Combined effects of the orally active cisplatin analog, JM216, and radiation in antitumor therapy

Purpose: We evaluated the orally administered platinum agent, JM216, in com bination with ionizing radiation both in vivo and in vitro against human tu mor cells. Methods: H460 human lung carcinoma cells were used as a subcutan eous xenograft in nude mice. JM216 (30 mg/kg) was administered orally, and radiation treatments (2 Gy) were given 1 h after JM216 delivery for five co nsecutive days. For in vitro analysis, attached H460 cells were treated wit h JM216 (15 muM) for 1 h and then irradiated. Cells were rinsed 20 min late r, and survival was determined by clonogenic assay. Results: Tumor growth d elay measurements showed that the combination of JM216 and radiation was ad ditive in vivo, with an enhancement ratio of 1.24. Tn vitro clonogenic surv ival experiments demonstrated a dose enhancement ratio of 1.23. Isobologram analysis showed that this interaction was also additive. Conclusions: Thes e data demonstrate that the combination of JM216 and fractionated radiother apy is more effective against human lung cancer xenografts than either agen t alone, and the in vivo results were supported by those observed using an in vitro system with the same tumor cell line.