Summary
Fractional incorporation (FI) of 3H-thymidine (i.e., the proportion of total tissue 3H incorporated into DNA) has been used as a parameter for judging temporal scheduling of cyclophosphamide and cis-dichlorodiammine platinum (DDP). Differences in the recovery times of FI following a dose of 100 mg CY/kg, between tumor (>12 days), gut (2–3 days), and bone marrow (4 days) suggested a basis for a normal tissue-sparing drug regimen when administering double-agent CY-DDP therapy. When 100 mg CY/kg and 8 mg DDP/kg were administered simultaneously or when the doses were separated by 1 day the survival was 0/10 or 1/10, respectively. However, when the doses were separated by 4 days all rats survived. This 4-day interval was considered to allow time for gut and bone marrow recovery prior to a second insult. Such factors appear crucial to the survival of the animal. These three combinations were similar in their antitumor effect, giving a greater than additive response. Cyclophosphamide was more myelotoxic than DDP, but DDP showed greater gut toxicity. The recovery of bone marrow cellularity was delayed by 2 days compared with FI. Peripheral white blood cell counts returned to normal after a further 2-day delay.
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Tew, K.D., Taylor, D.M. Cyclophosphamide and cis-dichlorodiammine platinum (11). Cancer Chemother. Pharmacol. 4, 103–109 (1980). https://doi.org/10.1007/BF00254030
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DOI: https://doi.org/10.1007/BF00254030