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To assess postoperative complications after secondary cytoreductive surgery (SCS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC), we conducted an exploratory analysis of patients with platinum-sensitive recurrent ovarian cancer enrolled in a randomized phase II trial. Complications occurring within 30 days of surgery were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0; only hemoglobin and platelet levels were assessed. Patients were grouped by CTCAE grade ≥ 3 and < 3 complications. Among 83 eligible patients, 33 (40%) had grade ≥ 3 complications and 50 (60%) had grade < 3 complications; anemia and abdominal infections were the most common. There were no perioperative mortalities. Time to initiation of postoperative chemotherapy for patients with grade ≥ 3 and grade < 3 events was 34 days (range, 18–60) and 31 days (range, 21–43), respectively (P =.017). Median progression-free survival (PFS) did not significantly differ between patients with grade ≥ 3 and grade < 3 complications (11.2 months [95% CI: 9.3–14.4] vs 14.9 months [95% CI: 11.3–16.5], respectively; P =.186), nor did median overall survival (OS) (46.9 months [95% CI: 34-NE] vs 68.2 months [95% CI: 52.1-NE], respectively; P =.053). Postoperative complications following SCS with or without HIPEC were associated with slight delays in chemotherapy initiation but did not significantly impact oncologic outcomes. • Morbidity after secondary cytoreductive surgery (SCS) for recurrent ovarian cancer does not impact survival outcomes • The most common complications after SCS are anemia and abdominal infections • Postoperative morbidity after SCS leads to a 3-day delay to chemotherapy initiation [ABSTRACT FROM AUTHOR]

To assess long-term outcomes of patients with advanced-stage ovarian cancer by treatment type. Patients with newly diagnosed stage III-IV ovarian cancer who underwent primary treatment at our tertiary cancer center from 01/01/2015–12/31/2015 were included. We reviewed electronic medical records for clinicopathological, treatment, and survival characteristics. Of 153 patients, 88 (58%) had stage III and 65 (42%) stage IV disease. Median follow-up was 65.8 months (range, 3.6–75.3). Eighty-nine patients (58%) underwent primary debulking surgery (PDS), 50 (33%) received neoadjuvant chemotherapy followed by interval debulking surgery (IDS), and 14 (9%) received chemotherapy alone, without surgery (NSx). Median PFS to first recurrence was 26.2 months (range, 20.1–36.2), 13.5 months (range, 12–15.1), and 4.2 months (range, 1.1–5.8) in the PDS, IDS, and NSx groups, respectively (P <.001). At first recurrence/progression, 80 patients (72.7%) were treated with chemotherapy, 28 (25.5%) underwent secondary cytoreductive surgery (CRS) followed by chemotherapy, and 2 (1.8%) received no treatment. Seven patients (4.6%) underwent palliative surgery for malignant bowel obstruction. Overall, 62.7% received 1–3 lines of chemotherapy. The 5-year OS rates were 53.2% (95% CI: 44.7%–61%) for the entire cohort, 71.5% (95% CI: 60.2%–80%) for the PDS group, 35.2% (95% CI: 22.2–48.5%) for the IDS group, and 7.9% (95% CI: 0.5%–29.9%) for the NSx group. The longitudinal treatment modalities and outcomes of patients with advanced ovarian cancer described here can be useful for patient counseling, long-term planning, and future comparison studies. • The 5-year OS rate in our cohort was favorably longer compared to what is described in the literature. • The majority of patients (62.7%) received 1–3 lines of chemotherapy. • Nearly 5% of patients underwent palliative surgery for malignant bowel obstruction. • Longitudinal data on treatment modalities and outcomes are useful for patient counseling, planning, and comparison studies. [ABSTRACT FROM AUTHOR]

Anti-angiogenic rechallenge with bevacizumab plus chemotherapy is effective in recurrent ovarian cancer (rOC); however, data are limited on tyrosine kinase inhibitors after progression on maintenance bevacizumab. In the randomized phase II TAPAZ trial, patients with rOC during the first year of bevacizumab maintenance therapy were assigned 2:1 to either weekly paclitaxel 65 mg/m2 plus pazopanib 600–800 mg daily or standard weekly paclitaxel 80 mg/m2. The primary endpoint was 4-month progression-free survival (PFS) rate. Overall, 116 patients were randomized and treated: 79 with combination therapy and 37 with single-agent paclitaxel. Median follow-up was 13.1 months. There was no difference between treatment arms in 4-month PFS rate (61% [95% CI, 51–73%] with the combination versus 68% [95% CI, 54–85%] with paclitaxel alone), median PFS (4.9 [95% CI, 4.1–6.1] versus 5.8 [95% CI, 4.8–7.4] months, respectively) or median overall survival (13.6 versus 12.9 months, respectively). The combination was associated with more grade 3/4 toxicities (87% versus 70%, respectively) and toxicity-related paclitaxel discontinuations (22% versus 11%). Pazopanib was discontinued for toxicity in 44% of patients, most commonly for gastrointestinal and vascular events. There were two treatment-related deaths, both in the combination arm (pulmonary embolism and gastrointestinal perforation). At month 4, patient-reported outcomes deteriorated from baseline in the combination arm, particularly for abdominal/gastrointestinal symptoms, which showed a clinically important difference versus paclitaxel alone. In rOC progressing during maintenance bevacizumab, adding pazopanib to paclitaxel did not improve efficacy, increased toxicity, and compromised chemotherapy delivery. ClinicalTrials.gov registration: NCT02383251. • We tested anti-angiogenic rechallenge for ovarian cancer progressing on bevacizumab. • Pazopanib rechallenge did not improve efficacy vs paclitaxel alone. • Adding pazopanib to paclitaxel increased toxicity, compromising paclitaxel delivery. • The combination had a detrimental effect on abdominal/gastrointestinal symptoms. [ABSTRACT FROM AUTHOR]

The Measure of Ovarian Symptoms and Treatment (MOST) concerns is a validated patient-reported symptom assessment tool for assessing symptom benefit and adverse effects of palliative chemotherapy in women with recurrent ovarian cancer (ROC). We aimed to examine (i) how symptoms within MOST symptom indexes track together (i.e. co-occur) and (ii) the association between MOST symptom indexes and key aspects of health-related quality of life (HRQL). A prospective cohort of women with ROC completed the MOST-T35, EORTC QLQ-C30 and EORTC QLQ-OV28 at baseline and before each cycle of chemotherapy. Analyses were conducted on baseline and end-of-treatment data. Exploratory factor analysis and hierarchical cluster analysis identified groups of co-occurring symptoms. Path models examined associations between MOST symptom indexes and HRQL. Data from 762 women at baseline and 681 at treatment-end who completed all 22 symptom-specific MOST items and at least one HRQL measure were analysed. Four symptom clusters emerged at baseline and treatment-end: abdominal symptoms, symptoms associated with peripheral neuropathy, nausea and vomiting, and psychological symptoms. Psychological symptoms (MOST-Psych) and symptoms due to disease (ovarian cancer) or treatment (MOST-DorT) were associated with poorer scores on QLQ-C30 and OV28 functioning domains and worse overall health at both time points. Four MOST symptom clusters were consistent across statistical methods and time points. These findings suggest that routine standardized assessment of psychological and physical symptoms in clinical practice with MOST plus appropriate symptom management referral pathways is an intervention for improving HRQL that warrants further research. • Four MOST symptom clusters were observed: abdominal, peripheral neuropathy, nausea/ vomiting, psychological symptoms. • Psychological and disease or treatment-related symptoms were consistently associated with worse functioning. • Routine symptom screening with the MOST and appropriate management could reduce symptom burden and improve quality of life. [ABSTRACT FROM AUTHOR]

We sought to determine the safety and efficacy of the oral androgen receptor antagonist enzalutamide in patients with previously treated, recurrent, AR-positive (AR+) ovarian cancer. This was a single-institution phase II study of patients with AR+ ovarian cancer with measurable disease with 1–3 prior lines of chemotherapy; patients were screened for enrollment from 11/2013–7/2018. Following consent, archival tissue was evaluated for AR+. Enrolled patients received daily enzalutamide 160 mg until progression of disease or treatment discontinuation. Adverse events were graded by CTCAE v4.0. Co-primary endpoints were 6-month progression-free survival (PFS 6) and overall response rate (ORR) by RECIST 1.1 criteria. During the study period, 160 patients were screened and 59 (45 high-grade serous [HGS] and 14 low-grade serous [LGS]) consented to treatment on study. There was 1 confirmed and 1 unconfirmed partial response. The ORR was 1.7% (90% CI: 0.2–100%). The overall PFS 6 rate (as binary) was 22% (90% CI: 15.1–100%). The 6-month PFS rate (as time to event) was 19.8% for HGS patients (90% CI: 12.7–100%) and 38.5% (90% CI: 21.7%–100%) for LGS patients. Grade 3 toxicities occurred in 6 patients (one toxicity (Grade 3 rash) was considered a dose-limiting toxicity). One patient died of cardiac arrest after 42 days on treatment of a cardiac arrest not attributed to study drug. The study met its primary endpoint, with a PFS 6 rate of 22% (n = 13); however, the overall response rate was low. Enzalutamide was well tolerated and may be a potential treatment option in select patients. • Enzalutamide was well-tolerated in AR+ recurrent ovarian cancer patients and demonstrated a suitable safety profile. • This study met its primary endpoint, as enzalutamide afforded modest progression-free survival. • The overall response rate to enzalutamide was low, with less than 2% of patients demonstrating radiographic response. • Further study of enzalutamide may be warranted, particularly in patients with AR+ low-grade serous ovarian cancer. [ABSTRACT FROM AUTHOR]

Despite radical surgery and chemotherapy, most patients with ovarian cancer die due to disease progression. M-Trap is an implantable medical device designed to capture peritoneal disseminated tumor cells with the aim to focalize the disease. This trial analyzed the safety and performance of the device. This first-in-human prospective, multi-center, non-blinded, single-arm study enrolled 23 women with high-grade serous advanced ovarian cancer. After primary or interval debulking surgery, 3 M-Trap devices were placed in the peritoneum of the abdominal cavity. 18-months post-implantation or at disease progression, devices were initially removed by laparoscopy. The primary safety endpoint was freedom from device and procedure-related major adverse events (MAEs) through 6-months post-implantation compared to an historical control. The primary performance endpoint was histopathologic evidence of tumor cells capture. Only one major adverse event was attributable to the device. 18 women were free of device and procedure related MAEs (78.3%). However, the primary safety endpoint was not achieved (p = 0.131), primarily attributable to the greater surgical complexity of the M-Trap patient population. 62% of recurrent patients demonstrated tumor cell capture in at least one device with a minimal tumor cell infiltration. No other long-term device-related adverse events were reported. The secondary performance endpoint demonstrated a lack of disease focalization. The M-Trap technology failed to meet its primary safety objective, although when adjusted for surgical complexity, the study approved it. Likewise, the devices did not demonstrate the anticipated benefits in terms of tumor cell capture and disease focalization in recurrent ovarian cancer. • M-Trap safety&performance clinical trial in high-grade serous advanced ovarian cancer • M-Trap implantable medical device to capture peritoneal disseminated tumor cells • Adverse events of complex debulking surgeries conditioned primary safety endpoint. • Devices captured tumour cells but focalization was minimal in recurrent patients. [ABSTRACT FROM AUTHOR]

This randomized open-label phase II study evaluated the safety and clinical activity of EP-100 plus weekly paclitaxel in patients with recurrent ovarian cancer expressing positive LHRH receptor. In a limited "run-in" dose escalation phase for EP-100, six patients were treated with ascending dose levels (13 mg/m2, 20 mg/m2, 30 mg/m2). In the randomized phase, patients received weekly paclitaxel (80 mg/m2 intravenously) plus twice weekly EP-100 (30 mg/m2 intravenously; combination arm) or weekly paclitaxel alone (80 mg/m2 intravenously; paclitaxel arm). The primary study endpoint was overall response rate (ORR). Forty-four patients were then randomized to either the experimental combination arm (n = 23) or the standard of care paclitaxel monotherapy arm (n = 21). The ORR was 35% (95%CI 16%–57%) for the combination arm and 33% (95% CI 15%–57%) for the paclitaxel arm. An interesting observation from an unplanned analysis was that a subset of patients with target liver lesions showed a greater overall response rate to the combination (69%) compared to paclitaxel alone (16%). The frequency of treatment-related grade 3–4 adverse events was similar between treatment arms: 48% vs 43% for the combination and paclitaxel arms, respectively. ORR in the EP-100 combination arm was similar to that in the group treated with paclitaxel alone; however, a subset of patients with liver metastases appeared to benefit from the combination. The addition of EP-100 did not appear to augment the adverse event profile of paclitaxel and was well tolerated. • EP-100 with weekly paclitaxel was shown to be safe and well tolerated. • Patients in the combination arm received extended treatment beyond 6 cycles. • Liver metastasis demonstrated greater benefit from combination as compared to paclitaxel in a posthoc analysis. • There was no difference in response rate with the addition of EP-100 to paclitaxel in the overall population. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy and toxicity of extended duration pegylated liposomal doxorubicin (PLD) in women with recurrent epithelial ovarian carcinoma (rEOC). Women with rEOC who received >7 cycles of PLD were retrospectively identified. Response was determined by RECIST 1.1. Progression free survival (PFS) and overall survival (OS) were calculated from PLD initiation. Toxicity was assessed by CTCAE v5.0. Kaplan Meier estimates and Cox proportional hazards were used to evaluate differences in time to recurrence or survival. 69 patients with rEOC received a median of 11.0 cycles (range, 7–115) at a median cumulative dose of 400 mg/m2 (range, 210–4600 mg/m2); 29.0% (n = 20) had platinum sensitive and 71.0% (n = 49) had platinum resistant disease. Of the observed grade ¾ toxicities (31.9%; n = 22), dermatologic were most frequent (n = 13; 18.8%). 41 women (59.4%) experienced clinical benefit; complete response in 17.4% (n = 12), partial response in 13.0% (n = 9) and stable disease in 29.0% (n = 20). Median PFS for all patients was 13.0 months (95% CI, 10.7, 15.2); there were no significant differences between platinum sensitive versus resistant disease (15.9 months vs. 12.3 months; HR 1.15, 95% CI, 0.66, 2.00; p =.61). With extended duration PLD, median OS was 40.2 months (95% CI 30.0, 49.0); no significant differences were noted for platinum sensitive versus resistant disease (44.7 months vs. 33.3 months; HR 1.85, 95% CI, 0.91, 3.78; p =.07). Four cases (5.8%) of oral squamous cell carcinoma occurred during treatment. Among women with both platinum sensitive and resistant rEOC who received >7 cycles of PLD, approximately one-half experienced sustained clinical benefit with acceptable toxicity. PLD may be considered for extended usage and maintenance in initially responding women with rEOC at least stable disease. • Pegylated liposomal doxorubicin (PLD) improves survival in women with recurrent platinum resistant or platinum sensitive EOC. • PLD may be considered for extended use after clinical response, but data for efficacy and toxicity is limited. • In this retrospective study in women with recurrent EOC, one half experienced clinical benefit with PLD use after six cycles. • PLD may be considered for extended usage in women with rEOC at least stable disease and acceptable toxicity. [ABSTRACT FROM AUTHOR]

Recurrent ovarian, fallopian tube, and peritoneal cancers have limited potential for cure with traditional therapies. Preliminary results from a phase I study of everolimus and bevacizumab in advanced solid tumors showed it to be a promising combination. The primary objective of this study was to evaluate the 6-month progression-free survival for everolimus and bevacizumab in recurrent ovarian, peritoneal, and fallopian tube cancer. Secondary objectives included evaluation of efficacy and safety. In this open-label, single-institution, phase II trial, patients received everolimus 10 mg/day by mouth and bevacizumab 10 mg/kg intravenously every 14 days on a 28-day cycle. Treatment continued until disease progression or adverse event. Fifty patients were enrolled. Median age was 60.5 years (range 28–82). Forty-six (92%) subjects had measurable disease. Thirteen (26%) (24% adjusted) were progression-free at 6 months (95% CI 16.67–42.71%). One patient had a complete response, while six had a partial response and 35 had stable disease as their best response. Patients with both platinum-sensitive and -resistant disease demonstrated responses, as did some prior bevacizumab exposure. There were two grade 4 and 31 grade 3 toxicities noted in 25 distinct patients. The most common reported toxicities included oral mucositis, fatigue, diarrhea, hypertension, pain, nausea and anorexia. Thirty-eight (76%) patients came off study because of disease progression. Unique molecular profiles were identified in long-term responders. Combining everolimus and bevacizumab does not distinctly improve response compared to bevacizumab alone, but further study of selected patients with alterations in the PI3K/mTOR pathway may document benefit. • In the entire cohort, response rate was not better than historical response with bevacizumab alone. • Patients with clear cell cancers had the longest responses to treatment. • Long term responders had alterations leading to activation of the mTOR pathway or mutations in homologous recombination. [ABSTRACT FROM AUTHOR]

Abstract Objectives The hallmarks of germline(g) and/or somatic(s) BRCA1/2 mutation ovarian cancer (BMOC) patients are increased sensitivity to platinum-based chemotherapy (PCT) and PARP inhibitors (PARPi). There is little information on the effectiveness of chemotherapy in heavily pretreated (≥3 CT lines) g/sBMOC patients. Methods g/sBMOC patients who received CT from 2006 to 2016 at 4 cancer centers in Spain were selected. Overall survival (OS) and time to progression (TTP) were calculated with Kaplan Meier and Cox models. Results 135 g/sBMOC patients were identified (6% s BRCA1 / 2 mutations). The median number of chemotherapy lines was 2 (1–7). The 6-years OS rate was 69.4% and 71% in BRCA1 or BRCA2 mutation carriers (p = 0.98). A total of 57 (42%) patients had ≥3 CT lines (3–7), which encompassed a total of 155 treatments. The median overall TTP across all treatment lines beyond 2nd line was 10.2 months (CI 95% 8.4–11.9 months). In the platinum-sensitive setting, TTP was improved with PCT plus PARPi (17.1 m), PCT (12.6 m) or PARPi (12.4 m) versus non-PCT (4.9 m; p < 0.001 all comparisons). In the platinum-resistant setting, these differences in TTP were not statistically significant. A multivariate model confirmed that primary platinum-free interval (PFI) > 12 months and exposure to PCT and PARPi associated with improved outcomes. PARPi exposure did not compromise benefit of subsequent CT beyond 2nd relapse. Conclusions Heavily pretreated g/sBMOC demonstrated CT sensitivity, including for non-PCT choices. Primary platinum-free interval (PFI) >12 months and exposure to both platinum-based chemotherapy and PARPi associate with improved prognosis in heavily pretreated g/sBMOC patients. Highlights • Heavily pretreated g/sBMOC patients remain responsive to chemotherapy in the refractory setting. • Primary platinum-free interval is a strong predictor of the outcome of heavily pretreated g/sBMOC patients. • Exposure to both platinum-based chemotherapy and PARPi correlates with TTP in heavily pretreated g/sBMOC patients. • Our data provide benchmarks for design and interpretation of trials in recurrent disease. [ABSTRACT FROM AUTHOR]

Abstract Epithelial ovarian cancer (EOC) is the leading cause of death due to gynecologic malignancy. The majority of advanced stage EOC patients, even those who respond well to frontline therapy, will ultimately recur and succumb to their disease. In platinum-sensitive EOC patients, or those who recur ≥6 months from initial diagnosis, treatment of recurrent disease has traditionally consisted of repeat platinum-based chemotherapy. Secondary cytoreduction remains controversial. Due to recent advances in molecularly targeted treatment options, outcomes for advanced stage EOC patients are significantly improving and hold great promise. This review discusses pivotal trials establishing platinum-based combination chemotherapy as the standard of care and addresses the utility of increasing a patient's platinum-free interval. It then discusses the role of anti-angiogenesis therapeutics, specifically bevacizumab, cediranib, and trebananib and their side effects. Lastly, it reviews key trials for the three poly-adenosine diphosphate [ADP]-ribose polymerases (PARP) inhibitors that have been FDA-approved for maintenance therapy in platinum-sensitive recurrent EOC: olaparib, rucaparib, and niraparib. This review concludes with a discussion regarding ongoing and future clinical trials. Highlights • The standard of care for the treatment of platinum-sensitive recurrent ovarian cancer is platinum-combination chemotherapy. • Platinum therapy should not be delayed in order to prolong the progression free interval. • This review discusses various angiogenesis inhibitors including bevacizumab, cediranib, and trebananib. • This review assesses the benefits, side effects, and future development of PARPi in platinum-sensitive recurrent patients. • More research is necessary to optimize molecularly targeted therapy leading to improved survival for ovarian cancer patients. [ABSTRACT FROM AUTHOR]

Background Modified Glasgow Prognostic Score (mGPS) is predictive of survival in many advanced cancers, but has not been evaluated in recurrent ovarian cancer (ROC). The aim was to determine validity of mGPS in ROC, investigate its associations with health related quality of life (HRQL) and ECOG performance status (PS). Methods mGPS is based on serum C reactive protein (CRP) and albumin, with scores ranging from 0 (least) to 2 (most). HRQL was measured with EORTC QLQ C-30 and OV-28. χ 2 tests for trend were used to examine the relationship between HRQL, PS and mGPS. Cox proportional hazards regression was used to assess associations between mGPS, HRQL, clinicopathological factors, and overall survival (OS). Results Inflammatory markers were available in 516 of 948 patients in GCIG SBS. 200(39%) had potentially platinum sensitive ROC with ≥ 3 lines of chemotherapy, 316(61%) had platinum resistant ROC. 282(55%), 123(24%), 111(22%) had mGPS of 0, 1, 2, respectively. Median OS (months) was 18.1, 9.6, and 6.6 for mGPS 0, 1, and 2 respectively. mGPS was an independent predictor of OS after adjusting for PS and platinum sensitivity (p < 0.001). mGPS remained a predictor of OS after adjusting for physical function, role function, global health status, abdominal/GI symptoms, and multiple clinicopathologic factors (p = 0.02). Worse PS and higher mGPS were associated with poorer HRQL (p < 0.001). Higher mGPS was associated with worse HRQL, independent of PS. Conclusion The mGPS is an independent predictor of OS in ROC after adjusting for HRQL and clinicopathological factors. Higher mGPS is associated with worse HRQL independent of PS. mGPS is simple, inexpensive and may be suitable for clinical practice, clinical trial patient selection and stratification. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the impact of tertiary cytoreductive surgery (TCS) on survival in recurrent epithelial ovarian cancer (EOC), and to determine predictors of complete cytoreduction. Methods A multi-institutional retrospective study was conducted within the MITO Group on a 5-year observation period. Results A total of 103 EOC patients with a ≥ 6 month treatment-free interval (TFI) undergoing TCS were included. Complete cytoreduction was achieved in 71 patients (68.9%), with severe post-operative complications in 9.7%, and no cases of mortality within 60 days from surgery. Multivariate analysis identified the complete tertiary cytoreduction as the most potent predictor of survival followed by FIGO stage I–II at initial diagnosis, exclusive retroperitoneal recurrence, and TCS performed ≥ 3 years after primary diagnosis. Patients with complete tertiary cytoreduction had a significantly longer overall survival (median OS: 43 months, 95% CI 31–58) compared to those with residual tumor (median OS: 33 months, 95% CI 28–46; p < 0.001). After multivariate adjustment the presence of a single lesion and good (ECOG 0) performance status were the only significant predictors of complete surgical cytoreduction. Conclusions This is the only large multicentre study published so far on TCS in EOC with ≥ 6 month TFI. The achievement of postoperative no residual disease is confirmed as the primary objective also in a TCS setting, with significant survival benefit and acceptable morbidity. Accurate patient selection is of utmost importance to have the best chance of complete cytoreduction. [ABSTRACT FROM AUTHOR]

Purpose In 2012, due to a shortage of pegylated liposomal doxorubicin, single agent trabectedin was proposed as an alternative of treatment to our patients with recurrent ovarian cancer (ROC) at our center. The aim of this retrospective study was to evaluate efficacy and tolerability of trabectedin in this context. Patients and methods This retrospective study included all patients who received intravenous trabectedin 1.3 mg/m 2 over 3 h every 3 weeks for ROC between January 2012 and December 2015 at the Centre hospitalier de l'Université de Montreal. The primary outcome was the progression-free survival (PFS) based on CA-125 levels, clinical exam and/or Response Evaluation Criteria in Solid Tumors criteria. We also evaluated overall survival (OS), response rate and toxicities. Results A total of 42 patients with a median age of 59 years received trabectedin in 2nd or 3rd line (12% of patients), 4th or 5th line (43%), and ≥ 6 lines (45%) and 45% were platinum-resistant. The median number of cycles received was 6 (range 1–19 cycles). Complete response (CR), partial response (PR), stable disease (SD) and progression occurred in 19%, 29%, 33% and 19% of patients, respectively. The median PFS and OS was 4.3 months (95% CI, 3.4–5.1) and 16.2 months (95% CI, 9.0–23.5), respectively. In patients with a clinical benefit (CR, PR, SD), the median PFS was 4.6 months. Trabectedin was well tolerated with few adverse events. Conclusion Our results demonstrate that trabectedin has an interesting efficacy as a single agent in heavily treated ROC patients. [ABSTRACT FROM AUTHOR]

Objective To assess whether the addition of oncolytic reovirus (Reolysin®) to weekly paclitaxel prolonged progression-free survival (PFS) in the treatment of women with recurrent or persistent ovarian, tubal or primary peritoneal cancer. Patients and methods Patients with recurrent or persistent epithelial ovarian, tubal, or peritoneal carcinoma, measurable or detectable disease, and three or fewer prior regimens were randomly assigned to paclitaxel (80 mg/m 2 intravenously days 1, 8, and 15 every 4 weeks) or the combination of paclitaxel (80 mg/m 2 intravenously days 1, 8, and 15) plus reovirus 3 × 10 10 TCID 50 /day intravenously on days 1–5, both every 4 weeks until disease progression or toxicity. The primary end point was PFS. The study was designed with 80% power for a one-sided alternative at a 10% level of significance to detect a reduction in the hazard by 37.5%. Results The study accrued 108 patients, 100 of whom were evaluable for toxicity. Median PFS was 4.3 months for paclitaxel and 4.4 months for paclitaxel plus reovirus (hazard ratio, 1.11; 90% two-sided CI, 0.78 to 1.59; one-sided P = 0.687). The proportion responding (overall response rate) to paclitaxel was 20% among 45 patients with measurable disease receiving paclitaxel alone, and 17.4% among the 46 patients treated with the combination. The asymptotic relative probability of responding was 0.87 (90% CI, 0.42 to 1.79). Severe adverse events were more common in the combination regimen than in paclitaxel arm for severe neutropenia (grade ≥ 4, 12% versus 0%), and severe respiratory adverse events (grade ≥ 3, 25% versus 2%). No deaths were considered treatment related. Conclusion The addition of reovirus to weekly paclitaxel in the treatment of women with recurrent or persistent ovarian, tubal or peritoneal cancer did not sufficiently reduce the hazard of progression or death to warrant further investigation. [ABSTRACT FROM AUTHOR]

Objective We sought to compare symptoms identified as a priority by patients with recurrent ovarian cancer to symptoms most frequently documented by their clinicians, and examine the association between clinician documentation of symptoms and subsequent clinical intervention. Methods Single-institution, retrospective chart review of patients enrolled in WRITE Symptoms Study (GOG 259), a randomized controlled trial of internet-based recurrent ovarian cancer symptom management. As part of the trial, women completed the Symptom Representation Questionnaire for 28 symptoms and selected 3 priority symptoms (PS). We compared patient-reported PS to clinician documentation of symptoms and interventions over the time period corresponding to study enrollment. Results At least one PS was documented in 92% of patients. Of 150 PS reported by patients, 53% were never documented by clinicians; these symptoms tended to be less directly related to disease or treatment status. Symptoms not identified by patients as PS were frequently documented by clinicians; these symptoms tended to relate to physiologic effects of disease and treatment toxicity. 58% of patients had at least one PS intervention. PS intervened for were documented at 2.58 visits vs 0.50 visits for PS not receiving intervention ( p ≤ 0.0001). Conclusions Discordance was identified between symptoms reported by patients as important and symptoms documented by clinicians. Symptoms more frequently documented were also more frequently intervened for. Our study illustrates the need to improve identification of symptoms important to patients, and suggests that improving communication between patients and clinicians could increase intervention rates to enhance quality of life in women with recurrent ovarian cancer. [ABSTRACT FROM AUTHOR]

Objective To evaluate the timing and pattern of relapse, and duration of response to second line chemotherapy in advanced ovarian cancer (AOC) patients treated with first line carboplatin-paclitaxel chemotherapy with or without bevacizumab. Patients and methods This is a case-control study including 222 AOC patients. Seventy-four women treated with first line carboplatin-paclitaxel-bevacizumab chemotherapy (Cases) were matched based on laparoscopic predictive index value, and residual tumor at first surgery with 148 AOC patients treated with carboplatin-paclitaxel. Distribution of pattern of relapse, and response to second line chemotherapy was compared between the two groups. Time to Progression (TTP) for second line chemotherapy was also analyzed for study purpose. Results Median platinum-free interval (PFI) was 16 months (range 2–65) in Cases, compared with 9 months (1–83) in Controls (p-value = 0.001). Twenty patients (51.3%) among Cases showed recurrence in multiple anatomic sites, compared with 31 (31.9%) in the Control group (p-value = 0.035). Peritoneal recurrence occurred as diffuse in 30 Cases (96.8%), and 60 Controls (82.2%; p-value = 0.046). Secondary cytoreductive surgery (SCS) was successfully completed in 53.5% of Controls compared to 10.0% of Cases (p-value = 0.016). In women with fully platinum-sensitive relapse, response rate to second line chemotherapy was 85.2% in Controls, compared to 38.4% in Cases (p-value = 0.002). Finally, Cases showed a shorter TTP, compared to Controls (5 months vs 8 months; p-value = 0.041). Conclusions Incorporation of bevacizumab into upfront regimens prolongs PFI in AOC patients, but is associated with wider presentation of relapse, lower rate of complete SCS, and shorter TTP to second line chemotherapy in women with platinum-sensitive disease. [ABSTRACT FROM AUTHOR]

Most patients with advanced-stage epithelial ovarian cancer will experience a relapse of disease despite a complete response after surgical cytoreduction and platinum-based chemotherapy. Treatment of recurrent ovarian cancer mainly comprises various combinations of systemic chemotherapy with or without targeted agents. The role of cytoreductive surgery for recurrent ovarian cancer is not well established. Although the literature on survival benefit of cytoreductive surgery for recurrent disease has expanded steadily over the past decade, most studies were retrospective, single-institution series with small numbers of patients. Given the balance between survival benefit and surgery-related morbidity during maximum cytoreductive surgical effort, it is essential to establish the optimal selection criteria for identifying appropriate candidates who will benefit from surgery without worsening quality of life. Three phase III randomized trials for this issue are currently underway. Herein, we present contemporary evidence supporting the positive role of cytoreductive surgery and offer selection criteria for optimal candidates for surgery in the treatment of recurrent ovarian cancer. [ABSTRACT FROM AUTHOR]

Objectives Determine the predictive value of the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) score, and prognostic factors for survival, in patients undergoing secondary cytoreductive surgery (SCS) for recurrent ovarian cancer in a high-volume U.S. center. Methods Medical records of women undergoing SCS between 12/1/1998 and 12/31/2013 were reviewed. Women with no gross residual disease (RD0) at primary surgery, ECOG performance status (PS) ≤ 1 at recurrence, and no ascites on CT at recurrence were classified as AGO score positive. Women with incomplete information to determine the AGO score were excluded. Overall survival (OS) and progression-free survival (PFS) following SCS, respectively, were estimated from multivariable Cox proportional hazards models. Results 192 women met inclusion criteria. Median disease-free interval (DFI) was 1.9 years (IQR, 1.0–3.5). Of the 102 (53.1%) AGO score positive cases, 84.3% (95% CI, 77.3–91.4%) achieved RD0 at SCS. However, 64.4% of AGO score negative cases also reached RD0. Patients with RD0 after SCS survived longer (median OS, 5.4 years) vs. RD ≤ 1 cm (2.4 years) vs. RD > 1 cm (1.3 years) (p < 0.001). Median PFS was also longer in patients with RD0 (1.5 years) vs. RD ≤ 1 cm (0.9 years) vs. RD > 1 cm (1.0 years) (p = 0.001). Among those with RD0 at SCS, AGO score was not associated with survival benefit, however, number of disease sites at recurrence, ECOG PS at recurrence, and DFI were associated with OS and PFS. Conclusions AGO score can identify patients with a high likelihood of complete secondary cytoreduction and improved survival. However, most AGO score negative cases were also completed resected at SCS. Additional refinement of the score is needed to exclude women from SCS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Objective: OCEANS, a randomized, placebo-controlled, phase III trial, found that adding bevacizumab to gemcitabine–carboplatin (GC) significantly improved investigator-determined progression-free survival (PFS) and objective response rate (ORR) in platinum-sensitive, recurrent ovarian cancer. To evaluate the reliability of assessment of progression and objective response per RECIST, radiologic and clinical data were assessed by an independent review committee (IRC). Methods: Radiologic images and clinical data were provided prospectively to the IRC for all randomized patients (N=484). Data were reviewed in a blinded fashion per RECIST (modified v1.0). PFS and ORR were analyzed based on the IRC assessment. Concordance between investigator- and IRC-assessed progression and objective response was assessed. Results: The IRC analysis demonstrated a statistically significant increase in PFS (hazard ratio [HR]=0.451; 95% confidence interval [CI]=0.351 to 0.580, p<0.0001) consistent with the benefit reported by investigators (HR=0.484; 95% CI=0.388 to 0.605, p<0.0001). The concordance rate, defined by agreement on progression status, was 74.2% overall, and comparable between treatment arms (bevacizumab, 75.2% vs. placebo, 73.1%). IRC-assessed ORR was significantly improved with bevacizumab (bevacizumab, 74.8% vs. placebo, 53.7%; p<0.0001), consistent with the investigator-assessed results. The concordance rate for objective response was 79.8% overall, and comparable between treatment arms (bevacizumab, 78.9% vs. placebo, 80.6%). Conclusions: IRC-determined results were highly consistent with those determined by investigators, demonstrating that bevacizumab plus GC provides a significant improvement in PFS and ORR. These results suggest that investigators can reliably assess disease progression and objective response in recurrent ovarian cancer using RECIST, without the necessity of a full IRC review. [Copyright &y& Elsevier]

Abstract: Objective: To assess the activity of laparoscopic Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) in women with recurrent, platinum-resistant ovarian cancer. Methods: Prospective case series using repeated courses q 28–42days of PIPAC containing cisplatin 7.5mg/m2 and doxorubicin 1.5mg/m2 at 12mmHg and 37°C for 30min. Objective tumor response was defined as tumor regression on histology and peritoneal carcinomatosis index (PCI) improvement on repeated video-laparoscopy. Results: 34 PIPAC procedures were performed in 18 women, in 8 instances combined with cytoreductive surgery (CRS). Eight women had repeated PIPAC and objective tumor response was observed in 6 (complete remission: 1; partial remission: 2; stable disease: 3). Five adverse events WHO grade≥2 were noted, 3 of them after combined CRS. No perioperative mortality occurred. Median follow-up was 192days (min. 13–max. 639). Cumulative survival after 400days was 62% and mean actuarial survival time was 442days. In a multivariable regression analysis with objective tumor response (yes vs. no) as the dependent variable and PIPAC (1 vs.>1), patient age (<75 vs.≥75years), serum CA-125 (<1000 vs.>1000U/mL), and the presence of ascites (yes vs. no) as independent variables, PIPAC independently predicted objective tumor response. Conclusion: PIPAC has activity in women with recurrent, platinum-resistant ovarian cancer and should be investigated in prospective clinical trials. [Copyright &y& Elsevier]

Abstract: Objective: Evidence of randomized comparative clinical trials on surgery in recurrent platinum-sensitive ovarian cancer is non-existing. Three randomized phase 3 trials are ongoing. The aim of this study is to evaluate the current opinion of Dutch gynecologists and medical oncologists awaiting the results of these three trials. Methods: A 16-item questionnaire was sent to all gynecologists (N =124) and medical oncologists (N =195) with special interest in gynecologic oncology in the Netherlands. The data were collected and analyzed using descriptive statistics. Results: In total, 80 (65.0%) gynecologists and 67 (34.0%) medical oncologists responded. Among the respondents, 11.3% and 26.9% were not convinced of the benefit of secondary cytoreductive surgery, respectively. For most gynecologists and medical oncologists completeness of primary surgery (74.6% and 75.5%, respectively) and performance status (100% and 98%, respectively) were important factors when considering surgery. For only about 17.5% of all respondents diagnostic laparoscopy before surgery is a prerequisite. Most respondents (81.7% and 87.8%, respectively) would use platinum-based chemotherapy with paclitaxel as their agents of choice after surgery. In general medical oncologists settle for a smaller gain in both progression free as well as overall survival than gynecologists. Conclusions: Although most gynecologists and medical oncologists are already convinced of the usefulness of secondary cytoreductive surgery in certain patients, a better understanding of the real advantages and disadvantages and patient's selection criteria for secondary cytoreductive surgery will be achieved after the completion of three ongoing randomized controlled trials (DESKTOP III, GOG 213 and the SOCceR). [Copyright &y& Elsevier]

Abstract: Objective: We aimed to evaluate the efficacy and safety of combination bevacizumab/pemetrexed for the treatment of recurrent epithelial ovarian cancer (EOC). Methods: Platinum-sensitive or -resistant patients with recurrent or persistent EOC were eligible if they had received up to 2 prior chemotherapy regimens, including a platinum/taxane regimen without prior bevacizumab. Pemetrexed 500mg/m2 IV and bevacizumab 15mg/kg IV were administered every 3weeks. The primary endpoint was 6-month progression-free survival (PFS); other endpoints included toxicities, PFS and overall survival (OS). Results: Thirty-four patients received a median of 7 treatment cycles (range, 2–26). Median follow-up was 25.7months (range, 3.0–47.2). Six month progression-free survival (PFS) was 56% (95% CI: 38–71). The following response rates were documented (%; 95% CI): 0 complete response, 14 partial responses (41%; 25–59), 18 stable disease (53%; 35–70) and 2 progressive disease (6%; 1–20). Median PFS was 7.9months (95% CI, 4.6–10.9), with a median OS of 25.7months (95% CI, 15.4–29.8). Twenty-two patients (64.7%) had a platinum-free interval (PFI) of >6months prior to enrollment. Grade 3–4 hematologic toxicities included neutropenia (50%), leukopenia (26%), thrombocytopenia (12%) and anemia (9%). Non-hematologic grade 3–4 toxicities included metabolic (29%), constitutional (18%), pain (18%) and gastrointestinal (15%). Two patients developed hematologic malignancies within one year of treatment. Conclusions: Combination bevacizumab/pemetrexed is an active option for both platinum-sensitive and -resistant recurrent EOC. Further investigation of cost and novel toxicities associated with this regimen may be warranted. [Copyright &y& Elsevier]

Abstract: Objective: We evaluated the clinical outcome and prognostic factors for post-relapse survival (PRS) in a large retrospective series of ovarian cancer patients with localized relapse. Patients and methods: The following radiological inclusion criteria were adopted: relapse in single anatomic site and ≤3 nodules. All cases were followed for at least 24months after recurrent disease. Results: Two hundred twenty ovarian cancer patients met the inclusion criteria. Serous histotype and G3 tumors were observed in 173 (78.6%) and 151 (77.4%) cases, respectively. All women received platinum-based first-line chemotherapy. Overall, the median follow-up was 46 (8–249) months, and platinum-resistant relapse was documented in 51 women (23.2%). Eighty-one patients (36.8%) recurred in the peritoneum (LPeR), 76 patients (34.5%) in the abdominal lymph nodes (LLNR), and 63 patients (28.7%) in parenchymal organs (LPaR); 142 patients (64.5%) recurred with a single nodule; and 78 patients (35.5%) recurred with 2–3 nodules. Secondary cytoreductive surgery (SCS) was attempted in 73 cases (33.2%), and complete debulking was achieved in all patients. On multivariate analysis, platinum-free interval (PFI, χ 2 =13.457, p value=0.001), complete SCS (median PRS, 69months vs 25months, p =0.001), anatomic site of relapse (median PRS, 41months in LPeRs, 63months in LLNRs and 24months in LPaRs, p =0.001), and number of nodules (median PRS, 58months in patients with one nodule, 24months in patients with 2–3 nodules, p =0.001) were identified as predictors of PRS. Conclusions: Beside the duration of PFI, the complete SCS, the anatomic site of relapse, and the number of nodules were independent prognostic factor for duration of PRS. [Copyright &y& Elsevier]

Abstract: Objective: To compare the progression free survival (PFS) and overall survival (OS) in patients with epithelial ovarian cancer (EOC) who received Bev after Bev (BAB) vs. those who were not re-treated with Bev (NOTBev) after initially experiencing a complete response (CR) to a Bev-containing regimen (BCR). Methods: We performed a retrospective chart review of patients with EOC that received Bev in either the front-line or recurrent setting. Patients who received additional therapy after achieving a CR to BCR were analyzed. Results: 36 patients who had a CR to a BCR were included, 17 who received Bev at the time of their subsequent recurrence vs. 19 that did not. More patients in the NOTBev group received Bev as primary therapy (21% vs. 6%, p=0.2), but this was not statistically significant. Patients in the BAB group had significantly higher mean PFS compared to the NOTBev group (20 vs. 6months, p=0.0019). On adjusting for covariates, there was a 78% improvement in their PFS (HR 0.22, p=0.0048). No difference in overall survival was noted between the groups (23 vs. 26months, p=0.7244). Conclusions: Re-treatment with Bev after a prior Bev response is associated with a significantly improved PFS. This is the first of such reports in this patient population. The 14-month improvement in PFS strongly supports the re-use of Bev in patients who demonstrate an initial response to Bev. This strategy should be formally tested in future clinical trials and further investigation should include evaluation of predictors of response to Bev therapy. [Copyright &y& Elsevier]

Abstract: Objective: The aim of this study was to select the best catumaxomab regimen for further investigation in ovarian cancer based on confirmed tumour response. Methods: Randomised open-label phase IIa study in women with platinum-resistant or -refractory epithelial ovarian cancer. Catumaxomab (6-hour intraperitoneal infusion on days 0, 3, 7 and 10) was administered at a low (10, 10, 10 and 10μg) or high dose (10, 20, 50 and 100μg). Responders were patients with either a complete (CR) or partial (PR) response. Results: Forty-five patients were randomised to receive either low dose (23) or high dose (22). There were no responders in the low-dose versus one patient (5%) in the high-dose group with a PR. In the low-dose group, two patients (9%) had stable disease compared with five patients (23%) in the high-dose group. Catumaxomab was well tolerated and there was no difference between the dose groups in the incidence of treatment-induced adverse events, the most common of which were gastrointestinal and injection-site reactions. Conclusion: Catumaxomab had modest activity in platinum-resistant ovarian cancer. The high-dose regimen was associated with a slightly better therapeutic index than the low dose regimen. [Copyright &y& Elsevier]

Abstract: Objective: To evaluate morbidity and mortality rates associated with the use of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) after optimal cytoreduction (CRS) in a large single-institutional series of platinum-sensitive recurrent ovarian cancer patients. Moreover, disease free (DFS) and overall survival (OS) of previously studied patients have been assessed after a longer follow-up period. Method: From May 2005 to October 2010, recurrent ovarian cancer patients with a platinum-free interval of at least 6months have been prospectively enrolled in a protocol of CRS plus HIPEC with oxaplatinum (460mg/m2) heated to 41.5°C for 30min, followed by 6 cycles of systemic chemotherapy with taxotere 75mg/m2 and oxaliplatin 100mg/m2. Results: Forty-one patients experienced 43 procedures (CRS+HIPEC). An optimal cytoreduction was achieved in all cases (CC-0 95.3%; CC-1 4.7%). A complication rate of 34.8% was registered, with no case of intraoperative death or within 30days after surgery. Survival curves have been calculated in a group of 25 patients with a minimum follow-up of 18months, obtaining a median DFS and OS of 24 (range 6–60) and 38months (range 18–60), respectively. Conclusion: In recurrent platinum-sensitive ovarian cancer patients, the use of CRS plus HIPEC represents a safe treatment, able to significantly influence the survival rates compared to chemotherapy alone or surgery plus standard chemotherapy. [Copyright &y& Elsevier]

Abstract: Objective: Weekly paclitaxel has been shown to be an effective cytotoxic regimen for recurrent epithelial ovarian cancer (EOC), and may act through inhibition of angiogenesis. Bevacizumab, a potent angiogenesis inhibitor, has also been shown to have activity in patients with EOC. Therefore, we sought to determine if the addition of bevacizumab to weekly paclitaxel led to an increased survival compared to weekly paclitaxel alone. Methods: A single institutional review was conducted for patients with recurrent EOC treated with weekly paclitaxel (60–70mg/m2) on days 1, 8, 15, and 22 of a 28day cycle and those treated with weekly paclitaxel and bevacizumab (10–15mg/kg on day 1 and 15). Response rates (RR) were calculated, and progression-free survival (PFS), and overall survival (OS) were compared using Kaplan–Meier survival analysis. Results: Twenty-nine patients treated with weekly paclitaxel and 41 patients treated with paclitaxel/bevacizumab were identified. The groups were similar in demographics, initial optimal cytoreduction, stage, histology, grade, platinum sensitivity, and median number of previous regimens (4 vs. 4, p=0.69).The overall response rate (ORR) was 63% (complete response (CR) 34% and partial response (PR) 29%) for paclitaxel/bevacizumab and 48% (CR 17% and PR 31%) for weekly paclitaxel (p=0.23). Improvement in PFS was seen in those treated with paclitaxel/bevacizumab in comparison to weekly paclitaxel alone (median PFS 13.2 vs. 6.2months, p<.01). There was a trend towards improved OS for paclitaxel/bevacizumab (median OS 20.6 vs. 9.1months; p=0.12). Toxicities were similar between the two regimens although more bowel perforations (2 vs. 0) were seen in the paclitaxel/bevacizumab group. Conclusion: A significant increase in PFS with a trend towards improved OS was demonstrated in this heavily pretreated population treated with paclitaxel/bevacizumab as compared to weekly paclitaxel alone. This data should be helpful in guiding future trials to determine the optimal care for women with recurrent EOC. [Copyright &y& Elsevier]

Abstract: Objective. : To evaluate the efficacy and safety of topotecan in patients with recurrent ovarian, primary peritoneal, and fallopian tube carcinomas. Methods. : A randomized phase II analysis of platinum-sensitive patients with measurable disease was performed independently assessing intravenous topotecan 1.25mg/m2 daily × 5 every 21days (regimen I) and topotecan 4.0mg/m2/day on days 1, 8, and 15 of a 28-day cycle (regimen II). All patients were treated until disease progression, unmanageable toxicity, or patient refusal. Insufficient accrual related to regimen I resulted in a redesign of the study as a single arm phase II trial assessing only regimen II. More complete efficacy data is presented for regimen II as enrollment on regimen I was insufficient for some analyses. Results. : A total of 81 patients were enrolled. One patient was ineligible. Fifteen patients received regimen I, while 65 patients were treated with regimen II. The response rate on regimen I (daily × 5) was 27% (90% CI: 10–51%) and 12% (90% CI: 6–21%) on regimen II (weekly). The median PFS and OS were 4.8 and 27.8months, respectively, for regimen II. Grade 3/4 neutropenia rate was 93% with daily × 5 dosing and 28% for weekly treatment. Febrile neutropenia was very low in both groups. Conclusion. : The weekly regimen of topotecan appeared less active but resulted in less toxicity than the daily regimen in platinum-sensitive recurrent ovarian cancer patients. [Copyright &y& Elsevier]

Abstract: Objectives: To evaluate the response rate and toxicity of a regimen comprised of monthly carboplatin and weekly paclitaxel for recurrent ovarian cancer. Methods: We performed a retrospective chart review of patients with recurrent ovarian cancer treated between 2001 and 2006 at a single institution with carboplatin AUC 5 (day 1), and paclitaxel 80 mg/m2 (days 1, 8, 15) of a 28-day cycle. Primary endpoints were response rate, progression-free survival and overall survival. Results: Twenty patients were treated with this regimen from 2001 to 2006. Stage ranged from stages IC to IV. All received intravenous platinum and taxane as their initial therapy. Histologic subtypes included papillary serous (17), carcinosarcoma (1), and clear cell (2). The median number of prior regimens was 1 (range 1–3). The overall response rate was 85.0% (15 complete responses, 2 partial responses). Patients with tumors categorized as platinum sensitive had a response rate of 93.3% (14/15) and those with tumors deemed platinum resistant had a response rate of 60.0% (3/5). The median survival has not yet been reached after a median follow-up of 28 months. Neutropenia was the only grade 3/4 toxicity, occurring in 7 patients (35.0%). Platinum hypersensitivity reactions occurred in 5 patients (25.0%) who all successfully continued treatment using a carboplatin desensitization protocol. Conclusions: A monthly carboplatin and weekly paclitaxel regimen is highly active for women with recurrent platinum-sensitive and platinum-resistant epithelial ovarian cancer. The regimen is well tolerated. This pilot series demonstrates the potential for this regimen as treatment of choice among doublet first salvage regimens for patients with recurrent epithelial ovarian cancer, thus warranting multi-institutional study. [Copyright &y& Elsevier]

Abstract: Objectives: Pegylated liposomal doxorubicin is one of the preferred alternatives for ovarian cancer patients with early relapse (<6 months) and taxane/carboplatin for late relapse (>12 months), but the optimal therapy for the partially platinum-sensitive (6–12 months) population has not been defined. This single-arm phase II trial was designed to assess the efficacy of pegylated liposomal doxorubicin (PLD)/carboplatin in ovarian cancer patients who relapse between 6 and 12 months after initial treatment with platinum-based chemotherapy. Methods: Ovarian cancer patients who previously completed a course of therapy with paclitaxel/carboplatin were administered PLD 30 mg/m2 followed by carboplatin AUC 5 mg/mL/minute every 4 weeks. Results: Fifty-eight patients were enrolled in the study and 54 were eligible for the efficacy analysis, of whom most (75%) received at least 6 cycles of PLD/carboplatin. The objective response rate was 46% (4% CR and 42% PR), with an additional 33% experiencing disease stabilization >6 months. For those patients with measurable CA-125, the response rate was 66% (28% CR and 38% PR), with an additional 18% experiencing disease stabilization >6 months. Median time-to-progression was 10 months (1.5–25). Median overall survival was 19.1 months (2.2–38.9). The most frequent adverse effects were neutropenia, thrombocytopenia, and constipation. Conclusions: The combination of PLD/carboplatin is efficacious and well tolerated in women with partially platinum-sensitive ovarian cancer and represents a valuable alternative for patients who relapse within 6–12 months of completing paclitaxel/carboplatin chemotherapy. [Copyright &y& Elsevier]

Abstract: Objective: To evaluate the effectiveness and toxicity of distearoylphosphatidylcholine pegylated liposomal doxorubicin (DPLD) combined with carboplatin for the treatment of platinum-sensitive, paclitaxel-pretreated, recurrent, epithelial ovarian cancer. Methods: A phase II study of carboplatin/DPLD treatment for platinum-sensitive, paclitaxel-pretreated, recurrent, epithelial ovarian cancer was initiated in July 2002. As of March 2008, a total of 32 patients were enrolled. Results: Of the 32 patients, one achieved a complete response; 19 (59%) achieved a partial response. The overall objective response rate was 62% (95% confidence interval [CI], 45%–80%). The median progression-free survival and overall survival for all 32 patients was 9.1 months (95% CI, 6.4–10.4 months) and 27.9 months (95% CI, 13.9–38.6 months), respectively. Toxicity was tolerable. The most common grade 3 or 4 toxicities were anemia (n=3) and nausea/vomiting (n=3). Grade 3/4 leukopenia (n=2), grade 3/4 thrombocytopenia (n=2) and grade 4 hepatitis (n=1) occurred in five patients. Conclusion: Carboplatin/DPLD appears to be an effective regimen with low toxicity for treatment of patients with platinum-sensitive, paclitaxel-pretreated, recurrent, epithelial ovarian cancer. [Copyright &y& Elsevier]

Abstract: Objective: To assess the efficacy and toxicity profile in patients with recurrent ovarian or primary peritoneal cancer treated with topotecan at 2.5 mg/m2 days 1 and 8 plus vinorelbine at 25 mg/m2 days 1 and 8 every 3 weeks. Materials and methods: Eligibility criteria included patients with recurrent primary peritoneal or epithelial ovarian cancer with either platinum-resistant or platinum-sensitive disease. Patients were required to have a performance status of ≤2 and normal hepatic and renal function. Response to therapy and toxicity were assessed using standard criteria. Chi square and Student''s t-tests were used as appropriate. Survival was assessed with Kaplan–Meier method. Results: All 40 patients enrolled were assessable for response. The median age of the patients was 58 years (range 30–82). Median treatment-free interval was 4.0 months. A total of 216 cycles of chemotherapy were administered with a median of 5.0 cycles per patient. Overall median TTP with this treatment regimen was 19 weeks (range 2–136 weeks). The response rate was 30% overall, and the response for platinum-sensitive and platinum-resistant patients was 44% (95% CI:22–69%) and 18% (95% CI:5–40%) respectively. Median progression-free survival was 3.0 months (range 1–9 months). Median overall survival was 16.4 months (range 1.5–51.7 months). Assessment of toxicity by patient showed 58% demonstrating grade 3/4 neutropenia with the vast majority being uncomplicated. No severe non-hematological toxicity was observed. Conclusion: Administration of topotecan and navelbine is feasible with demonstrable activity and tolerable toxicity. This regimen may be considered especially in platinum-sensitive patients if a non-platinum based doublet is desired. [Copyright &y& Elsevier]

Abstract: Objectives: The aim of the study was to investigate i) the association between the Ca125 based and the RECIST assessed response in recurrent ovarian cancer patients enrolled in a Phase III randomized trial (MITO-3) comparing salvage treatment with pegylated liposomal doxorubicin (PLD) versus gemcitabine (GEM); ii) the correlation between the early modifications of Ca125 levels during treatment and the RECIST assessed response; iii) the prognostic value of response based on Ca125 and the RECIST criteria. Methods: Assessment of response was performed by the RECIST and the GCIG criteria. The prognostic impact of the response by the RECIST criteria and the GCIG criteria was analyzed by the landmark method. Results: Overall, of 30 cases defined as responders on the basis of the GCIG criteria, 20 resulted as responders according to the RECIST criteria (NPV=66.7%); conversely, 93.7% of the cases considered not responders based on the GCIG criteria were defined as unresponsive at RECIST evaluation. Early modifications of Ca125 levels were not completely predictive of the ultimate RECIST defined response. Overall survival (OS) was longer in RECIST defined responders versus non responders, although the statistical significance was not reached (p value=0.092); conversely, median OS was significantly longer in GCIG defined responders than in non responding patients (p value=0.0059). In multivariate analysis, the GCIG assessed response maintained its independent association with OS. Conclusions: GCIG criteria for tumor response could replace the conventional assessment of response in the decision making process relative to the discontinuation or prolongation of the salvage treatment in ovarian cancer. [Copyright &y& Elsevier]

Abstract: Objective.: To investigate the efficacy and safety of bevacizumab in heavily pretreated patients with recurrent ovarian cancer. Methods.: Patients with recurrent ovarian cancer were treated with intravenous bevacizumab 10 mg/kg every other week plus oral cyclophosphamide 50 mg daily until disease progression or undue toxicity. Adverse events were graded according to the NCI Common Toxicity Criteria. Response rates were determined by CA-125 levels or changes in target lesions according to RECIST. Results.: Fifteen patients were treated. Median age was 57 years (range 42–69). The median number of previous chemotherapy regimens was 8 (range 5–15). The median time from the first diagnosis to treatment with bevacizumab was 68.9 months (range, 26.5–177.2). The median number of bevacizumab infusions was 8 (range, 2–12), and the total number was 113. Two patients (13.3%) had a complete response after 4 months of therapy. Six patients (40.0%) had a partial response. The median duration of this response was 3.9 months (range, 2.3–10.4). Three patients (20%) had stable disease of 4.0, 5.2 and 5.5 months'' duration, and 4 patients (26.7%) had progressive disease. Despite being heavily pre-treated and having confirmed intra-abdominal cancer, no gastrointestinal perforations developed. Other toxicities included: grade 3 pancreatitis in 1 patient; grade 2 proteinuria and hypertension in another, which resolved with the cessation of bevacizumab. Conclusion.: In our population of very heavily pre-treated patients, with at least five prior regimens, bevacizumab in combination with oral cyclophosphamide has significant activity with a response rate of 53%, without significant toxicity. [Copyright &y& Elsevier]