Functional profiling with cell culture assays that predicts for patient survival in ovarian cancer
There is Functional Profiling (whole cell profiling) that shows data indicating a near doubling in the survival of patients with platinum-resistant ovarian cancer, striking correlations between platinum activity and patient survival in previously-untreated ovarian cancer, and a comprehensive meta-analysis of scores of studies reporting response and survival correlations in thousands of patients.
With relapsed, platinum-resistant ovarian cancer, every clinical trial in history has just shown a 10-12 month median survival in this setting. However, background data (680 fresh surgical specimens) for the design of a cliinical trial to determine the efficacy of assay-directed therapy of platinum-resistant ovarian cancer, submitted to the 2003 Society of Gynecologic Oncology meeting, had a 27 month median survival and a fair number of long-term survivors. All specimens were tested with two separate Medicare-approved cell culture assays (DISC and MTT) having cell-death endpoints.
Cell culture drug resistance testing in platinum-resistant ovarian cancer
Sub-category: Translational research
Control/Tracking Number: 2004-AB-171-SGO
Activity: Abstract Richard H. Nalick, Hospital of the Good Samaritan, Los Angeles, CA; Larry M. Weisenthal, Weisenthal Cancer Group, Huntington Beach, CA
Objectives: Obtained background data required for the design of a clinical trial to determine the efficacy of assay-directed therapy of platinum-resistant ovarian cancer.
Methods: 680 fresh surgical specimens of ovarian cancer were submitted from outside hospitals for the purpose of obtaining cell culture assay data to assist in the choice of chemotherapy on a non-investigational basis. Virtually all surgical specimens were tested with two separate Medicare-approved cell culture assays (DISC and MTT) having cell-death endpoints.
Results: Validation of cell culture assays for identifying platinum resistance was as follows.
1. Surgical specimens from platinum-treated patients had significantly greater in vitro resistance to platinum than surgical specimens from untreated patients.
2. Untreated patients without in vitro resistance to platinum had significantly better long-term, overall survival than patients with in vitro resistance to platinum (2775 vs 713 days, P2=0.0066).
3. Surgical specimens obtained within 6 months of platinum-based therapy had significantly greater in vitro resistance to platinum than surgical specimens obtained more than 6 months after the last platinum-based therapy.
4. In patients more than 6 months after the last platinum-based therapy, in vitro resistance to platinum predicted for significantly inferior long-term, overall survival (950 days vs median not reached, P2<0.05).
Comparing early relapse surgical specimens with untreated surgical specimens, the following regimens showed significantly inferior activity in early relapse surgical specimens: cisplatin, carboplatin, oxaliplatin, melphalan, thiotepa, mitomycin, paclitaxel, and the topotecan + cicplatin combination. The following did not show significantly inferior activity in ER surgical specimens: gemcitabine, etoposide, vinorelbine, fluorouracil, epirubicin, pegylated doxorubicin, topotecan, irinotecan, docetaxel, and all 3 gemcitabine + platinum combinations. Although the gemcitabine + platinum combination was the only active regimen in 25% of the early relapse surgical specimens, in 30% there was at least one active single agent, and in another 20%, other drug combinations were superior to gemcitabine + platinum, some of these being irinotecan + mitomycin, paclitaxel + cyclophosphamide, cyclophosphamide + etoposide, platinum + topotecan, and gemcitabine + melphalan. With a minimum follow-up of 3 years post-assay, early relapse (primary refractory and first relapse) patients had a median long-term, overall survival of 849 days, while all early relapse patients (including multiple relapse) had a median survival of 612 days. All late relapse patients had a median long-term, overall survival of 1244 days.
Conclusions: These results support a 3-armed, prospective randomized trial in early relapse patients to compare physician's choice chemotherapy, assay-directed therapy, and the 3 gemcitabine + platinum combination.
There have been 5 different studies of the relationship between the results of Cell Culture Assay Testing and patient survival in ovarian cancer, and all 5 studies show significant correlations between these assays and patient survival.