13-cis-retinoic acid with alpha-2a-interferon enhances radiation cytotoxicity in head and neck squamous cell carcinoma in vitro.
The treatment of locally advanced squamous cell carcinomas of the head and neck presents a challenge for oncologists. Radiation therapy alone fails to control many of these tumors. Chemotherapy added to radiation therapy has not clearly demonstrated an improvement in survival in the majority of trials reported to date. In this study, we have evaluated whether IFN-alpha-2a and/or 13-cis-retinoic acid (RA) enhance radiation cytotoxicity in a head and neck squamous cell carcinoma cell line (FaDu). Using a clonogenic cell survival assay, IFN-alpha-2a (1000 units/ml) or RA (1 microM) alone did not significantly enhance radiation cytotoxicity. The combination of the two agents, however, significantly increased the cytotoxicity of radiation against FaDu cells. The calculated survival fraction at 2 Gy was decreased from 0.649 with radiation alone to 0.477 when combined with the other two agents (P = 0.016), and the MID was decreased from 3.318 to 2.499 Gy (P = 0.028). A Phase I clinical trial to combine IFN-alpha-2a and/or RA in patients with unresectable head and neck cancer has been initiated.
DeLaney
T F
TF
Department of Radiation Oncology, Boston University Medical Center, Massachusetts 02118-2393, USA.
Afridi
N
N
Taghian
A G
AG
Sanders
D A
DA
Fuleihan
N S
NS
Faller
D V
DV
Nogueira
C P
CP
D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000473:pathology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D015474:Isotretinoin / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D014410:Tumor Stem Cell Assay
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011838:Radiation-Sensitizing Agents; D011994:Recombinant Proteins; D015474:Isotretinoin