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. 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.
