The purpose of this study was to assess the prognostic value of in vitro
drug chemosensitivity testing using the Hamburger-Salmon human
tumor colony-forming assay (
HTCA) in fresh
tumor samples obtained from newly diagnosed patients with stage II-IV
ovarian cancer undergoing maximum
cytoreductive surgery and prior to
platinum-based
chemotherapy. The
HTCA was performed on fresh
ovarian cancers obtained from 93 patients at their initial exploratory
laparotomy to evaluate in vitro sensitivity to
cisplatin,
carboplatin, and
cyclophosphamide following a 1-hr
drug exposure. Prospective clinical follow-up was performed on all patients with the primary study endpoints being pathologically proven complete response at
second-look surgery and disease-free and overall survival durations. In vitro
drug sensitivity was strongly dose-dependent. At a concentration of 5 micrograms/ml only 23% of
tumor samples were sensitive (as defined by a > or = 50% decrease in
tumor colony-forming units compared to controls) to
cisplatin; 13% of
tumors were sensitive to
carboplatin at a concentration of 50 micrograms/ml and 11% to 4-OH-cyclophosphamide at a concentration of 1 microgram/ml. At doses which were 10 times the previously stated concentrations, the sensitivity rates to
cisplatin,
carboplatin, and 4-OH-cyclophosphamide increased to 72, 63, and 53%, respectively. Subjects were categorized as having
drug-sensitive disease if
HTCA results showed in vitro
drug sensitivity to at least one of the agents used in their primary
chemotherapy. Multivariate analysis failed to show any advantage in clinical response rate, progression-free interval, or survival duration for patients with
drug-sensitive disease compared to
drug-resistant disease; however, there was evidence of a trend toward an enhanced pathologically proven complete response rate in patients who had chemosensitive
tumors in vitro.
Second-look surgery was performed in 28 of 55 patients with optimal surgical resections and no clinical evidence of disease at the completion of their primary
chemotherapy. Fifty percent (5/10) of patients with
drug-sensitive disease achieved a
pathologic complete response, while only 3/18 (17%) patients with
drug-resistant
tumors had a documented
pathologic complete response (P = 0.13). As reported in other
ovarian cancer studies, patient characteristics which were found to be significantly associated with survival were stage of disease (II-III vs IV), optimal primary surgical resection (i.e., < 1 cm2
residual tumor) vs suboptimal resection, clinical measurability of disease at initiation of
chemotherapy, and response to primary
chemotherapy. In conclusion, in vitro
drug sensitivity, as measured by the
HTCA, does not appear to be an independent prognostic factor for survival in patients with stage II-IV
epithelial ovarian cancer who undergo standard treatment with
tumor debulking surgery and primary
platinum-based
chemotherapy.(ABSTRACT TRUNCATED AT 400 WORDS)