Objective. This is a phase II group- wide study of liposomal doxorubicin chemotherapy in patients with advanced or recurrent uterine leiomyosarcomas. The aim was to evaluate clinical response and toxicity. Methods. Pa...Objective. This is a phase II group- wide study of liposomal doxorubicin chemotherapy in patients with advanced or recurrent uterine leiomyosarcomas. The aim was to evaluate clinical response and toxicity. Methods. Patients with histologically confirmed persistent or recurrent leiomyosarcomas of the uterus with documented disease progression after appropriate local therapy were invited to participate in this study. Bidimensionally measurable disease, GOG performance status of 0, 1, or 2 (Karnofsky 80- 100) was required; all patients must have failed local therapeutic measures and be considered incurable. Other eligibility criteria included adequate hepatic, renal, and hematologic function. Patients were ineligible if they had received previous chemotherapy or had other noncutaneous malignancies. Patients received liposomal doxorubicin 50 mg/m2 IV over 1 h. Courses were repeated every 4 weeks until disease progression or adverse side effects supervened. Results. Thirty- five patients were entered into this study between May 2000 and June 2001. Three patients were determined ineligible because of wrong pathological cell type or inadequate pathology information and one was inevaluable for lack of data. Median age was 52 years (range 36- 78 years). GOG performance status was 2 in 1 instance, 1 in 15 cases, and 0 in 15 others. Eleven patients (35.5% ) had received radiotherapy. A median of 2.0 courses was given (range 1- 8). Five patients (16.1% )- experienced grade 3 or 4 neutropenia, and seven (22.6% ) had grade 3 or 4 anemia. Two patients developed grade 3 and one patient developed grade 4 cardiovascular adverse events, not necessarily drug related. There were seven cases of grade 3 or 4 gastrointestinal toxicity and two patients developed grade 3 dermatologic toxicity. One complete (3.2% ) and four partial (12.9% ) responses were reported. Ten patients (32.3% ) had stable disease, 15 (48.4% ) had increasing disease, and response could not be assessed in 1 (3.2% ). Conclusion. The dose and schedule of liposomal doxorubicin employed in this trial showed no advantage over historical results with doxorubicin in the treatment of uterine leiomyosarcoma.展开更多
Objectives. To estimate the anti- tumor activity, nature and degree of toxicity of tirapazamine in combination with cisplatin in patients with recurrent platinum- sensitive ovarian or primary peritoneal cancers. Metho...Objectives. To estimate the anti- tumor activity, nature and degree of toxicity of tirapazamine in combination with cisplatin in patients with recurrent platinum- sensitive ovarian or primary peritoneal cancers. Methods. Eligible consenting patients had to have recurrent epithelial ovarian or primary peritoneal carcinoma with measurable disease. Patients were not allowed to have received any additional cytotoxic chemotherapy for management of recurrent or persistent disease, including retreatment with initial chemotherapy regimens. Patients must have been platinum- sensitive, meaning a treatment- free interval of >6 months after response to a platinum- based regimen. The RECIST criteria were used for parameters of response. Tirapazamine was administered at a dose of 390 mg/m2 IV over 2 h followed 1 h later by cisplatin 60 mg/m 2 IV every 3 weeks until disease progression or adverse effects prohibited further therapy. Results. Between June 2001 and February 2004, 65 patients were entered onto this study by 27 institutions; one patient was excluded due to ineligible tumor type. Twenty- six patients (41% ) received six or more cycles of therapy; however, 16 (25% ) received one course of therapy (mainly due to side effects or patient request). There were six (9% ) complete responders and 28 (44% ) partial responders for a total response rate of 53% . Only two patients (3% ) developed increasing disease on this protocol, and response could not be assessed in 18 patients (28% ). The median progression- free and overall survival for all patients is 10.9 and 26.4 months, respectively. The regimen did not cause major hematologic toxicity,however, it did cause frequent constitutional (23% ) and gastrointestinal (mostly nausea/vomiting) (44% ) grade 3 or 4 toxicity. Conclusions. The combination of tirapazamine and cisplatin has definite activity in the treatment of recurrent platinum- sensitive ovarian or primary peritoneal cancer. However, toxicity, primarily non- hematologic,was substantial. Reducing the toxicity of a tirapazamine- platinum combination should be pursued in future trials.展开更多
文摘Objective. This is a phase II group- wide study of liposomal doxorubicin chemotherapy in patients with advanced or recurrent uterine leiomyosarcomas. The aim was to evaluate clinical response and toxicity. Methods. Patients with histologically confirmed persistent or recurrent leiomyosarcomas of the uterus with documented disease progression after appropriate local therapy were invited to participate in this study. Bidimensionally measurable disease, GOG performance status of 0, 1, or 2 (Karnofsky 80- 100) was required; all patients must have failed local therapeutic measures and be considered incurable. Other eligibility criteria included adequate hepatic, renal, and hematologic function. Patients were ineligible if they had received previous chemotherapy or had other noncutaneous malignancies. Patients received liposomal doxorubicin 50 mg/m2 IV over 1 h. Courses were repeated every 4 weeks until disease progression or adverse side effects supervened. Results. Thirty- five patients were entered into this study between May 2000 and June 2001. Three patients were determined ineligible because of wrong pathological cell type or inadequate pathology information and one was inevaluable for lack of data. Median age was 52 years (range 36- 78 years). GOG performance status was 2 in 1 instance, 1 in 15 cases, and 0 in 15 others. Eleven patients (35.5% ) had received radiotherapy. A median of 2.0 courses was given (range 1- 8). Five patients (16.1% )- experienced grade 3 or 4 neutropenia, and seven (22.6% ) had grade 3 or 4 anemia. Two patients developed grade 3 and one patient developed grade 4 cardiovascular adverse events, not necessarily drug related. There were seven cases of grade 3 or 4 gastrointestinal toxicity and two patients developed grade 3 dermatologic toxicity. One complete (3.2% ) and four partial (12.9% ) responses were reported. Ten patients (32.3% ) had stable disease, 15 (48.4% ) had increasing disease, and response could not be assessed in 1 (3.2% ). Conclusion. The dose and schedule of liposomal doxorubicin employed in this trial showed no advantage over historical results with doxorubicin in the treatment of uterine leiomyosarcoma.
文摘Objectives. To estimate the anti- tumor activity, nature and degree of toxicity of tirapazamine in combination with cisplatin in patients with recurrent platinum- sensitive ovarian or primary peritoneal cancers. Methods. Eligible consenting patients had to have recurrent epithelial ovarian or primary peritoneal carcinoma with measurable disease. Patients were not allowed to have received any additional cytotoxic chemotherapy for management of recurrent or persistent disease, including retreatment with initial chemotherapy regimens. Patients must have been platinum- sensitive, meaning a treatment- free interval of >6 months after response to a platinum- based regimen. The RECIST criteria were used for parameters of response. Tirapazamine was administered at a dose of 390 mg/m2 IV over 2 h followed 1 h later by cisplatin 60 mg/m 2 IV every 3 weeks until disease progression or adverse effects prohibited further therapy. Results. Between June 2001 and February 2004, 65 patients were entered onto this study by 27 institutions; one patient was excluded due to ineligible tumor type. Twenty- six patients (41% ) received six or more cycles of therapy; however, 16 (25% ) received one course of therapy (mainly due to side effects or patient request). There were six (9% ) complete responders and 28 (44% ) partial responders for a total response rate of 53% . Only two patients (3% ) developed increasing disease on this protocol, and response could not be assessed in 18 patients (28% ). The median progression- free and overall survival for all patients is 10.9 and 26.4 months, respectively. The regimen did not cause major hematologic toxicity,however, it did cause frequent constitutional (23% ) and gastrointestinal (mostly nausea/vomiting) (44% ) grade 3 or 4 toxicity. Conclusions. The combination of tirapazamine and cisplatin has definite activity in the treatment of recurrent platinum- sensitive ovarian or primary peritoneal cancer. However, toxicity, primarily non- hematologic,was substantial. Reducing the toxicity of a tirapazamine- platinum combination should be pursued in future trials.
