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.
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.
Authors: W M Koch; J A Brennan; M Zahurak; S N Goodman; W H Westra; D Schwab; G H Yoo; D J Lee; A A Forastiere; D Sidransky Journal: J Natl Cancer Inst Date: 1996-11-06 Impact factor: 13.506
Authors: P N Lara; R Higdon; N Lim; K Kwan; M Tanaka; D H Lau; T Wun; J Welborn; F J Meyers; S Christensen; R O'Donnell; C Richman; S A Scudder; J Tuscano; D R Gandara; K S Lam Journal: J Clin Oncol Date: 2001-03-15 Impact factor: 44.544
Authors: G L Clayman; A K el-Naggar; S M Lippman; Y C Henderson; M Frederick; J A Merritt; L A Zumstein; T M Timmons; T J Liu; L Ginsberg; J A Roth; W K Hong; P Bruso; H Goepfert Journal: J Clin Oncol Date: 1998-06 Impact factor: 44.544
Authors: J A Brennan; J O Boyle; W M Koch; S N Goodman; R H Hruban; Y J Eby; M J Couch; A A Forastiere; D Sidransky Journal: N Engl J Med Date: 1995-03-16 Impact factor: 91.245