Phase I and pharmacokinetic study of ABI-007, albumin-bound paclitaxel, administered every 3 weeks in Japanese patients with solid tumors.
OBJECTIVE
ABI-007 is a novel Cremophor EL-free nanoparticle albumin-bound paclitaxel. This Phase I study was designed to evaluate tolerability and determine recommended dose for Japanese patients when ABI-007 was administered in every-3-week schedule. Pharmacokinetics of paclitaxel was also assessed.


METHODS
Patients with advanced solid tumors refractory to standard therapy received a 30 min intravenous infusion of ABI-007 every 3 weeks without pre-medications at 200, 260 or 300 mg/m(2), respectively. Tolerability and recommended dose were determined by the standard '3 + 3' rule.


RESULTS
No dose-limiting toxicity was observed, despite the dose escalation. In another cohort, 260 mg/m(2) was re-evaluated and resulted in no dose-limiting toxicity. Grade 3 or 4 neutropenia was reported for the majority of patients (n = 8) but no incidence of febrile neutropenia. Non-hematological toxicities were generally mild except for Grade 3 sensory neuropathy (n = 3). Pharmacokinetic study demonstrated the area under the curve of paclitaxel increased with increasing the dosage, and comparable pharmacokinetic parameters to the western population. Partial response was observed in three non-small cell lung cancer patients. Two of whom had received docetaxel-containing chemotherapy prior to the study.


CONCLUSIONS
ABI-007 administered in every-3-week schedule was well tolerated up to 300 mg/m(2), and recommended dose was determined at 260 mg/m(2) in consideration of efficacy, toxicities and similarity of pharmacokinetic profile in western studies. Additional studies of single-agent ABI-007 as well as platinum-based combinations, particularly in patients with non-small cell lung cancer, are warranted.
Department of Internal Medicine, National Cancer Center Hospital, Tokyo 104-0045, Japan.
Kazuhiko
K
Yamada
Noboru
N
Yamamoto
Yasuhide
Y
Yamada
Toru
T
Mukohara
Hironobu
H
Minami
Tomohide
T
Tamura
D000328:Adult; D000368:Aged; D000068196:Albumin-Bound Paclitaxel; D000418:Albumins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D044466:Asian People; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D007564:Japan; D016014:Linear Models; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D053758:Nanoparticles; D009369:Neoplasms / Q000188:drug therapy* / Q000208:ethnology; D020258:Neurotoxicity Syndromes / Q000209:etiology; D017239:Paclitaxel / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*
D000068196:Albumin-Bound Paclitaxel; D000418:Albumins; D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel