A phase-I study evaluating the combination of pegylated liposomal doxorubicin and paclitaxel as salvage chemotherapy in metastatic breast cancer previously treated with anthracycline
Journal
Cancer Chemotherapy and Pharmacology
Journal Volume
61
Journal Issue
5
Pages
847-853
Date Issued
2008
Author(s)
Abstract
Purpose: The two main goals of this phase-I study were to determine the maximum-tolerated dose (MTD) and to characterize the toxicity of the combination of pegylated liposomal doxorubicin (PLD; Lipo-Dox) and paclitaxel (PTX) administered on a 3-week schedule in patients with metastatic breast cancer (MBC) who had previously been treated with anthracycline-based therapy. Methods: This phase-I study was performed via a two-staged dose escalation schema. The initial doses were PLD 30 mg/m2 and PTX 150 mg/m2, administered intravenously once every 21 days. The dose of PLD was escalated in increments of 5 mg/m2 until the MTD was reached, at which time the PTX was then increased in increments of 10 mg/m2 until the MTD was reached. Results: Twenty-three patients received between 1 and 13 treatment cycles. In stage I of the study, 14 patients received a fixed dose of PTX 150 mg/m2 while PLD escalated from 30 mg/m2. At 40 mg/m 2, PLD resulted in dose-limiting toxicities (DLT) including febrile neutropenia and palmar-plantar erythrodysesthesia that occurred in two of five patients. In stage II of the study, nine patients received fixed dose of PLD 35 mg/m2 and escalating doses of PTX starting at 160 mg/m2. At PTX 170 mg/m2 and dose-limiting neutropenic fever occurred in two of five patients. Out of 19 evaluable patients, 10 (52.6%) achieved objective response (one complete response and nine partial response), and 5 had stable disease. Conclusions: The maximal tolerated doses of PLD and PTX are 35 and 160 mg/m2, respectively, administered every 3 weeks. The combination of PLD (30-35 mg/m2) and PTX (150-160 mg/m2) constitutes an active regimen with mild toxicity that merits further study. ? 2007 Springer-Verlag.
SDGs
Other Subjects
anthracycline; cimetidine; cyclophosphamide; dexamethasone; diphenhydramine; doxorubicin; epirubicin; fluorouracil; paclitaxel; adult; aged; alanine aminotransferase blood level; anemia; article; aspartate aminotransferase blood level; asthenia; breast cancer; breast metastasis; cancer chemotherapy; cancer survival; clinical article; clinical trial; diarrhea; drug dose escalation; drug dose increase; drug dose reduction; drug hypersensitivity; drug megadose; edema; febrile neutropenia; female; hand foot syndrome; human; maximum tolerated dose; multicenter study; multiple cycle treatment; nausea and vomiting; neutropenia; phase 1 clinical trial; priority journal; salvage therapy; sensory neuropathy; side effect; stomatitis; thrombocytopenia; treatment response; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Doxorubicin; Drug Administration Schedule; Female; Fever; Foot Dermatoses; Hand Dermatoses; Humans; Liposomes; Maximum Tolerated Dose; Middle Aged; Neoplasm Metastasis; Neutropenia; Paclitaxel; Paresthesia; Polyethylene Glycols; Salvage Therapy; Treatment Outcome
Type
journal article