Hello, I have read some papers about hematologic malignancies. And, I wondered why investigators compare short-term infusion and continuous infusion during phase I study.
And also, I wondered why they use 'peripheral blast' and 'bone marrow blast' to check the effects of drug. (before and after)
Please explain. Thank you!
Kim,
You can achieve the same exposure levels of drug in plasma with either short infusion of high dose of it, or by using lower dose for extended period of time. The efficacy can be very different in both cases, depending on what is driving the effects - highest drug concentration in the blood (then the short term infusion will be better) or duration of exposure to a lower concentration of the drug (then the continuous infusion is better). Side effects will be different too, especially if the drug is quite toxic - then you really want to smooth over the concentration vs time curve to avoid dangerous spike at the beginning of the dosing. As for the blasts, they don't normally appear in the blood unless you have a malignancy, and usually they are the spill-over blasts from bone marrow after that gets choke-full of immature BM cells most of which are transformed BM cells. So the peripheral blasts are a reflection of disease progression that is initiated in the bone marrow. When drug works, it kills most the peripheral cells and significant portion of BM blasts, but often some of the BM blasts remain intact and, if not destroyed completely, lead to relapse
Hi Kim, phase-1 studies are all about how well the drug is tolerated in humans using escalating doses with different infusions. If it has adverse side effects in phase-1 it will not make it to phase-2.
I don't know about the "blast" and will refer to Vadim's explanation.
The chemotherapy drugs are classified as Mild , Moderate and Severe - due to their components and adverse effects of chemotherapy drugs. The Phase I for example Leukemia children - Induction Phase -Inj.Vincristine , Inj.Doxorubicin with antiemetic drug Inj. Ondansetran and Cortico steroids will be administered - based on treatment protocol ( 4-6 weeks).
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