Abstract
A series of human bronchial-carcinoma xenografts (3 small-cell anaplastic, 2 large-cell anaplastic and 3 adenocarcinomas) established in immune-suppressed mice were treated with combination chemotherapy based on clinical regimes. Xenograft response was assessed by the in situ endpoint of growth delay in s.c. tumours. Dose-response relationships of 3 triple-drug combinations and their component agents were explored, allowing the relative contributions of single agents in each combination to be assessed. The results demonstrate that the effects produced in the xenografts were generally consistent with clinical experience. Procarbazine, cyclophosphamide and CCNU stood out as the most effective drugs in small cell carcinoma, but were ineffective in the other histological types. These was some evidence for individuality of therapeutic response among the grafts, supporting the case for incorporating panels of histologically similar xenografts into primary drug-screening programmes to complement existing syngeneic rodent tumour systems.
MeSH Terms
Adenocarcinoma/drug therapy
Animals
Antineoplastic Agents/therapeutic use
Antineoplastic Combined Chemotherapy Protocols
Carcinoma, Small Cell/drug therapy
Cyclophosphamide/therapeutic use
Dose-Response Relationship, Drug
Doxorubicin/therapeutic use
Drug Therapy, Combination
Female
Fluorouracil/therapeutic use
Humans
Lomustine/therapeutic use
Lung Neoplasms/drug therapy,pathology
Methotrexate/therapeutic use
Mice
Mice, Inbred CBA
Neoplasm Transplantation
Neoplasms, Experimental/drug therapy
Procarbazine/therapeutic use
Transplantation, Heterologous
Vincristine/therapeutic use
Chemicals
Antineoplastic Agents
Procarbazine
Vincristine
Lomustine
Doxorubicin
Cyclophosphamide
Fluorouracil
Methotrexate
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Shorthouse A J
Jones J M
Steel G G
Peckham M J
Supplementary Concepts
CAF protocol (Protocol)
MCC protocol (Protocol)
VAP combination (Protocol)
References (20)
20 references, click to expand
-
Quantitative comparison of toxicity of anticancer agents in mouse, rat, hamster, dog, monkey, and man.
Cancer Chemother Rep. 1966 May;50(4):219-44
PMID: 4957125
-
Comparison of the dose- and timesurvival curves for normal hematopoietic and lymphoma colony-forming cells exposed to vinblastine, vincristine, arabinosylcytosine, and amethopterin.
J Natl Cancer Inst. 1969 Jun;42(6):1015-25
PMID: 5793185
-
Panel report. Morphologic classification of bronchogenic carcinoma.
Cancer Chemother Rep 3. 1973 Mar;4(2):299-301
PMID: 4729334
-
Heterotransplantation of human malignant tumors in "nude" thymusless mice. I. Breeding and maintenance of "nude" mice.
J Natl Cancer Inst. 1973 Aug;51(2):615-9
PMID: 4765375
-
Drugs 5 years later: procarbazine.
Ann Intern Med. 1974 Dec;81(6):795-800
PMID: 4611297
-
The therapeutic response of three human tumor lines maintained in immune-suppressed mice.
Cancer Res. 1975 Oct;35(10):2704-13
PMID: 1157045
-
Advances in small cell bronchogenic carcinoma.
Cancer Treat Rep. 1977 May-Jun;61(3):333-42
PMID: 194690
-
Tumour volume response, initial cell kill and cellular repopulation in B16 melanoma treated with cyclophosphamide and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea.
Br J Cancer. 1977 Sep;36(3):313-21
PMID: 921888
-
Maintenance of biological and biochemical characteristics of human colorectal tumours during serial passage in immune-deprived mice.
Br J Cancer. 1978 Feb;37(2):199-212
PMID: 629858
-
Improved immune-suppression techniques for the exongrafting of human tumours.
Br J Cancer. 1978 Feb;37(2):224-30
PMID: 343803
-
Quantitation of differential sensitivity of human-tumor stem cells to anticancer drugs.
N Engl J Med. 1978 Jun 15;298(24):1321-7
PMID: 77475
-
Treatment of small cell carcinoma: evolution and future directions.
Semin Oncol. 1978 Sep;5(3):299-308
PMID: 211641
-
The growth and therapeutic response of human tumours in immune deficient mice.
Bull Cancer. 1978;65(4):465-72
PMID: 371709
-
Results of two sequential chemotherapy studies in WHO Types I, III and IV lung cancer: cyclophosphamide-5-fluorouracil (CF) and cyclophosphamide-5-fluorouracil-adriamycin (CAF).
Eur J Cancer. 1979 Mar;15(3):331-5
PMID: 376316
-
Tumour-cell killing by X-rays and immunity quantitated in a mouse model system.
Br J Cancer. 1979 May;39(5):603-6
PMID: 486318
-
Small-cell lung cancer. A curable disease.
Cancer Chemother Pharmacol. 1980;4(3):173-7
PMID: 6249514
-
The Ara-C pretreated mouse as a host for human tumour xenografts.
Br J Cancer Suppl. 1980 Apr;4:158
PMID: 6932921
-
The human tumour xenograft--a valid model in experimental chemotherapy?
Br J Surg. 1980 Oct;67(10):715-22
PMID: 6253000
-
Failure of intensive combination therapy (cyclophosphamide, adriamycin, 5-fluorouracil) to control adenocarcinoma or large-cell anaplastic carcinoma of lung.
Cancer Chemother Pharmacol. 1980;4(4):271-3
PMID: 6254685
-
Current results of the screening program at the Division of Cancer Treatment, National Cancer Institute.
Eur J Cancer. 1981 Feb;17(2):129-42
PMID: 6894902