Preventive Effects of Phenolic Compound Extra Virgin Olive Oil (EVOO) on the Incidence of Hand Foot Syndrome Induced Capecitabine

Hand foot syndrome (HFS) is a reaction that occurs on the skin of the palms and soles. feet, caused by the toxicity of chemotherapy drugs with symptoms such as tingling, pain, erythema, dry skin, swelling, increased pigmentation and itching. This condition is still a problem in the treatment of patients given capecitabine. Although HFS does not cause death, in severe cases it can affect the quality of treatment and interfere with daily activities. The cause of HFS is still unclear but from research it is known that capecitabine and its metabolites will increase the expression of the COX-2 enzyme, inhibit the arachidonic pathway, increase PGE2 activity, causing inflammatory reactions in the form of erythema, edema and pain. The phenolic components contained in EVOO, namely oleocanthal and hydroxytyrosol compounds in several studies have the same properties as celecoxib and ibuprofen as anti-COX-2, will inhibit the arachidonic synthesis pathway, reduce prostaglandin activity and reduce inflammatory reactions.

The Clinical Value of Chemotherapy Combined With Capecitabine in Triple-Negative Breast Cancer—A Meta-Analysis

Purpose: Triple-negative breast cancer (TNBC) is the most dangerous subtype of breast cancer with high rates of metastasis and recurrence. The efficacy of capecitabine in chemotherapy for TNBC is still controversial. This study evaluated the efficacy and safety of capecitabine combining with standard, adjuvant or neoadjuvant chemotherapy for TNBC.Methods: We systematically searched clinical studies through PubMed, Cochrane library, Embase, Wanfang Database, China Academic Journals (CNKI), and American Society of Clinical Oncology’s (ASCO) annual conference report. Studies were assessed for design and quality by the Cochrane risk of bias tool. A meta-analysis was performed using Review Manager to quantify the effect of capecitabine combined with standard, adjuvant or neoadjuvant chemotherapy on the disease-free survival (DFS) rate and overall survival (OS) rate of TNBC patients. Furthermore, safety analysis was performed to evaluate the adverse events.Results: Twelve randomized controlled clinical trials involving totally 4854 TNBC patients were included, of which 2,214 patients received chemotherapy as control group, and 2,278 patients received capecitabine combining with chemotherapy. The results indicated that capecitabine could significantly improve the DFS [hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.71–0.90, P = 0.0003] and OS (HR 0.83, 95% CI 0.74–0.93, P = 0.001). In subgroup analysis, the combination of capecitabine and cyclophosphamide exhibited a significant benefit in all outcomes (DFS HR 0.75, 95% CI 0.63–0.90, P = 0.002; OS HR 0.65, 95% CI 0.52–0.80, p < 0.0001). Additionally, defferent dose of capecitabine subgroup showed same significant effect on the results. Safety analysis showed that the addition of capecitabine was associated with a much higher risk of hand-foot syndrome, diarrhea and mucositis or stomatitis.Conclusion: The results showed that adjuvant capecitabine could bring significant benefits on DFS and OS to unselected TNBC patients, the combination of capecitabine and cyclophosphamide could improve the survival rate of patients, although the addition of capecitabine could bring significant side effects such as hand foot syndrome (HFS) and diarrhea.

Efficacy of Aidi Injection and Brucea javanica Oil Emulsion Injection in Rectal Cancer during CapeOX Adjuvant Chemotherapy

Background. Adjuvant chemotherapy with CapeOX regimen is widely used in resected rectal cancer, which brings benefits to patients. But drug-related toxicities are severe during this process; thus, survival outcomes may potentially be affected. This study explored the efficacy of two Chinese herbal injections, Aidi injection (ADI) and Brucea javanica oil emulsion injection (BJOEI), as adjuvant drugs in CapeOX adjuvant chemotherapy on rectal cancer patients. Methods. A total of 240 cases were enrolled in this retrospective study. 80 cases received CapeOX with ADI (the ADI group), 80 cases received CapeOX with BJOEI (the BJOEI group), and the rest 80 cases received CapeOX alone (the control group). After four cycles’ chemotherapy, adverse reactions (ADRs) and quality of life (QOL) were analyzed. Then, patients received follow-up for at least one year, and the endpoint was disease-free survival (DFS). Results. All patients completed at least four cycles’ adjuvant chemotherapy. The incidence of leukopenia and thrombocytopenia was significantly lower in the ADI group; the incidence of nausea was significantly lower in the BJOEI group; the incidence of hand-foot syndrome was significantly lower in both the ADI group and BJOEI group. Significant difference was found in the control group regarding the Karnofsky Performance Status (KPS) scores prior and posttreatment. No difference was found among three groups regarding one-year DFS. Conclusion. As adjuvant drugs for rectal cancer during CapeOX chemotherapy, ADI shows advantages in decreasing leukopenia and thrombocytopenia, while BJOEI results better in remitting nausea. Both two CHIs had positive impacts on decreasing hand-foot syndrome and the maintenance of patients’ QOL. It is worthy of further study and promotion for CHIs.

A phase I study of the tyrosine kinase inhibitor anlotinib combined with platinum/pemetrexed-based chemotherapy in untreated nonsquamous non-small-cell lung cancer

SummaryBackground. Anlotinib hydrochloride is an oral small molecule inhibitor of multiple tyrosine kinases, and it has been approved as a third-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) in China. This dose-exploration study was designed to investigate the feasibility of anlotinib in combination with other chemotherapy regimens in patients with nonsquamous NSCLC. Methods. This phase I study followed a 3 + 3 dose reduction design with three doses of anlotinib (12 mg, 10 mg, and 8 mg). Anlotinib was given at an initial dose of 12 mg with pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) or carboplatin (AUC = 5) on 21-day cycles for 4 cycles. The primary goal of the study was to identify the maximum tolerated dose (MTD), and secondary endpoints included progression-free survival (PFS) and overall survival (OS). Results. A total of eight participants were enrolled. Dose-limiting toxicities (DLTs) were observed in two patients (pts) at anlotinib 12 mg (grade 3 hand-foot syndrome and grade 3 appetite loss). No DLTs occurred with 10 mg anlotinib, and the MTD was 10 mg. Among seven evaluable pts, four achieved a confirmed partial response (PR), and three had stable disease (SD). With a median follow-up of 10.05 months, the median PFS was 7.00 months (95% CI: 2.76 to NE). Grade 3 treatment-related adverse events (TRAEs) included appetite loss (n = 2), hypertension (n = 2), thrombocytopenia (n = 1), diarrhea (n = 1) and hand-foot syndrome (n = 1). No grade 4 or grade 5 TRAEs were observed during the treatment. Conclusion. The feasible dose of anlotinib in combination with platinum/pemetrexed-based chemotherapy as a first-line regimen was 10 mg, which was well tolerated and showed promising antitumor activity in advanced nonsquamous NSCLC.

345 Phase I/II trial of cabozantinib plus durvalumab in advanced gastroesophageal cancer and other gastrointestinal malignancies (CAMILLA): phase Ib safety and efficacy results

BackgroundCabozantinib is a multi-tyrosine kinase inhibitor primarily targeting VEGFR, MET, and AXL. These targets promote a tumor immune permissive microenvironment. Cabozantinib has demonstrated immunomodulatory properties & clinical synergy when paired with PD-L1 inhibitors such as durvalumab. Here, we present final results of phase Ib of the Camilla trial assessing cabozantinib plus durvalumab in advanced GE adenocarcinoma (GEA), colorectal cancer (CRC), and hepatocellular carcinoma (HCC). This is an investigator-initiated trial funded by Exelixis & Astrazeneca.MethodsPatients were administered cabozantinib + durvalumab in a dose escalation (3+3) then expansion to find the Dose Limiting Toxicities (DLTs), Recommended Phase 2 Dose (RP2D), ORR, PFS, and OS. Subgroup analysis was conducted to assess efficacy in patients with PD-L1 Combined Positive Score (CPS) ≥ 5. Dosing of cabozantinib was 20mg QD, 40mg QD, and 60mg QD PO in the 1st, 2nd, and 3rd cohorts. Dosing of durvalumab was 1500mg IV Q4W in all cohorts. DLT window was 28 days. Treatment beyond progression was allowed following modified RECIST v1.1 criteria.Results35 patients (14F, 21M), median age 53 years (range 27–79) were enrolled. 10 patients had GEA, 20 had CRC, and 5 had HCC; none had MMR deficiency. Median number of prior systemic therapies was 3 (range 0–3). No DLTs were observed during dose escalation. Per mature tolerability data, 11/14 patients receiving cabozantinib 60mg required dose-reduction post cycle 2 to 40mg. RP2D was determined to be cabozantinib 40mg QD plus durvalumab 1500mg Q4W. Of the 247 observed Treatment-Related Adverse Events (TRAEs), 10% (24) were grade≥3. Most common TRAEs were grade 1–2 fatigue (57%), nausea (43%), anorexia (40%), diarrhea (37%), transaminitis (34%), hand-foot syndrome (23%), & weight loss (23%). 2 patients each developed grade≥3 fatigue, weight loss, & abdominal pain. Overall, 30 pts were evaluable for efficacy. ORR 26.7%; DCR 83.3%; median PFS 4.5 months; 6-month PFS 36.7%; and median OS 9.1 months. 12 patients had PD-L1 CPS ≥5. In this subgroup, ORR 33.33%; DCR 91.67%; median PFS 6.13 months; 6-month PFS 50%; and median OS was not reached.ConclusionsCabozantinib plus durvalumab demonstrated promising efficacy and was fairly tolerated without new safety signals. High PD-L1 expression defined as CPS ≥ 5 was associated with improved efficacy & survival. The phase II multi-cohort part of the trial is currently ongoing.Trial RegistrationNCT03539822Ethics ApprovalThe study was approved by the participating site’s local IRB.ConsentAll study participants granted a written informed consent prior to treatment initiation.

GENDER-SPECIFIC SIDE EFFECTS OF CHEMOTHERAPY IN PANCREATIC CANCER PATIENTS

Pancreatic carcinoma incidence showed a significant increase in men over the last few years and the prognosis remains poor. Patients are treated with different pharmacological plans with no evidence about gender-specific adverse effects. We aimed to investigate differences in the incidence of chemotherapy side effects in the treatment of pancreatic cancer, in order to provide insights toward a personalized assistance based in individual needs. The sample population is composed of 207 patients. Regression model highlighted the predictive role of female gender for alopecia, constipation, hand-foot syndrome and epigastric pain. Also considering single therapeutic schemes, gender differences have been reported. Moreover, evaluating the effect of age, a general reduced risk of toxicity has been reported in younger patients. In order to personalize chemotherapy and increase patients survival rate and life quality during the therapy, gender medicine and pharmacology studies are recommended.

Sustained erythrocytosis due to the use of Lenvatinib

Introduction Tyrosine kinase inhibitors have become the mainstay of treatment for many malignancies, but their use can be accompanied by unusual and often puzzling side effects. Case report We describe herein a 64-year-old patient who developed a robust and sustained erythrocytosis shortly after starting treatment with lenvatinib. Our patient also experienced elevated blood pressure, mucositis, and hand-foot syndrome that are not uncommonly seen with this agent. The clinico-laboratory work-up suggested that lenvatinib was the likely culprit in this case. Management & Outcome Lenvatinib had to be discontinued due to suboptimal tolerance and a short-lived response. With the discontinuation of lenvatinib, hemoglobin trended downwards and subsequently resolved. A score of 6 on the Naranjo nomogram supported a probable causality relationship between lenvatinib and the observed erythrocytosis. Discussion Erythrocytosis has previously been described with sunitinub, sorafenib and pazopanib. The exact mechanism of this phenomenon is not known. It might increase the risk of venous and arterial thromboses in cancer patients that are already in a hypercoagulable state due to cancer itself. In addition, laboratory work-up for polycythemia may prove extensive and costly. Therefore, clinicians need to be aware of this important side effect of tyrosine kinase inhibitors.