Details

Autor(en) / Beteiligte

• HADDAD, Robert I
• WEINSTEIN, Lisa J
• DEROSA, Carolyn
• YULE, Murray
• MILLER, Linda P
• LODA, Massimo
• POSNER, Marshall R
• SHAPIRO, Geoffrey I
• WIECZOREK, Tad J
• BHATTACHARYA, Nandita
• RAFTOPOULOS, Harry
• OSTER, Martin W
• XINXIN ZHANG
• LATHAM, Vaughan M
• COSTELLO, Rosemary
• FAUCHER, Jarrod

Titel

A phase II clinical and pharmacodynamic study of E7070 in patients with metastatic, recurrent, or refractory squamous cell carcinoma of the head and neck: Modulation of retinoblastoma protein phosphorylation by a novel chloroindolyl sulfonamide cell cycle inhibitor

Ist Teil von

• Clinical cancer research, 2004-07, Vol.10 (14), p.4680-4687

Ort / Verlag

Philadelphia, PA: American Association for Cancer Research

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• E7070 is a synthetic sulfonamide cell cycle inhibitor that induces hypophosphorylation of the retinoblastoma (Rb) protein and G(1) arrest in vitro. This Phase II study was conducted to explore the efficacy, safety, and pharmacodynamics of E7070 in squamous cell carcinoma of the head and neck (SCCHN). Patients with metastatic, recurrent, or refractory SCCHN, treated with no more than one prior therapy for recurrent disease, received E7070 at 700 mg/m(2) over 1 h every 3 weeks. Pre- and posttreatment tumor fine needle aspirates were subjected to immunohistochemistry with a panel of phospho-specific anti-Rb antibodies. End points included progression-free survival, response rate and duration, overall survival, toxicity profile, and inhibition of Rb phosphorylation. Because none of the first 15 patients achieved progression-free survival > 4 months, the early stopping rule was invoked. Eleven patients had oropharyngeal cancer and 12 were male. Median age was 59 years (range, 49-73 years). Thirty-nine cycles of E7070 were delivered (median, 2.6 cycles/patient; range, 1-5 cycles). Six patients had stable disease after 2 cycles and 2 patients each subsequently received 1, 2, and 3 additional cycles, respectively, before experiencing progression. Immunohistochemistry of tumor cell aspirates from 3 patients demonstrated reduced Rb phosphorylation posttreatment. At this dose and schedule, E7070 is unlikely to be superior over single-agent chemotherapy in SCCHN. However, the data suggest that cdk activity can be inhibited in tumor cells, resulting in posttreatment modulation of Rb phosphorylation. In the absence of cytotoxicity, more frequent administration of E7070 may be required to sustain Rb hypophosphorylation and cytostatic growth arrest.