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Phase I/II study of oncolytic HSV GM-CSF in combination with radiotherapy and cisplatin in untreated stage III/IV squamous cell cancer of the head and neck.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2010 Aug 01; Vol. 16 (15), pp. 4005-15. - Publication Year :
- 2010
-
Abstract
- Purpose: This study sought to define the recommended dose of JS1/34.5-/47-/GM-CSF, an oncolytic herpes simplex type-1 virus (HSV-1) encoding human granulocyte-macrophage colony-stimulating factor (GM-CSF), for future studies in combination with chemoradiotherapy in patients with squamous cell cancer of the head and neck (SCCHN).<br />Experimental Design: Patients with stage III/IVA/IVB SCCHN received chemoradiotherapy (70 Gy/35 fractions with concomitant cisplatin 100 mg/m(2) on days 1, 22, and 43) and dose-escalating (10(6), 10(6), 10(6), 10(6) pfu/mL for cohort 1; 10(6), 10(7), 10(7), 10(7) for cohort 2; 10(6), 10(8), 10(8), 10(8) for cohort 3) JS1/34.5-/47-/GM-CSF by intratumoral injection on days 1, 22, 43, and 64. Patients underwent neck dissection 6 to 10 weeks later. Primary end points were safety and recommended dose/schedule for future study. Secondary end points included antitumor activity (radiologic, pathologic). Relapse rates and survival were also monitored.<br />Results: Seventeen patients were treated without delays to chemoradiotherapy or dose-limiting toxicity. Fourteen patients (82.3%) showed tumor response by Response Evaluation Criteria in Solid Tumors, and pathologic complete remission was confirmed in 93% of patients at neck dissection. HSV was detected in injected and adjacent uninjected tumors at levels higher than the input dose, indicating viral replication. All patients were seropositive at the end of treatment. No patient developed locoregional recurrence, and disease-specific survival was 82.4% at a median follow-up of 29 months (range, 19-40 months).<br />Conclusions: JS1/34.5-/47-/GM-CSF combined with cisplatin-based chemoradiotherapy is well tolerated in patients with SCCHN. The recommended phase II dose is 10(6), 10(8), 10(8), 10(8). Locoregional control was achieved in all patients, with a 76.5% relapse-free rate so far. Further study of this approach is warranted in locally advanced SCCHN.<br /> ((c) 2010 AACR.)
- Subjects :
- Adult
Aged
Antibodies, Viral blood
Antigens, Viral biosynthesis
Antineoplastic Agents adverse effects
Carcinoma, Squamous Cell mortality
Carcinoma, Squamous Cell pathology
Cisplatin administration & dosage
Cisplatin adverse effects
Combined Modality Therapy
Female
Granulocyte-Macrophage Colony-Stimulating Factor administration & dosage
Granulocyte-Macrophage Colony-Stimulating Factor adverse effects
Head and Neck Neoplasms mortality
Head and Neck Neoplasms pathology
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Male
Maximum Tolerated Dose
Middle Aged
Neoplasm Staging
Oncolytic Virotherapy adverse effects
Radiotherapy adverse effects
Simplexvirus immunology
Treatment Outcome
Antineoplastic Agents administration & dosage
Carcinoma, Squamous Cell therapy
Head and Neck Neoplasms therapy
Oncolytic Virotherapy methods
Radiotherapy methods
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3265
- Volume :
- 16
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 20670951
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-10-0196