Phase I study of escalating doses of mitoxantrone and paclitaxel with granulocyte-macrophage colony stimulating factor support.
BACKGROUND
Both paclitaxel and mitoxantrone demonstrate significant antineoplastic activity in breast cancer patients. Colony stimulating factor support allows significant dose escalation of each of these drugs when administered as a single agent.


METHODS
We performed a Phase I study employing escalating doses of paclitaxel and mitoxantrone with granulocyte-macrophage colony stimulating factor (GM-CSF) support. Initially the paclitaxel dose was fixed at 175 mg/m2 and an attempt was made to escalate mitoxantrone from the starting dose of 14 mg/m2. Subsequently, the dose of mitoxantrone was fixed at 14 mg/m2 and the dose of paclitaxel was increased. Treatments were given every three weeks.


RESULTS
In neither case could we safely escalate beyond a combination of paclitaxel 175 mg/m2 and mitoxantrone 14 mg/m2 which is, therefore, the recommended Phase II dose. The dose limiting toxicity was neutropenia. No unexpected toxicities were observed, although two patients were removed from the study because of chest pain possibly related to GM-CSF. There were no complete or partial remissions.


CONCLUSIONS
We conclude that GM-CSF does not allow significant dose escalation of this combination of agents.
Fleming
G F
GF
Department of Medicine, University of Chicago, Illinois 60637-1470, USA.
Janisch
L
L
Vogelzang
N J
NJ
Vokes
E E
EE
Ratain
M J
MJ
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects; D009369:Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011994:Recombinant Proteins / Q000627:therapeutic use; D017211:Treatment Failure
D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008942:Mitoxantrone; D017239:Paclitaxel