Purpose. The standard treatment of peritoneal pseudomyxoma is based on cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC). The establishment of newer systemic treatments is an unmet clinical need for unresectable or relapsed peritoneal pseudomyxoma. The aim of our study was to assess the activity of chemotherapy with 5‐fluorouracil and oxaliplatin (FOLFOX‐4 regimen) in terms of response rate in this subset of patients. Materials and Methods. Patients were included in a single‐center, observational study and treated with FOLFOX‐4 administered every 2 weeks for up to 12 cycles or until progressive disease or unacceptable toxicity. Results. Twenty consecutive patients were reviewed from July 2011 to September 2013. Only partial responses were observed, with an objective response rate of 20%. Median progression‐free survival and overall survival were 8 months and 26 months, respectively. Two patients were able to undergo laparotomy with complete cytoreduction and HIPEC in one case. Safety data for FOLFOX‐4 were consistent with the literature. By means of a mutant enriched polymerase chain reaction, KRAS mutation was found in 16 of 19 cases (84%), and MGMT promoter methylation was found in 8 (42%, all KRAS mutant). Conclusion. FOLFOX‐4 chemotherapy is tolerable and active in patients with peritoneal pseudomyxoma when disease is deemed unresectable or relapsed after peritonectomy and HIPEC. The identification of predictive biomarkers, such as KRAS for resistance to anti‐epidermal growth factor receptor monoclonal antibodies and MGMT for response to temozolomide, is a priority for the development of evidence‐based treatment strategies for peritoneal pseudomyxoma.

Chemotherapy is a cornerstone in treatments of gastric cancer, but despite its benefit, less than 60% of patients receive salvage therapy in clinical practice. We performed a systematic review and meta-analysis based on trial data on the role of second-line treatment of advanced gastric cancer. MEDLINE/PubMed and Cochrane Library were searched for randomized phase III trials that compared active therapy to best supportive care in advanced gastric cancer. Data extraction was conducted according to the PRISMA statement. Summary HR for OS was calculated using a hierarchical Bayesian model and subgroup analysis was performed based on baseline Eastern Cooperative Oncology Group Performance Status (ECOG) performance status (0 vs. 1 or more). A total of 1,407 patients were evaluable for efficacy, 908 were treated in the experimental arms, with chemotherapy (231 pts) or with targeted therapies (677 pts). The risk of death was decreased by 18% (HR = 0.82; 95% CI, 0.79–0.85; posterior probability HR≥1: <0.00001) with active therapies. Chemotherapy and ramucirumab were able to decrease this risk by 27% and 22%, respectively. No differences were found between chemotherapy and ramucirumab. In patients with ECOG = 0 a greater benefit was found for chemotherapy with a reduction of the risk of death by 43% and no benefits were found for ramucirumab or everolimus. In patients with ECOG = 1 or more a significant reduction of the risk of death by 32% was reported in patients treated with ramucirumab, even if no significant difference was reported between chemotherapy and ramucirumab. This analysis reports that active and available therapies are able to prolong survival in patients with advanced gastric cancer with a different outcome based on initial patient’s performance status. New trials based on a better patient stratification are awaited.

AIMCapecitabine is an oral fluoropyrimidine that can effectively replace infusional 5-fluorouracil (5-FU) for treatment of colorectal, gastric and breast cancer. This study aims to analyze the incidence and the relative risk of grade 3 and 4 diarrhoea in patients treated with capecitabine or 5-FU in randomized clinical trials (RCTs). METHODSMEDLINE and Cochrane Library were reviewed for RCTs that compared capecitabine with 5-FU for treatment of solid malignancies. The incidence and relative risk (RR) of grade 3/4 diarrhoea were estimated for each arm in the overall population and in colorectal cancer (CRC) patients RESULTSTwenty-three studies and 15 761 patients were included. Among these 8303 and 7458 patients received capecitabine or 5-FU based therapies, respectively. In the overall populations severe diarrhoea was reported in 16.6% (95% CI 15.8, 17.4) and in 12.7% (95% CI 11.9, 13.4) of patients treated with capecitabine or 5-FU-based therapies, respectively. The RR was 1.39 (95% CI 1.14, 1.69, P = 0.0010). In 14 899 CRC patients, the incidence of severe diarrhoea was 17.0% (95% CI 16.2, 17.9) and 12.9% (95% CI 12.1, 13.7), respectively, with a RR of 1.46 (95% CI 1.18, 1.81, P < 0.0001). In CRC patients treated with combined chemotherapy, the RR was 1.40 (95% CI 1.07, 1.82; P = 0.01) for patients receiving oxaliplatin and 2.35 (95% CI 1.76, 3.13; P < 0.0001) for patients receiving irinotecan. CONCLUSIONSTreatment with capecitabine is characterized by an increased risk of severe diarrhoea, mainly in patients affected by CRC and treated with polichemotherapy. Combination treatment with irinotecan doubles the risk over 5-FU.

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.

Introduction: The second-generation 5-hydroxytryptamine-3 (5-HT3) receptor antagonist palonosetron is effective in the prevention of chemotherapy-induced nausea and vomiting (CINV) associated with highly and moderately emetogenic chemotherapy (HEC and MEC, respectively). In addition, palonosetron has been the first and, at present, the only 5-HT3 receptor antagonist to have a specific indication for the prevention of delayed CINV associated with MEC. The unique pharmacology of this antagonist is thought to partly explain its improved efficacy against delayed symptoms.Aims: To review the evidence underlying the use of palonosetron in preventing CINV.Evidence review: A recent meta-analysis consistently showed that palonosetron significantly increases the control of both emesis and nausea during the acute and delayed phases after single-day HEC or MEC. Consistent with these findings from trials that did not include an neurokinin-1 (NK-1) receptor antagonist, randomized controlled trials recently showed that a triple combination with palonosetron achieves significantly better control of delayed CINV, particularly delayed nausea, in patients undergoing HEC or the high-risk combination of an anthracycline and cyclophosphamide (AC). Evidence from randomized studies also supports palonosetron as a valuable option to reduce the total corticosteroid dose administered in patients undergoing multiple cycles of MEC or AC chemotherapy. Additional benefits of palonosetron include the lack of a warning on cardiac safety and no known clinically significant drug–drug interactions.Place in therapy and conclusion: Evidence currently available indicates that palonosetron significantly adds to the clinician’s ability to effectively control CINV in patients undergoing HEC or MEC. It is recommended in the international guidelines for the prevention of CINV caused by MEC. The high safety profile and the opportunity to reduce the total corticosteroid dose with no loss in efficacy against delayed CINV should also contribute to a wider use of palonosetron in clinical practice.