Association between in Vitro Platinum Resistance in the EDR Assay and Clinical Outcomes for Ovarian Cancer Patients

Holloway, Robert W.; Mehta, Rita S.; Finkler, Neil J.; Li, Kuo-Tung; McLaren, Christine E.; Parker, Ricardo J.; Fruehauf, John P.

doi:10.1006/gyno.2002.6797

Cited by 82 publications

(52 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Figure 7A depicts the Kaplan-Meier survival curves for these cases, and demonstrates a clear relationship between the degrees of in vitro resistance seen in the assay and clinical outcome. Konecny et al (2000) and Holloway et al (2001) both reported similar results for newly diagnosed stage III and IV ovarian cancer patients treated with platinum-based chemotherapy after initial cytoreductive surgery. The study of Konecny et al (2000) employed the ATP assay, while Holloway et al (2001) utilized the EDR assay.…”

Section: In Vitro Drug Response and Patient Survivalmentioning

confidence: 66%

“…Konecny et al (2000) and Holloway et al (2001) both reported similar results for newly diagnosed stage III and IV ovarian cancer patients treated with platinum-based chemotherapy after initial cytoreductive surgery. The study of Konecny et al (2000) employed the ATP assay, while Holloway et al (2001) utilized the EDR assay. These two groups independently found that in vitro resistance to either cisplatin or carboplatin was an adverse factor, with significantly reduced progression-free survival seen in patients with tumors that were resistant to platinum in vitro.…”

Section: In Vitro Drug Response and Patient Survivalmentioning

confidence: 66%

“…These two groups independently found that in vitro resistance to either cisplatin or carboplatin was an adverse factor, with significantly reduced progression-free survival seen in patients with tumors that were resistant to platinum in vitro. Konecny et al (2000) found that median time to progression was 2.3-fold shorter for the platinum-resistant group, while Holloway et al (2001) found a 4-fold difference. Figure 7B shows the Kaplan-Meier overall survival curves for the cases studied by Holloway et al (2001).…”

Section: In Vitro Drug Response and Patient Survivalmentioning

confidence: 98%

See 2 more Smart Citations

In vitro assay-assisted treatment selection for women with breast or ovarian cancer.

Fruehauf¹

2002

Endocrine-Related Cancer

View full text Add to dashboard Cite

The selection of chemotherapy for women with breast or ovarian carcinoma has been traditionally based on results from phase III comparative trials that define the most active drugs and drug combinations. This approach has led to a significant prolongation of the lives of these patients. Unfortunately, few patients with advanced stage IV disease are cured using the currently available regimens. In order to improve the selection process for individual patients, various types of in vitro tests that assess the activity of standard drugs on a patient's tumor have been developed over the past five decades. As with bacterial culture and sensitivity tests, significant predictive correlations between in vitro drug-response assays and cancer patient response and survival have been demonstrated. Medicare currently covers in vitro drug-resistance assays. This review discusses the historical development of in vitro drug-response assays and the clinical validation of various technologies currently available to assist the clinician in selecting the optimal therapy for each patient.

show abstract

Section: In Vitro Drug Response and Patient Survivalmentioning

confidence: 66%

Section: In Vitro Drug Response and Patient Survivalmentioning

confidence: 66%

Section: In Vitro Drug Response and Patient Survivalmentioning

confidence: 98%

See 1 more Smart Citation

In vitro assay-assisted treatment selection for women with breast or ovarian cancer.

Fruehauf¹

2002

Endocrine-Related Cancer

View full text Add to dashboard Cite

show abstract

“…In this study, we applied a third-generation in vitro drug response assay to determine if drug resistance patterns for paired synchronous cases were related to the metastatic process and possibly subject to clonal divergence [9,11,12]. Separation of the large number of tumor specimens into primary ovarian and metastatic groups did not uncover any striking differences in chemoresistance profiles for the four agents studied.…”

Section: Discussionmentioning

confidence: 99%

“…Focusing on drug resistance, Holloway et al correlated the clinical outcome of 79 evaluable chemotherapy naïve patients with advanced ovarian cancer to the EDR assay results for cisplatin and carboplatin [11]. In vitro platinum resistance remained an independent predictor of progression-free survival (6 months vs. 24 months) and overall survival (19% vs. 68%) in a multivariate analysis.…”

Section: Discussionmentioning

confidence: 99%

Conservation of in vitro drug resistance patterns in epithelial ovarian carcinoma

Tewari

Mehta

Burger

et al. 2005

Gynecologic Oncology

Self Cite

View full text Add to dashboard Cite

Purpose. To compare the in vitro drug resistance profiles of advanced stage primary and recurrent epithelial ovarian cancer specimens using the tritiated thymidine uptake assay.Methods. Extreme drug resistance (EDR) to cisplatin, paclitaxel, 4-hydroxycyclophosphamide, and topotecan was determined for an unselected population of primary and metastatic malignant ovarian tissues, synchronous tumors (primary and metastatic tissues obtained from the same patient at diagnosis), and metachronous lesions (specimens from the same patient before and after chemotherapy).Results. For the large unselected population of malignant tissues (total, N = 6990; primary ovarian, N = 2031; metastatic ovarian, N = 4959), no statistically significant differences were discovered between primary tissues and metastatic lesions when a comparison was made between the percentage of tumors from each group that exhibited extreme drug resistance to the agents assayed. From the library of 6990 specimens, 119 synchronous pairings were identified. These synchronous lesions did not differ significantly in the %EDR between primary and metastatic sites in the same patient; approximately 10% shifted between low drug resistance and EDR. A total of 334 metachronous pairings were identified and the percentage of tissues that exhibited EDR also failed to show a significant difference when primary tumors were compared with matched recurrences in the same patient.Conclusions. For the agents studied, acquired resistance was not a function of disease site. In vitro drug resistance observed at recurrence was not influenced significantly by intervening therapy. It is possible that assay results at diagnosis could be used to guide subsequent therapy at relapse, especially when recurrent tissue is not available for analysis. D

show abstract

BRCA‐related ovarian carcinoma

Rubin¹

2003

Cancer

View full text Add to dashboard Cite

A lthough only about 10% of all epithelial ovarian carcinomas occur as a result of inherited mutations in cancer predisposition genes, primarily BRCA1 and BRCA2, this subset of ovarian carcinomas has been the subject of intense interest and study, with fascinating results. The familial cancer syndromes involved were identified first by clinical epidemiologists in the 1970s and 1980s. With the advent of the molecular era, the BRCA1 and BRCA2 genes were identified in the 1990s, and we now have a relatively clear understanding of many aspects of their contribution to ovarian carcinomas. 1 The frequency of BRCA mutations varies widely according to population: In the general population of the United States, it may be approximately 1 per 1000 population; whereas, in women of eastern European Jewish ancestry, approximately 2% carry 1 of 3 founder mutations in BRCA1 or BRCA2.2,3 The lifetime risk of developing ovarian carcinoma in women who carry BRCA mutations has been estimated over a fairly broad range, with a greater risk for BRCA1 carriers. The factors that affect penetrance, which are likely to be both clinical and molecular, remain unclear to date. Loss of function of both alleles of BRCA1 or BRCA2 is required for the disease phenotype to develop, consistent with the classic model of a tumor suppressor gene. It has been shown that hereditary and sporadic carcinomas have a number of differences at the molecular level, including the fact that BRCA mutations are not found commonly in sporadic carcinomas. Information about the function of the BRCA proteins is developing, and we know that gene mutation may be only one of several pathways to the absence of a functional protein, with promoter hypermethylation and other mechanisms perhaps playing a role. 4 Translational researchers have been interested in the clinical features of BRCA-related ovarian carcinomas. Although, based on what we know about the actions of the BRCA proteins, it seems likely that BRCA mutations would have an impact on tumor biology and clinical behavior, the medical and scientific community has had a healthy skepticism regarding this possibility. After the initial report of an improved prognosis for women with ovarian carcinoma carrying BRCA1 mutations, 5 a number of authors have examined this issue. For the most part, the larger studies with long-term follow-up have confirmed this observation. To date, the most definitive data on this issue come from Boyd et al., 6 who published a large, well-designed, and well-analyzed single-institutional study using multivariate analysis to show that BRCA mutation status was a significant predictor of survival 2127

show abstract

Association between in Vitro Platinum Resistance in the EDR Assay and Clinical Outcomes for Ovarian Cancer Patients

Cited by 82 publications

References 16 publications

In vitro assay-assisted treatment selection for women with breast or ovarian cancer.

In vitro assay-assisted treatment selection for women with breast or ovarian cancer.

Conservation of in vitro drug resistance patterns in epithelial ovarian carcinoma

BRCA‐related ovarian carcinoma

Contact Info

Product

Resources

About