Abstract
The response of the B16 melanoma to the simultaneous combination of CY plus CCNU was examined using cell survival and growth delay endpoints. Combination data were evaluated either by applying the simple concept that an additive combination response is equal to the sum of the single agent responses or by constructing additivity envelopes as described recently by Steel & Peckham (1979), in order to take account of non-linear dose-response curves. Although cell survival was additive on the simple basis, tumour growth delay was greater than predicted by the simple concept, but still within the additivity envelopes. This apparent anomaly may, however, be explained by considering the relationship between the two endpoints. Although the extent of growth delay of a tumour is dependent on the level of tumor cell survival, it is also influenced by other factors such as the rate of regrowth of surviving tumour cells, which may in turn be affected by systemic host effects resulting from the same treatment. We have recently shown that tumour cell repopulation after CY treatment is much slower than after CCNU, and in this paper we demonstrate by means of a transplantation experiment that this is probably due to a systemic host effect of CY. Thus, the observed growth delay response of the combination is consistent with a model in which the agents produce additive cell killing, but the subsequent tumour cell repopulation is retarded by a systemic effect of CY.
Full text
PDF
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Mulder J. H., Edelstein M. B., Lelieveld P., van Putten I. M. Synergism and schedule dependent cytotoxicity of cyclophosphamide and CCNU in experimental cancer chemotherapy. Eur J Cancer. 1978 May;14(5):537–542. doi: 10.1016/0014-2964(78)90257-8. [DOI] [PubMed] [Google Scholar]
- Steel G. G., Adams K., Stephens T. C. Clonogenic assays in the B16 melanoma: response to cyclophosphamide. Br J Cancer. 1977 Nov;36(5):618–624. doi: 10.1038/bjc.1977.239. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Steel G. G., Peckham M. J. Exploitable mechanisms in combined radiotherapy-chemotherapy: the concept of additivity. Int J Radiat Oncol Biol Phys. 1979 Jan;5(1):85–91. doi: 10.1016/0360-3016(79)90044-0. [DOI] [PubMed] [Google Scholar]
- Stephens T. C., Peacock J. H., Steel G. G. Cell survival in B16 melanoma after treatment with combinations of cytotoxic agents: lack of potentiation. Br J Cancer. 1977 Jul;36(1):84–93. doi: 10.1038/bjc.1977.158. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stephens T. C., Peacock J. H. 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):313–321. doi: 10.1038/bjc.1977.195. [DOI] [PMC free article] [PubMed] [Google Scholar]