Abstract | BACKGROUND: The EORTC New Drug Development Office has initiated a multicenter collaborative program to evaluate the use of human tumor xenografts to predict phase II clinical activity. A first study confirmed the efficacy of doxorubicin and inactivity of amsacrine against human tumor xenografts (Boven et al., Cancer Res: 52, 5940, 1992). In the follow-up study reported here, the activities of cisplatin, AZQ ( diaziquone), pazelliptine and retelliptine have been evaluated against a panel of 40 established tumor lines grown subcutaneously in nude mice. DESIGN: RESULTS: When activity was defined as a specific growth delay > 1 and a tumor growth inhibition > 50%, then cisplatin demonstrated activity in 15 of 40 xenografts tested (3 of 5 breast, 1 of 6 colon, 0 of 5 head+neck, 2 of 6 NSCLC, 4 of 7 SCLC, 1 of 5 melanoma and 4 of 6 ovarian cancers); AZQ was active in 23 of 38 xenografts (2 of 3 breast, 2 of 7 colon, 4 of 5 head+neck, 3 of 6 NSCLC, 6 of 6 SCLC, 2 of 5 melanoma, 4 of 6 ovarian cancers); pazelliptine was active in 2 of 38 xenografts (1 of 5 breast cancers, 1 of 5 melanoma) while retelliptine was active in 1 of 39 xenografts (a breast cancer xenograft) tested. CONCLUSIONS: These results are reasonably consistent with the clinical activity of cisplatin, but overpredict the clinical efficacy of AZQ. Since pazelliptine and retelliptine are investigational compounds, the clinical phase II studies will provide a prospective test for this model. The results of the present study and the previous one indicate that the human tumor xenograft model could be suitable for predicting the activity of novel compounds to be developed for treatment of cancer patients.
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Authors | S P Langdon, H R Hendriks, B J Braakhuis, G Pratesi, D P Berger, O Fodstad, H H Fiebig, E Boven |
Journal | Annals of oncology : official journal of the European Society for Medical Oncology
(Ann Oncol)
Vol. 5
Issue 5
Pg. 415-22
(May 1994)
ISSN: 0923-7534 [Print] England |
PMID | 8075048
(Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Aziridines
- Benzoquinones
- Ellipticines
- Indoles
- Isoquinolines
- pazelliptine
- diaziquone
- Cisplatin
- retelliptine
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology)
- Aziridines
(pharmacology)
- Benzoquinones
(pharmacology)
- Cisplatin
(pharmacology)
- Drug Screening Assays, Antitumor
- Ellipticines
(pharmacology)
- Europe
- Female
- Follow-Up Studies
- Humans
- Indoles
(pharmacology)
- Isoquinolines
(pharmacology)
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Neoplasm Transplantation
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