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Abstract
Objective. The initial clinical response to platinum is a major determinant of outcome for patients
with ovarian cancer. This retrospective study was undertaken to correlate the response
and survival of newly diagnosed advanced ovarian cancer patients who received platinum-based
therapy with in vitro drug response to cisplatin or carboplatin measured as percentage cell inhibition
(PCI) in the in vitro Extreme Drug Resistance (EDR) assay.
Methods. Outcomes for newly diagnosed ovarian cancer patients with tumor specimens submitted
in a serial fashion for the EDR assay were studied. EDR assay results for cisplatin
and carboplatin were correlated with clinical outcome for 79 evaluable chemotherapy
naı̈ve cases who presented with advanced (stages IIC, III, and IV) ovarian
cancer. Stage IV and suboptimally debulked stage IIIc accounted for 16 cases, while
63 cases were optimally debulked Stage III/IIc. All patients were treated with platinum-based
combination chemotherapy at a single institution. In vitro results for patient tumors were classified as low drug resistance (PCI > median),
intermediate drug resistance [PCI between the median and 1 standard deviation (SD)
below the median], or extreme drug resistance (PCI more than 1 SD below the median).
For the purpose of this analysis, in vitro EDR to either cisplatin or carboplatin was considered to represent extreme resistance
to platinum (EDRP), while the absence of EDR to either cisplatin or carboplatin was
considered to represent low resistance to platinum (LDRP). Patients demonstrating
relative in vitro resistance to paclitaxel and non-cross-resistance to cyclophosphamide and/or doxorubicin
received cyclophosphamide plus platinum (CP); cyclophosphamide, doxorubicin, and platinum
(CAP); or platinum alone in place of paclitaxel plus platinum (TP). Progression-free
survival (PFS) and overall survival (OS) were correlated with EDR assay results.
Results. Median PFS was 6 months for the 17 cases exhibiting EDRP, compared to 24 months for
the 62 cases exhibiting LDRP in vitro [relative risk (RR) 3.78, confidence intervals (CI) 1.82–7.83], adjusted for stage,
debulking status, in vitro response to 3-OH-cyclophosphamide, and histological grade. Estimated overall 5-year survival was 19%
for patients with tumors showing EDRP, compared to 68% for patients with tumors showing
LDRP (RR 2.32, CI 1.06–5.07). Patients treated with CP (n = 20) showed no significant difference in OS compared to patients treated with TP
(n = 54), CAP (n = 4), or cisplatin (n = 1) alone. In vitro platinum response remained an independent predictor of PFS and OS in multivariate
analyses adjusted for CP versus TP, CAP, or platinum administration, and adjusted
for debulking status. Median PFS for all 79 patients was 22 months, with an estimated
5-year survival of 57%.
Conclusions. Patients with tumors demonstrating in vitro EDR to platinum were at significantly increased risk for progression and death when
treated with standard platinum-based regimens. Such patients may therefore benefit
from entry onto trials with novel agents or combinations.
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Article info
Publication history
Received:
January 2,
2001
Footnotes
☆The WDMCI received a data management grant from Oncotech, Inc. There are no financial conflicts of interest to report for Drs. Holloway or Finkler. Dr. Mehta is a former employee of Oncotech who holds stock options in Oncotech, Inc. She is on Oncotech's speaker's bureau. Drs. Parker and Fruehauf are employed by Oncotech, Inc.
Identification
Copyright
© 2002 Elsevier Science (USA). Published by Elsevier Inc. All rights reserved.
