Histocultures of patient head and neck tumors for pharmacodynamics studies.
This investigation was to establish a clinically relevant experimental model to evaluate the pharmacodynamics of drugs used for head and neck cancers. A total of 83 surgical samples of primary and lymph nodal metastatic tumors was obtained from 66 patients. Fragments of these tumors were cultured on a collagen gel matrix. The tumor cell labeling index (LI) was determined by [3H]thymidine incorporation and autoradiography. Seventeen tumors (20%) were contaminated. About 80% of the remaining 65 tumors were successfully cultured for at least 2 weeks. The cultured tumor fragments retained the morphology and architecture of the freshly removed specimens; both tumor and stromal cells were present. The tumor cell LI after 2-3 weeks in culture, determined from the most proliferative area of the tissue, averaged 77 +/- 12% for primary tumors and 78 +/- 12% for nodal metastases. The activity of three clinically active agents, 5-fluorouracil (FU), cisplatin (DDP), and mitomycin C (MMC), was evaluated in 47 tumors. All three drugs inhibited the tumor LI. The concentrations needed to produce a 50% inhibition of the tumor LI (IC50) were within the clinically achievable concentration range. The intertumor variation in the IC50 for FU (60-fold) was considerably greater than that for DDP and MMC (7- to 8-fold). The nodal metastatic tumors appeared to be less sensitive to FU than the primary tumors, while there were no apparent differences for DDP or MMC.(ABSTRACT TRUNCATED AT 250 WORDS)
Au
J L
JL
College of Pharmacy, Ohio State University, Columbus 43210.
Wientjes
M G
MG
Rosol
T J
TJ
Koolemans-Beynen
A
A
Goebel
E A
EA
Schuller
D E
DE
D000328:Adult; D000368:Aged; D002945:Cisplatin / Q000494:pharmacology*; D046508:Culture Techniques; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D008937:Mitomycins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D008937:Mitomycins; D002945:Cisplatin; D005472:Fluorouracil