Abstract
Dolastatin-10 is a novel pentapeptide agent originally isolated from the marine mollusk Dolabella auricularia with a mechanism of antitumor activity that involves the inhibition of microtubule assembly. We performed a Phase II trial of Dolastatin-10, 400 μg/m2, in patients with advanced melanoma who had received no prior chemotherapy. Dolastatin-10 pharmokinetics were evaluated in a subset of patients following courses 1 and 2. Twelve patients were treated with a median of 2 cycles of Dolastatin-10, and no patient experienced an objective response. The only grade >2 toxicities were grade 3 neutropenia uncomplicated by infection, occurring in 4 patients following the first treatment cycle. The total systemic clearance and volume of distribution at steady-state were 2.61 ± 1.9 L/h/m2 and 28.4 ± 13 L/m2, respectively. Due to prolonged terminal elimination, Dolastatin-10 plasma concentrations of greater than 1 nM were sustained for 24 h in all patients studied. Dolastatin-10 is unlikely to have substantial activity in the treatment of melanoma.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 335-340 |
| Number of pages | 6 |
| Journal | Investigational New Drugs |
| Volume | 19 |
| Issue number | 4 |
| DOIs | |
| State | Published - 2001 |
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Keywords
- Dolastatin-10
- Metastatic melanoma
- Pharmokinetics
ASJC Scopus subject areas
- Molecular Medicine
- Pharmacology
Cite this
Dolastatin-10 in metastatic melanoma : A phase II and pharmokinetic trial of the California Cancer Consortium. / Margolin, Kim; Longmate, Jeffrey; Synold, Timothy W.; Gandara, David R; Weber, Jeffrey; Gonzalez, Rene; Johansen, Mary J.; Newman, Robert; Baratta, Tracey; Doroshow, James H.
In: Investigational New Drugs, Vol. 19, No. 4, 2001, p. 335-340.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Dolastatin-10 in metastatic melanoma
T2 - A phase II and pharmokinetic trial of the California Cancer Consortium
AU - Margolin, Kim
AU - Longmate, Jeffrey
AU - Synold, Timothy W.
AU - Gandara, David R
AU - Weber, Jeffrey
AU - Gonzalez, Rene
AU - Johansen, Mary J.
AU - Newman, Robert
AU - Baratta, Tracey
AU - Doroshow, James H.
PY - 2001
Y1 - 2001
N2 - Dolastatin-10 is a novel pentapeptide agent originally isolated from the marine mollusk Dolabella auricularia with a mechanism of antitumor activity that involves the inhibition of microtubule assembly. We performed a Phase II trial of Dolastatin-10, 400 μg/m2, in patients with advanced melanoma who had received no prior chemotherapy. Dolastatin-10 pharmokinetics were evaluated in a subset of patients following courses 1 and 2. Twelve patients were treated with a median of 2 cycles of Dolastatin-10, and no patient experienced an objective response. The only grade >2 toxicities were grade 3 neutropenia uncomplicated by infection, occurring in 4 patients following the first treatment cycle. The total systemic clearance and volume of distribution at steady-state were 2.61 ± 1.9 L/h/m2 and 28.4 ± 13 L/m2, respectively. Due to prolonged terminal elimination, Dolastatin-10 plasma concentrations of greater than 1 nM were sustained for 24 h in all patients studied. Dolastatin-10 is unlikely to have substantial activity in the treatment of melanoma.
AB - Dolastatin-10 is a novel pentapeptide agent originally isolated from the marine mollusk Dolabella auricularia with a mechanism of antitumor activity that involves the inhibition of microtubule assembly. We performed a Phase II trial of Dolastatin-10, 400 μg/m2, in patients with advanced melanoma who had received no prior chemotherapy. Dolastatin-10 pharmokinetics were evaluated in a subset of patients following courses 1 and 2. Twelve patients were treated with a median of 2 cycles of Dolastatin-10, and no patient experienced an objective response. The only grade >2 toxicities were grade 3 neutropenia uncomplicated by infection, occurring in 4 patients following the first treatment cycle. The total systemic clearance and volume of distribution at steady-state were 2.61 ± 1.9 L/h/m2 and 28.4 ± 13 L/m2, respectively. Due to prolonged terminal elimination, Dolastatin-10 plasma concentrations of greater than 1 nM were sustained for 24 h in all patients studied. Dolastatin-10 is unlikely to have substantial activity in the treatment of melanoma.
KW - Dolastatin-10
KW - Metastatic melanoma
KW - Pharmokinetics
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UR - http://www.scopus.com/inward/citedby.url?scp=0034851434&partnerID=8YFLogxK
U2 - 10.1023/A:1010626230081
DO - 10.1023/A:1010626230081
M3 - Article
VL - 19
SP - 335
EP - 340
JO - Investigational New Drugs
JF - Investigational New Drugs
SN - 0167-6997
IS - 4
ER -