Background.:To determine the pathologic complete response rate of advanced ovarian cancer to weekly paclitaxel plus gemcitabine and carboplatin with filgrastim,and assess the longitudinal impact of this regimen on qua...Background.:To determine the pathologic complete response rate of advanced ovarian cancer to weekly paclitaxel plus gemcitabine and carboplatin with filgrastim,and assess the longitudinal impact of this regimen on quality-of-life and cognitive functioning. Methods.:Fourteen patients with advanced ovarian,peritoneal,or fallopian tube cancer were treated in the phase I portion of the study. Initial doses were paclitaxel:60 mg/m2 days 1,8,and 15; gemcitabine:800 mg/m2 days 1 and 8; and carboplatin:area under the curve (AUC) 5 day 1,every 21 days for 6 cycles with filgrastim. Twenty-seven patients were treated at the phase II dose. Pathologic response was assessed by second-look laparoscopy in patients with complete response. Patients completed longitudinal assess- ments of quality-of-life and cognitive functioning. Results.:Maximally tolerated doses were paclitaxel:80 mg/m2 days 1 and 8; gemcitabine:800 mg/m2 days 1 and 8; and carboplatin:AUC 5 day 1,every 21 days. Forty-eight percent of patients (13/27) experienced at least 1 grade 3 nonhematologic toxicity. Fifty percent (95%confidence interval CI ,31-69%) of assessable patients achieved pathologic complete response. Median progression-free survival was 27.3 months (95%CI,17.7 months to not reached),and overall survival 43.6 months (95%CI,42 months to not reached). Cognitive functioning did not decline during or after chemotherapy. More highly educated women reported a perceived decline in concentration and memory while on chemotherapy. Quality-of-life scores were maintained during therapy. Conclusions.:Fifty percent of patients with advanced stage ovarian cancer achieved pathologic complete response to weekly paclitaxel plus gemcitabine and carboplatin. Cognitive functioning did not decline by objective measures,although highly educated women reported subjective impairment.展开更多
Objective. Incorporating topotecan into standard platinum/taxane chem otherapy for advanced ovarian cancer has been complicated by myelosuppression. This study evaluated sequential doublets of topotecan and carboplati...Objective. Incorporating topotecan into standard platinum/taxane chem otherapy for advanced ovarian cancer has been complicated by myelosuppression. This study evaluated sequential doublets of topotecan and carboplatin, followed by paclita xel and carboplatin, in newly diagnosed advanced ovarian cancer patients. Method s. Forty-five patients (median age, 56 years; range, 38-77 years) with stage I II/IV disease and GOG performance status < 2 were enrolled and received four cyc les of topotecan (1.0 mg/m2/day on days 1 to 3) and carboplatin (AUC 4 on day 1) , followed by four cycles of paclitaxel (175 mg/m2 via 3-h IV infusion on day 1 ) and carboplatin (AUC 5 on day 1). All cycles were 21 days. Antitumor response was assessed after four and eight cycles; patients with clinical complete respon se (CR) underwent second-look laparotomy for determination of pathologic CR (PC R). Dose reductions were instituted for grade 4 neutropenia and thrombocytopenia , and for grade 3/4 nonhematologic toxicity. Results. Among 41 CA-125 evaluable patients, complete and partial responses were observed in 29 (70.7%) and 11 (26.8%) patients, r espectively. Of the 12 clinical CRs (43%) in 28 evaluable patients, 10 patients underwent second-look laparotomy, with 3 PCRs (30%). Median time to progressi on was 14 months and actuarial survival was 23 months. Neutropenia was the prima ry toxicity and cause of dose adjustments and delays, including two deaths. Conc lusion. The antitumor activity observed is comparable with other series, althoug h neutropenic complications were increased. Progression-free and actuarial surv ivals were slightly inferior. A Phase Ⅲtrial (GOG182) of sequential doublets in the reverse sequence is ongoing.展开更多
To determine toxicity and establish a maximum tolerated dose of outpatient therapy with ifosfamide, paclitaxel, and carboplatin in women with advanced and recurrent cervical cancer. Eligible patients had stage IVB, re...To determine toxicity and establish a maximum tolerated dose of outpatient therapy with ifosfamide, paclitaxel, and carboplatin in women with advanced and recurrent cervical cancer. Eligible patients had stage IVB, recurrent or persistent cervical cancer that was not amenable to curative treatment with surgery or radiation therapy. A dose escalation through four dose levels was planned. Dose limiting toxicities were defined as grade 3 or grade 4 hematologic toxicity persistent to day 1 of the next scheduled cycle, grade 2 or higher central neurologic symptoms related to ifosfamide and grade 3 or grade 4 peripheral neuropathy. Twelve patients, aged 29 to 71, received 64 treatments and were evaluable for toxicity. No patient was withdrawn from the study due to toxicity. Two patients had received prior radiation therapy without chemotherapy, and seven patients had received radiation therapy with concurrent chemotherapy. No dose limiting toxicity occurred at dose levels 1 or 2. Three dose reductions occurred at dose level 3 due to neutropenia and thrombocytopenia. The maximum tolerated dose is ifosfamide 2g/m2 over 2 h, paclitaxel 175 mg/m2 over 1 h, and carboplatin at an AUC of 5 over 45 min. Grade 3 or grade 4 neutropenia was seen in 11 subjects. Two patients required growth factor support. Grade 3 or grade 4 anemia was seen in one patient. Grade 3 or grade 4 neuropathy was seen in one patient. Other grade 3 or grade 4 non hematologic toxicity included muscle weakness, myalgia, cough, and shortness of breath. Combination therapy with ifosfamide 2 g/m2, paclitaxel 175 mg/m2, carboplatin AUC 5 appears to be a safe regimen for the outpatient treatment of women with advanced or recurrent cervical cancer and warrants phase II investigation.展开更多
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Background.:To determine the pathologic complete response rate of advanced ovarian cancer to weekly paclitaxel plus gemcitabine and carboplatin with filgrastim,and assess the longitudinal impact of this regimen on quality-of-life and cognitive functioning. Methods.:Fourteen patients with advanced ovarian,peritoneal,or fallopian tube cancer were treated in the phase I portion of the study. Initial doses were paclitaxel:60 mg/m2 days 1,8,and 15; gemcitabine:800 mg/m2 days 1 and 8; and carboplatin:area under the curve (AUC) 5 day 1,every 21 days for 6 cycles with filgrastim. Twenty-seven patients were treated at the phase II dose. Pathologic response was assessed by second-look laparoscopy in patients with complete response. Patients completed longitudinal assess- ments of quality-of-life and cognitive functioning. Results.:Maximally tolerated doses were paclitaxel:80 mg/m2 days 1 and 8; gemcitabine:800 mg/m2 days 1 and 8; and carboplatin:AUC 5 day 1,every 21 days. Forty-eight percent of patients (13/27) experienced at least 1 grade 3 nonhematologic toxicity. Fifty percent (95%confidence interval CI ,31-69%) of assessable patients achieved pathologic complete response. Median progression-free survival was 27.3 months (95%CI,17.7 months to not reached),and overall survival 43.6 months (95%CI,42 months to not reached). Cognitive functioning did not decline during or after chemotherapy. More highly educated women reported a perceived decline in concentration and memory while on chemotherapy. Quality-of-life scores were maintained during therapy. Conclusions.:Fifty percent of patients with advanced stage ovarian cancer achieved pathologic complete response to weekly paclitaxel plus gemcitabine and carboplatin. Cognitive functioning did not decline by objective measures,although highly educated women reported subjective impairment.
文摘Objective. Incorporating topotecan into standard platinum/taxane chem otherapy for advanced ovarian cancer has been complicated by myelosuppression. This study evaluated sequential doublets of topotecan and carboplatin, followed by paclita xel and carboplatin, in newly diagnosed advanced ovarian cancer patients. Method s. Forty-five patients (median age, 56 years; range, 38-77 years) with stage I II/IV disease and GOG performance status < 2 were enrolled and received four cyc les of topotecan (1.0 mg/m2/day on days 1 to 3) and carboplatin (AUC 4 on day 1) , followed by four cycles of paclitaxel (175 mg/m2 via 3-h IV infusion on day 1 ) and carboplatin (AUC 5 on day 1). All cycles were 21 days. Antitumor response was assessed after four and eight cycles; patients with clinical complete respon se (CR) underwent second-look laparotomy for determination of pathologic CR (PC R). Dose reductions were instituted for grade 4 neutropenia and thrombocytopenia , and for grade 3/4 nonhematologic toxicity. Results. Among 41 CA-125 evaluable patients, complete and partial responses were observed in 29 (70.7%) and 11 (26.8%) patients, r espectively. Of the 12 clinical CRs (43%) in 28 evaluable patients, 10 patients underwent second-look laparotomy, with 3 PCRs (30%). Median time to progressi on was 14 months and actuarial survival was 23 months. Neutropenia was the prima ry toxicity and cause of dose adjustments and delays, including two deaths. Conc lusion. The antitumor activity observed is comparable with other series, althoug h neutropenic complications were increased. Progression-free and actuarial surv ivals were slightly inferior. A Phase Ⅲtrial (GOG182) of sequential doublets in the reverse sequence is ongoing.
文摘To determine toxicity and establish a maximum tolerated dose of outpatient therapy with ifosfamide, paclitaxel, and carboplatin in women with advanced and recurrent cervical cancer. Eligible patients had stage IVB, recurrent or persistent cervical cancer that was not amenable to curative treatment with surgery or radiation therapy. A dose escalation through four dose levels was planned. Dose limiting toxicities were defined as grade 3 or grade 4 hematologic toxicity persistent to day 1 of the next scheduled cycle, grade 2 or higher central neurologic symptoms related to ifosfamide and grade 3 or grade 4 peripheral neuropathy. Twelve patients, aged 29 to 71, received 64 treatments and were evaluable for toxicity. No patient was withdrawn from the study due to toxicity. Two patients had received prior radiation therapy without chemotherapy, and seven patients had received radiation therapy with concurrent chemotherapy. No dose limiting toxicity occurred at dose levels 1 or 2. Three dose reductions occurred at dose level 3 due to neutropenia and thrombocytopenia. The maximum tolerated dose is ifosfamide 2g/m2 over 2 h, paclitaxel 175 mg/m2 over 1 h, and carboplatin at an AUC of 5 over 45 min. Grade 3 or grade 4 neutropenia was seen in 11 subjects. Two patients required growth factor support. Grade 3 or grade 4 anemia was seen in one patient. Grade 3 or grade 4 neuropathy was seen in one patient. Other grade 3 or grade 4 non hematologic toxicity included muscle weakness, myalgia, cough, and shortness of breath. Combination therapy with ifosfamide 2 g/m2, paclitaxel 175 mg/m2, carboplatin AUC 5 appears to be a safe regimen for the outpatient treatment of women with advanced or recurrent cervical cancer and warrants phase II investigation.
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.
