abstract: Progression-free and overall survival of a modified outpatient regimen of primary intravenous/intraperitoneal paclitaxel and intraperitoneal cisplatin in ovarian, fallopian tube, and primary peritoneal cancer

Progression-free and overall survival of a modified outpatient regime... [Gynecol Oncol. 2012] - PubMed - NCBI

Abstract

OBJECTIVE:

GOG study 172 demonstrated improved progression-free (PFS) and overall (OS) survival for patients with stage III optimally debulked ovarian and peritoneal carcinoma treated with IV/IP paclitaxel and IP cisplatin compared to standard IV therapy. The inpatient administration, toxicity profile, and limited completion rate have been blamed for the lack of acceptance and widespread use of this regimen. We sought to evaluate the PFS, OS, toxicity, and completion rate of a modified outpatient IP regimen.


 CONCLUSIONS:
By modifying the GOG 172 treatment regimen, convenience, toxicity, and tolerability appear improved, with survival outcomes similar to those of GOG 172. This modified IV/IP regimen warrants further study.

abstract: Prognostic Value of Biomarkers Related to Drug Resistance in Patients with Advanced Epithelial Ovarian Cancer

Prognostic Value of Biomarkers Related to Drug Resistance in Patients with Advanced Epithelial Ovarian Cancer:

Background/Aim:
We aimed to investigate the prognostic value of biomarkers [Ki-67, adenosine triphosphate-binding cassette sub-family B member 1 (ABCB1), adenosine triphosphate-binding cassette sub-family C member 1 (ABCC1), adenosine triphosphate-binding cassette sub-family C member 2 (ABCC2), p53, cyclin E and v-akt murine thymoma viral oncogene homolog 2 (AKT2)] in patients with advanced epithelial ovarian cancer (EOC).

Materials and Methods:
The levels of expression of biomarkers in tumor tissues of 47 patients with stage 3 or 4 EOC were estimated via immunohistochemical staining using tissue microarrays. The associations of biomarker expression with progression-free survival (PFS) and overall survival (OS) were evaluated using a log-rank test and Cox regression analysis.

Results:
Based on multivariate analysis, high expression of Ki-67 (p=0.003) and low expression of ABCC2 (p=0.048) were associated with a prolonged PFS. However, other biomarkers were not associated with PFS. Residual tumor <1 cm (p=0.023) and PFS >6 months (p=0.005) were associated with prolonged OS. However, none of the biomarkers were associated with OS. 

Conclusion: High expression of Ki-67 and low expression of ABCC2 appear to be useful as markers for prolonged PFS in patients with advanced EOC.

Identifying Clinical Improvement in Consolidation Single-Arm Phase 2 Trials in Patients With Ovarian Cancer in Second or Greater Clinical Remission

Abstract

Objective: Estimates of progression-free survival (PFS) from single-arm phase 2 consolidation/maintenance trials for recurrent ovarian cancer are usually interpreted in the context of historical controls. We illustrate how the duration of second-line therapy (SLT), the time on the investigational therapy (IT), and patient enrollment plan can affect efficacy measures from maintenance trials and might result in underpowered studies.

Conclusions:

Designs of nonrandomized consolidation trials that aim to prolong PFS must consider the effect of the duration of SLT on the end point definition and on required sample size. If IT is given concurrently with SLT, and after SLT, then SLT duration must be restricted per protocol eligibility, so that a comparison with historical data from other single-arm phase 2 studies is unbiased. If IT is given after SLT, the duration of SLT should be taken into account in the design stage because it will affect statistical power and sample size.

abstract: Correlation between CA-125 serum level and response by RECIST in a phase III recurrent ovarian cancer study.

OBJECTIVES:

To evaluate in a large phase III recurrent ovarian cancer trial (OVA-301): 1) the concordance between CA-125 level vs. best overall response (OR) and progression-free survival (PFS) determined by radiological assessment 2) the impact of early CA-125 changes over the subsequent radiological response, and 3) the prognostic value of CA-125 response and CA-125 PFS to predict radiological response and PFS.

Correlation of extreme drug resistant assay results and progression-free survival following intraperitoneal chemotherapy for advanced ovarian cancer (Oncotech assay)

Abstract

The aim of this study was to determine if in vitro extreme drug resistance (EDR) to platinum and/or taxane chemotherapy was predictive of patient response to intraperitoneal (I.P.) chemotherapy in patients with stage III or recurrent epithelial ovarian cancer (EOC).

Fifty-six patients were retrospectively identified who underwent optimal cytoreductive surgery for primary or recurrent eOC and then received at least three cycles of either intravenous (I.V.) or I.P. chemotherapy with platinum and paclitaxel-based chemotherapy. EDR to platinum and/or paclitaxel was determined using a commercially available assay (Oncotech, Inc., Tustin, CA).

The primary outcome measure was progression-free survival (PFS).

Twenty-nine (52%) patients received I.P. chemotherapy and 27 (48%) received I.V. chemotherapy. The patients were well matched in terms of age, stage, grade and histology. Ten (35%) patients in the I.OP. arm and ten (37%) patients in the I.V. arm showed EDR to either platinum and/or paclitaxel. Median PFS for all I.P. chemotherapy patients was 23 months, compared with 13 months for those receiving I.V. chemotherapy (p = 0.04).

Patients with EDR to platinum and/or taxane who underwent I.V. chemotherapy had a median PFS of 13.5 months, whereas those who underwent I.P. treatment had a median PFS of 15 months (p = 0.69). Median overall survival had not been reached at the time of analysis. No significant difference in PFS was noted between patients who underwent I.P. and those who underwent I.V. chemotherapy when EDR was predicted to either platinum or paclitaxel or both. These data suggest that the decision to offer I.P. chemotherapy, with the attendant increase in morbidity, in the setting of EDR to platinum and/or taxane chemotherapy, may not be beneficial. 

Prospective studies, preferably analyzing platinum or taxane EDR individually, are required to validate these observations.