Standard primary treatment for locally advanced cervix cancer is radiation (RT) with concomitant platinum-based chemotherapy (CT). I ncomplete local control and the appearance of distant disease herald poor surviv al ...Standard primary treatment for locally advanced cervix cancer is radiation (RT) with concomitant platinum-based chemotherapy (CT). I ncomplete local control and the appearance of distant disease herald poor surviv al and warrant evaluation of new primary strategies. Paclitaxel and carboplatin are active agents in recurrent cervical carcinoma, have potent, synergistic in v itro radiosensitization, and are cytotoxic in weekly schedules. This study was d one to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (D LT) of weekly pacli-taxel/carboplatin chemoradiotherapy in locally advanced cer vix cancer. Women with primary, previously untreated, squamous cell or adenocarc inoma of the cervix, FIGO stage IB2 to IVA, negative para-aortic lymph nodes, a dequate organ function and performance status were eligible. Pelvic RT (45 Gy ov er 5 weeks-180 cGy/day, four-field) was followed by two brachytherapy applicat ions (Point A low dose rate (LDR): 90 Gy, high dose rate (HDR): 75 Gy). Concurre nt weekly CT was paclitaxel 50 mg/m2 and carboplatin, starting at AUC 1.5 and es calating in three-patient cohorts by AUC 0.5 (Max AUC 3.5). Dose escalation fol lowed a 4-week observation period for toxicity. A grade III-IV toxicity prompt ed up to three additional patients per dose level. A second event defined DLT. C T was administered concurrently throughout brachytherapy. Fifteen patients were enrolled and treated over four dose levels until DLT was reached. Median age was 44 years (range, 23-70); stages: IB2: 1, IIB: 9, IIIA: 1, IIIB: 4. Median RT t reatment time was 61 days (range, 55-79). Fourteen patients received brachyther apy (LDR: 8, HDR: 6), and one received external RT only due to cervical stenosis . The median number of weekly CT cycles was seven (range, 6-7). One CT dose was dropped in one patient for a grade II thrombocytopenia. One grade III ANC was o bserved at dose level II (AUC 2.0) but not seen in three additional patients. At dose level IV (AUC 3.0), two grade III-IV ANC toxicities were observed in two patients (DLT). Nine patients had grade II anemia. One patient had grade III ane mia. Grade III/IV nonhematologic toxicity was rare (1/15 GI-nausea/vomiting, 1/ 15 pneumonia, 1/15 hypokalemia). The MTD of carboplatin is AUC 2.5 with paclitax el 50 mg/m 2. Median follow-up is 17 months; three patients have recurred and t wo have died. The estimated 2-year PFS and OS are 80%and 86%. Weekly paclitax el and carboplatin chemoradiation is feasible and active. The MTD for a phase II trial is 50 mg/m2 and AUC 2.5, respectively.展开更多
文摘Standard primary treatment for locally advanced cervix cancer is radiation (RT) with concomitant platinum-based chemotherapy (CT). I ncomplete local control and the appearance of distant disease herald poor surviv al and warrant evaluation of new primary strategies. Paclitaxel and carboplatin are active agents in recurrent cervical carcinoma, have potent, synergistic in v itro radiosensitization, and are cytotoxic in weekly schedules. This study was d one to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (D LT) of weekly pacli-taxel/carboplatin chemoradiotherapy in locally advanced cer vix cancer. Women with primary, previously untreated, squamous cell or adenocarc inoma of the cervix, FIGO stage IB2 to IVA, negative para-aortic lymph nodes, a dequate organ function and performance status were eligible. Pelvic RT (45 Gy ov er 5 weeks-180 cGy/day, four-field) was followed by two brachytherapy applicat ions (Point A low dose rate (LDR): 90 Gy, high dose rate (HDR): 75 Gy). Concurre nt weekly CT was paclitaxel 50 mg/m2 and carboplatin, starting at AUC 1.5 and es calating in three-patient cohorts by AUC 0.5 (Max AUC 3.5). Dose escalation fol lowed a 4-week observation period for toxicity. A grade III-IV toxicity prompt ed up to three additional patients per dose level. A second event defined DLT. C T was administered concurrently throughout brachytherapy. Fifteen patients were enrolled and treated over four dose levels until DLT was reached. Median age was 44 years (range, 23-70); stages: IB2: 1, IIB: 9, IIIA: 1, IIIB: 4. Median RT t reatment time was 61 days (range, 55-79). Fourteen patients received brachyther apy (LDR: 8, HDR: 6), and one received external RT only due to cervical stenosis . The median number of weekly CT cycles was seven (range, 6-7). One CT dose was dropped in one patient for a grade II thrombocytopenia. One grade III ANC was o bserved at dose level II (AUC 2.0) but not seen in three additional patients. At dose level IV (AUC 3.0), two grade III-IV ANC toxicities were observed in two patients (DLT). Nine patients had grade II anemia. One patient had grade III ane mia. Grade III/IV nonhematologic toxicity was rare (1/15 GI-nausea/vomiting, 1/ 15 pneumonia, 1/15 hypokalemia). The MTD of carboplatin is AUC 2.5 with paclitax el 50 mg/m 2. Median follow-up is 17 months; three patients have recurred and t wo have died. The estimated 2-year PFS and OS are 80%and 86%. Weekly paclitax el and carboplatin chemoradiation is feasible and active. The MTD for a phase II trial is 50 mg/m2 and AUC 2.5, respectively.
