TY - JOUR
T1 - A phase 2 trial of surgery with perioperative INGN 201 (Ad5CMV-p53) gene therapy followed by chemoradiotherapy for advanced, resectable squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx
T2 - Report of the southwest oncology group
AU - Yoo, George H.
AU - Moon, James
AU - LeBlanc, Michael
AU - Lonardo, Fulvio
AU - Urba, Susan
AU - Kim, Harold
AU - Hanna, Ehab
AU - Tsue, Terry
AU - Valentino, Joseph
AU - Ensley, John
AU - Wolf, Gregory
PY - 2009/9
Y1 - 2009/9
N2 - Objective: To assess the feasibility of treating patients with high-risk stage III and IV squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx with perioperative adenovirus-p53 (INGN 201) gene therapy along with surgery and chemoradiotherapy. Design and Setting: A phase 2 study in a multi-institutional setting within the Southwest Oncology Group. Patients: Thirteen individuals who met the following entry criteria: newly diagnosed, previously untreated squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx; selected stage III or IV disease without distant metastases; and surgically resectable disease. Interventions: Surgery, perioperative INGN 201 gene therapy, and postoperative chemoradiotherapy. Main Outcome Measures: Overall patient status, tumor status, adverse effects, accrual rate, and percentage of patients successfully receiving the required doses of INGN 201. Results: All 13 patients received surgery and perioperative INGN 201 injections in the primary tumor bed and the ipsilateral neck. In addition, 3 patients received injections in the contralateral neck. Three patients did not receive chemoradiotherapy. One patient had a grade 2 fistula of the oral cavity. Of the 10 patients with evaluable data, 2 experienced grade 4 adverse events, 1 owing to hypokalemia, hyponatremia, vomiting, leukopenia, and neutropenia and 1 owing to increased aspartate aminotransferase and alanine aminotransferase levels. Seven other patients experienced grade 3 adverse events. The estimate of 1-year progression-free survival is 92%. Conclusions: This trial demonstrated the feasibility of handling and delivering a very complex gene vector safely in multiple cooperative group institutions without significant incident. Intraoperative INGN 201 gene therapy is technically feasible, but it has many logistical problems when performed in a multi-institutional setting. Regulatory requirements might have hindered accrual in this multi-institutional setting. Disease control seems to be promising; however, no definitive conclusion can be made with this small sample size. Trial Registration: clinicaltrials.gov Identifier: NCT00017173.
AB - Objective: To assess the feasibility of treating patients with high-risk stage III and IV squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx with perioperative adenovirus-p53 (INGN 201) gene therapy along with surgery and chemoradiotherapy. Design and Setting: A phase 2 study in a multi-institutional setting within the Southwest Oncology Group. Patients: Thirteen individuals who met the following entry criteria: newly diagnosed, previously untreated squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx; selected stage III or IV disease without distant metastases; and surgically resectable disease. Interventions: Surgery, perioperative INGN 201 gene therapy, and postoperative chemoradiotherapy. Main Outcome Measures: Overall patient status, tumor status, adverse effects, accrual rate, and percentage of patients successfully receiving the required doses of INGN 201. Results: All 13 patients received surgery and perioperative INGN 201 injections in the primary tumor bed and the ipsilateral neck. In addition, 3 patients received injections in the contralateral neck. Three patients did not receive chemoradiotherapy. One patient had a grade 2 fistula of the oral cavity. Of the 10 patients with evaluable data, 2 experienced grade 4 adverse events, 1 owing to hypokalemia, hyponatremia, vomiting, leukopenia, and neutropenia and 1 owing to increased aspartate aminotransferase and alanine aminotransferase levels. Seven other patients experienced grade 3 adverse events. The estimate of 1-year progression-free survival is 92%. Conclusions: This trial demonstrated the feasibility of handling and delivering a very complex gene vector safely in multiple cooperative group institutions without significant incident. Intraoperative INGN 201 gene therapy is technically feasible, but it has many logistical problems when performed in a multi-institutional setting. Regulatory requirements might have hindered accrual in this multi-institutional setting. Disease control seems to be promising; however, no definitive conclusion can be made with this small sample size. Trial Registration: clinicaltrials.gov Identifier: NCT00017173.
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U2 - 10.1001/archoto.2009.122
DO - 10.1001/archoto.2009.122
M3 - Article
C2 - 19770418
AN - SCOPUS:70349348934
VL - 135
SP - 869
EP - 874
IS - 9
ER -