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.
Abstract | PURPOSE: 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. 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). 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.
|
Authors | Kevin J Harrington, Mohan Hingorani, Mary Anne Tanay, Jennifer Hickey, Shreerang A Bhide, Peter M Clarke, Louise C Renouf, Khin Thway, Amen Sibtain, Iain A McNeish, Kate L Newbold, Howard Goldsweig, Robert Coffin, Christopher M Nutting |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 16
Issue 15
Pg. 4005-15
(Aug 01 2010)
ISSN: 1557-3265 [Electronic] United States |
PMID | 20670951
(Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article)
|
Copyright | (c) 2010 AACR. |
Chemical References |
- Antibodies, Viral
- Antigens, Viral
- Antineoplastic Agents
- Granulocyte-Macrophage Colony-Stimulating Factor
- Cisplatin
|
Topics |
- Adult
- Aged
- Antibodies, Viral
(blood)
- Antigens, Viral
(biosynthesis)
- Antineoplastic Agents
(administration & dosage, adverse effects)
- Carcinoma, Squamous Cell
(mortality, pathology, therapy)
- Cisplatin
(administration & dosage, adverse effects)
- Combined Modality Therapy
- Female
- Granulocyte-Macrophage Colony-Stimulating Factor
(administration & dosage, adverse effects)
- Head and Neck Neoplasms
(mortality, pathology, therapy)
- Humans
- Immunohistochemistry
- Kaplan-Meier Estimate
- Male
- Maximum Tolerated Dose
- Middle Aged
- Neoplasm Staging
- Oncolytic Virotherapy
(adverse effects, methods)
- Radiotherapy
(adverse effects, methods)
- Simplexvirus
(immunology)
- Treatment Outcome
|
|
Join CureHunter, for free Research Interface BASIC access!
Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease.
Find out why thousands of doctors, pharma researchers and patient activists
around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!
|