1 patient due to grade III skin rashes over face. Among 18 patients with skin toxicity, 8 continue to be disease-free compared to 6 of 30 without skin toxicity (p=0.07). Conclusions: Gefitinib was tolerated well with mild toxicities limited to skin and GIT. Correlations between EGFR expressions vs. response may help to identify patients likely to benefit from gefitinib therapy. No significant financial relationships to disclose.

In vitro extreme drug resistance assay to taxanes or platinum compounds for the prediction of clinical outcomes in epithelial ovarian cancer: a prospective cohort study

We sought to investigate the efficacy of in vitro extreme drug resistance (EDR) assay for the prediction of drug response, platinum-resistance (progression-free survival, PFS <6 months) and survival in patients with epithelial ovarian cancer (EOC) who received taxane- and platinum-based chemotherapy after surgery. Between December 2005 and August 2007, 43 patients were enrolled prospectively. They underwent staging laparotomy followed by six or nine cycles of taxane- and platinum-based chemotherapy, and their tumors were submitted for in vitro EDR assay to taxanes (paclitaxel or docetaxel) and platinum compounds (carboplatin or cisplatin). The rates of EDR to taxanes and platinum compounds were 20.9% (9/43) and 23.3% (10/43). Patients with EDR to platinum compounds showed a lower rate of overall response (60 vs. 100%), a higher rate of platinum-resistance (50 vs. 18.2%) and poor overall survival (OS) (median OS; 29.2 vs. 33.7 months) than those without EDR to platinum compounds (P < 0.05), whereas patients with EDR to taxanes showed poor PFS than those without EDR to taxanes (12.5 vs. 19 months, P < 0.01). Moreover, suboptimal debulking surgery and EDR to taxanes were poor prognostic factors for PFS (adjusted hazard ratio 3.215 and 3.984; 95% confidence interval 1.845-7.895 and 3.814-11.674, respectively) although there was no independent risk factor for poor OS by the multivariate Cox's proportional hazard analysis. In vitro EDR assay to taxanes and platinum compounds may be helpful for predicting drug response, platinum-resistance and survival in patients with EOC who received taxane- and platinum-based chemotherapy after staging laparotomy.

Significance of preoperative serum CA‐125 levels in the prediction of lymph node metastasis in epithelial ovarian cancer

To investigate preoperative serum CA-125 levels as a predictive factor for evaluation of lymph node metastasis in epithelial ovarian cancer. Retrospective study. Medical records at Seoul National University Hospital. Ninety-nine patients with epithelial ovarian cancer between January 2004 and March 2007. The significance of the preoperative serum CA-125 level for the prediction of lymph node metastasis was determined using the receiver operating characteristic (ROC) curve, McNemar's test and logistic regression analysis. Clinical prognostic factors affecting survival were evaluated using the Kaplan-Meier analysis with the log-rank test and Cox's proportional hazard analysis. The ROC curve showed the best cut-off value (535 U/mL) of the preoperative serum CA-125 level with regard to sensitivity (70.0%) and specificity (83.1%). Imaging studies combined with the preoperative serum CA-125 level showed the highest sensitivity (90.0%), whereas imaging studies alone showed the highest specificity (89.8%) for the prediction of lymph node metastasis. FIGO stage III-IV, the preoperative serum CA-125 level (> or =535 U/mL) and lymph node involvement on imaging studies were significant factors for the prediction of lymph node metastasis (p<0.05). Suboptimal debulking surgery and lymph node metastasis were poor prognostic factors for progression-free survival and overall survival, respectively (p<0.05). The preoperative serum CA-125 level (> or =535 U/mL) may be important for the prediction of lymph node metastasis in patients with epithelial ovarian cancer. Furthermore, it can be helpful in selecting patients who should undergo systemic lymphadenectomy for the detection of hidden lymph node metastasis.

Primary cytoreductive surgery or neoadjuvant chemotherapy: A retrospective analysis of 214 patients with stage IIIc and IV ovarian, tubal and peritoneal cancer from the Norwegian Radium Hospital

16035 Background: We evaluated clinical prognostic factors in ovarian carcinoma for their association with upfront treatment in advanced stage ovarian cancer patients with effusions. Methods: Our study consists of a retrospective analysis of 214 patients with stage IIIc and IV primary ovarian cancer, primary peritoneal carcinoma and tubal cancer, treated at the Norwegian Radium Hospital (NRH) in the period 1998–2003. One-hundred and thirty-eight patients underwent primary cytoreduction, 51 patients received neoadjuvant chemotherapy followed by delayed debulking and 25 patients received only chemotherapy. Results: Residual disease of less than 1 cm was achieved in 31.9 % of primary surgery patients and in 47.1 % of delayed surgery patients. Standard taxane/platinum treatment was given to 79.7 % and 67.1 % patients in the surgery and neoadjuvant treatment group, respectively. Hazard ratio for relapse was significantly higher for upfront treatment with neoadjuvant chemotherapy (1.69, CI 95 % 1.12–2.55) compared to primary surgery and for suboptimal debulking surgery and/or suboptimal chemotherapy (1.66, CI 95 % 1.14–2.41) compared to optimal treatment. The incidence of disease-related death was also significantly higher for the neoadjuvant chemotherapy group (1.83, CI 95 % 1.21–2.79) and for patients treated suboptimally (1.50, CI 95 % 1.03–2.19). Median cancer-specific survival was 31 months for the primary surgery group and 15 months for the neoadjuvant treatment group. Conclusions: In this retrospective analysis, the two most important prognostic factors for advanced ovarian, tubal and peritoneal cancer with malignant pleural and/or abdominal effusion were surgical treatment as first-line therapy and combination of optimal tumor debulking (&lt;1cm) and taxane/platinum chemotherapy. The role of neoadjuvant chemotherapy is still controversial. No significant financial relationships to disclose.

Topotecan, paclitaxel, and carboplatin in advanced ovarian cancer: A phase II trial of the Minnie Pearl Cancer Research Network

15015 Background: Topotecan (T) is standard therapy for patients (pts) with relapsed platinum refractory ovarian cancer (OC). The addition of T to paclitaxel/carboplatin (PC) may improve the first-line therapy for pts with stage III/IV OC. Methods: The primary endpoints were to assess the toxicity and response rate of TPC in previously untreated pts with advanced OC. Pts with previously untreated stage III/IV OC with performance (PS) 0 or 1, normal hematologic and organ function were eligible. Topotecan 1mg/m2 per day IV days 1, 2, and 3; paclitaxel 175mg/m2 IV on day 3 and carboplatin (AUC=5) IV on day 3 were administered at 21-day intervals for 6 cycles with standard dose modifications for toxicities. Responses were assessed clinically after 2 cycles and at completion of therapy. Second look laporatory (SLL) was required for pts without evaluable tumor. Results: 50 pts were enrolled: age range 27–79 (median 63); performance status 0=16, 1=34; suboptimal debulking surgery (tumor &gt; 1 cm) 32; 70% high grade tumors. Intent to treat response rates: complete response (CR) 20 pts (40%); partial response (PR) 12 pts (24%); stable (S) 13 pts (26%); progression 2 pts (4%); not evaluable 3 pts (6%). 13 pts had SLL with 5 CR, 5 PR and 3 S. Toxicities included: grade 3/4 neutropenia/thrombocytopenia 84%/44%; grade 3/4 fatigue/infection 10%/10%; no treatment-related deaths. Median progression-free survival (PFS) for all pts was 13.6 months and 1-, 2-, 3-year PFS 60%, 42%, 36%. Median survival 33.9 months for all pts with 1-, 2-, 3-year survivals 90%, 65%, 49%. Conclusions: The combination of TPC is active and relatively well tolerated with PC given on day 3. The response rates, PFS, and survivals appear similar to standard regimens. Randomized prospective trials will be required to determine the value of T added to PC for first-line therapy of advanced OC. [Table: see text]

Paclitaxel, cisplatin, and cyclophosphamide (PCC) first-line chemotherapy for advanced ovarian carcinoma: Long-term results of a phase II study

5135 Background: Despite high responses to cisplatin-based combination chemotherapy, the overall survival rate for advanced ovarian cancer remains poor. The combination of PCC as 1st-line treatment for ovarian cancer (OC) has significant activity with high primary response rates. To evaluate long-term results and to assess prognostic factors which have an impact on overall survival we analysed the data from a prospective phase II trial of this treatment combination Methods: 54 patients with OC ( FIGO IIc n=9, IIIc the n=38, IV n=7) were treated between January 1997 and December 2000 with six cycles of P (175mg/m2), C (75mg/m2) and C (600mg/m2) after optimal (n=22) or suboptimal (n=32) debulking surgery. Median age at treatment was 52 years. Tumour histology was adenocarcinoma in all cases (34 of endometrioid subtype, 6 clear cells, and 4 undifferentiated). CA 125 was elevated after surgery in 44 patients and at the end of chemotherapy in 6 patients. A second laparotomy was performed after chemotherapy to 14 patients with macroscopic disease Results: Of 30 evaluable patients for response, 15 achieved a clinical complete response (50%), 12 a partial response (40%), and 3 disease stabilization (10%). With a median follow-up of 56 months (range: 28–153), 26 patients remain alive (49%) and 15 free of recurrence (28%). Median progression-free survival (PFS) was 19 months, and median overall survival (OS) 46 months. 5 years rates of PFS and OS were 26% and 43% respectively. OS rate for FIGO IIIc-IV patients was 35%. In a multivariate analysis, the only negative prognostic factors for survival were: FIGO stage IIIc-IV (p<0.04), suboptimal debulking surgery (p<0.001), and elevated CA 125 at the end of chemotherapy (p<0.05) Conclusions: Our study confirms the effectiveness of PCC regimen in the treatment of epithelial OC in the long term. FIGO stage, extend of debulking surgery, and CA 125 at the end of chemotherapy, are independent prognostic factors for overall survival. These long-term results support the conduct of randomised studies to determine the impact of this triplet in the treatment of advanced ovarian cancer No significant financial relationships to disclose.

Paclitaxel, cisplatin, and cyclophosphamide (PCC) first-line chemotherapy for advanced ovarian carcinoma: Long-term results of a phase II study

5135 Background: Despite high responses to cisplatin-based combination chemotherapy, the overall survival rate for advanced ovarian cancer remains poor. The combination of PCC as 1st-line treatment for ovarian cancer (OC) has significant activity with high primary response rates. To evaluate long-term results and to assess prognostic factors which have an impact on overall survival we analysed the data from a prospective phase II trial of this treatment combination Methods: 54 patients with OC ( FIGO IIc n=9, IIIc the n=38, IV n=7) were treated between January 1997 and December 2000 with six cycles of P (175mg/m2), C (75mg/m2) and C (600mg/m2) after optimal (n=22) or suboptimal (n=32) debulking surgery. Median age at treatment was 52 years. Tumour histology was adenocarcinoma in all cases (34 of endometrioid subtype, 6 clear cells, and 4 undifferentiated). CA 125 was elevated after surgery in 44 patients and at the end of chemotherapy in 6 patients. A second laparotomy was performed after chemotherapy to 14 patients with macroscopic disease Results: Of 30 evaluable patients for response, 15 achieved a clinical complete response (50%), 12 a partial response (40%), and 3 disease stabilization (10%). With a median follow-up of 56 months (range: 28–153), 26 patients remain alive (49%) and 15 free of recurrence (28%). Median progression-free survival (PFS) was 19 months, and median overall survival (OS) 46 months. 5 years rates of PFS and OS were 26% and 43% respectively. OS rate for FIGO IIIc-IV patients was 35%. In a multivariate analysis, the only negative prognostic factors for survival were: FIGO stage IIIc-IV (p<0.04), suboptimal debulking surgery (p<0.001), and elevated CA 125 at the end of chemotherapy (p<0.05) Conclusions: Our study confirms the effectiveness of PCC regimen in the treatment of epithelial OC in the long term. FIGO stage, extend of debulking surgery, and CA 125 at the end of chemotherapy, are independent prognostic factors for overall survival. These long-term results support the conduct of randomised studies to determine the impact of this triplet in the treatment of advanced ovarian cancer No significant financial relationships to disclose.

The value of abdominal CT scans in decision-making during chemotherapy in ovarian cancer.

During chemotherapy of ovarian cancer many CT scans are performed to assess tumor response during treatment. The aim of this study was to determine the value of abdominal CT scan in the decision to continue chemotherapy or not, after the standard six cycles. All ovarian cancer patients diagnosed between 1991 and 1997 were retrospectively included in the study. Clinical parameters, surgical results, diagnostic test results, and therapeutic strategies were collected from medical records. With logistic modeling those parameters were chosen that predicted best the chance of receiving additional chemotherapy. The chance of receiving further chemotherapy after six cycles based on these parameters was computed and compared to the chance based on CT scan results in addition to these parameters. Arbitrarily we defined a change of over 20% as meaningful. Eighteen of 50 included patients (36%) received over six cycles of chemotherapy; 29 patients (10%) were at low risk for receiving over six cycles, because they had an optimal debulking surgery and low levels of CA-125 at cycle six. The chance of receiving continued chemotherapy after taking into account positive tumor signs on CT-scan was 22%. This figure further increased to 33% if tumor presence was based on judgment of two CT scans. High-risk patients were patients with suboptimal debulking surgery or patients with an optimal debulking, but high CA-125 levels at cycle six (n = 21). Based on these parameters their chance of receiving additional chemotherapy was 71%, and after taking into account results of one or two CT-scans, the risks increased to 74% and 81%, respectively. CT scans are of no value in deciding the number of chemotherapy cycles in the initial treatment for ovarian cancer. They cost a lot of money, can add a lot of confusion, and offer no benefit over results of debulking surgery and CA-125 levels.

The role of interval debulking surgery in ovarian cancer.

The mainstay of treatment for advanced ovarian cancer is the multimodality approach of debulking surgery and paclitaxel--platinum chemotherapy. The size of residual lesions after primary surgery remains the most important prognostic factor for survival. Optimal primary debulking surgery can be performed in approximately 40% of patients and up to 80% if it is done by gynecologic oncologists, but sometimes at the cost of considerable morbidity and even mortality. Based on a trial conducted by the European Organization for Research and Treatment of Cancer, optimal as well as suboptimal interval debulking surgery increases overall (P=0.0032) and progression-free survival (P=0.0055). However, not all patients who have undergone suboptimal primary debulking surgery seem to benefit from interval debulking surgery. Preliminary data from the Gynecologic Oncology Group interval debulking study (GOG-152) indicate that, if the gynecologic oncologist makes a maximal effort to resect the tumor, patients who have undergone suboptimal debulking surgery probably gain little benefit from interval debulking surgery.

High-Dose Platinum versus Standard Dose in Advanced Ovarian Carcinoma: A Randomized Trial from the Gynecologic Cooperative Group of the French Comprehensive Cancer Centers (FNCLCC)

Objective. The aim of this study was to evaluate the impact of platinum dose intensity on pathological response rate and overall survival in patients with advanced ovarian adenocarcinoma.Methods. Between February 1992 and December 1996, 195 previously untreated patients with FIGO stage IIb-c, IIIb-c, or IV with macroscopic residual disease after suboptimal debulking surgery were randomized to receive CCC (100 mg/m2 of cisplatin, 300 mg/m2 of cyclophosphamide, 300 mg/m2 of carboplatin, n = 96) or CC (100 mg/m2 of cisplatin, 600 mg/m2 of cyclophosphamide, n = 99) for six courses at 28-day intervals. A second-look laparotomy was planned at the end of chemotherapy.Results. In the CCC arm, the platinum compound received dose intensity and relative total dose were 85 and 76%; in the CC arm, they were 94 and 85%. Grade 3–4 toxicity was more frequent in the CCC arm than in the CC arm for leukopenia (56% vs 26%, P < 0.001), febrile neutropenia (18% vs 4%, P = 0.002), anemia (31% vs 5%, P < 0.001), thrombopenia (55% vs 4%, P < 0.001), and ototoxicity (8% vs 0%, P < 0.001). The pathologic complete response rate was 22 and 14% in the CCC and CC arms, respectively (P = 0.19). With a median follow-up of 53 months, the median time to failure and the 3-year treatment failure-free survival rate were 17.4 months and 22% vs 13 months and 11% in the two arms, respectively (P = 0.01). The median survival time and the 3-year overall survival rate were, respectively, 30 months and 42% vs 25 months and 33% (P < 0.20).Conclusion. The platinum dose intensification (1.6-fold increase) obtained with the CCC association improves the treatment failure-free survival without significant impact on overall survival when compared with the CC regimen in suboptimal debulked ovarian adenocarcinoma. However, because of its high rate of hematologic toxicity and ototoxicity, this association cannot be recommended for routine practice.

Interval debulking surgery: An alternative for primary surgical debulking?

Retrospective analyses suggest that a subgroup of patients with Stage III and IV ovarian carcinoma can be treated with neo-adjuvant chemotherapy followed by interval debulking surgery. The absolute indications for neo-adjuvant chemotherapy appear to be Stage IV disease (excluding pleural fluid) or metastases of more than 1 g at sites where resection is impossible. In patients with an estimated total metastatic tumor load of >100 g, the presence of at least two of the following relative indications for neo-adjuvant chemotherapy are considered to be necessary: 1) uncountable (>100) peritoneal metastases, 2) estimated metastatic tumor load of >1000 g, 3) presence of large (>10 g) peritoneal metastatic plaques, 4) large volume ascites, and 5) World Health Organization (WHO) status II or III. Interval debulking surgery in patients with suboptimal primary debulking surgery has been proven effective in increasing overall survival and progression-free survival in a large prospective, randomized trial of the European Organization for Research and Treatment of Cancer (EORTC). The strategy of neo-adjuvant chemotherapy, followed by interval debulking surgery, should be confirmed in a prospective randomized trial. The EORTC 55971 trial is currently addressing this issue. We will review the studies on primary chemotherapy, interval debulking surgery, and the indications for primary chemotherapy followed by interval debulking surgery, and ongoing trials. Semin. Surg. Oncol. 19:49–53, 2000. © 2000 Wiley-Liss, Inc.

Interval debulking surgery: an alternative for primary surgical debulking?

Retrospective analyses suggest that a subgroup of patients with Stage III and IV ovarian carcinoma can be treated with neo-adjuvant chemotherapy followed by interval debulking surgery. The absolute indications for neo-adjuvant chemotherapy appear to be Stage IV disease (excluding pleural fluid) or metastases of more than 1 g at sites where resection is impossible. In patients with an estimated total metastatic tumor load of >100 g, the presence of at least two of the following relative indications for neo-adjuvant chemotherapy are considered to be necessary: 1) uncountable (>100) peritoneal metastases, 2) estimated metastatic tumor load of >1000 g, 3) presence of large (>10 g) peritoneal metastatic plaques, 4) large volume ascites, and 5) World Health Organization (WHO) status II or III. Interval debulking surgery in patients with suboptimal primary debulking surgery has been proven effective in increasing overall survival and progression-free survival in a large prospective, randomized trial of the European Organization for Research and Treatment of Cancer (EORTC). The strategy of neo-adjuvant chemotherapy, followed by interval debulking surgery, should be confirmed in a prospective randomized trial. The EORTC 55971 trial is currently addressing this issue. We will review the studies on primary chemotherapy, interval debulking surgery, and the indications for primary chemotherapy followed by interval debulking surgery, and ongoing trials.

Advanced ovarian cancer: Long-term results following chemotherapy and second-look laparotomy

Thirty patients who showed a complete clinical response to cis-platinum-containing combination chemotherapy underwent second-look laparotomy. Seventeen patients (56.7%) achieved a pathologically confirmed complete remission as documented by a negative second-look laparotomy. After a minimum follow-up of 60 months, 6 of 17 patients developed recurrent disease and subsequently died. Due to the occurrence of late relapse in these negative second-look patients routine second-look laparotomy to confirm pathological response cannot be justified. Ten of thirty patients underwent secondary cytoreductive surgery at second-look operation. All ten patients had suboptimal initial debulking surgery. Five of these ten patients (50%) survived 4 years. Secondary cytoreductive surgery may improve survival in patients who undergo suboptimal initial debulking surgery.