Comparative analysis of ATP-based tumor chemosensitivity assay-directed chemotherapy versus physician-decided chemotherapy in platinum-resistant recurrent ovarian cancer

Objective The aim of the study was to evaluate the role of ATP-based tumor chemosensitivity assay(ATP-TCA) in patients with platinum-resistant recurrent ovarian cancer(PRROC).Methods A total of 43 patients with PRROC who underwent chemotherapy based on the results of ATPTCA in the Cancer Hospital,Chinese Academy of Medical Sciences were included in the present study.As controls,we selected another 43 patients with PRROC who were treated at the physician's discretion within the same time period and had the same clinical characteristics as the patients in the ATP-TCA group.Logrank test and Cox proportional hazards model were adopted for analysis.Results A total of 86 patients were retrospectively analyzed in the present study.Patients were routinely monitored to evaluate the rate of progression-free survival(PFS).The median follow-up time was 13 months.The PFS for the ATP-TCA and control groups was 5 and 3 months,respectively(P = 0.027).Multivariate analysis showed that the type of treatment was an independent prognostic factor for PFS(P = 0.040;HR:0.623;95% CI:0.313–0.973).Subgroup analysis showed that among patients with a treatmentfree interval(TFI) of ≥ 3 months(n = 50),those in the ATP-TCA group had longer PFS than those in the control group(7 vs 4 months,P = 0.010).Meanwhile,the median PFS of patients who underwent ≤ 2 prior chemotherapy regimens(PCR,n = 52) in the ATP-TCA and control groups was 6 months and 4 months,respectively(P = 0.025).Conclusion ATP-TCA-directed chemotherapy might improve the PFS in PRROC.In particular,the survival benefit from ATP-TCA is higher in patients with a TFI of ≥ 3 months or treated with ≤ 2 PCR.

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

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.

Pegylated liposomal doxorubicin/carboplatin combination in ovarian cancer, progressing on single-agent pegylated liposomal doxorubicin

AIM: To assess the efficacy and safety of the combination of pegylated liposomal doxorubicin(PLD) and carboplatin in patients with recurrent epithelial ovarian carcinoma(ROC), following disease progression on single agent PLD. METHODS: An analysis of the medical records of 10 patients with ROC, treated in our institution with a combination of PLD and carboplatin following progression on single-agent PLD therapy was performed. The median age was 59.1 years(range, 45 to 77 years). All diagnoses were histological-proven. Eight of the 10 patients were platinum-resistant. Following disease progression on single-agent PLD treatment, carboplatin area under the curve(AUC)-5 was added to PLD in all 10 patients. In order to assess disease status, Ca-125 was assessed before each PLD/carboplatin treatment. Relative changes in Ca-125 values were calculated, and response defined as a greater than 50% reduction in Ca-125 from baseline. Radiographic studies were reevaluated and responses to therapy based on com-puter tomography(CT) scans carried out on a regular basis every 2-3 mo in each patient. Statistical analysis was performed using SPSS(V19).RESULTS: A median of 10 cycles(range, 2-26) of the carboplatin-PLD combination was given. Of the 10 treated patients, 6 had > 50% reduction in Ca-125 levels from baseline, 4 of these had a partial response according to Response Evaluation Criteria in Solid Tumors(RECIST) criteria, and the other 2 patients had no measurable disease. In a further 2 patients with a best response of disease stabilization and < 50% reduction of Ca-125 levels, one had progression of disease after 26 cycles, and the second progressed with brain metastases following 12 cycles. Seven of the eight patients who were platinum-resistant showed evidence of clinical benefit on carboplatin-PLD combination therapy; 5 of these had > 50% reduction in Ca-125 level, 4 also showed a partial response on CT scan. The treatment was generally well-tolerated by the patients. CONCLUSION: Addition of carboplatin to PLD, after disease progression on single-agent PLD therapy, is both effective and safe in patients with ROC, even in those with Platinum-resistant disease.