One of the most pressing needs in clinical oncology today is for a system which will allow selection of the most effective chemotherapeutic agent against an individual patient's tumor. The human tumor cloning system potential for predicting which drug will or will not work against a patient's tumor. However, there are considerable problems with the conventional two layer agar system performed in 35 mm petri dishes. With support provided by this grant, we have introduced a new system called the capillary cloning system. This system allows more than 80% of patients' tumors to form colonies, increases cloning efficiencies, and requires fewer tumor cells than the conventional petri dish technique. A recently completed prospective clinical trial performed by our group randomized patients with a variety of refractory solid tumors to a selection of a single chemotherapeutic agent by this capillary significantly higher response rate for the group treated according to the capillary results. However, there was not improvement in survival. These data (a higher response rate noted with the capillary system) provide a lead for further investigation. If the capillary system were used to select a combination chemotherapy regimen for patients, perhaps, that selection would have an impact on patient's survival. We propose to perform a prospective randomized trial of the capillary cloning system for patients with extensive small cell lung cancer. Small cell lung cancer was chosen because it is a common disease (25,000 deaths/year), and while the response rate to standard combination chemotherapy regimens is high (70-80%) the average survival is short (6 months). With this high response rate (of short duration) any impact of drug selection by the capillary system on response or survival should easily be detected. After stratification for important prognostic factors, patients with previously untreated extensive small cell lung cancer will be randomized to receive treatment with either a standard regimen (vincristine + Adriamycin + cytoxan) or treatment with a capillary cloning choice of drugs (most effective two or three agents in the capillary system). Tumor response, response duration, and patient survival will be assessed. This trail should define what place, if any, the capillary cloning system has in the care of the patient with extensive small cell lung cancer and may have implications for the utility of the capillary system in the care of patients with other types of malignancies.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA027733-08
Application #
3167791
Study Section
Experimental Therapeutics Subcommittee 2 (ET)
Project Start
1980-07-15
Project End
1991-01-31
Budget Start
1989-02-01
Budget End
1990-01-31
Support Year
8
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Von Hoff, D D; Sandbach, J F; Clark, G M et al. (1990) Selection of cancer chemotherapy for a patient by an in vitro assay versus a clinician. J Natl Cancer Inst 82:110-6
Von Hoff, D D (1990) He's not going to talk about in vitro predictive assays again, is he? J Natl Cancer Inst 82:96-101
Hanauske, A R; Osborne, C K; Chamness, G C et al. (1987) Alteration of EGF-receptor binding in human breast cancer cells by antineoplastic agents. Eur J Cancer Clin Oncol 23:545-51
Von Hoff, D D (1987) In vitro predictive testing: the sulfonamide era. Int J Cell Cloning 5:179-90
Harris, G J; Von Hoff, D D (1986) Drug sensitivity testing of carcinoma of the gallbladder and biliary tree in a human tumor cloning assay. Cancer Drug Deliv 3:197-204
Harris, G J; Turner, J N; Von Hoff, D D (1986) Growth of carcinoma of the esophagus and gastroesophageal junction in a human tumor cloning assay. Cancer Drug Deliv 3:273-8
Morris, G L; Zeltzer, P M; Schneider, S L et al. (1986) Cloning of pediatric malignancies for drug sensitivity testing in the human tumor cloning assay. Am J Pediatr Hematol Oncol 8:52-7
Scheithauer, W; Von Hoff, D D; Forseth, B et al. (1986) Direct effects of the hypoxic cell sensitizer misonidazole on colony formation in a human tumor cloning assay. Cancer Drug Deliv 3:15-24
Von Hoff, D D; Clark, G M; Weiss, G R et al. (1986) Use of in vitro dose response effects to select antineoplastics for high-dose or regional administration regimens. J Clin Oncol 4:1827-34
Hanauske, A R; Hanauske, U; Von Hoff, D D (1985) The human tumor cloning assay in cancer research and therapy: a review with clinical correlations. Curr Probl Cancer 9:1-66

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