Phase I study of weekly outpatient paclitaxel and concurrent cranial irradiation in adults with astrocytomas.
OBJECTIVE
Astrocytomas are extremely resistant to currently available treatments. Cranial irradiation is a mainstay of frontline therapy, but tumor recurrence is nearly universal. Paclitaxel has shown antitumor efficacy against astrocytoma cell lines, and is a potent radiosensitizer. For these reasons, we conducted a phase I study of weekly paclitaxel and concurrent cranial irradiation in patients with newly diagnosed astrocytomas.


METHODS
Patients with astrocytomas were eligible for this study following initial surgery if they had a Karnofsky performance score (KPS) > or = 60%; normal hematologic, liver, and renal function; and could give informed consent. Beginning on day 1 of treatment, patients received paclitaxel by 3-hour infusion once weekly for 6 weeks, concurrent with standard cranial irradiation. Pharmacokinetic studies were performed on 10 patients.


RESULTS
Sixty patients were enrolled; 56 were fully assessable. Forty-eight had glioblastomas (GBMs), 10 anaplastic astrocytomas (AAs), and two astrocytomas. Age ranged from 21 to 81 years (median, 55); KPS ranged from 60 to 100 (median, 70). The paclitaxel dose was escalated from 20 mg/m2 to 275 mg/m2. No clinically significant anemia or thrombocytopenia occurred. Only one patient (175 mg/m2) became neutropenic. Sensory neuropathy was dose-limiting. The maximum tolerated dose (MTD) was 250 mg/m2. Paclitaxel pharmacokinetic profiles in study patients were identical to those of previously reported patients with other solid tumors.


CONCLUSIONS
The MTD of paclitaxel administered weekly for 6 weeks by 3-hour infusion is 250 mg/m2. Since patients with brain tumors often have preexisting neurologic deficits, we suggest 225 mg/m2 as the optimum dose for phase II trials in this group of patients.
Glantz
M J
MJ
Department of Medicine, Brown University School of Medicine, Providence, RI.
Choy
H
H
Kearns
C M
CM
Cole
B F
BF
Mills
P
P
Zuhowski
E G
EG
Saris
S
S
Rhodes
C H
CH
Stopa
E
E
Egorin
M J
MJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001254:Astrocytoma / Q000532:radiotherapy / Q000628:therapy*; D001932:Brain Neoplasms / Q000532:radiotherapy / Q000628:therapy*; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005909:Glioblastoma / Q000628:therapy; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel