AIM： To report the results of two phase Ⅱ studies of chemotherapy in patients with platinum-resistant and platinum-refractory ovarian cancer and discuss the cur-rent status of systemic therapy in this disease.METHOD...AIM： To report the results of two phase Ⅱ studies of chemotherapy in patients with platinum-resistant and platinum-refractory ovarian cancer and discuss the cur-rent status of systemic therapy in this disease.METHODS： Two subsequent Austrian Arbeitsgemein-schaft für Gynkologische Onkologie （AGO） phase Ⅱ studies have been carried out. Patients either had platinum-refractory or platinum-resistant disease, i.e., disease progression during first line platinum-based therapy or recurrence within 6 mo following the last platinum-containing chemotherapy, respectively. In the first study, 6 cycles of irinotecan at 55 mg/m2 and docetaxel 25 mg/m2 were both administered on days 1, 8 and 15 of a 4 wk cycle. In the second phase Ⅱ study, either non-pegylated （PEG） liposomal doxorubi-cin （L-DXR） 60 mg/m2 monotherapy on day 1 and PEG filgrastim on day 2 （arm A） or L-DXR at 50 mg/m2 and gemcitabine （GEM） at 650 mg/m2 on day 1 and GEM on day 8 （arm B） were administered every 4 wk. Patients in arm B received prophylactic filgrastim 5 μg/kg per day from days 3 to 6 and from days 9 to 12, respec-tively. RESULTS： Response rates in studies were 14% and 17%, respectively. The progression-free survival was less than 3 mo. Diarrhea was most prevalent in patients treated with irinotecan ＋ docetaxel, while stomatitis/mucositis occurred in a quarter of patients treated with L-DXR ＋/- GEM ＋ granulocyte colony stimulating factor, respectively. Following treatment with the latter regi-men, a total of 11 serious adverse events were record-ed among the 12 patients included. The rate of remis-sions of the regimens used in these two Austrian AGOstudies was low and their toxicity significant. Due to their low therapeutic index, neither of these regimens can be recommended in this heavily pretreated patient population with platinum-resistant ovarian cancer ex-hibiting a high tumor-associated symptom burden. CONCLUSION： The two reported phase Ⅱ studies of the Austrian AGO in platinum-resistant disease had to be terminated prematurely due to a low therapeutic index. Treatment of this disease remains a clinical di-lemma. Bevacizumab seems to be active at this late-stage disease but may be associated with significant bowel toxicity.展开更多
文摘AIM： To report the results of two phase Ⅱ studies of chemotherapy in patients with platinum-resistant and platinum-refractory ovarian cancer and discuss the cur-rent status of systemic therapy in this disease.METHODS： Two subsequent Austrian Arbeitsgemein-schaft für Gynkologische Onkologie （AGO） phase Ⅱ studies have been carried out. Patients either had platinum-refractory or platinum-resistant disease, i.e., disease progression during first line platinum-based therapy or recurrence within 6 mo following the last platinum-containing chemotherapy, respectively. In the first study, 6 cycles of irinotecan at 55 mg/m2 and docetaxel 25 mg/m2 were both administered on days 1, 8 and 15 of a 4 wk cycle. In the second phase Ⅱ study, either non-pegylated （PEG） liposomal doxorubi-cin （L-DXR） 60 mg/m2 monotherapy on day 1 and PEG filgrastim on day 2 （arm A） or L-DXR at 50 mg/m2 and gemcitabine （GEM） at 650 mg/m2 on day 1 and GEM on day 8 （arm B） were administered every 4 wk. Patients in arm B received prophylactic filgrastim 5 μg/kg per day from days 3 to 6 and from days 9 to 12, respec-tively. RESULTS： Response rates in studies were 14% and 17%, respectively. The progression-free survival was less than 3 mo. Diarrhea was most prevalent in patients treated with irinotecan ＋ docetaxel, while stomatitis/mucositis occurred in a quarter of patients treated with L-DXR ＋/- GEM ＋ granulocyte colony stimulating factor, respectively. Following treatment with the latter regi-men, a total of 11 serious adverse events were record-ed among the 12 patients included. The rate of remis-sions of the regimens used in these two Austrian AGOstudies was low and their toxicity significant. Due to their low therapeutic index, neither of these regimens can be recommended in this heavily pretreated patient population with platinum-resistant ovarian cancer ex-hibiting a high tumor-associated symptom burden. CONCLUSION： The two reported phase Ⅱ studies of the Austrian AGO in platinum-resistant disease had to be terminated prematurely due to a low therapeutic index. Treatment of this disease remains a clinical di-lemma. Bevacizumab seems to be active at this late-stage disease but may be associated with significant bowel toxicity.
