Phase II study of ispinesib in recurrent or metastatic squamous cell carcinoma of the head and neck.
Ispinesib (SB-715992) inhibits the mitotic kinesin spindle protein (KSP), a novel target for anticancer therapy. A phase II study was conducted to examine the efficacy of ispinesib in recurrent or metastatic head and neck squamous cell carcinoma (RMHNSC). Patients with up to one prior line of chemotherapy for RMHNSC were treated with ispinesib 18 mg/m2 IV over 1 hour every 21 days. Twenty-one patients were enrolled onto this study with a target stage I sample size of 19. Of 20 evaluable patients, no objective responses were seen and stable disease > 2 cycles was observed in five patients (25%). The median time to progression was 1.4 (95% CI 1.3-2.3) months, median survival was 3.5 (95% CI 2.8-7.8) months, and 1 year overall survival was 20% (95% CI 8.3-48.1%). The most frequent attributable grades III-V adverse events were neutropenia (60% of patients) and leukopenia (55%). The pharmacokinetic profile was consistent with results from phase I studies. Archival tissues (n = 14) demonstrated low to moderate KSP expression by immunohistochemistry. In addition, no pharmacodynamic changes were observed in peripheral blood mononuclear cells. We detected no antitumor activity of ispinesib in RMHNSC on this dosing schedule.
Tang
Patricia A
PA
Princess Margaret Phase II Consortium, Toronto, ON, Canada.
Siu
Lillian L
LL
Chen
Eric X
EX
Hotte
Sebastien J
SJ
Chia
Stephen
S
Schwarz
James K
JK
Pond
Gregory R
GR
Johnson
Caitlin
C
Colevas
A Dimitrios
AD
Synold
Timothy W
TW
Vasist
Lakshmi S
LS
Winquist
Eric
E
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001549:Benzamides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D016547:Kinesins / Q000037:antagonists & inhibitors; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D009503:Neutropenia / Q000139:chemically induced; D011799:Quinazolines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; C470243:KIF11 protein, human; D011799:Quinazolines; C508757:ispinesib; D016547:Kinesins