Boccia Ralph, Cooper William, O'Boyle Erin
Center for Cancer and Blood Disorders, Bethesda, Maryland, USA.
TFS International, Flemington, New Jersey, USA.
J Community Support Oncol. 2015 Feb;13(2):38-46. doi: 10.12788/jcso.0107.
A phase 3 trial in patients with cancer who received chemotherapy has shown that subcutaneous (SC) APF530, a sustained-delivery formulation of granisetron, is noninferior to palonosetron in preventing acute (0-24 hours) and delayed (>24-120 hours) chemotherapy-induced nausea and vomiting (CINV).
To investigate the sustainability of APF530 antiemetic responses during multiple chemotherapy cycles.
1,395 patients receiving moderately or highly emetogenic chemotherapy (MEC and HEC, respectively) were randomized either to APF530 250 or 500 mg SC (containing granisetron 5 or 10 mg, respectively) or palonosetron 0.25 mg intravenously before cycle 1 of chemotherapy. Patients who received palonosetron in cycle 1 were rerandomized in cycles 2-4 to APF530 250 or 500 mg; those who received APF530 in cycle 1 continued their APF530 dose. Between-group response rates were compared using the Fisher exact test.
Complete response (CR; no emesis, no rescue medication) for APF530 500 mg with HEC increased from 81.3% to 87.8% over 4 cycles in the acute phase of CINV, and from 67.1% to 83.1% in the delayed phase. Rates were slightly lower with MEC. Within-cycle CR rates between APF530 doses showed no significant differences. With HEC, APF530 500 mg provided sustained CRs through 4 cycles of chemotherapy in 68.4% of patients in the acute phase and in 57.9% in the delayed phase; with MEC, corresponding CRs were 56.5% and 41.3%. Nausea prevention was nearly as effective as emesis prevention.
Chemotherapy emetogenicity was classified according to Hesketh criteria during the time of this study. However, subsequent post hoc analyses indicate that reclassification according to newer ASCO emetogenicity guidelines did not alter the original study noninferiority conclusions.
CR rates with APF530 during the acute and delayed phases of CINV in MEC and HEC were maintained over multiple cycles.
一项针对接受化疗的癌症患者的3期试验表明，格拉司琼的缓释制剂皮下注射（SC）APF530在预防急性（0 - 24小时）和延迟性（>24 - 120小时）化疗引起的恶心和呕吐（CINV）方面不劣于帕洛诺司琼。
研究APF530在多个化疗周期中的止吐反应可持续性。
1395例接受中度或高度致吐性化疗（分别为MEC和HEC）的患者在化疗第1周期前被随机分为皮下注射250或500 mg APF530（分别含5或10 mg格拉司琼）组或静脉注射0.25 mg帕洛诺司琼组。在第1周期接受帕洛诺司琼治疗的患者在第2 - 4周期重新随机分为250或500 mg APF530组；在第1周期接受APF530治疗的患者继续使用其原剂量。使用Fisher精确检验比较组间反应率。
在CINV急性期，接受HEC且使用500 mg APF530的患者完全缓解（CR；无呕吐、无救援药物）率在4个周期内从81.3%提高到87.8%，在延迟期从67.1%提高到83.1%。MEC患者的该比率略低。APF530不同剂量组的周期内CR率无显著差异。对于HEC，500 mg APF530在急性期使68.4%的患者和在延迟期使57.9%的患者在4个化疗周期中保持持续CR；对于MEC，相应的CR率分别为56.5%和41.3%。预防恶心的效果与预防呕吐几乎相同。
在本研究期间，化疗致吐性是根据赫斯基思标准分类的。然而，随后的事后分析表明，根据更新的美国临床肿瘤学会致吐性指南重新分类并未改变原研究的非劣效性结论。
在MEC和HEC中，APF530在CINV急性期和延迟期的CR率在多个周期中得以维持。
