Safety, efficacy, and patient acceptability of single-dose fosaprepitant regimen for the prevention of chemotherapy-induced nausea and vomiting

Control of chemotherapy-induced nausea and vomiting (CINV) is a crucial factor in ensuring that patients undergoing cancer chemotherapy can get the full benefit of therapy. Current antiemetic guidelines recommend that the neurokinin-1 receptor (NK-1R) antagonist aprepitant should be used as part of a combination regimen with dexamethasone and a serotonin receptor antagonist for the prevention of CINV in patients receiving highly emetogenic chemotherapy (HEC). Fosaprepitant is a water-soluble N-phosphoryl derivative of aprepitant that, when infused, is rapidly metabolized back to an active aprepitant. The existing literature in PubMed about fosaprepitant was screened and selected in order to address the emerging data from two randomized clinical trials evaluating the efficacy and safety of a single-dose fosaprepitant regimen. These phase III trials demonstrated that fosaprepitant given as a single intravenous dose of 150 mg was either noninferior to the conventional 3-day aprepitant or significantly superior to placebo for the prevention of acute and delayed CINV in patients receiving high-dose cisplatin. In both trials, fosaprepitant was well tolerated although more frequent infusion-site adverse events were observed with fosaprepitant. The new dosage regimen of fosaprepitant, therefore, would be an option for CINV control in patients receiving cisplatin-based chemotherapy. The clinical efficacy is consistent with the findings from a time-on-target, positron-emission tomography study evaluating the NK-1R occupancy in the central nervous system (CNS) over 5 days after a single-dose infusion of 150 mg fosaprepitant in healthy participants. The single-dose regimen is capable of blocking more than 90% of the NK-1Rs in the CNS for at least 48 hours after infusion, which is sufficient to control delayed CINV for 2 to 5 days after HEC. The new dosage regimen of fosaprepitant can provide a simplified treatment option that maintains high protection while ensuring adherence to scheduled antiemetic medication throughout most of the 5-day period encompassing the major risk for CINV

Neuroendocrine tumour arising inside a retro-rectal tailgut cyst: report of two cases and a review of the literature

Tailgut cysts (or retro-rectal cyst-hamartomas (RCHs)) are developmental abnormalities consisting of multiloculated cysts lined by squamous, transitional or glandular epithelium which, albeit rarely, may give rise to malignant transformations. Carcinoid tumours arising in the presacral region are extremely rare and usually benign, and only a few are described in the literature. Case 1: A 63-year-old female diagnosed as having bilateral ovarian cysts underwent surgery to remove a right adnexial mass that was histopathologically diagnosed as a well-differentiated carcinoid tumour. She is currently disease free after 18 months of follow-up. Case 2: A 41-year-old-female diagnosed with hepatic metastases and a solid pelvic mass arising from a moderately differentiated neuroendocrine carcinoma is currently alive with disease after having undergone surgical removal of the mass and several medical treatments. We here describe two different clinical histories of well- and moderately differentiated neuroendocrine tumours (NETs) arising from tailgut cysts in the prerectal space together with a review of the relevant literature

Three-times daily radiotherapy after chemotherapy in stage III non-small cell lung cancer. Single-institution prospective study

Aim: A prospective study for stage IIIA-B non-small cell lung cancer (NSCLC), with three-times daily (3td) radiotherapy (RT), after induction chemotherapy (iCT), with or without surgery. Patients and Methods: Induction cisplatin and gemcitabine chemotherapy was delivered. Surgery and postoperative (post-op) radiotherapy were planned for responsive stage IIIA patients; definitive irradiation was performed in unresectable III A and IIIB patients. Doses of 54.4 and 64.6 Gy were delivered for the post-op and definitive treatments, respectively. Results: Out of 52 patients (pts), 37 received 3tdRT as definitive (18 pts) or post-op treatment (19 pts). Overall, the failures were similar between post-op and definitive 3tdRT (78.9% vs. 77.8%). In the post-op treatment, metastases and local failures were 52.6% and 10.5%, respectively and in the definitive radiotherapy, the incidence was similar (local 33.3% vs. systemic 44.4%). The five-year overall survival (OS) was 25% for the post-op and 21% for the definitive patients (p=0.87). Conclusion: Three-times daily postoperative radiotherapy did not improve the outcome in NSCLC, but for unresectable patients, this approach may have a role in selected cases

Adjuvant treatment of colorectal cancer in the elderly : where do we come from and where are we going?

Objective: Colorectal cancer is the third most commonly reported cancer in the world and about 50% of patients are diagnosed over the age of 70 years. The authors discuss age-related changes in organ function, comorbidities and frailty in the elderly, and their impact on chemotherapy toxicity. Methods: The authors review data from observational studies and subgroup analyses of randomized clinical trials on adjuvant chemotherapy in elderly colorectal cancer patients. Results: Several large population-based studies suggest that adjuvant chemotherapy is offered less frequently to elderly patients, although in recent years the prescription patterns tended to significantly increase. In fact, data from retrospective analyses of randomized trials indicate that elderly stage III colorectal cancer patients may get similar clinical advantage from adjuvant treatment with fluoropyrimidines, although major comorbidities may substantially limit life expectancy and minimize the survival benefits. The use of oxaliplatin-based regimens needs to take into account the individual risk/benefit profile due to lack of unequivocal evidence of positive literature data. Conclusions: Adjuvant chemotherapy of colorectal cancer should be investigated by prospective trials specifically designed for the elderly. Fit elderly patients should be offered standard adjuvant treatments, while modified schedule, attenuated doses or even treatment omission can be offered to more frail patients

Neoadjuvant eribulin mesylate following anthracycline and taxane in triple negative breast cancer: Results from the HOPE study

Background Eribulin mesylate (E) is indicated for metastatic breast cancer patients previously treated with anthracycline and taxane. We argued that E could also benefit patients eligible for neoadjuvant chemotherapy. Methods Patients with primary triple negative breast cancer 2 cm received doxorubicin 60 mg/m2 and paclitaxel 200 mg/m2 x 4 cycles (AT) followed by E 1.4 mg/m2 x 4 cycles. Primary endpoint was pathological complete response (pCR) rate; secondary and explorative endpoints included clinical/metabolic response rates and safety, and biomarker analysis, respectively. Using a two-stage Simon design, 43 patients were to be included provided that 4 of 13 patients had achieved pCR in the first stage of the study. Results In stage I of the study 13 women were enrolled, median age 43 years, tumor size 2–5 cm in 9/13 (69%), positive nodal status in 8/13 (61%). Main grade 3 adverse event was neutropenia (related to AT and E in 4 and 2 cases, respectively). AT followed by E induced clinical complete + partial responses in 11/13 patients (85%), pCR in 3/13 (23%). Median measurements of maximum standardized uptake value (SUVmax) resulted 13, 3, and 1.9 at baseline, after AT and E, respectively. Complete metabolic response (CMR) occurred after AT and after E in 2 and 3 cases, respectively. Notably, 2 of the 5 (40%) patients with CMR achieved pCR at surgery. Immunostaining of paired pre-/post-treatment tumor specimens showed a reduction of β-catenin, CyclinD1, Zeb-1, and c-myc expression, in the absence of N-cadherin modulation. The study was interrupted at stage I due to the lack of the required patients with pCR. Conclusions Despite the early study closure, preoperative E following AT showed clinical and biological activity in triple negative breast cancer patients. Furthermore, the modulation of β-catenin pathway core proteins, supposedly outside the domain of epithelial–mesenchymal transition, claims for further investigation. Trial registration EU Clinical Trial Register, EudraCT number 2012-004956-12

Should clinicians always administer dexamethasone beyond 24 h after chemotherapy to control delayed nausea and vomiting caused by moderately emetogenic regimens? : insight from the re-evaluation of two randomized studies

Purpose Data from two noninferiority trials of a dexamethasone-sparing regimen were assessed for the impact of acute nausea and vomiting on delayed outcome in patients undergoing moderately emetogenic chemotherapy (MEC) or anthracycline plus cyclophosphamide (AC). Methods Chemo-naive patients were randomized to receive palonosetron (0.25 mg IV) plus dexamethasone (8 mg IV) on day 1 of chemotherapy, or the same regimen followed by oral dexamethasone on days 2 and 3 in the MEC (n = 237) and AC (n = 380) cohorts. Patients were divided into two groups according to whether or not they experienced vomiting and/or moderate-to-severe nausea during the acute phase (high- and low-risk groups, respectively). Primary efficacy endpoint was the complete protection (CP) against delayed vomiting and moderate-to-severe nausea. Patient's satisfaction (0-100 mm visual analog scale) was also analyzed. Results Among the 209 low-risk patients undergoing MEC, delayed CP occurred in 82.9 % of those who received single-dose dexamethasone and 89.8 % of those who received 3-day dexamethasone (P = 0.165). Of the 271 low-risk patients undergoing AC, CP was achieved in 71.7 % of those treated with single-dose dexamethasone and 84.2 % treated with 3-day dexamethasone (P = 0.019). In spite of these observations, the patient satisfaction data was not influenced by dexamethasone regimen. In both cohorts, occurrence of acute vomiting or moderate-to-severe nausea was the key independent-predictor for delayed vomiting or nausea, respectively. Conclusions The dexamethasone-sparing regimen provides adequate delayed protection in patients undergoing MEC who are at low risk for delayed symptoms, and can still be discussed for low-risk AC patients as the daily difference in control is modest. Additional dexamethasone doses can be customized on the basis of occurrence or absence of acute symptoms in the first cycle of MEC and even AC

Imatinib administration in two patients with liver metastases from GIST and severe jaundice

Imatinib is the only effective and approved systemic therapy for the treatment of patients with advanced gastrointestinal stromal tumours (GISTs). Although metastases from GISTs most commonly involve the liver, yielding hyperbilirubinaemia, very few data on imatinib administration in subjects with jaundice are available. We provide evidence that imatinib tolerability was not adversely affected by jaundice in two patients with advanced GIST