Phase I study of docetaxel administered by bi-weekly infusion to patients with metastatic breast cancer.
BACKGROUND
To find a more convenient and tolerable schedule than the tri-weekly or weekly schedules, we conducted a dose escalation study of bi-weekly docetaxel.


METHODS
Between March 1998 and June 1999, 16 patients entered this phase I study. The starting dose was 40 mg/m2, with planned dose escalation to 45, 50 and 55 mg/m2, in consecutive patient cohorts. Patients continued to receive the assigned treatment at the same dose level bi-weekly, provided that they did not develop progressive disease, refuse further treatment, or experience unacceptable toxicity.


RESULTS
Grade 4 neutropenia lasting for more 4 days was seen at dose level 3 in all three patients. Only one patient who had previously received intensive chemotherapy required granulocyte colony stimulating factor (G-CSF) to prevent neutropenic fever and there were no actual episodes of neutropenic fever. Grade 3 asthenia and Grade 3 elevation of serum glutamic oxaloacetic transaminase were noted in only one patient treated at a dose of 40 mg/m2. Grade 3 skin toxicity and grade 2 elevation of serum glutamic oxaloacetic transaminase were seen in only one patient treated at a dose of 55 mg/m. Cumulative toxicity was not severe in all patients. Although grade 3 and/or grade 4 neutropenia were noted in eight patients (50%), all except one who received treatment at dose of 55 mg/m2 did not need G-CSF. Nail toxicity and peripheral edema seemed to be related to the number of treatment cycles. Severe fatigue and asthenia were never seen in all patients.


CONCLUSIONS
1) The maximum-tolerated dose of docetaxel when administered by this bi-weekly schedule was 55 mg/m2; 2) Docetaxel administered on a bi-weekly basis well tolerated.
Shin
E
E
Department of Surgery, Osaka National Hospital, Hoenzaka 2-1-14, Chyuo-ku, Osaka 540-0006, Japan.
Ishitobi
M
M
Hiraoia
M
M
Kazumasa
F
F
Hideyuki
M
M
Nishisho
I
I
Toshiro
S
S
Yasunori
H
H
Tosimasa
T
T
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects*; D001247:Asthenia / Q000139:chemically induced; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004487:Edema / Q000139:chemically induced; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives*; D011994:Recombinant Proteins; D043823:Taxoids
D000972:Antineoplastic Agents, Phytogenic; D011994:Recombinant Proteins; D043823:Taxoids; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; D017239:Paclitaxel