Platinum-resistant ovarian cancer: Prematurely stopped phase II Austrian AGO chemotherapy studies

Table 1 Patient characteristics and efficacy results of weekly irinotecan + docetaxel and non-pegylated liposomal doxorubicin +/- gemcitabine + G-CSF in the 27 patients with platinum-resistant or platinum-refractory ovarian cancer n (%)

	Weekly Irinotecan + docetaxel	Liposomal doxorubicin +/- gemcitabine + G-CSF
Included/planned	15/45	12/80
Years of study inclusion	2005-2006	2008-2011
Age (yr), median (range)	56 (33-77)	65 (46-77)
Previous regimens, median (range)	1.9 (1-4)	1.6 (1-3)
Platinum-refractory disease	8 (53)	1 (8)
Platinum-resistant disease	7 (47)	11 (92)
No. of previous chemotherapy regimens
1	8 (53)	1 (8)
2	3 (13)	10 (83)
3	2 (13)	1 (8)
4	2 (13)	0 (0)
Previous taxanes	12 (80)	12 (100)
Complete response	1 (7)	0 (0)
Partial response	1 (7)	2 (17)
Stable disease	2 (13)	2 (17)
Progressive disease	11 (73)	8 (67)
Progression-free survival (mo), median (range)	2.8 (2.0-3.6)	2.1 (1.0-9.0)
Overall survival from study inclusion (mo), median (range)	10 (7.8-12.2)	10 (2.1-44.2)

Table 2 Worst grade 3 and 4 toxicities (National Cancer Institute-common toxicity criteria) per patient with platinum-resistant or platinum-refractory ovarian cancer undergoing weekly irinotecan + docetaxel and non-pegylated liposomal doxorubicin +/- gemcitabine + G-CSF n (%)

Grade 3 and 4 toxicity	Weekly irinotecan + docetaxel	Liposomal doxorubicin +/- gemcitabine + G-CSF
Patients	15 (100)	12 (100)
Neutropenia grade 4	0 (0)	2 (17)
Neutropenia grade 3	2 (13)	4 (33)
Febrile neutropenia grade 4	1 (7)	2 (17)
Leucopenia grade 3	2 (13)	3 (25)
Leucopenia grade 4	0 (0)	1 (8)
Thrombocytopenia grade 4	0 (0)	2 (17)
Nausea grade 3	0 (0)	1 (7)
Stomatitis/mucositis grade 3	0 (0)	3 (25)
Diarrhea grade 3	4 (27)	0 (0)
Diarrhea grade 4	1 (7)	0 (0)
Infection grade 3	0 (0)	2 (17)
Fatigue grade 3	1 (7)	2 (17)
Pain grade 3	1 (7)	2 (17)
Thromboembolism grade 3	2 (13)	1 (7)
Weight gain grade 3	1 (7)	0 (0)

Table 3 Serious adverse events observed in the two Austrian Arbeitsgemeinschaft für Gynäkologische Onkologie phase II studies using irinotecan + docetaxel or liposomal doxorubicin +/- gemcitabine + G-CSF in patients with platinum-resistant and platinum-refractory ovarian cancer n (%)

Type of SAE	Weekly irinotecan + docetaxel (n = 15)	Liposomal doxorubicin +/- gemcitabine (n = 12)
Subileus and fatigue	0	3 (25)
Uncontrollable vomiting and fever	0	2 (17)
Febrile neutropenia	0	1 (8)
Pulmonary embolism/deep pelvic vein thrombosis	2 (13)	1 (8)
Pneumonia	0	1 (8)
Significant pleural effusion	0	1 (8)
Mucositis/diarrhea	1 (7)	1 (8)
Generalized edema	0	1 (8)
Total number of SAE	3 (20)	11 (91)

SAE: Serious adverse events.

Table 4 Commonly used systemic therapy regimens in patients with platinum-resistant or platinum-refractory ovarian cancer

Chemotherapy regimen	Dose	Interval	Remarks
PEG-liposomal doxorubicin	40-45 mg/m2 per day iv	day 1 every 4 wk	No alopecia, non-significant nausea/emesis, minor myelosuppression, significant hand-foot syndrome in 10% to 20%, respectively
Paclitaxel weekly	80 mg/m2 per day iv (1-h-infusion)	Once weekly for three doses followed by 2 wk rest	Complete alopecia, no peroral premedication with dexamethasone necessary, minor myelosuppression, less neurotoxicity compared with 3-weekly paclitaxel
Gemicitabine	1000-1250 mg/m2 per day iv	Days 1 + 8 every 3 wk	No alopecia, minor nausea/emesis, significant myelosuppression
Topotecan weekly	4 mg/m2 per day iv	Days 1, 8, 15 every 4 wk	Moderate myelosuppression, rarely emesis/nausea, rarely significant alopecia
Bevacizumab	15 mg/kg per day iv	Day 1 every 3 wk	Significant hypertension, gastrointestinal perforations in up to 11%
Tamoxifen	20 mg/d	Daily	Response rate around 10%, mild toxicity

iv: Intravenously; PEG: Pegylated.