A Prospective Study Of Adenosine Triphosphate-tumor Chemosensitivity Assay Directed Chemotherapy In Patients With Recurrent Ovarian Cancer

Objective To investigate the efficacy and adverse events of adenosine triphosphate (ATP)-tumor chemosensitivity assay (TCA) directed chemotherapy in patients with recurrent epithelial ovarian cancer.Methods From August2010to June2012, patients of recurrent epithelial ovarian cancer were prospectively enrolled in Cancer Hospital&Institute, Chinese Academy of Medical Sciences and Peking Union Medical College.The Entry criteria:(1) Patients with previously histologically proven epithelial ovarian cancer (2) Patients of recurrent ovarian cancer with bidimensionally measurable tumor or ascitic/pleural fluid for testing (3) Karnofsky Performance Status>60(4) A life expectancy of at least6months(5)Be able to sign the informed consent,good compliance during treatment and follow-ups.Patients were randomly assigned into two groups:assay-directed therapy group and physician’s-choice therapy group,but in several cases, were assigned regarding to their wishes.Patients’clinical and pathological characteristics,response rate to chemotherapy,median progression-free survival and adverse events were compared between two groups.Results A total of120patients of recurrent epithelial ovarian cancer were prospectively enrolled to assay-directed chemotherapy (n=60) or physician’s-choice chemotherapy (n=60).There was no difference in median age,residual disease at first cytoreductive surgery, surgical-pathological stage,pathological type,tumor grade, types of recurrence,times of recurrence,residual disease at secondary cytoreductive surgery between assay-directed group and physician’s-choice group.The results of ATP-TCA were lack of highly sensitive chemotherapy drugs in9patients whose overall response rate(ORR) and median progression-free survival(PFS) was3/9and4months respectively,while the ORR and median PFS of remaining47cases in ATP-TCA group was72.3%(34/47,)=0.049)and7months(P=0.015)respectively.Response was assessable in113patients:66.1%(37/56) achieved a partial or complete response in the assay-directed group compared with45.6%(26/57;P=0.037) in the physician’s-choice group (61.7versus43.3%by intention-to-treat analysis respectively,P=0.044).In platinum-sensitive patients with ATP-TCA directed chemotherapy the ORR was72.4%(21/29), in the physician’s-choice group the ORR was65.5%(19/29;P=0.570)(70.0versus63.3%by intention-to-treat analysis respectivelyrP=0.584).In platinum-resistant patients with ATP-TCA directed chemotherapy the ORR was59.3%(16/27), in the physician’s-choice group the ORR was25.0%(7/28;P=0.010)(53.3versus23.3%by intention-to-treat analysis respectively,.P=0.028). Intention-to-treat analysis showed a median progression-free survival of7months in the assaydirected group and4months in the physician’s-choice group CP=0.029). In platinum-sensitive patients with ATP-TCA directed chemotherapy intention-to-treat analysis showed a median PFS was8months and5months in the physician’s-choice group (P=0.097). In platinum-resistant patients with ATP-TCA directed chemotherapy intention-to-treat analysis showed a median PFS was5months and2months in the physician’s-choice group (P=0.004).The adverse events were similar between the two groups,the most frequent side effects were haematological or gastrointestinal,Grade3/4haematological adverse events occured to9patients in ATP-TCA group while11patients in control group (P=0.653), grade3/4gastrointestinal events were reported for7patients in the ATP-TCA group compared with9patients in the control group (P=0.616)Conclusion The results of ATP-TCA are well correlated with response to chemotherapy of patients with recurrent epithelial ovarian cancer,and to a certain extent ATP-TCA could predict clinical outcome of patients with recurrent epithelial ovarian cancer.ATP-TCA directed chemotherapy can improve ORR and PFS in patients with recurrent epithelial ovarian cancer,especially in platinum-resistant patients.The adverse events were similar in assay-directed therapy group and physician’s-choice therapy group.