Chronometaanalysis: circasemiseptan (3.5-day) pattern in mitotic activity of murine sarcoma after treatment with cyclophosphamide.

This note focuses attention upon infradians in mitotic activity of a murine sarcoma. Starting on day 8 after the inoculation of mice with a sarcoma, three different doses of cyclophosphamide, one dose at three different circadian times, were injected and tumor was sampled with serial independence, mostly at 12-hour intervals during the 4 ensuing days. A metachronanalysis of these heterogeneous data, collected for a different purpose with different doses and at different circadian times, reveals the presence of a circasemiseptan pattern (P < 0.05 by population-mean cosinor). Without a longitudinal replication, the result is described only as a pattern rather than as a (recurring) rhythm, characterizing malignant growth after treatment with cyclophosphamide. For cancer chronotherapy, the analyses serve to suggest the desirability to replace exclusive focus upon circadian aspects of drug timing and drug effect by a broader view that takes into account as much of the chronome as is practical. Among the different components of a chronome (i.e., the time structure of rhythms with different frequencies and trends in a given variable), the circasemiseptans (and circa-septans) are more readily accessible than infradians with even lower frequencies; they may also be pertinent to the scheduling of infusions covering several days, particularly those using drug administration devices, some of which are programmable. Since circaseptans and circasemiseptans may characterize the host as well as the tumor, infradian drug administration schedules could be sought that optimize both treatment efficacy and host tolerance.