By Paul V. Woolley
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Extra resources for Mechanisms of Drug Resistance in Neoplastic Cells. Bristol–Myers Cancer Symposia, Volume 9
Sample text
If we envisage the process of mutation involving more than one step, then this has the effect of permitting the mutant phenotypes to accumulate within the stem-cell compartment at a greater overall rate than the rate at which they are being lost by random events. Over time this will greatly magnify the proportion of resistant stem cells that will appear as compared to a system in which no cell loss emerges. This probability of resistance developing in the presence of cell loss, Pc, is given by the equation Pc = e x p [ - a * ( J V - l ) / ( 2 P - l ) ] (4) where a* is the net overall mutation rate.
C O L D M A N followed by all the vincristine, then all of the procarbazine, etc. A randomized study of this approach compared to using the MOPP protocol has not been carried out, nor would it be ethically permissible at this time. Nonetheless, this sequential application of agents corresponds roughly to what was the treatment of Hodgkin's disease in the early 1960s before the MOPP protocol was developed. We know from experience at that time that this sequential application of active agents almost never resulted in cure, though it did result in a series of remissions of varying duration.
S. Ettinger, C. R. Mehla, Μ. D. Abeloff, J. C. Ruckdeschel, and S. Aisner, A randomized comparison of conventional chemotherapy with immediate alternation of non-cross resistant chemotherapy in extensive disease (ED) small cell lung cancer (SCLC). Proc. Am. Soc. Clin. Oncol. 5, 666 (1986). W. Hryniuk and H. Bush, The importance of dose intensity in chemotherapy of metastatic breast cancer. J. Clin. Oncol. 2, 1281-1288 (1984). M. Goodyear, W. Hryniuk, D. , Relationship of dose intensity (DI) to outcome in chemotherapy of advanced breast carcinoma.