Combined effect of charged particles irradiation and anticancer drugs in cultured tumor cells.(RDH_IRPT WP2; INFN_Milano, CNAO and Istituto Tumori) The rationale for combining chemotherapy and radiotherapy is to exploit the benefits of radiotherapy in terms of sensitising tumour to radiation locally and reducing the risk of distant failures. Many studies have evaluated the combined effect of radiation and chemotherapy using photons. Combined radio-chemotherapy protocols are already used in the treatment of many cancers, such as glioblastoma multiforme or non-small-cell lung cancer. We investigated the effects of combining hadrons ( protons or C ions) with Epothilone B, a Microtubule Stabilizing Agent ( defective mitotic spindle formation, accumulation of cells in the most radiosensitive G2-M phase of the cell cycle) in cultured human tumor cells: A549 (Non-Small Cell Lung Cancer, U251MG, glioblastoma, Daoy (medulloblastoma, the most common malignant brain tumor of childhood).

Results: 1. protons and Epothilone B interaction: For all the cell lines Epothilone B increases protons and photons cytotoxicity and the effect is more than additive. a) Data on U 251MG cells:

Results: b) data on A549 cells : DEF ( Dose Enhancement factor )of Epothilone B and protons is 1.4 and 1.2 for the two cell lines 2. protons RBE RBE 10% ( 6MV photons): U251MG cells, 1.4 +/- 0.1; A549 cells,1.5+/-0.2; Daoy,1.2+/-0.1.

Results: 3) data on C ions and Epothilone B interaction: DEF of Epothilone B for Carbons is lower than that of protons ( 1.2 and 1.1 for U 251 and A 549 cells )

Results: 4) C ions RBE C ions RBE at 10% survival is 3

Results: 5) C ions and photons ( +/- Epothilone B) effects on cell invasion C ions are more effective than photons against cell invasion ( similar results for A549 cells)

Results: 6) C ions ( +/- Epothilone B) effects on cell growth C ions and Epothilone B effectively induce growth delay