NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines

PURPOSE: To evaluate the relative effect of percent maximal cytoreductive surgery and other prognostic variables on survival among cohorts of patients with advanced-stage ovarian carcinoma treated with platinum-based chemotherapy. MATERIALS AND METHODS: Eighty-one cohorts of patients with stage III or IV ovarian carcinoma (6,885 patients) were identified from articles in MEDLINE (1989 through 1998). Linear regression models, with weighted correlation calculations, were used to assess the effects on log median survival time of the proportion of each cohort undergoing maximal cytoreduction, dose-intensity of the platinum compound administered, proportion of patients with stage IV disease, median age, and year of publication. RESULTS: There was a statistically significant positive correlation between percent maximal cytoreduction and log median survival time, and this correlation remained significant after controlling for all other variables (P < .001). Each 10% increase in maximal cytoreduction was associat...

Survival Effect of Maximal Cytoreductive Surgery for Advanced Ovarian Carcinoma During the Platinum Era: A Meta-Analysis

Of the 670 patients randomly 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; ClinicalTrials.gov number, NCT00003636.)

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Neoadjuvant Chemotherapy or Primary Surgery in Stage IIIC or IV Ovarian Cancer

BACKGROUND:
Primary surgery followed by platinum-taxane based chemotherapy has been the standard therapy in advanced ovarian cancer. However, the prognostic role of complete and so-called optimal and suboptimal debulking and its interaction with biological factors has not been not fully defined.

METHODS:
Exploratory analysis was conducted of 3 prospective randomized trials (AGO-OVAR 3, 5, and 7) investigating platinum-taxane based chemotherapy regimens in advanced ovarian cancer conducted between 1995 and 2002.

RESULTS:
A total of 3126 patients were analyzed. Approximately one-third each fulfilled criteria for complete resection (group A), small residual tumor burden of 1-10 mm (group B), or macroscopic residual disease exceeding 1 cm in diameter (group C). Multivariate analysis showed improved progression-free and overall survival for group A with complete resection compared with groups B or C (P < .0001). The impact of so-called optimal debulking as in group B showed a smaller prognostic impact compared with group C. Further independent prognostic factors for overall survival were age, performance status, grade, FIGO stage, and histology, namely the mucinous subtype. An interaction between residual tumor and some biologic factors was demonstrated.

CONCLUSIONS:
The goal of primary surgery should be complete resection. The prognostic impact of tumor biology seemed to be partially overruled by residual tumor and further evaluation of biologic factors should stratify for residual tumor. Cancer 2009. © 2009 American Cancer Society.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.24149

Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials: by the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d'Investigateurs Nationaux Pour les Etudes des Cancers de l'Ovaire (GINECO).

BACKGROUND: A randomized trial conducted by the Gynecologic Oncology Group (GOG, study #111) in the United States showed a better outcome for patients with advanced ovarian cancer on the paclitaxel-cisplatin regimen than for those on a standard cyclophosphamide-cisplatin regimen. Before considering the paclitaxel-cisplatin regimen as the new "standard," a group of European and Canadian investigators planned a confirmatory phase III trial. METHODS: This intergroup trial recruited 680 patients with broader selection criteria than the GOG #111 study and administered paclitaxel as a 3-hour instead of a 24-hour infusion; progression-free survival was the primary end point. Patient survival was analyzed by use of the Kaplan-Meier technique. Treatment effects on patient survival were estimated by Cox proportional hazards regression models. All statistical tests were two-sided. RESULTS: The overall clinical response rate was 59% in the paclitaxel group and 45% in the cyclophosphamide group; the complete clinical remission rates were 41% and 27%, respectively; both differences were statistically significant (P =.01 for both). At a median follow-up of 38.5 months and despite a high rate of crossover (48%) from the cyclophosphamide arm to the paclitaxel arm at first detection of progression of disease, a longer progression-free survival (log-rank P =.0005; median of 15.5 months versus 11.5 months) and a longer overall survival (log-rank P =. 0016; median of 35.6 months versus 25.8 months) were seen in the paclitaxel regimen compared with the cyclophosphamide regimen. CONCLUSIONS: There is strong and confirmatory evidence from two large randomized phase III trials to support paclitaxel-cisplatin as the new standard regimen for treatment of patients with advanced ovarian cancer.

/pdf/randomized-intergroup-trial-of-cisplatin-paclitaxel-versus-my9m93ns8r.pdf

Randomized Intergroup Trial of Cisplatin–Paclitaxel Versus Cisplatin–Cyclophosphamide in Women With Advanced Epithelial Ovarian Cancer: Three-Year Results

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 randomized 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 randomly assigned to undergo either debulking surgery or no surgery, followed by further cycles of cyclophosphamide and cisplatin. The study end points were progression-free survival 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 randomization, 278 could be evaluated (140 patients who underwent surgery and 138 patients who did not). Progression-free and overall survival were bo...

/pdf/the-effect-of-debulking-surgery-after-induction-chemotherapy-2y68kblytk.pdf

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

The Gynecological Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer.The Effect of Debulking Surgery After Induction Chemotherapy on the Prognosis in Advanced Epithelial Ovarian Cancer

BACKGROUND: A dose-response relationship for doxorubicin in ovarian cancer (OC) cell lines has been demonstrated in vitro. However, this has never been carefully addressed in the clinic. These data and the more favourable toxicity profile of the anthracycline analogue epirubicin were reasons to study high-dose epirubicin (HDE) in OC patients who relapsed on/after platinum-based chemotherapy. This was done both in a phase I/II feasibility study (n = 27; HDE dose 120-200 mg/m2 q3 weeks) and a still ongoing straightforward phase II study (n = 91; HDE dose 150-180 mg/m2 q 3 weeks). RESULTS: Responses were observed at all dose levels. Overall 24 of the 118 patients responded (20%), which is much higher than reported with lower doses (7% with doses of 60-110 mg/m2). The most important side effects were myelosuppression, alopecia, nausea and vomiting and mucositis. CONCLUSION: HDE is tolerable and has activity in second-line after platinum-based chemotherapy in OC patients.

High-dose epirubicin in platinum-pretreated patients with ovarian carcinoma: the EORTC-GCCG experience.

A phase II study of high-dose epirubicin in ovarian cancer patients previously treated with cisplatin

https://research.vumc.nl/ws/files/9070578/7566

A. Kobierska

Papers

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

The Gynecological Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer.The Effect of Debulking Surgery After Induction Chemotherapy on the Prognosis in Advanced Epithelial Ovarian Cancer

High-dose epirubicin in platinum-pretreated patients with ovarian carcinoma: the EORTC-GCCG experience.

A phase II study of high-dose epirubicin in ovarian cancer patients previously treated with cisplatin

High-dose intensity regimens with epirubicin in ovarian cancer.