Busulfan and melphalan significantly improve event-free survival over carboplatin, etoposide, and melphalan in children with high-risk neuroblastoma, with fewer severe adverse events, phase III clinical trial data show.

This review discusses the safety and efficacy data for aprepitant and fosaprepitant from key clinical trials on the prevention of chemotherapy-induced nausea and vomiting (CINV). Summary Early clinical trials revealed that, compared with dual therapy, triple therapy with aprepitant, a serotonin (5-hydroxytryptamine-3; 5-HT 3 ) receptor antagonist and dexamethasone provided improved control of acute and delayed CINV. The safety and efficacy of aprepitant were subsequently evaluated in several milestone clinical trials in patients receiving highly emetogenic chemotherapy. Research into multiple-day dosing revealed: Aprepitant and fosaprepitant were more effective than ondansetron for control of delayed-phase emesis and need for rescue medication Aprepitant plus dexamethasone was effective for control of delayed emesis with highly emetogenic chemotherapy Aprepitant treatment was associated with significantly improved complete response rate over the total treatment period and during acute and delayed phases. Although originally recommended to be given for 3 days to control CINV, single doses (oral or intravenous) of aprepitant have been shown to be effective in preventing both acute and delayed CINV. Studies have also shown aprepitant to protect against CINV over multiple cycles of cisplatin-based chemotherapy, with control of CINV sustained over six cycles. Studies have shown aprepitant to be generally well tolerated. A systematic review of 17 trials of neurokinin-1 (NK 1 ) receptor antagonists added to antiemetic regimens for the prevention of CINV showed statistically significant, but clinically trivial differences, in fatigue, hiccups and lower constipation than controls. Importantly, aprepitant does not appear to alter the pharmacokinetics of high-dose melphalan when used as conditioning therapy prior to stem cell transplantation in patients with multiple myeloma. Clinical trials have demonstrated that most drug-drug interactions with aprepitant have few/no clinical consequences, with no differences in severe adverse events noted between treatment arms with or without aprepitant. All clinical practice guidelines recommend aprepitant be added to combination 5-HT 3 receptor antagonist and dexamethasone for patients receiving highly emetogenic chemotherapy; adherence to antiemetic clinical practice guidelines resulted in a significantly reduced incidence of CINV. Aapro M et al.  Oncologist 2015; 20: 450–458. doi: 10.1634/theoncologist.2014-0229

And a nonsense RB1 mutation detected in AH samples from a third child who initially received intravitreous injections of melphalan for vitreous seeding was subsequently confirmed in a tissue sample available after secondary enucleation following relapse.

All study participants had received induction therapy with R-DHAP (rituximab, dexamethasone, cytarabine, and platinum derivative), achieving either complete remission or a partial response (≥75% reduction in tumor mass) before receiving conditioning with R-BEAM (rituximab, carmustine, etoposide, cytarabine, and melphalan) and undergoing HSCT.

Therefore “[m]ore data from the use of the safer MAC approach of higher-dose busulfan/ fludarabine compared with busulfan/fludarabine RIC or compared with fludarabine/melphalan RIC are needed to make a more compelling argument for use of RIC for MDS, especially for advanced MDS,” he concludes.

The IFM 2009 study investigators randomly assigned 700 patients, aged 65 years and older, with newly diagnosed multiple myeloma to receive induction therapy with three cycles of RVD and then consolidation therapy with either five additional cycles of RVD (n=350) or high-dose melphalan plus stem-cell transplantation followed by two additional cycles of RVD (n=350).

One group received consolidation with one round of ASCT alongside carboplatin, etoposide plus melphalan (CEM) chemotherapy.

Unlike at the NCI or UPenn, the protocol investigated administering CAR T cells in the setting of high-dose chemotherapy (BEAM regimen; carmustine, etoposide, cytarabine, melphalan) followed by autologous stem-cell rescue (ASCR).