Oblimersen in combination with temozolomide and albumin-bound paclitaxel in patients with advanced melanoma: a phase I trial.
OBJECTIVE
The combination of oblimersen, a bcl-2 antisense oligonucleotide, and dacarbazine lead to superior progression-free survival in advanced melanoma patients. Albumin-bound paclitaxel (nab-paclitaxel) has single-agent activity in melanoma.


METHODS
In a phase I trial, chemotherapy-naïve patients with metastatic melanoma and normal LDH levels were enrolled on 3 cohorts. The treatment regimen consisted of 56-day cycles of oblimersen (7 mg/kg/day continuous IV infusion on day 1-7 and 22-28 in cohort 1 and 2; 900 mg fixed dose, twice weekly in weeks 1-2, 4-5 for cohort 3), temozolomide (75 mg/m(2), days 1-42), and nab-paclitaxel (175 mg/m(2) in cohort 1 and 3, 260 mg/m(2) in cohort 2 on day 7 and 28). Apoptosis markers were tested in pre- and post-treatment specimens of a subset of patients.


RESULTS
Six grade 3 events (neutropenia, renal insufficiency, hyponatremia, elevated creatinine, allergic reaction, and neuropathy) and 2 grade 4 events (neutropenia and thrombocytopenia) were seen in 32 patients. The objective response rate was 40.6% (2 complete responses and 11 partial responses) and 11 patients had stable disease, for a disease control rate of 75%.


CONCLUSIONS
The combination of oblimersen, temozolomide, and nab-paclitaxel was well tolerated and demonstrated encouraging activity in patients with advanced melanoma.
Division of Medical Oncology, NYU Cancer Institute, New York University School of Medicine, New York, NY 10016, USA. Patrick_Ott@DFCI.harvard.edu
Patrick A
PA
Ott
Jason
J
Chang
Kathleen
K
Madden
Rajni
R
Kannan
Caroline
C
Muren
Crystal
C
Escano
Xin
X
Cheng
Yongzhao
Y
Shao
Sandra
S
Mendoza
Alex
A
Gandhi
Leonard
L
Liebes
Anna C
AC
Pavlick
D000328:Adult; D000368:Aged; D000068196:Albumin-Bound Paclitaxel; D000418:Albumins / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage; D017239:Paclitaxel / Q000008:administration & dosage; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077204:Temozolomide; D013873:Thionucleotides / Q000008:administration & dosage; D016896:Treatment Outcome
D000068196:Albumin-Bound Paclitaxel; D000418:Albumins; D016376:Oligonucleotides, Antisense; D013873:Thionucleotides; D003606:Dacarbazine; C408162:oblimersen; D017239:Paclitaxel; D000077204:Temozolomide