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Rationale for Intralesional Valrubicin in Chemoradiation of Squamous Cell Carcinoma of the Head and Neck
Author(s) -
Wani Manish K.,
Koseki Yoshihiro,
Yarber Robert H.,
Sweatman Trevor W.,
Ahmed Asif,
Samant Sanjiv,
Hengesteg Arne,
Israel Mervyn,
Thomas Robbins K.
Publication year - 2000
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1097/00005537-200012000-00009
Subject(s) - cisplatin , medicine , radiation therapy , cheek pouch , cancer research , head and neck squamous cell carcinoma , cytotoxic t cell , squamous carcinoma , cell , cytotoxicity , oncology , head and neck cancer , pathology , pharmacology , chemotherapy , carcinoma , in vitro , hamster , chemistry , biochemistry
Objectives/Hypothesis With some advanced squamous cell carcinomas (SCCs) of the head and neck, chemoradiation therapy may obviate the need for surgical intervention. However, both modalities are known to produce organ to‐icities, and tumor insensitivity remains problematic. Thus there is a clear need for the development of new treatment strategies. Accordingly, preclinical studies to evaluate the use of valrubicin, a contact‐safe, mechanistically novel antitumor agent, combined with low‐dose radiation for the therapy of SCC have been conducted. Methods The comparative in vitro antitumor activities of valrubicin with or without irradiation versus cisplatin were evaluated using human‐derived sensitive and cisplatin‐resistant SCC cell lines. A hamster cheek pouch model of SCC was used to assess the efficacy of weekly intratumoral valrubicin injections with and without concurrent low‐dose irradiation. Results Valrubicin cytoto‐icity was found to be comparable in both sensitive and platinum‐resistant cell lines and superior to cisplatin. The addition of minimally cytoto‐ic cell irradiation (300–450 cGy) resulted in prolonged G 2 /M cell cycle arrest and a supra‐additive increase in apoptotic cell death. In hamsters, once a week × 3 intratumoral drug injections (3, 6, or 9 mg) were growth inhibitory; however, when valrubicin (6 mg) was combined with minimally cytotoxic irradiation (150, 250, or 350 cGy) significant tumor shrinkage was observed. Conclusions Valrubicin produces supra‐additive effects against SCC when combined with low‐dose irradiation. This effect appears to correlate with the ability of valrubicin, a cytoplasmic‐localizing drug, to inhibit protein kinase C. Therapeutic use of valrubicin against SCC could provide for reduced radiation doses with consequent improved efficacy and reduction in host to‐icity.