Objectives. The Gynecologic Oncology Group (GOG) compared methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) with topotecan and cisplatin (TC) or cisplatin alone (C) in advanced cervical cancer. The primary ...Objectives. The Gynecologic Oncology Group (GOG) compared methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) with topotecan and cisplatin (TC) or cisplatin alone (C) in advanced cervical cancer. The primary endpoint was overall survival (OS), with response rate, progression-free survival (PFS), and quality of life (QOL) as secondary objectives. Methods. Eligible patients were randomly allocated to receive either cisplatin 50 mg/m2 q 3 weeks (C) or cisplatin 50 mg/m2 day 1 and topotecan 0.75 mg/m2 days 1- 3 q 3 weeks (TC) or methotrexate 30 mg/m2 days 1, 15, and 22, vinblastine 3 mg/m2 days 2, 15, and 22, doxorubicin 30 mg/m2 day 2, and cisplatin 70 mg/m2 day 2 q 4 weeks (MVAC). QOL was assessed at four time points using the Functional Assessment of Cancer Therapy- Cervix (FACT- Cx), Neurotoxicity Subscale (FACT/GOG- NTX subscale), and Brief Pain Inventory (BPI). Results. One hundred eighty- six patients (C = 60; TC = 63; MVAC = 63) were enrolled before MVAC was closed by the GOG Data Safety Monitoring Board after four treatment- related deaths occurred on that arm. MVAC produced a 22% overall response rate (95% CI: 0.13 to 0.34) and median PFS and OS of 4.4 months and 9.4 months, respectively. Compared with C and TC, there was more hematologic toxicity with MVAC. There were no appreciable differences in QOL scores after controlling for baseline scores. Conclusions. MVAC’ s clinical activity tended to be similar to that of TC but with an unacceptable risk of death from sepsis at this dose and schedule. Nevertheless, QOL, as measured by these instruments, was not substantially impaired by this regimen.展开更多
Objectives. The North Central Cancer Treatment Group Phase III trial compared efficacy of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) with doxorubicin plus cisplatin (AC) for patients with advanced en...Objectives. The North Central Cancer Treatment Group Phase III trial compared efficacy of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) with doxorubicin plus cisplatin (AC) for patients with advanced endometrial cancer. Methods. Twenty- eight patients were randomly assigned to treatment with doxorubicin 30 mg/m2 + cisplatin 70 mg/m2 IV q 4 weeks vs. methotrexate 30 mg/m2 IV days 1, 15, and 22, vinblastine 3 mg/m2 IV days 2, 15, and 22, doxorubicin 30 mg/m2 IV day 2, and cisplatin 70 mg/m2 day 2 of a 4- week cycle. The trial was terminated prematurely due to slow accrual. Results. Prior to early closure of the protocol, there were 15 patients entered on the AC regimen and 13 to the MVAC regimen. There were 3 PR (20% ) for AC and 3 CR (23% ) and 3 PR (23% ) for MVAC. Median PFS was 4.0 months for AC and 6.9 months for MVAC. Median survival was 13.2 months for AC and 16.8 months for MVAC. Toxicity was substantial for MVAC vs. AC with severe leukopenia seen in 69% vs. 33% of patients and severe thrombocytopenia 23% vs. 0% . No treatment-related deaths were seen. Discussion. MVAC and AC are active regimens in the treatment of advanced/recurrent or metastatic endometrial cancer. The premature closure of the protocol resulted in small patient numbers that left the protocol underpowered to address the primary objective of demonstrating improved CR rate for MVAC over AC. MVAC has substantial toxicity compared to AC and is not substantially superior to AC. MVAC cannot be considered as a standard for treatment in this patient population.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Objectives. The Gynecologic Oncology Group (GOG) compared methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) with topotecan and cisplatin (TC) or cisplatin alone (C) in advanced cervical cancer. The primary endpoint was overall survival (OS), with response rate, progression-free survival (PFS), and quality of life (QOL) as secondary objectives. Methods. Eligible patients were randomly allocated to receive either cisplatin 50 mg/m2 q 3 weeks (C) or cisplatin 50 mg/m2 day 1 and topotecan 0.75 mg/m2 days 1- 3 q 3 weeks (TC) or methotrexate 30 mg/m2 days 1, 15, and 22, vinblastine 3 mg/m2 days 2, 15, and 22, doxorubicin 30 mg/m2 day 2, and cisplatin 70 mg/m2 day 2 q 4 weeks (MVAC). QOL was assessed at four time points using the Functional Assessment of Cancer Therapy- Cervix (FACT- Cx), Neurotoxicity Subscale (FACT/GOG- NTX subscale), and Brief Pain Inventory (BPI). Results. One hundred eighty- six patients (C = 60; TC = 63; MVAC = 63) were enrolled before MVAC was closed by the GOG Data Safety Monitoring Board after four treatment- related deaths occurred on that arm. MVAC produced a 22% overall response rate (95% CI: 0.13 to 0.34) and median PFS and OS of 4.4 months and 9.4 months, respectively. Compared with C and TC, there was more hematologic toxicity with MVAC. There were no appreciable differences in QOL scores after controlling for baseline scores. Conclusions. MVAC’ s clinical activity tended to be similar to that of TC but with an unacceptable risk of death from sepsis at this dose and schedule. Nevertheless, QOL, as measured by these instruments, was not substantially impaired by this regimen.
文摘Objectives. The North Central Cancer Treatment Group Phase III trial compared efficacy of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) with doxorubicin plus cisplatin (AC) for patients with advanced endometrial cancer. Methods. Twenty- eight patients were randomly assigned to treatment with doxorubicin 30 mg/m2 + cisplatin 70 mg/m2 IV q 4 weeks vs. methotrexate 30 mg/m2 IV days 1, 15, and 22, vinblastine 3 mg/m2 IV days 2, 15, and 22, doxorubicin 30 mg/m2 IV day 2, and cisplatin 70 mg/m2 day 2 of a 4- week cycle. The trial was terminated prematurely due to slow accrual. Results. Prior to early closure of the protocol, there were 15 patients entered on the AC regimen and 13 to the MVAC regimen. There were 3 PR (20% ) for AC and 3 CR (23% ) and 3 PR (23% ) for MVAC. Median PFS was 4.0 months for AC and 6.9 months for MVAC. Median survival was 13.2 months for AC and 16.8 months for MVAC. Toxicity was substantial for MVAC vs. AC with severe leukopenia seen in 69% vs. 33% of patients and severe thrombocytopenia 23% vs. 0% . No treatment-related deaths were seen. Discussion. MVAC and AC are active regimens in the treatment of advanced/recurrent or metastatic endometrial cancer. The premature closure of the protocol resulted in small patient numbers that left the protocol underpowered to address the primary objective of demonstrating improved CR rate for MVAC over AC. MVAC has substantial toxicity compared to AC and is not substantially superior to AC. MVAC cannot be considered as a standard for treatment in this patient population.
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.
