Phase I study of high-dose piroxantrone with granulocyte colony-stimulating factor

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Information Services, Academic Computing Services; Department of Cell Biology

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Document Type



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.


J Clin Oncol. 1993 Sep;11(9):1795-803.

Journal/Book/Conference Title

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

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Link to article in PubMed

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