Endometrial carcinoma in vitro chemosensitivity testing of single and combination chemotherapy regimens using the novel microculture kinetic apoptosis assay: implications for endometrial cancer treatment / 부인종양

OBJECTIVE: The in vitro microculture kinetic (MiCK) apoptosis assay has been used to predict single or combination chemotherapy response in leukemia patients. This feasibility study addressed MiCK in endometrial cancer specimens. METHODS: Endometrial cancer specimens from total abdominal hysterectomies were processed at a central laboratory. Single cell suspensions of viable endometrial cancer cells were plated in individual wells. Single and combination regimens were tested: combinations of doxorubicin, cisplatin, and paclitaxel and carboplatin and paclitaxel (Gynecologic Oncology Group [GOG] 209 endometrial cancer phase III trial arms) as well as single agent testing with paclitaxel, carboplatin, doxorubicin, cisplatin, ifosfamide, and vincristine (active agents in GOG trials). Apoptosis was measured continuously over 48 hours. RESULTS: Fifteen of nineteen patients had successful assays. The highest mean chemo sensitivity was noted in the combination of cisplatin, doxorubicin, and paclitaxel with lower mean chemosensitivity for carboplatin and paclitaxel. Combination chemotherapy had higher chemosensitivity than single drug chemotherapy. However, in 25% of patients a single drug had higher chemosensitivity than combination chemotherapy. As single agents, ifosfamide, cisplatin, and paclitaxel had the highest kinetic unit values. CONCLUSION: Using a panel of agents simulating clinical dose regimens, the MiCK assay was feasible in evaluating in vitro chemosensitivity of endometrial cancer. MiCK assay results correlated with GOG clinical trial results. However, 25% of patients might be best treated with single agent chemotherapy selected by MiCK. Ifosfamide, cisplatin, and paclitaxel appear to have high activity as single agents. MiCK may be useful in future new drug testing and individualizing endometrial cancer patient's chemotherapy management.

Present status and future direction of clinical trials in advanced endometrial carcinoma / 부인종양

Endometrial adenocarcinoma is staged surgically, and advanced endometrial carcinoma is considered to be FIGO stage III and IV. The Gynecologic Oncology Group (GOG) has come a long way in developing new strategies in the management of advanced endometrial carcinoma. Combining surgery, radiation, and chemotherapy, the 5-year survival has improved to between 40-60% in newly diagnosed advanced endometrial carcinoma. Recent findings in GOG184 indicate that multiple risk factors noted at the time of surgical staging could lead to concurrent clinical trials that could be completed expeditiously rather than a subsequent ten year long phase III trial including all the various risk subgroups of patients. This review is a focus on the accomplishments of the GOG in advanced endometrial carcinoma with an emphasis on future challenges.