Abstract
During a two-year experience treating patients with refractory acute leukemia with a fixed 12-hour schedule of high-dose ara-C, cellular ara-CTP pharmacodynamics were ascertained in circulating blasts of these patients. A strong correlation was found between achievement of complete remission and cellular ara-CTP levels. We therefore, attempted to improve the complete remission rate in patients with low ara-CTP levels by decreasing the intermittent ara-C dosing interval, thereby raising the minimum ara-CTP level in leukemic cells between doses. This initial attempt at pharmacologic direction of chemotherapy was successful in elevating minimum ara-CTP levels but did not produce an increase in response rate, probably because the total duration of ara-CTP exposure was decreased when the dose intervals were shortened. Currently we are engaged in a new approach based on the knowledge accumulated over the past three years. Patients receive a test ara-C dose from which data on ara-CTP cellular metabolism is derived, followed by a CI of ara-C at a dose calculated individually for each patient. Preliminary results of this approach thus far indicate an increased response rate and a different spectrum of toxicity than that observed with intermittent dose ara-C. Further clinical trials will determine the true effectiveness of this approach.
Original language | English (US) |
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Pages (from-to) | 20-30 |
Number of pages | 11 |
Journal | Seminars in oncology |
Volume | 12 |
Issue number | 2 SUPPL. 3 |
State | Published - Jun 1985 |
ASJC Scopus subject areas
- Hematology
- Oncology