selinexor and Nausea

Clinical observations of cancer patients treated with selinexor have reported high incidence of nausea and anorexia. The study objective was to investigate the adoption of prophylactic olanzapine for the prevention of nausea, vomiting and anorexia in cancer patients receiving selinexor and standard chemotherapy.. We retrospectively reviewed supportive care interventions in patients receiving selinexor and recorded frequency of adverse events (NCI-CTAE). Association between categorical variables were analyzed using Fisher's exact tests; repeated measures analysis was performed to assess weight changes over time.. Of 124 evaluable patients, 83 (66.9%) were female, 93 were white (75.0%), and the most common cancer was ovarian (N = 30, 24.2%). One hundred and four patients (83.9%) received olanzapine, of which 93 (89.4%) were prophylactically treated, the majority (86.5%) receiving low 2.5 mg daily dose. Other anti-emetics included ondansetron in 90 patients (72.6%), dexamethasone prescribed in 50 patients (40.3%) and metoclopramide in 49 patients (39.5%), while aprepitant/fosaprepitant (N = 2, 1.6%) were prescribed infrequently. Cancer patients receiving prophylactic olanzapine (N = 93) compared to patients who never received olanzapine (N = 20) had more Grade 1 + anorexia (31.2% vs 20.0%), less nausea (53.8% vs 70.0%), less vomiting (33.3% vs 40.0%), and increased hyperglycemia (29.0% vs 10.0%), but differences were non-statistically significant. In addition, there was minimal weight loss over time in both groups and no statistically significant differences in weight loss between groups.. Prophylactic olanzapine decreased nausea, vomiting and maintained weight over 3 months but did not prevent anorexia in patients receiving selinexor and chemotherapy. Low dose olanzapine was well tolerated but associated with hyperglycemia.

Topics: Adult; Aged; Anorexia; Antiemetics; Female; Humans; Hydrazines; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Triazoles; Vomiting; Young Adult

Carboplatin and paclitaxel (CT) is one of the standard chemotherapy regimens used in various tumor types. Preclinical models have suggested that selinexor, a first-in-class oral potent selective inhibitor of nuclear export Exportin-1, and CT exerts antitumor activity in multiple malignancies.. This was a single-center, multi-arm phase Ib study utilizing a "basket type" expansion. CT and selinexor was employed as one of the 13 parallel arms. Advanced relapsed/refractory solid tumors following standard therapy or where the addition of selinexor to standard regimens deemed appropriate, were eligible.. Of 13 patients treated, 12 patients were evaluable for response. The most common cancers were breast (n = 4), esophageal (n = 2), ovarian (n = 2) and non-small cell lung cancers (n = 2). All 13 patients had at least one treatment-related adverse events (TRAEs) and the most common were neutropenia (85%), leukopenia (85%), thrombocytopenia (85%), anemia (69%), nausea (54%), vomiting (46%), and fatigue (46%). One patient at 60 mg QW experienced DLT with grade 3 nausea and vomiting lasting 3 days. Unconfirmed partial response (uPR) was observed in 3 patients; one patient each with esophageal, breast, and ovarian cancer. One patient with esophageal adenocarcinoma had confirmed PR, however, was discontinued from the study due to clinical progression. Five patients achieved stable disease (SD). Disease control rate was 8%. Majority of patients (77%), including two patients who had uPR, had prior exposure to carboplatin and/or paclitaxel. Time-to-treatment failure (TTF) ranged from 1 to 153 weeks.. The RP2D of selinexor was 60 mg QW in combination with CT. The combination conferred viable clinical activity with durable objective responses which should further be explored in tumor types for which CT is used as standard of care. Trial information.. gov Identifier: NCT02419495. Sponsor(s): Karyopharm Therapeutics. (Trial registration: NCT02419495. Registered 14 April 2015, https://clinicaltrials.gov/ct2/show/NCT02419495 ).

Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Female; Humans; Hydrazines; Lung Neoplasms; Nausea; Neoplasms; Ovarian Neoplasms; Paclitaxel; Thrombocytopenia; Triazoles; Vomiting

Selinexor is an oral, small molecule inhibitor of the nuclear export protein exportin 1 with demonstrated activity in hematologic and solid malignancies. Side effects associated with selinexor include nausea, vomiting, fatigue, diarrhea, decreased appetite, weight loss, thrombocytopenia, neutropenia, and hyponatremia. We reviewed 437 patients with multiple myeloma treated with selinexor and assessed the kinetics of adverse events and impact of supportive care measures. Selinexor reduced both platelets and neutrophils over the first cycle of treatment and reached a nadir between 28 and 42 days. Platelet transfusions and thrombopoietin receptor agonists were effective at treating thrombocytopenia, and granulocyte colony stimulating factors were effective at resolving neutropenia. The onset of gastrointestinal side effects (nausea, vomiting, and diarrhea) was most common during the first 1-2 weeks of treatment. Nausea could be mitigated with 5-HT3 antagonists and either neurokinin 1 receptor antagonists, olanzapine, or cannbainoids. Loperamide and bismuth subsalicylate ameliorated diarrhea. The primary constitutional side effects of fatigue and decreased appetite could be managed with methylphenidate, megestrol, cannabinoids or olanzapine, respectively. Hyponatremia was highly responsive to sodium replacement. Selinexor has well-established adverse effects that mainly occur within the first 8 weeks of treatment, are reversible, and respond to supportive care.

Topics: Aged; Antineoplastic Agents; Appetite; Clinical Trials as Topic; Diarrhea; Fatigue; Female; Humans; Hydrazines; Hyponatremia; Male; Middle Aged; Multiple Myeloma; Nausea; Thrombocytopenia; Triazoles