Adenocarcinoma of unknown primary: retrospective analysis of chemosensitivity of 313 freshly explanted tumors in a tumor cloning system

Abstract

Cancer of unknown primary origin is the eighth most common form of malignancy and accounts for up to 10% of all neoplasms diagnosed. It is a set of heterogenous tumors with widely varying sensitivity to systemic chemotherapy. Over the past years progress has been made in identifying subsets of patients that can be effectively treated with chemotherapy and may achieve long-term survival even with metastatic disease. However, the large majority of cancers of unknown origin still is resistant to chemotherapy. In an attempt to identify conventional and investigational new agents with possible activity against cancers of unknown primary, we have retrospectively analyzed the results of chemosensitivity testing in a soft agar cloning systemin vitro and have compared these data with published clinical trials. Between 1978 and 1993, a total of 19584 tumor specimens were studied using a variety of investigational or established antitumor agents. Of these, 615 (3.1%) were tumors of unknown origin and confirmed on pathology review. The largest histologic subgroup was adenocarcinoma (332, 54%). Sufficient numbers of cells forin vitro testing were obtained from 313 tumor specimens (94.3%). Of 278 agents tested in adenocarcinoma of unknown origin, borderline activity (in vitro response) was noted for 5-FU, doxorubicin, bleomycin, mitoxantrone, mitomycin-C, cisplatin, and etoposide.In vitro response rates of ≥20% were observed for actinomycin-D, BCNU, melphalan, methotrexate, taxol, and vinblastine. In addition, several investigational agents including fludarabine, methotrexate, taxol, and vinblastine. In addition, tiazofurin, LY104208 (vinzolidine), intoplicine, and topotecan had activity. We conclude that clinical inactivity of frequently used conventional antitumor compounds is reflected in the results of soft agar colony formation. However, several concentional and investigational agents have been identified that may hold some clinical promise, and further development of these agents with Phase II trials for patients with adenocarcinoma of unknown origin is warranted.