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Objective: To determine the rates of germline BRCA1 and BRCA2 mutations in Scottish patients with ovarian cancer, before and after a change in testing policy.Design: Retrospective cohort study.Setting: Four cancer/genetics centres in Scotland.Population: Patients with ovarian cancer undergoing germline BRCA1 and BRCA2 (gBRCA1/2) sequencing before 2013 (under the 'old criteria', with selection based solely on family history), after 2013 (under the 'new criteria', with sequencing offered to newly presenting patients with non-mucinous ovarian cancer), and in the 'prevalent population' (who presented before 2013, but were not eligible for sequencing under the old criteria but were sequenced under the new criteria).Methods: Clinicopathological and sequence data were collected before and for 18 months after this change in selection criteria.Main Outcome Measures: Frequency of germline BRCA1, BRCA2, RAD51C, and RAD51D mutations.Results: Of 599 patients sequenced, 205, 236, and 158 were in the 'old criteria', 'new criteria', and 'prevalent' populations, respectively. The frequency of gBRCA1/2 mutations was 30.7, 13.1, and 12.7%, respectively. The annual rate of gBRCA1/2 mutation detection was 4.2 before and 20.7 after the policy change. A total of 48% (15/31) 'new criteria' patients with gBRCA1/2 mutations had a Manchester score of <15 and would not have been offered sequencing based on family history criteria. In addition, 20 patients with gBRCA1/2 were identified in the prevalent population. The prevalence of gBRCA1/2 mutations in patients aged >70 years was 8.2%.Conclusions: Sequencing all patients with non-mucinous ovarian cancer gives a much higher annual gBRCA1/2 mutation detection rate, with the frequency of positive tests still exceeding the 10% threshold upon which many family history-based models operate.Tweetable Abstract: BRCA sequencing all non-mucinous cancer patients increases mutation detection five fold. [ABSTRACT FROM AUTHOR]

Background: Sagopilone, the first fully synthetic epothilone, has shown promising preclinical activity in tumour models. This open-label randomised phase II study investigated two infusion schedules of sagopilone in women with ovarian cancer.Patients and methods: Women with ovarian cancer recurring within 6 months of end of last platinum-containing treatment received sagopilone 16 mg/m2 as a 3- or 0.5-h i.v. infusion every 21 days for up to 6 weeks.Results: Sixty-three patients received sagopilone as a 3-h (n = 38) or 0.5-h (n = 25) infusion. There were nine confirmed tumour responses [by modified RECIST (n = 8) and by Gynecologic Cancer Intergroup CA-125 criteria (n = 1)] in 57 patients assessable for efficacy overall [three (13%) with 0.5-h and six (18%) with 3-h infusions]. The 0.5-h arm was closed when it failed to meet its target efficacy. Main drug-related adverse events were peripheral sensory neuropathy (73%; 16% grade 3), nausea (37%; 2% grade 3), fatigue (35%; 3% grade 3) and arthralgia (30%; 5% grade 3). Overall incidence of peripheral sensory neuropathy was similar in both treatment arms, with no grade 4 neuropathy events. No acute allergic infusion reactions were observed.Conclusion: Sagopilone is effective, with balanced tolerability, in patients with recurrent platinum-resistant ovarian cancer. [ABSTRACT FROM AUTHOR]

OBJECTIVE To investigate tolerability and efficacy of weekly carboplatin and paclitaxel in treatment resistant epithelial ovarian cancer (EOC). DESIGN Retrospective case note review. SETTING The Beatson West of Scotland Cancer Centre. POPULATION Patients with EOC, fallopian tube, or primary peritoneal cancer progressing on or recurring within 6 months of their last treatment who received weekly carboplatin and paclitaxel. METHODS Chemotherapy records of the patients described above were retrospectively reviewed. MAIN OUTCOME MEASURES Dose delay, dose reduction, dose intensity, toxicity, response rate, progression free survival, and overall survival. RESULTS Forty-two patients were identified. Thirteen patients were treated with carboplatin and paclitaxel, given once per week for 3 weeks followed by a week off. Twenty-nine patients were treated on a continuous weekly basis. Mean dose intensity was 80>91% for carboplatin and 79>87% for paclitaxel. Of 38 assessable patients, grade three or four neutropenia affected 15 patients, anemia and thrombocytopenia affected five, and there were two cases of neutropenic sepsis. Nonhematological toxicity included lethargy and alopecia. Overall response rate by CA125 or CT was 54% (7/13) for the 3 weeks out of 4 regimen and 45% (13/29) for the continuous regimen. Median overall and progression free survivals were 22 and 17 weeks, respectively, for the 3 out of 4 week regimen and 18 and 7 weeks with the continuous schedule. CONCLUSION Weekly treatment with carboplatin and paclitaxel is feasible, reasonably well tolerated, and active in heavily pretreated patients with treatment-resistant EOC. [ABSTRACT FROM AUTHOR]

Background: We assess the prognostic value of chemotherapy-induced leukopenia and sensory neuropathy in the CALYPSO trial patients treated with carboplatin-paclitaxel (CP) or carboplatin-liposomal doxorubicin (CPLD).Methods: We performed a landmark analysis at first month after randomisation to correlate leukopenia (nadir white blood cell <4.0 × 10(9) per litre or severe infection) during cycle 1 of chemotherapy with progression-free survival (PFS). Using time-dependent proportional-hazards models, we also investigated the association between neuropathy and PFS.Results: Of 608 patients with nadir blood and did not receive growth factors, 72% (CP=70%, CPLD=73%) had leukopenia. Leukopenia was prognostic for PFS in those receiving CP (adjusted hazard ratio (aHR) 0.66, P=0.01). Carboplatin-liposomal doxorubicin was more effective than CP in patients without leukopenia (aHR 0.51, P=0.001), but not those experiencing leukopenia (aHR 0.93, P=0.54; interaction P=0.008).Of 949 patients, 32% (CP=62%, CPLD=28%) reported neuropathy during landmark. Neuropathy was prognostic for PFS in the CP group only (aHR 0.77, P=0.02). Carboplatin-liposomal doxorubicin appeared to be more effective than CP among patients without neuropathy (aHR 0.70, P<0.0001), but not those with neuropathy (aHR 0.96, P=0.81; interaction P=0.15).Conclusion: First-cycle leukopenia and neuropathy were prognostic for patients treated with CP. Efficacy of CP treatment was similar to CPLD in patients who developed leukopenia. These findings support further research to understand the mechanisms of treatment-related toxicity. [ABSTRACT FROM AUTHOR]

The feasibility of sequential carboplatin followed by docetaxel-based therapy for untreated ovarian cancer was determined. Patients received four q3w cycles of carboplatin AUC 7, then four q3w cycles of either docetaxel 100 mg m(-2) (day 1) (arm A); docetaxel 75 mg m(-2) (day 8) and gemcitabine 1250 mg m(-2) (days 1,8) (arm B) or docetaxel 25 mg m(-2) and gemcitabine 800 mg m(-2) (both given weekly (days 1,8,15)) (arm C). A total of 44 patients were randomised to each treatment arm. None of the arms demonstrated an eight cycle completion rate (70.5/72.7/45.5% in arms A/B/C, respectively), which was statistically greater than 60% (P=0.102, P=0.056, P=0.982) which was our formal feasibility criteria, although only the completion rate in arm C was clearly worse than this level. The overall response rate (ORR) after carboplatin was 65.7% in 70 evaluable patients. In evaluable patients, ORRs after docetaxel-based cycles were: arm A 84.0% (21 out of 25); arm B 77.3% (17 out of 22); arm C 69.6% (16 out of 23). At follow-up (median 30 months), median progression-free survival times were: arm A 15.5 months (95% CI: 10.5-20.6); arm B 18.1 months (95% CI: 15.9-20.3); arm C, 13.7 months (95% CI: 12.8-14.6). Neutropenia was the predominant grade 3-4 haematological toxicity: 77.8/85.7/54.4% in arms A/B/C, respectively. Dyspnoea was markedly increased in both gemcitabine-containing arms (P=0.001) but was worse in arm C. Although just failing to rule out eight cycle completion rates less than 60%, within the statistical limitations of these small cohorts, the overall results for arms A and B are encouraging. Larger phase III studies are required to test these combinations. [ABSTRACT FROM AUTHOR]

Oral capecitabine is a highly active, well-tolerated and convenient treatment for breast and colorectal cancer. This trial assessed the efficacy and safety of single-agent capecitabine in patients with previously treated ovarian cancer. A total of 29 patients with platinum-pretreated relapsed ovarian cancer were enrolled in this prospective, open-label, single-centre, phase II study. Patients received oral capecitabine 1250 mg m(-2) twice daily on days 1-14 of a 21-day cycle. Tumour response was evaluated using serum CA125. Out of 29 enrolled patients, 28 were evaluable, and a response was observed in eight patients (29%, 95% confidence interval (CI), 13-49%). Median progression-free and overall survivals were 3.7 (95% CI, 2.8-4.6) and 8.0 (95% CI, 4.1-11.8) months, respectively. After 6 months of treatment, 28% (95% CI, 13-48%) of patients remained progression-free and 62% (95% CI, 42-79%) were still alive. The most common clinical adverse events were hand-foot syndrome (HFS), nausea and diarrhoea. Grade 3 HFS occurred in 14% of patients, grade 3 vomiting in 10%. Efficacy and safety of capecitabine compare favourably with other monotherapies in platinum-refractory epithelial ovarian cancer. The convenience and improved safety profile of capecitabine compared with intravenous. regimens make it an ideal agent for administration in the outpatient setting. [ABSTRACT FROM AUTHOR]

Details a gynecologic oncology phase II trial of capecitabine in recurrent epithelial ovarian cancer. Impact of the increase in chemotherapeutic options on patients with recurrent ovarian cancer; Major consideration during a palliative treatment; Examples of oral agents and their effectiveness.

The article focuses on the clinical practice guidelines for the diagnosis, treatment and reexamination of patients with non-epithelial ovarian cancer. It says that computed tomography (CT) and magnetic resonance imaging (MRI) are used to assist the staging and planning surgery. It mentions that symptoms of a pelvic mass and suspicions of germ cell tumour (GCT) should be considered in the diagnosis of non-epithelial ovarian cancer for younger women. Moreover, 5 years of follow-up is recommended.

Background: A previous dose-escalation trial of the vascular disrupting agent combretastatin A4 phosphate (CA4P) given before carboplatin, paclitaxel, or both showed responses in 7 of 18 patients with relapsed ovarian cancer.Patients and methods: Patients with ovarian cancer that had relapsed and who could start trial therapy within 6 months of their last platinum chemotherapy were given CA4P 63 mg/m2 minimum 18 h before paclitaxel 175 mg/m2 and carboplatin AUC (area under the concentration curve) 5, repeated every 3 weeks.Results: Five of the first 18 patients’ disease responded, so the study was extended and closed after 44 patients were recruited. Grade ≥2 toxic effects were neutropenia in 75% and thrombocytopenia in 9% of patients (weekly blood counts), tumour pain, fatigue, and neuropathy, with one patient with rapidly reversible ataxia. Hypertension (23% of patients) was controlled by glyceryl trinitrate or prophylactic amlodipine. The response rate by RECIST was 13.5% and by Gynecologic Cancer InterGroup CA 125 criteria 34%.Conclusions: The addition of CA4P to paclitaxel and carboplatin is well tolerated and appears to produce a higher response rate in this patient population than if the chemotherapy was given without CA4P. A planned randomised trial will test this hypothesis. [ABSTRACT FROM AUTHOR]

Objective Etirinotecan pegol (EP) is a novel polyethylene glycol conjugated form of irinotecan with documented activity in platinum-resistant ovarian cancer (PROC). We report the results of the expanded portion of a phase II study of EP in patients with PROC who received prior pegylated liposomal doxorubicin (PLD) or who were unable to receive it. Methods This multicenter, open-label, phase II study evaluated EP q21d for PROC. The primary endpoint was objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors version 1.0. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Patient populations evaluated included a modified intent-to-treat (mITT) group consisting of all patients who received at least one dose and with measurable disease and a primary efficacy (pEFF) group (subset of the mITT population who received prior PLD). Results One hundred thirty-nine patients were enrolled. Of the 132 patients in the mITT group, 20 achieved an ORR (15.2%; 95% CI 9.5–22.4); median PFS and OS were 4.4 months and 10.2 months, respectively. In the pEFF group (n = 104), 15 patients (14.4%; 95% CI 8.3–22.7) achieved an ORR; median PFS and OS were 4.4 months and 10.9 months, respectively. The most common grade 3/4 toxicities were diarrhea (20%), abdominal pain (17%), vomiting (14%), dehydration (13%), and nausea (13%). Severe diarrhea was reduced to 15% with strict adherence to screening and management guidelines. Conclusions This study confirms the activity and safety of single-agent EP in patients with PROC, including patients who received prior PLD. Further evaluation earlier in the disease course and in combination is warranted. [ABSTRACT FROM AUTHOR]

Background In the CALYPSO trial, carboplatin–pegylated liposomal doxorubicin (CD) demonstrated superior therapeutic index versus carboplatin–paclitaxel (CP) in patients with recurrent ovarian cancer. This paper reports the health-related quality of life (HRQoL) findings. Materials and methods HRQoL was measured with the EORTC QoL-QC30 questionnaire and OV28 ovarian cancer module. Mean change scores from baseline in HRQoL subscales (five functional scales and global health status) in each arm and the proportion of patients improved or worsened were calculated every 3 months until 12 months. Results Compliance was 90% at baseline and 76%, 64%, 57% at 3, 6, and 9 months, respectively. Baseline HRQoL showed already impaired global scores (mean 62/100) and considerable symptom burden (90% of patients reporting nonzero scores). Global QoL and abdominal symptom scores improved over time in both arms; at 6 months, 36% of patients met criteria for improved symptoms. Treatment with CD resulted in less peripheral neuropathy (9.8 versus 24.2), fewer other chemotherapy side-effects (9.5 versus 16.2), and less impact on body image (3.8 versus 10.4) versus CP (all P < 0.02) at 6 months. Conclusions These patient-reported outcomes confirm the overall lower toxicity of CD versus CP. The improved disease-related outcomes achieved with CD were not at the expense of QoL. [ABSTRACT FROM AUTHOR]

Background: To perform a subset analysis of patients with partially platinum-sensitive recurrent ovarian cancer (ROC) who received either CD [carboplatin–pegylated liposomal doxorubicin (PLD)] or CP (carboplatin–paclitaxel) in the CALYPSO trial. Patients and methods: CALYPSO, an international phase III, non-inferiority trial, enrolled women with ROC that relapsed >6 months following first- or second-line therapy. Patients were randomized to CD or CP. Patients with a treatment-free interval of >6 and ≤12 months were evaluated for progression-free survival (PFS), the primary end point of CALYPSO trial, and safety. Results: A total of 344 partially platinum-sensitive patients were included (N = 161, CD and N = 183, CP). The hazard ratio for PFS was 0.73 (95% confidence interval: 0.58–0.90; P = 0.004 for superiority) in favor of CD. Median PFS times were 9.4 months (CD) and 8.8 months (CP). Toxicities more common with CP versus CD included grade 3/4 neutropenia (50% versus 39%; P = 0.015), grade 2 alopecia (86% versus 9%; P < 0.001), neuropathy and hypersensitivity reactions. Hand-foot syndrome was more common with CD; however, grade 3/4 reactions were low (one patient in each arm). Conclusion: Carboplatin–PLD has a more favorable risk-benefit profile than CP in patients with partially platinum-sensitive ROC and should be considered an effective treatment option for these patients. [ABSTRACT FROM PUBLISHER]

Background: CALYPSO (CAeLYx in Platinum Sensitive Ovarian) patients compared carboplatin–pegylated liposomal doxorubicin (C–PLD) with carboplatin–paclitaxel (C–P) in patients with late-relapsing recurrent ovarian cancer (ROC). We analyzed outcomes in patients ≥70 years.Patients and methods: Nine hundred and seventy-six patients with taxane-pretreated ROC relapsing >6 months after first- or second-line platinum-based therapy were randomly assigned to 4-weekly C area under the curve (AUC) 5 plus PLD 30 mg/m2 or 3-weekly C AUC 5 plus P 175 mg/m2 for six or more cycles.Results: One hundred and fifty-seven (16%) patients ≥70 years (median: 74 years, C–PLD; 73 years, C–P; range 70–82 years) were included (n = 71, C–PLD; n = 86, C–P). In comparing elderly and younger, elderly patients experienced fewer grade ≥2 allergic reactions (P = 0.005) but more grade ≥2 sensory neuropathy (P = 0.007). Myelosuppression did not differ with age. Elderly patients completed planned treatment as frequently as younger (79%, C–PLD; 82%, C–P). In comparing arms within elderly patients, C–P was associated with more grade ≥2 alopecia, sensory neuropathy, arthralgia/myalgia (P < 0.001 for all), severe leukopenia plus febrile neutropenia; C–PLD was associated with more grade ≥2 hand–foot syndrome (P = 0.005). Median progression-free survival was 11.6 months (C–PLD) and 10.3 months (C–P; P = 0.44).Conclusions: Patients ≥70 years experienced more neuropathy, with a higher incidence in the C–P arm. Similar to all study patients, C–PLD provided a better therapeutic index with less toxicity than C–P in elderly women with platinum-sensitive ROC. [ABSTRACT FROM AUTHOR]