Impact of secondary cytoreductive surgery on survival in patients with platinum sensitive recurrent ovarian cancer: analysis of the CALYPSO trial.

OBJECTIVE: The role of secondary cytoreductive surgery (SCR) in platinum-sensitive recurrent ovarian cancer (ROC) remains controversial. The overall survival (OS) benefits for surgery reported in observational studies may be due to the selection of patients with better prognosis. METHODS: Using data from the CALYPSO trial, OS of patients who had SCR was compared to those treated with chemotherapy alone. Multivariate analyses were performed to adjust for prognostic factors. We also tested for an interaction between baseline prognostic groupings and the benefit of surgery. RESULTS: Of the 975 patients randomised in CALYPSO, 19% had SCR and 80% had chemotherapy alone. OS was longer for the SCR group than for chemotherapy alone (median, 49.9 vs. 29.7 months; adjusted hazard ratio (HR), 0.68; P = 0.004). For patients with SCR, the 3-year OS was 72% for those with no measurable disease, and 28% if residual tumour was larger than 5 cm. Patients with good prognostic features benefited the most from SCR (HR 0.43; P < 0.001). The benefit of SCR was less in patients with poorer prognostic features (test of trend P < 0.001). CONCLUSION: SCR was associated with improved OS in platinum-sensitive ROC, particularly in patients with favourable prognostic characteristics. However, these findings may be due to selection bias, and hence randomised trials are still essential.

Carboplatin and nonpegylated liposomal doxorubicin in primary advanced or recurrent endometrial cancer: a phase 2 trial conducted by AGO Austria.

OBJECTIVE: Recurrent/advanced endometrial carcinoma carries a poor prognosis. Chemotherapy usually consists of cisplatin/doxorubicin and paclitaxel or the doublet of carboplatin and paclitaxel.We report on final results of the Austrian phase 2 AGO trial of nonpegylated doxorubicin citrate and carboplatin in 39 patients with primary advanced or relapsed endometrial cancer. The main primary end point is response rate, and the main secondary end point is feasibility. METHODS: Thirty-nine patients received 60 mg/m nonpegylated doxorubicin citrate and carboplatin (area under the curve, 5) every 3 weeks for 6 to 9 cycles or until progression. Best response during therapy, progression-free survival, and the toxicity profile were recorded. RESULTS: Thirteen patients (33%) had primary advanced disease, and 26 patients (67%) had recurrent disease. Seventy-five percent of the tumors were adenocarcinomas, 15% were serous carcinomas, and 5% were clear cell and mixed müllerian carcinomas. We observed 1 complete response (3%) and 16 partial responses (41%) in the intention-to-treat population. The median progression-free survival was 7.2 months, and the median overall survival was 14.7 months. Overall, 177 cycles were administered; the mean number of cycles per patient was 4.5. Ten percent of patients received 9 cycles of chemotherapy, and 44% of patients received 6 cycles of chemotherapy. Grade 3/4 neutropenia occurred in 17%, grade 3/4 anemia in 5%, and grade 3/4 thrombopenia in 12% of the cycles. In 6% of the cycles, febrile neutropenia was noticed. Grade 3/4 nausea was seen in 5% of cycles. One patient (3%) experienced cardiac toxicity and had a reduction in the left ventricular ejection fraction to below 50%. CONCLUSIONS: The reported combination demonstrates considerable activity and should be evaluated further.

Prophylactic long-acting granulocyte-colony stimulating factors (G-CSF) in gynecologic malignancies: an oncologic expert statement.

We reviewed the status of the use of the prophylactic long-acting granulocyte colony-stimulating factors (G-CSFs) pegfilgrastim and lipegfilgrastim in gynecologic malignancies. Long-acting G-CSFs should not be used in weekly regimens. Filgrastim is not indicated in patients with febrile and/or severe neutropenia after administration of long-acting G-CSF in the same cycle. One study has shown a moderate effect on febrile neutropenia of ciprofloxacin when co-administered with pegfilgrastim. There is broad evidence from meta-analyses that pegfilgrastim effectively reduces severe neutropenia. In parallel, its adverse effects have been studied extensively. All-cause mortality was significantly reduced by pegfilgrastim. The glycopegylated long-acting G-CSF, lipegfilgrastim has demonstrated antineutropenic efficacy similar to that of pegfilgrastimin in one breast cancer study. In another pivitol non-small cell lung cancer study, impaired survival was observed in the lipegfilgrastim group during the first 30 days of study. The European Medicines Agency claimed more profound safety data to be provided for lipegfilgrastim by 2017.

Clinical consequences of the Calypso trial showing superiority of PEG-liposomal doxorubicin and carboplatin over paclitaxel and carboplatin in recurrent ovarian cancer: results of an Austrian gynecologic oncologists' expert meeting.

The Calypso trial showed an improved progression-free survival with PEG-liposomal doxorubicin (PLD) and carboplatin (P) as compared with the standard regimen paclitaxel (PCLTX) and P in the second- or third-line treatment of platinum-sensitive epithelial ovarian cancer [1]. A panel of Austrian gynecologic oncologists discussed the clinical consequences of the data from the Calypso study for the routine practice. PLD + P had a significantly lower rate of alopecia and neuropathy than the taxane regimen, both toxicities which compromise the quality of life. Due to possible significant thrombocytopenia, the blood counts of patients undergoing PLD + P therapy should be monitored weekly. Patients receiving PLD/P are at higher risk of nausea and vomiting. Palmoplantar erythrodysesthesia (hand-foot syndrome) is a significant toxicity of PLD + P most prevalent after the third or fourth cycle. Prophylaxis consists of avoiding pressure on feet and hands and other parts of the body. Similarly, prophylaxis of mucositis seems important and includes avoiding consumption of hot, spicy and salty foods and drinks. Mouth dryness should be avoided. Premedication with antiemetics and dexamethasone dissolved in 5% glucose is done to prevent hypersensitivity to PLD. In conclusion, the therapeutic index is more favorable for PLD + P than for PCTX + P.