Combination effects of irradiation and irinotecan on cervical squamous cell carcinoma cells in vitro.

Irinotecan HCl (CPT-11) has frequently been used in chemotherapy or concurrent chemoradiotherapy for patients with advanced cervical cancer, although an effective protocol for chemoradiotherapy with CPT-11 has not yet been established. Using the radiosensitive human cervical squamous cell carcinoma cell line ME180 and SN38, a major active metabolite of CPT-11, both the SN38 effects on radiosensitivity and irradiation effects on SN38 sensitivity were investigated to optimize the chemoradiotherapy protocol for CPT-11. SN38 had no effect on radiosensitivity, and irradiation did not affect SN38 sensitivity. Moreover, 3 of 4 post-irradiation surviving subclones obtained from repeatedly irradiated ME180 cells showed no significant changes in their SN38 sensitivities compared with the non-irradiated parent cells. On the other hand, all 7 SN38-resistant subclones established from ME180 cells showed strong reduction in their radiosensitivities. These results suggest that CPT-11 should be administered to advanced cervical cancer patients after, but not before, standard radiotherapy, and concurrent administration of SN38 with radiotherapy should be avoided in order to prevent severe adverse effects, such as watery diarrhea, which is the main adverse effect of pelvic radiotherapy or CPT-11.