BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China. METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion. RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon. CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings. REGISTRATION Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans ; Male ; Female ; Anemia/etiology* ; Middle Aged ; Renal Insufficiency, Chronic/complications* ; Glycine/adverse effects* ; Isoquinolines/adverse effects* ; Aged ; Prospective Studies ; Adult ; Hemoglobins/metabolism* ; Treatment Outcome ; China ; Registries ; East Asian People

OBJECTIVE: There is no research regarding the appropriate antiemetic agents for female patients, especially those receiving moderately emetogenic chemotherapy (MEC). We evaluated the antiemetic efficacy of a combination of 5-HT3 receptor with/without aprepitant in patients with gynecological cancer treated with the TC (paclitaxel and carboplatin) regimen of MEC. METHODS: We enrolled 38 patients diagnosed with gynecologic cancer and scheduled to receive the TC regimen. The patients were randomly assigned to receive a 5-HT3 receptor antagonist, either palonosetron in the first cycle followed by granisetron in the second cycle or vice versa. In the third cycle, all patients received a combination of the 5-HT3 receptor and dexamethasone with/without aprepitant. RESULTS: When three drugs were administered, palonosetron consistently produced an equivalent complete response (CR) rate to granisetron in the acute phase (89.5% vs. 86.8%, p=0.87) and delayed phase (60.5% vs. 65.8%, p=0.79). With regard to the change in dietary intake, palonosetron exhibited similar efficacy to granisetron in the acute phase (92.1% vs. 89.4%, p=0.19) and delayed phase (65.7% vs. 68.4%, p=0.14). However, in the delayed phase, the addition of aprepitant therapy with a 5-HT3 receptor antagonist and dexamethasone produced a higher CR rate than a 5-HT3 receptor antagonist with dexamethasone (93.3% vs. 47.8%, p<0.001) and allowed the patients to maintain a higher level of dietary intake (93.3% vs. 56.5%, p<0.001). CONCLUSION: The addition of aprepitant therapy was more effective than the control therapy of a 5-HT3 receptor antagonist, and dexamethasone in gynecological cancer patients treated with the TC regimen.
Adult ; Aged ; Antiemetics/*administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Carboplatin/administration & dosage/adverse effects ; Cross-Over Studies ; Diet ; Drug Administration Schedule ; Female ; Genital Neoplasms, Female/*drug therapy ; Granisetron/administration & dosage ; Humans ; Isoquinolines/administration & dosage ; Middle Aged ; Morpholines/administration & dosage ; Nausea/chemically induced/*prevention & control ; Paclitaxel/administration & dosage/adverse effects ; Quinuclidines/administration & dosage ; Serotonin 5-HT3 Receptor Antagonists ; Vomiting/chemically induced/*prevention & control

OBJECTIVETo evaluate the efficacy and toxicity of palonosetron for prevention of vomiting induced by high dose cisplatin-based chemotherapy.

METHODSOne-hundred and twenty-eight patients received tropisetron 5 mg plus dexamethasone 10 mg at the first cycle or palonosetron 0.25 mg plus dexamethasone 10 mg, respectively, each administered 30 min before the initiation of high dose cisplatin-based chemotherapy. To observe the remission rate of acute emetic episodes and delayed emetic episodes, adverse effects and daily food-intake in the patients after the chemotherapy.

RESULTSThe complete response (CR) rates for acute vomiting were not significantly different between the tropisetron and palonosetron cycles (75.8% vs. 79.7%, P>0.05). The complete control rate of delayed vomiting in the palonosetron cycle was significantly higher than that in the tropisetron cycle (70.3% vs. 50.8%, P<0.01). The food-intake decrease rate of palonosetron cycle was 18.8%, significantly lower than the 53.1% of the tropisetron cycle (P<0.05). The toxicity in the two cycles was similar and no grade 3-4 toxicity was observed.

CONCLUSIONSPalonosetron is superior to tropisetron with a lower remission rate of delayed emesis induced by high dose cisplatin-based chemotherapy and with tolerable toxicity. Moreover, the apparent emesis control of palonosetron treatment seems to provide an adequate food-intake in these patients.

Aged ; Antiemetics ; therapeutic use ; Antineoplastic Agents ; administration & dosage ; adverse effects ; therapeutic use ; Cisplatin ; administration & dosage ; adverse effects ; therapeutic use ; Eating ; drug effects ; Female ; Humans ; Indoles ; therapeutic use ; Isoquinolines ; therapeutic use ; Male ; Middle Aged ; Neoplasms ; drug therapy ; Quinuclidines ; therapeutic use ; Vomiting ; chemically induced ; prevention & control

OBJECTIVETo establish a protocol of automated synthesis of 1-(2-chlorophenyl)-N-[(11)C]methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide ((11)C-PK11195) as the positron-emitter-labeled ligand for peripheral benzodiazepine receptor (PBR) using a commercial synthesizer and explore the quality control methods for the resulting product.

METHODS(11)C-methyl iodide ((11)C-CH(3)I) was synthesized via liquid-phase distillation approach using a (11)C-iodomethane synthesizer. (11)C-PK11195 was prepared by (11)C-methylation of 1-(2-chlorophenyl)-N-(1-methylpropyl)-3-isoquinoline carboxamide (N-demethyl-PK 11195) as the precursor with (11)C-CH(3)I and purified by semi-preparative reversed phase high performance liquid chromatography (HPLC). The radiochemical purity, chemical purity and stability of the product were evaluated by HPLC, and the toxicity was assessed in normal mice. The factors that affected (11)C-PK11195 synthesis were also studied.

RESULTS(11)C-PK11195 was successfully synthesized using the TracerLab FX(F-N) synthesizer. The synthesis time was about 35 min from the end of (11)C-carbon dioxide production by cyclotron to the end of (11)C-PK11195 synthesis (EOS), with a (11)C-methylation reaction time of 3-4 min. The uncorrected radiochemical yield for (11)C-methylation was (33-/+5)%. Analysis with radio-analytical HPLC showed a radiochemical purity and chemical purity of the product both exceeding 99%, with a specific radioactivity of 30-65 GBq/micromol at EOS (from the end of radionuclide production). The (11)C-PK11195 synthesized was radiochemically stable at room temperature and showed low toxicity in normal mice.

CONCLUSIONThe (11)C-PK11195 injection can be conveniently prepared using an automated synthesizer for clinical use in positron emission tomography.

Animals ; Carbon Radioisotopes ; Contrast Media ; chemical synthesis ; Isoquinolines ; adverse effects ; chemical synthesis ; Mice ; Positron-Emission Tomography ; Radioligand Assay ; Radiopharmaceuticals ; adverse effects ; chemical synthesis ; Receptors, GABA-A ; metabolism