Mitoxantrone and high-dose ara-C in refractory malignancies: a phase I trial.
On the basis of in vitro studies demonstrating marked synergy between mitoxantrone and high-dose cytosine arabinoside (ara-C) (HiDAC) against L5178Y murine leukemia and clinical studies showing usefulness of the combination in patients with refractory acute myeloid leukemia, a phase I study was initiated to find tolerable doses for use in patients with refractory solid tumors. Initial dose levels were mitoxantrone 2 mg/m2 infused over 30 minutes, followed by high-dose ara-C 750 mg/m2 infused over 3 hours repeated once at 24 hours (total dose 4 mg/m2 mitoxantrone and 1,500 mg/m2 HiDAC per 2-day course), with planned subsequent escalation of mitoxantrone. Moderate-to-severe myelosuppression, however, required sequential dose reduction of both agents. Nonhematologic toxicity was restricted to manageable nausea and vomiting in one-half the patients and a single episode of transient delirium of uncertain etiology. No responses were observed in 23 heavily pretreated patients with a wide variety of malignancies. On the basis of this study, doses of 187-375 mg/m2 ara-C given every 24 hours for two doses following mitoxantrone 1 mg/m2 every 24 hours for two doses would be tolerated by most patients with subsequent dose escalation in some as allowed by myelosuppression.
Smith
W J
WJ
Cancer Center of Wake Forest University, Winston-Salem, North Carolina.
Muss
H B
HB
Capizzi
R L
RL
White
D R
DR
Richards
F
F
Jackson
D V
DV
Powell
B L
BL
Zekan
P J
PJ
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects; D003561:Cytarabine / Q000008:administration & dosage* / Q000627:therapeutic use; D004341:Drug Evaluation; D006801:Humans; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage* / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy*
D003561:Cytarabine; D008942:Mitoxantrone