A phase 2 clinical trial of nab-paclitaxel in previously treated and chemotherapy-naive patients with metastatic melanoma.
BACKGROUND
nab-Paclitaxel (ABI-007, Abraxane), a 130-nM, albumin-bound (nab) particle form of Cremophor-free paclitaxel, is approved for metastatic breast cancer. In the current study, the efficacy and safety of nab-paclitaxel were evaluated in previously treated and chemotherapy-naive patients with metastatic melanoma (MM).


METHODS
Patients with histologically or cytologically confirmed, measurable MM were enrolled. nab-Paclitaxel was administered intravenously weekly for 3 of 4 weeks at a dose of 100 mg/m(2) (in previously treated patients) or 150 mg/m(2) (in chemotherapy-naive patients).


RESULTS
Thirty-seven patients were treated in each cohort. The response rate was 2.7% in the previously treated cohort and 21.6% in the chemotherapy-naive cohort; the response plus stable disease rate was 37.8% and 48.6% in the previously treated and chemotherapy-naive cohorts, respectively. The median progression-free survival (PFS) was 3.5 months and 4.5 months, and the median survival was 12.1 months and 9.6 months, respectively. The probability of being alive and free of disease progression at 6 months was 27% for the previously treated cohort and 34% for the chemotherapy-naive cohort; the probability of surviving 1 year was 49% and 41%, respectively, for the previously treated and chemotherapy-naive cohorts. Approximately 78% of the previously treated patients and 49% of the chemotherapy-naive patients were treated without dose reduction. Eight (22%) chemotherapy-naive patients discontinued therapy because of toxicities. Drug-related toxicities included grade 3 to 4 (graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0]) neuropathy, alopecia, neutropenia, and fatigue.


CONCLUSIONS
nab-Paclitaxel was found to be well tolerated and demonstrated activity in both previously treated and chemotherapy-naive patients with MM. The response rate, PFS, and survival compared favorably with current standard dacarbazine therapy and combination therapies for melanoma. nab-Paclitaxel therapy of MM should be investigated further in controlled clinical trials. Cancer 2010. (c) 2010 American Cancer Society.
Hersh
Evan M
EM
Department of Medicine, Arizona Cancer Center, Tucson, AZ 85724, USA. hersh@azcc.arizona.edu
O'Day
Steven J
SJ
Ribas
Antoni
A
Samlowski
Wolfram E
WE
Gordon
Michael S
MS
Shechter
Deganit E
DE
Clawson
Alicia A
AA
Gonzalez
Rene
R
D000368:Aged; D000068196:Albumin-Bound Paclitaxel; D000418:Albumins / Q000009:adverse effects / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000009:adverse effects / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality
D000068196:Albumin-Bound Paclitaxel; D000418:Albumins; D000970:Antineoplastic Agents; D017239:Paclitaxel