S.-H. Cho

Comparison of two different S-1 plus cisplatin dosing schedules as first-line chemotherapy for metastatic and/or recurrent gastric cancer: a multicenter, randomized phase III trial (SOS)

BACKGROUNDnFive-weekly S-1 plus cisplatin (SP5) is one of the standard first-line regimens for advanced gastric cancer (GC), proven in a Japanese phase III study. To enhance the dose intensity of cisplatin, 3-weekly S-1 plus cisplatin (SP3) was developed.nnnPATIENTS AND METHODSnThis multicenter, randomized, open-label, phase III study evaluated whether SP3 (S-1 80 mg/m(2)/day on days 1-14 and cisplatin 60 mg/m(2) on day 1) was noninferior/superior to SP5 (S-1 80-120 mg/day on days 1-21 and cisplatin 60 mg/m(2) on day 1 or 8) in terms of progression-free survival (PFS). Chemotherapy-naive patients with metastatic, recurrent gastric or gastroesophageal junction adenocarcinoma were randomized 1 : 1 to receive either SP3 or SP5. The trial is registered at ClinicalTrials.gov (NCT00915382).nnnRESULTSnBetween February 2009 and January 2012, 625 patients were randomized at 42 sites in Korea and Japan. With a median follow-up duration of 32.4 months (range, 13.3-48.6 months) in surviving patients, SP3 was not only noninferior but also superior to SP5 in terms of PFS [median 5.5 versus 4.9 months; hazard ratio (HR) = 0.82; 95% confidence interval (CI) 0.68-0.99; P = 0.0418 for superiority). There was no difference in overall survival (OS) between the groups (median 14.1 versus 13.9 months; HR = 0.99; 95% CI 0.81-1.21; P = 0.9068). In patients with measurable disease, the response rates were 60% in the SP3 arm and 50% in the SP5 arm (P = 0.065). Both regimens were generally well tolerated, but grade 3 or higher anemia (19% versus 9%) and neutropenia (39% versus 9%) were more frequent in SP3.nnnCONCLUSIONSnSP3 is superior to SP5 in terms of PFS. However, since the improvement in PFS was only slight and there was no difference in OS, both SP3 and SP5 can be recommended as first-line treatments for patients with advanced GC.

Efficacy and safety findings from DREAM: A phase III study of DHP107 (oral paclitaxel) versus i.v. paclitaxel in patients with advanced gastric cancer after failure of first-line chemotherapy

BackgroundnPaclitaxel is currently only available as an intravenous (i.v.) formulation. DHP107 is a novel oral formulation of lipid ingredients and paclitaxel. DHP107 demonstrated comparable efficacy, safety, and pharmacokinetics to i.v. paclitaxel as a second-line therapy in patients with advanced gastric cancer (AGC). DREAM is a multicenter, open-label, prospective, randomized phase III study of patients with histologically/cytologically confirmed, unresectable/recurrent AGC after first-line therapy failure.nnnMethods and materialsnPatients were randomized 1xa0:xa01 to DHP107 (200u2009mg/m2 orally twice daily days 1, 8, 15 every 4u2009weeks) or i.v. paclitaxel (175u2009mg/m2 day 1 every 3u2009weeks). Patients were stratified by Eastern Cooperative Oncology Group performance status, disease status, and prior treatment; response was assessed (Response Evaluation Criteria in Solid Tumors) every 6u2009weeks. Primary end point: non-inferiority of progression-free survival (PFS); secondary end points: overall response rate (ORR), overall survival (OS), and safety. For the efficacy analysis, sequential tests for non-inferiority were carried out, first with a non-inferiority margin of 1.48, then with a margin of 1.25.nnnResultsnBaseline characteristics were balanced in the 236 randomized patients (nu2009=u2009118 per arm). Median PFS (per-protocol) was 3.0 (95% CI 1.7-4.0) months for DHP107 and 2.6 (95% CI 1.8-2.8) months for paclitaxel (hazard ratio [HR]u2009=u20090.85; 95% CI 0.64-1.13). A sensitivity analysis on PFS using independent central review showed similar results (HRu2009=u20090.93; 95% CI 0.70-1.24). Median OS (full analysis set) was 9.7 (95% CI 7.1u2009-u200911.5) months for DHP107 versus 8.9 (95% CI 7.1-12.2) months for paclitaxel (HRu2009=u20091.04; 95% CI 0.76-1.41). ORR was 17.8% for DHP107 (CR 4.2%; PR 13.6%) versus 25.4% for paclitaxel (CR 3.4%; PR 22.0%). Nausea, vomiting, diarrhea, and mucositis were more common with DHP107; peripheral neuropathy was more common with paclitaxel. There were only few Grade≥3 adverse events, most commonly neutropenia (42% versus 53%); febrile neutropenia was reported infrequently (5.9% versus 2.5%). No hypersensitivity reactions occurred with DHP107 (paclitaxel 2.5%).nnnConclusionsnDHP107 as a second-line treatment of AGC was non-inferior to paclitaxel for PFS; other efficacy and safety parameters were comparable. DHP107 is the first oral paclitaxel with proven efficacy/safety for the treatment of AGC.nnnClinicalTrials.govnNCT01839773.

Paradoxical cerebral embolism during endoscopic esophageal stenting in a patient with esophageal cancer.

A 77-year-old man with a recurrent esophageal cancer presented with progressive dysphagia. Computed tomography of the chest, esophagogastroscopy, and pharyngesophagography showed an approximately 8.3-cm long malignant stricture in the mid-esophagus (● Fig.1). A 10-cm long, esophageal self-expanding metallic stent (SEMS) was deployed under conscious sedation (● Fig.2). The patient’s level of consciousness deteriorated immediately following the procedure, with left hemiparesis, decreased mentation, and dysarthria. Magnetic resonance imaging of the brain revealed acute cortical infarction (● Fig.3). Transcranial Doppler ultrasound with an agitated saline test demonstrated a patent foramen ovale (PFO). It was concluded that during the procedure the patient had a paradoxical tumor embolism via the PFO, causing multifocal cerebral infarction [1]. The patient was discharged with no improvement in his symptoms. Several cases of air embolism during endoscopy have been published [2–4]. However, tumor embolization to the brain causing cerebral infarction during esophageal stenting has not been reported. In the present case, we suggest that the deployment of the SEMS at the malignant obstruction resulted in injury to the small vessels in the esophagus, allowing tumor cells to enter the venous circulation in response to the positive pressure inside the stent lumen, produced by self-expansion [3]. After entering the venous system, the tumor emboli traveled to the right side of the heart, passed through the PFO into the left atrium and then into the left ventricle, thus entering the systemic circulation and finally causing multiple cerebral infarctions [1,2,5]. Although tumor embolization to the brain during endoscopy is a rare cause of stroke in cancer patients, it causes serious neurological deficits. It is necessary to distinguish this complication from air embolism during endoscopy, as the treatment is different, although both have similar mechanisms. Early detection of neurological symptoms and a correct diagnosis may improve the outcome in these patients. Fig.1 Esophagogastroscopy in a 77-year-old man with a recurrent esophageal cancer and progressive dysphagia showing circumferential luminal narrowing due to an obstructive esophageal mass with easy-touch bleeding, located 35cm from the incisors.