Objective.:Doxorubicin has reported activity in advanced and recurrent cervical cancer but hematologic toxicity has limited its use in some combinations. To determine the level of activity and potential for use in fut...Objective.:Doxorubicin has reported activity in advanced and recurrent cervical cancer but hematologic toxicity has limited its use in some combinations. To determine the level of activity and potential for use in future combinations,a phase II trial of pegylated liposomal doxorubicin as second-line therapy in advanced and recurrent cervical cancer was performed. Methods.:Eligible patients had squamous cell carcinoma of the cervix,measurable disease,one prior chemotherapy regimen which did not include an anthracycline,absolute neutrophil count (ANC) > 1500/μl,platelet count > 100,000/μl,and adequate hepatic function. Pegylated liposomal doxorubicin 40 mg/m2 was administered intravenously over 1 h every 4 weeks. Results.:Twenty-seven patients were entered on this study. All patients were evaluable for toxicity and 26 were evaluable for response. A median of 2 courses of therapy (range 1-10)-was given. No grade 4 toxicities were noted. Three patients (11.1%) had partial responses. Conclusion.:Liposomal doxorubicin has limited activity,at the dose and schedule employed in previously-treated cervical cancer.展开更多
Objective.A phase Ⅱ study was conducted to determ inethe efficacy of single agent flavopiridol therapy in patients with recurrent or persistent endometrial adenocarcinoma refractory to established treatments. Methods...Objective.A phase Ⅱ study was conducted to determ inethe efficacy of single agent flavopiridol therapy in patients with recurrent or persistent endometrial adenocarcinoma refractory to established treatments. Methods. Eligible patients with measurable disease who failed primary therapy including one cytotoxic regim en were eligible for the trial.They were treated with single agentflavopiridol (50mg/m2/day,Ⅳ bolus days 1,2,3).Treatm entwas repeatedevery 21days with dose adjustm ents made for toxicity.Patients were treated untilprogression ofdisease oradverseside effects precluded further therapy.Results.A totalof26patientswere enrolled in the study ofwhom ,23patientswere eligible.There were no objective responses.Fivepatients had stable disease (22%),15 (65%)had in-creasing disease,and response could notbe assessed in 3(13%).The mostfrequentside effects included anemia,neutropenia,and diarrhea,allofwhich appeared manage-able.Conclusion.Flavopiridol as a single agent in theabove dosing schedule appears to have minim alactivity assecond-line chem otherapy ofendom etrialadenocarcinoma.展开更多
Purpose. A phase II trial was conducted to evaluate the antitumor activity and adverse effects of capecitabine in women with measurable platinum- sensitive ovarian cancer or platinum- sensitive primary peritoneal canc...Purpose. A phase II trial was conducted to evaluate the antitumor activity and adverse effects of capecitabine in women with measurable platinum- sensitive ovarian cancer or platinum- sensitive primary peritoneal cancer and to explore the ability of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and thymidine phosphorylase (TP) to predict response and toxicities. Experimental design. Patients were treated with a daily starting dose of 2500 mg/m2/day (divided in two doses given every 12 h) for 14 days of each 21- day cycle. Genotyping in the 5′ and 3′ ends of TS was performed in DNA from 23/23 pre- treatment blood specimens. Relative gene expression of TS, DPD, and TP was quantified in 18/21 paraffin- embedded tumor specimens. Results. Of the 27 patients enrolled on study, 2 were never treated leaving 25 patients evaluable. Two patients (8.0% ) achieved a partial response, 13 (52% ) exhibited stable disease, 5 (20% ) displayed increasing disease, and response could not be assessed in 5 (20% ). The median time to progression and survival was 3.9 and 21.2 months, respectively. The most common serious toxicities were nausea/vomiting, gastrointestinal, and dermatological. There was one treatment- related death. TS expression was associated with severe nausea/vomiting (P = 0.039), but not with other severe toxicities. TS genotype or expression of DPD or TP was not associated with any of the severe toxicities. Conclusions. Based on the low response rate, this trial was closed after the first stage of accrual, the drug was not selected for further study in this patient population, and biomarker associations with response could not be assessed.展开更多
Objectives. To estimate the antitumor activity of topotecan in patients with persistent or recurrent carcinosarcoma (malignant mixed mullerian tumors) of the uterus and to determine the nature and degree of toxicity o...Objectives. To estimate the antitumor activity of topotecan in patients with persistent or recurrent carcinosarcoma (malignant mixed mullerian tumors) of the uterus and to determine the nature and degree of toxicity of topotecan in this cohort of patients. Materials and methods. Eligible patients had measurable advanced or recurrent carcinosarcoma of the uterus. Topotecan at a target dose of 1.5 mg/m2 was administered IV daily for 5 days, every 3 weeks, until progression of disease or adverse affects prohibited further therapy. Results. Twenty-seven member institutions entered 51 patients. Of the patients entered, 48 were eligible. Patient characteristics included a median age of 65, with 33% having prior radiation and 92% having prior chemotherapy. Twenty-six patients (54% ) had a performance status (PS) of 0, 18 (38% ) had a PS of 1, and four (8% ) had a PS of 2. Patients received from 1 to 21 (with a median of 2) courses of treatment. The most frequently observed grade 4 toxicities were neutropenia seen in 35 (73% ) patients, leukopenia in 14 (29% ), and thrombocytopenia in 10 (21% ). Three (6% )- patients developed neutropenic sepsis and died shortly after their first treatment cycle. There were five (10% ) complete responses; 13 (27% ) patients maintained stable disease, 26 (54% ) experienced increasing disease, and reassessment did not occur in four (8% ). Conclusion. Topotecan at this dose and schedule does not appear to have major activity in patients with advanced or recurrent uterine carcinosarcoma previously treated with chemotherapy.展开更多
Objective. To evaluate the combination of cisplatin and irinotecan as first-l ine treatment of patients with advanced, persistent, or recurrent squamous cell carcinoma of the cervix. Methods. Patients with no prior tr...Objective. To evaluate the combination of cisplatin and irinotecan as first-l ine treatment of patients with advanced, persistent, or recurrent squamous cell carcinoma of the cervix. Methods. Patients with no prior treatment for metastati c disease, presence of measurable tumors, performance status of 0 or 1, and adeq uate bone marrow, renal, and hepatic functions were potentially eligible for thi s trial. Cisplatin and irinotecan were givenweekly at starting doses of 25 and 6 5mg/m2, respectively, for three con secutive weeks. Cycles were to be repeated every 28 days with dose adjustments as required. Patient accrual was based on a two-stage design with at least sev en responses out of 28 patients in the first stage required to proceed to a seco nd stage of accrual seeking a response rate of 40%or better. Results. Of 34 pat ients entered onto the study, 31 were eligible and 27 were evaluable for respons e. Ten had received prior chemoradiation containing cisplatin. Among the five (t wo complete and three partial) observed responses, two were in the subset of pat ients who had received prior chemoradiation. This level of activity was deemed i nsufficient to warrant a second stage of accrual. Predominant toxicities were my elosuppression and gastroin-testinal symptoms, although six patients experience d none of these adverse effects. Conclusion. At these doses, weekly cisplatin an d irinotecan failed to demonstrate sufficient activity to undertake a phase III study. Although not apparent in this study, prior chemoradiation may affect resp onse to platinumbased combinations and its impact should be considered in the de sign of future trials.展开更多
Objective. In patients with disseminated endometrial carcinoma, liposomal doxorubicin has possible advantages over doxorubicin which has proven single agent activity but well known cardiac toxicity. Before replacing d...Objective. In patients with disseminated endometrial carcinoma, liposomal doxorubicin has possible advantages over doxorubicin which has proven single agent activity but well known cardiac toxicity. Before replacing doxorubicin in clinical trials, the Gynecologic Oncology Group (GOG) decided to conduct a phase Ⅱ clinical trial of liposomal doxorubicin (Ortho Biotech Products L. P., Raritan, NJ) in first-line therapy of patients with disseminated endometrial carcinoma. Methods. Patients with initial histologic confirmation of endometrial carcinoma presenting with disseminated or recurrent cancer who had not previously received cytotoxic drugs were considered for participation in this clinical trial. Eligible patients had measurable disease, GOG performance status 0-2, and adequate bone marrow, renal, and hepatic function according to standard criteria. Liposomal doxorubicin 40 mg/m2 was given by intravenous injection on an every 4-week cycle until toxicity or progression. Patients who remained free from tumor progression or intolerable toxicity received at least one to a maximum of 20 cycles of liposomal doxorubicin. Results. Fifty-six patients were registered, of whom three were determined ineligible (prior malignancy = 2, inadequate pathology material = 1). One patient never received therapy, leaving 52 evaluable patients. Two patients (3.8% ) achieved a complete response, four (7.7% ) exhibited a partial response, and 31 (59.7% ) had stable disease. The most common adverse events were constitutional (32/52), anemia (28/52), pain (27/52), dermatologic (25/52), and cardiovascular (12/52). Conclusions. In this trial, liposomal doxorubicin had a response rate of 11.5% in first-line treatment of disseminated endometrial carcinoma when given at 40 mg/m2 every 4 weeks. In view of the associated skin toxicity at this dose, liposomal doxorubicin does not appear to be a suitable replacement for the more active doxorubicin for therapy of endometrial carcinoma.展开更多
Objective. Following a reported 23%response rate (RR) for mitomycin (M), doxorubicin (A), and cisplatin (P) and preliminary data suggesting a superior RR for dacarbazine (D) +MAP +sargramostim, the Gynecologic Oncolog...Objective. Following a reported 23%response rate (RR) for mitomycin (M), doxorubicin (A), and cisplatin (P) and preliminary data suggesting a superior RR for dacarbazine (D) +MAP +sargramostim, the Gynecologic Oncology Group (GOG) conducted a phase II trial of DMAP +sargramostim in patients with advanced uterine leiomyosarcoma. Methods. Eligibility required measurable disease, a GOG performance score of 0-2, and recovery from surgery/radiotherapy. Treatment consisted of sargramostim 250 μg/m2 SC q 12 h days -6 through -3, followed by D 750 mg/m2 IV over 2 h, M 6 mg/m2 IV, A 40 mg/m2 IV and P 60 mg/m2 IV over 2 h on day 1, followed by sargramostim 250 μg/m2 SC days 2-15. Cycles were repeated q 28 days (if ANC ≥1500/μl and platelets ≥100,000/μl) until disease progression or toxicity prevented further therapy. Doses were to be reduced by 20%for grade 4 neutropenia >7 days or any grade 4 thrombocytopenia and by 10%for a 1-to 2-week treatment delay for myelosuppression. Results. One of 19 patients who entered the study was ineligible. Eighteen patients received a median of 3.5 cycles (range: 1-6 cycles) of therapy. The overall RR was 27.8%(5.6%complete and 22.2%partial responses). Percent of patients with grade 3 or 4 toxicities included 78%neutropenia, 94%thrombocytopenia, 61%anemia, 44%GI, 28%infection, and 17%azotemia. Conclusions. DMAP +sargramostim produced a 27.8%RR, but its complexity and toxicity precluded further investigation, and the study was closed after the first stage of accrual.展开更多
文摘Objective.:Doxorubicin has reported activity in advanced and recurrent cervical cancer but hematologic toxicity has limited its use in some combinations. To determine the level of activity and potential for use in future combinations,a phase II trial of pegylated liposomal doxorubicin as second-line therapy in advanced and recurrent cervical cancer was performed. Methods.:Eligible patients had squamous cell carcinoma of the cervix,measurable disease,one prior chemotherapy regimen which did not include an anthracycline,absolute neutrophil count (ANC) > 1500/μl,platelet count > 100,000/μl,and adequate hepatic function. Pegylated liposomal doxorubicin 40 mg/m2 was administered intravenously over 1 h every 4 weeks. Results.:Twenty-seven patients were entered on this study. All patients were evaluable for toxicity and 26 were evaluable for response. A median of 2 courses of therapy (range 1-10)-was given. No grade 4 toxicities were noted. Three patients (11.1%) had partial responses. Conclusion.:Liposomal doxorubicin has limited activity,at the dose and schedule employed in previously-treated cervical cancer.
文摘Objective.A phase Ⅱ study was conducted to determ inethe efficacy of single agent flavopiridol therapy in patients with recurrent or persistent endometrial adenocarcinoma refractory to established treatments. Methods. Eligible patients with measurable disease who failed primary therapy including one cytotoxic regim en were eligible for the trial.They were treated with single agentflavopiridol (50mg/m2/day,Ⅳ bolus days 1,2,3).Treatm entwas repeatedevery 21days with dose adjustm ents made for toxicity.Patients were treated untilprogression ofdisease oradverseside effects precluded further therapy.Results.A totalof26patientswere enrolled in the study ofwhom ,23patientswere eligible.There were no objective responses.Fivepatients had stable disease (22%),15 (65%)had in-creasing disease,and response could notbe assessed in 3(13%).The mostfrequentside effects included anemia,neutropenia,and diarrhea,allofwhich appeared manage-able.Conclusion.Flavopiridol as a single agent in theabove dosing schedule appears to have minim alactivity assecond-line chem otherapy ofendom etrialadenocarcinoma.
文摘Purpose. A phase II trial was conducted to evaluate the antitumor activity and adverse effects of capecitabine in women with measurable platinum- sensitive ovarian cancer or platinum- sensitive primary peritoneal cancer and to explore the ability of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and thymidine phosphorylase (TP) to predict response and toxicities. Experimental design. Patients were treated with a daily starting dose of 2500 mg/m2/day (divided in two doses given every 12 h) for 14 days of each 21- day cycle. Genotyping in the 5′ and 3′ ends of TS was performed in DNA from 23/23 pre- treatment blood specimens. Relative gene expression of TS, DPD, and TP was quantified in 18/21 paraffin- embedded tumor specimens. Results. Of the 27 patients enrolled on study, 2 were never treated leaving 25 patients evaluable. Two patients (8.0% ) achieved a partial response, 13 (52% ) exhibited stable disease, 5 (20% ) displayed increasing disease, and response could not be assessed in 5 (20% ). The median time to progression and survival was 3.9 and 21.2 months, respectively. The most common serious toxicities were nausea/vomiting, gastrointestinal, and dermatological. There was one treatment- related death. TS expression was associated with severe nausea/vomiting (P = 0.039), but not with other severe toxicities. TS genotype or expression of DPD or TP was not associated with any of the severe toxicities. Conclusions. Based on the low response rate, this trial was closed after the first stage of accrual, the drug was not selected for further study in this patient population, and biomarker associations with response could not be assessed.
文摘Objectives. To estimate the antitumor activity of topotecan in patients with persistent or recurrent carcinosarcoma (malignant mixed mullerian tumors) of the uterus and to determine the nature and degree of toxicity of topotecan in this cohort of patients. Materials and methods. Eligible patients had measurable advanced or recurrent carcinosarcoma of the uterus. Topotecan at a target dose of 1.5 mg/m2 was administered IV daily for 5 days, every 3 weeks, until progression of disease or adverse affects prohibited further therapy. Results. Twenty-seven member institutions entered 51 patients. Of the patients entered, 48 were eligible. Patient characteristics included a median age of 65, with 33% having prior radiation and 92% having prior chemotherapy. Twenty-six patients (54% ) had a performance status (PS) of 0, 18 (38% ) had a PS of 1, and four (8% ) had a PS of 2. Patients received from 1 to 21 (with a median of 2) courses of treatment. The most frequently observed grade 4 toxicities were neutropenia seen in 35 (73% ) patients, leukopenia in 14 (29% ), and thrombocytopenia in 10 (21% ). Three (6% )- patients developed neutropenic sepsis and died shortly after their first treatment cycle. There were five (10% ) complete responses; 13 (27% ) patients maintained stable disease, 26 (54% ) experienced increasing disease, and reassessment did not occur in four (8% ). Conclusion. Topotecan at this dose and schedule does not appear to have major activity in patients with advanced or recurrent uterine carcinosarcoma previously treated with chemotherapy.
文摘Objective. To evaluate the combination of cisplatin and irinotecan as first-l ine treatment of patients with advanced, persistent, or recurrent squamous cell carcinoma of the cervix. Methods. Patients with no prior treatment for metastati c disease, presence of measurable tumors, performance status of 0 or 1, and adeq uate bone marrow, renal, and hepatic functions were potentially eligible for thi s trial. Cisplatin and irinotecan were givenweekly at starting doses of 25 and 6 5mg/m2, respectively, for three con secutive weeks. Cycles were to be repeated every 28 days with dose adjustments as required. Patient accrual was based on a two-stage design with at least sev en responses out of 28 patients in the first stage required to proceed to a seco nd stage of accrual seeking a response rate of 40%or better. Results. Of 34 pat ients entered onto the study, 31 were eligible and 27 were evaluable for respons e. Ten had received prior chemoradiation containing cisplatin. Among the five (t wo complete and three partial) observed responses, two were in the subset of pat ients who had received prior chemoradiation. This level of activity was deemed i nsufficient to warrant a second stage of accrual. Predominant toxicities were my elosuppression and gastroin-testinal symptoms, although six patients experience d none of these adverse effects. Conclusion. At these doses, weekly cisplatin an d irinotecan failed to demonstrate sufficient activity to undertake a phase III study. Although not apparent in this study, prior chemoradiation may affect resp onse to platinumbased combinations and its impact should be considered in the de sign of future trials.
文摘Objective. In patients with disseminated endometrial carcinoma, liposomal doxorubicin has possible advantages over doxorubicin which has proven single agent activity but well known cardiac toxicity. Before replacing doxorubicin in clinical trials, the Gynecologic Oncology Group (GOG) decided to conduct a phase Ⅱ clinical trial of liposomal doxorubicin (Ortho Biotech Products L. P., Raritan, NJ) in first-line therapy of patients with disseminated endometrial carcinoma. Methods. Patients with initial histologic confirmation of endometrial carcinoma presenting with disseminated or recurrent cancer who had not previously received cytotoxic drugs were considered for participation in this clinical trial. Eligible patients had measurable disease, GOG performance status 0-2, and adequate bone marrow, renal, and hepatic function according to standard criteria. Liposomal doxorubicin 40 mg/m2 was given by intravenous injection on an every 4-week cycle until toxicity or progression. Patients who remained free from tumor progression or intolerable toxicity received at least one to a maximum of 20 cycles of liposomal doxorubicin. Results. Fifty-six patients were registered, of whom three were determined ineligible (prior malignancy = 2, inadequate pathology material = 1). One patient never received therapy, leaving 52 evaluable patients. Two patients (3.8% ) achieved a complete response, four (7.7% ) exhibited a partial response, and 31 (59.7% ) had stable disease. The most common adverse events were constitutional (32/52), anemia (28/52), pain (27/52), dermatologic (25/52), and cardiovascular (12/52). Conclusions. In this trial, liposomal doxorubicin had a response rate of 11.5% in first-line treatment of disseminated endometrial carcinoma when given at 40 mg/m2 every 4 weeks. In view of the associated skin toxicity at this dose, liposomal doxorubicin does not appear to be a suitable replacement for the more active doxorubicin for therapy of endometrial carcinoma.
文摘Objective. Following a reported 23%response rate (RR) for mitomycin (M), doxorubicin (A), and cisplatin (P) and preliminary data suggesting a superior RR for dacarbazine (D) +MAP +sargramostim, the Gynecologic Oncology Group (GOG) conducted a phase II trial of DMAP +sargramostim in patients with advanced uterine leiomyosarcoma. Methods. Eligibility required measurable disease, a GOG performance score of 0-2, and recovery from surgery/radiotherapy. Treatment consisted of sargramostim 250 μg/m2 SC q 12 h days -6 through -3, followed by D 750 mg/m2 IV over 2 h, M 6 mg/m2 IV, A 40 mg/m2 IV and P 60 mg/m2 IV over 2 h on day 1, followed by sargramostim 250 μg/m2 SC days 2-15. Cycles were repeated q 28 days (if ANC ≥1500/μl and platelets ≥100,000/μl) until disease progression or toxicity prevented further therapy. Doses were to be reduced by 20%for grade 4 neutropenia >7 days or any grade 4 thrombocytopenia and by 10%for a 1-to 2-week treatment delay for myelosuppression. Results. One of 19 patients who entered the study was ineligible. Eighteen patients received a median of 3.5 cycles (range: 1-6 cycles) of therapy. The overall RR was 27.8%(5.6%complete and 22.2%partial responses). Percent of patients with grade 3 or 4 toxicities included 78%neutropenia, 94%thrombocytopenia, 61%anemia, 44%GI, 28%infection, and 17%azotemia. Conclusions. DMAP +sargramostim produced a 27.8%RR, but its complexity and toxicity precluded further investigation, and the study was closed after the first stage of accrual.
