A phase II trial of the BCL-2 homolog domain 3 mimetic AT-101 in combination with docetaxel for recurrent, locally advanced, or metastatic head and neck cancer

• Published in: Investigational new drugs 2016-08, Vol.34 (4), p.481-489
• Main Authors: Swiecicki, Paul L., Bellile, Emily, Sacco, Assuntina G., Pearson, Alexander T., Taylor, Jeremy M. G., Jackson, Trachette L., Chepeha, Douglas B., Spector, Matthew E., Shuman, Andrew, Malloy, Kelly, Moyer, Jeffrey, McKean, Erin, McLean, Scott, Sukari, Ammar, Wolf, Gregory T., Eisbruch, Avraham, Prince, Mark, Bradford, Carol, Carey, Thomas E., Wang, Shaomeng, Nör, Jacques E., Worden, Francis P.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer; Cancer therapies; Carcinoma, Squamous Cell - drug therapy; Chemotherapy; Clinical trials; Cytotoxicity; Disease-Free Survival; Drug Administration Schedule; Drug dosages; Female; Gossypol - administration & dosage; Gossypol - adverse effects; Gossypol - analogs & derivatives; Gossypol - therapeutic use; Head & neck cancer; Head and Neck Neoplasms - drug therapy; Humans; Kinases; Male; Medical research; Medicine; Medicine & Public Health; Metastasis; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Oncology; Patients; Pharmacology; Pharmacology/Toxicology; Phase II Studies; Radiation; Response rates; Squamous cell carcinoma; Studies; Taxoids - administration & dosage; Taxoids - adverse effects; Taxoids - therapeutic use; Toxicity; Treatment Outcome; Vascular endothelial growth factor
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-016-0364-5

Summary Background : AT-101 is a BCL-2 Homolog domain 3 mimetic previously demonstrated to have tumoricidal effects in advanced solid organ malignancies. Given the evidence of activity in xenograft models, treatment with AT-101 in combination with docetaxel is a therapeutic doublet of interest in metastatic head and neck squamous cell carcinoma. Patients and Methods : Patients included in this trial had unresectable, recurrent, or distantly metastatic head and neck squamous cell carcinoma (R/M HNSCC) not amenable to curative radiation or surgery. This was an open label randomized, phase II trial in which patients were administered AT-101 in addition to docetaxel. The three treatment arms were docetaxel, docetaxel plus pulse dose AT-101, and docetaxel plus metronomic dose AT-101. The primary endpoint of this trial was overall response rate. Results : Thirty-five patients were registered and 32 were evaluable for treatment response. Doublet therapy with AT-101 and docetaxel was well tolerated with only 2 patients discontinuing therapy due to treatment related toxicities. The overall response rate was 11 % (4 partial responses) with a clinical benefit rate of 74 %. Median progression free survival was 4.3 months (range: 0.7–13.7) and overall survival was 5.5 months (range: 0.4–24). No significant differences were noted between dosing strategies. Conclusion : Although met with a favorable toxicity profile, the addition of AT-101 to docetaxel in R/M HNSCC does not appear to demonstrate evidence of efficacy.