No abstract

LBA2009 Background: Cilengitide (CIL) is a selective αvβ3 and αvβ5 integrin inhibitor. In a phase II study in patients with newly diagnosed glioblastoma, CIL added to standard temozolomide (TMZ) and radiotherapy (RT) was well tolerated and appeared to confer improved survival in patients with glioblastoma and methylated MGMT gene promoter (Stupp et al. J Clin Oncol. 2010;28:2712-8). Methods: This multicenter, randomized, controlled, open-label, phase III study randomized (1:1) patients (≥ 18 years) with newly diagnosed, histologically proven supratentorial glioblastoma (WHO Grade IV) and centrally determined MGMT gene promoter methylation. Treatment consisted of CIL 2000 mg twice weekly i.v. plus standard TMZ/RT→TMZ (concomitant and adjuvant temozolomide and radiotherapy; Stupp et al. N Engl J Med. 2005;352:987-96) or standard TMZ/RT→TMZ alone. CIL was to be administered for ≥ 18 months, or until disease progression or unacceptable toxicity. Primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS) per investigator read and safety. Results: 272 patients received CIL plus TMZ/RT→TMZ, and 273 were treated with TMZ/RT→TMZ alone (intention-to-treat population). 54% and 52% of patients were male, and 42% and 44% had ECOG-PS ≥ 1, respectively. 75% of patients of both arms were ≥ 50 years old. Overall, baseline characteristics were well balanced across treatment arms. Median OS was 26.3 months in both arms (Hazard Ratio [HR] = 1.02 [95%CI: 0.81-1.29], p = 0.86). Median PFS per investigator read was 13.5 months in the CIL arm and 10.7 months in the control arm (HR = 0.93 [95%CI: 0.76-1.14], p = 0.48). Treatment was generally well tolerated and the known safety profile of CIL was confirmed. Conclusions: CIL failed to prolong PFS or OS in patients with newly diagnosed glioblastoma and methylated MGMT gene promoter. The previously reported safety profile of CIL in addition to standard therapy was confirmed. Clinical trial information: NCT00689221.

No abstract

aim of this study was to determine the effectiveness and safety of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery (ICS) in clinical practice Methods This is a prospective, multicenter, cohort study, a total of 205 patients were enrolled. 9 patients were excluded, because they did not meet the inclusion criteria. We enrolled stage III/IV ovarian cancer who had at least three cycles of neoadjuvant chemotherapy followed by ICS either with or without HIPEC at seven Korean Gynecologic Oncology Group institutions between 2017 and 2021. The primary end point was progression-free survival (PFS). Overall survival (OS) and safety profile were key secondary endpoint. Results 196 patients were included in this trial. 87 patients receive ICS without HIPEC and 109 patients receive ICS with HIPEC. The median duration of follow up was 28.2 months. 128 (65.3%) patients had disease recurrence and 30 (15.3%) patients had died. ICS with HIPEC was associated with significantly improved PFS (22.9 vs. 14.2 months; p = 0.005) and OS (not reached vs. 53.0; p = 0.002), compared with IDS without HIPEC. Grade III/IV postoperative complications were similar in the two groups (p = 1.000). Peritoneal recurrences were more common in ICS without HPEC compared to the ICS with HIPEC (41/64 [64.1%] vs 21/64 [32.8%], p = 0.001]. Conclusions The incorporation of HIPEC to IDS resulted in longer PFS and OS than IDS alone without higher rates of side effects in advanced-stage ovarian cancer. Lower rate of peritoneal recurrence after HIPEC might have a prominent impact on OS.

SummaryWe performed an international phase II trial to test the Purpose: To test the hypothesis that intensity modulated radiation therapy (IMRT) reduces acute hematologic and gastrointestinal (GI) toxicity for patients with locoregionally advanced cervical cancer. hypothesis that intensity modulated radiation therapy (IMRT) would reduce the acute toxicity for locoregionally advanced cervical cancer. For the 83 patients enrolled, acute gastrointestinal toxicity was significantly reduced with both IMRT and positron emission tomography-guided bone marrow sparing IMRT (IG-IMRT) compared with historical controls. The incidence of neutropenia was significantly reduced in patients who underwent IG-IMRT. We conclude that IMRT reduces acute toxicity compared with standard treatment in this population and that IG-IMRT warrants testing in randomized trials.Methods and Materials: We enrolled patients with stage IB-IVA cervical carcinoma in a single-arm phase II trial involving 8 centers internationally. All patients received weekly cisplatin concurrently with once-daily IMRT, followed by intracavitary brachytherapy, as indicated. The primary endpoint was the occurrence of either acute grade !3 neutropenia or clinically significant GI toxicity within 30 days of completing chemoradiation therapy. A preplanned subgroup analysis tested the hypothesis that positron emission tomography-based image-guided IMRT (IG-IMRT) would lower the risk of acute neutropenia. We also longitudinally assessed patients' changes in quality of life. Results: From October 2011 to April 2015, 83 patients met the eligibility criteria and initiated protocol therapy. The median follow-up was 26.0 months. The incidence of any primary event was 26.5% (95% confidence interval [CI] 18.2%-36.9%), significantly lower than the 40% incidence hypothesized a priori from historical data (PZ.012). The incidence of grade !3 neutropenia and clinically significant GI toxicity was 19.3% (95% CI 12.2%-29.0%) and 12.0% (95% CI 6.7%-20.8%), respectively. Compared with patients treated without IG-IMRT (nZ48), those treated with IG-IMRT (nZ35) had a significantly lower incidence of grade !3 neutropenia (8.6% vs 27.1%; 2-sided c 2 PZ.035) and nonsignificantly lower incidence of grade !3 leukopenia (25.7% vs 41.7%; PZ.13) and any grade !3 hematologic toxicity (31.4% vs 43.8%; PZ.25). Conclusions: IMRT reduces acute hematologic and GI toxicity compared with standard treatment, with promising therapeutic outcomes. Positron emission tomography IG-IMRT reduces the incidence of acute neutropenia. Ó