Phase I study of high-dose piroxantrone with granulocyte colony-stimulating factor
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Adult; Aged; Anthraquinones; Antineoplastic Agents; Bone Marrow Diseases; Drug Administration Schedule; Female; Granulocyte Colony-Stimulating Factor; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Neoplasms; Pyrazoles
Musculoskeletal Diseases | Oncology | Pharmacy and Pharmaceutical Sciences
PURPOSE: We performed a phase I trial of piroxantrone with and without granulocyte colony-stimulating factor (G-CSF) to determine whether the use of this cytokine would enable us to increase the dose-intensity of piroxantrone.
PATIENTS AND METHODS: Thirty-eight patients received 121 courses of piroxantrone administered once every 21 days. Initial patient cohorts received piroxantrone alone starting at 150 mg/m2 and the dose was escalated in subsequent patients until dose-limiting toxicity (DLT) was reached. Patient cohorts then received escalating doses of piroxantrone starting at 185 mg/m2 administered with G-CSF beginning day 2.
RESULTS: Dose-limiting neutropenia occurred in three of six patients treated with 185 mg/m2 piroxantrone; the maximum-tolerated dose (MTD) of piroxantrone alone was 150 mg/m2. Three of six patients treated with piroxantrone and G-CSF exhibited dose-limiting thrombocytopenia at 445 mg/m2; the MTD of piroxantrone with G-CSF was thus 355 mg/m2. Seven patients developed symptomatic congestive heart failure (CHF) at cumulative piroxantrone doses ranging from 855 to 2,475 mg/m2 and two have died of cardiotoxicity. Of these patients, six of seven had previously received doxorubicin. Other nonhematologic toxicity was mild.
CONCLUSION: The use of G-CSF results in a more than twofold increase in the MTD of piroxantrone. However, symptomatic cardiotoxicity is prominent, especially in patients who have received prior treatment with anthracyclines.
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Citation: J Clin Oncol. 1993 Sep;11(9):1795-803.
Savarese, Diane M. F.; Denicoff, Andrea M.; Berg, Stacey L.; Hillig, Marianne; Baker, Stephen P.; O'Shaughnessy, Joyce A.; Chow, Catherine; Otterson, Gregory A.; Balis, Frank M.; Poplack, David G.; and Cowan, Kenneth H., "Phase I study of high-dose piroxantrone with granulocyte colony-stimulating factor" (1993). Information Technology Publications and Presentations. Paper 40.