Paclitaxel by 72-hour continuous infusion followed by bolus intravenous ifosfamide or epirubicin: results of two phase I studies.
STUDY PURPOSES: To determine the maximum-tolerated dose (MTD) of paclitaxel administered by 72-hour continuous infusion followed by bolus intravenous ifosfamide on days 4 and 5 or epirubicin on day 4, every 21 days. To assess the toxicity and preliminary activity in patients with advanced refractory solid tumors.


METHODS
Sixteen patients with progressive disease after standard chemotherapy for advanced disease were treated with the combination paclitaxel-ifosfamide and 10 patients with the combination paclitaxel-epirubicin.


RESULTS
In the first phase I study the MTDs were: paclitaxel 135 mg/m2 and ifosfamide 2.5 mg/m2/day; hematologic toxicity was the dose-limiting toxicity (DLT) during the first cycle of therapy at dose level 4. Paclitaxel administered at 135 mg/m2 and epirubicin 50 mg/m2 were the MTDs in the second phase I study; grade 4 stomatitis was the DLT of this combination.


CONCLUSIONS
Paclitaxel by 72-hour continuous infusion followed by bolus ifosfamide was a manageable regimen with an acceptable hematologic toxicity in the absence of neurotoxicity. Preliminary activity of this combination was encouraging in a group of patients with ovarian cancer. The optimal way to combine paclitaxel and epirubicin and the best schedule relative to such a long paclitaxel infusion time in this combination regimen remain to be determined.
Miglietta
L
L
Professorial Unit of Medical Oncology, University and National Cancer Institute, University of Genoa, Italy.
Marenghi
C
C
Nizzo
R
R
Foglia
G
G
Ragni
N
N
Boccardo
F
F
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage* / Q000009:adverse effects*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects*; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D015251:Epirubicin; D017239:Paclitaxel; D007069:Ifosfamide