Clinical and Nutritional Effectiveness of a Nutritional Protocol with Oligomeric Enteral Nutrition in Patients with Oncology Treatment-Related Diarrhea.

(1) Background: Poor nutritional status and diarrhea are common complications in cancer patients. (2) Methods: This multicenter, observational, prospective study evaluated the effectiveness of an oligomeric enteral nutrition (OEN) protocol in the improvement of nutritional status and reduction of diarrhea symptoms. Nutritional status was assessed with the Subjective Global Assessment (SGA), Body Mass Index (BMI) and albumin levels. Diarrhea was evaluated by the frequency and consistency of stools (Bristol Stool form scale). (3) Results: After 8 weeks of OEN protocol, the nutritional status improved in 48.3% of patients, with an increased proportion of patients at risk of malnourishment (+27.3%) at the expense of a decrease of moderately (-19.9%) and severely (-7.3%) malnourished patients (p < 0.001). Serum albumin and BMI significantly increased after 8 weeks of OEN treatment (p < 0.005). OEN showed a 71.1% effectiveness in the improvement of stool consistency. The mean number of stools per day significantly decreased from baseline (4.17 stools/day) to week 8 (1.42 stools/day; p = 0.0041). The nutritional status significantly improved even in those patients with persistent diarrhea. (4) Conclusion: The proposed OEN protocol seemed to be effective in improving the nutritional status, frequency and consistency of stools in patients with oncology treatment-related diarrhea even in persistent cases.

Impact of an Oral Nutritional Protocol with Oligomeric Enteral Nutrition on the Quality of Life of Patients with Oncology Treatment-Related Diarrhea.

(1) Background: Nutritional status can influence the quality of life (QoL) of cancer patients. (2) Methods: This subanalysis evaluated the impact of an oral oligomeric enteral nutrition (OEN) protocol on the QoL of patients with oncology treatment-related diarrhea (OTRD) in a multicenter, observational, prospective study (DIAPOENO study). QoL was assessed with the Nottingham Health Profile (NHP) at baseline and after eight weeks of OEN treatment. (3) In the overall population, all the NHP categories significantly improved after eight weeks of OEN treatment: energy levels (p < 0.001), pain (p < 0.001), emotional reactions (p < 0.001), sleep (p < 0.001), social isolation (p = 0.023), and physical abilities (p = 0.001). QoL improvement was higher in patients with improved or maintained nutritional status and in those with improved consistency of stools with the OEN protocol. However, QoL did not significantly improve in patients with worse nutritional status and with worse or maintained stool consistency with the OEN protocol. QoL improved regardless of disease severity. Multivariate logistic regression analysis showed that weight change was significantly associated with improved QoL (OR 2.90-5.3), except for social isolation, in models unadjusted and adjusted to age, sex, oncology treatment, and stool consistency. (4) Conclusion: In this subanalysis, the OEN protocol was associated with improved QoL.

Oligomeric Enteral Nutrition in Undernutrition, due to Oncology Treatment-Related Diarrhea. Systematic Review and Proposal of An Algorithm of Action.

Oncology treatment-related diarrhea and malnutrition appear together in oncological patients because of the disease itself, or the treatments that are administered for it. Therefore it is essential to carry out a nutritional treatment. Enteral nutrition formulas, containing peptides and medium chain triglycerides, can facilitate absorption in cases of malabsorption. There are few references to the use of enteral nutrition in the clinical society guidelines of patient management with oncology treatment-related diarrhea (OTRD). A bibliographic review of the studies with oligomeric enteral nutrition in OTRD found only nine studies with chemotherapy (all with the same oligomeric formula in which oral mucositis improves, while the rest of the outcomes show different results), and eight studies with radiotherapy (with different products and very heterogeneous results). We hereby present our action algorithm to supplement the diet of OTRD patients with an oligomeric enteral nutrition formula. The first step is the nutritional assessment, followed by the assessment of the functional capacity of the patient's intestine. With these two aspects evaluated, the therapeutic possibilities available vary in degrees of complexity: These will range from the usual dietary recommendations, to supplementation with oral oligomeric enteral nutrition, along with complete enteral nutrition with oligomeric formula, and up to potentially total parenteral nutrition.

Nilotinib as Coadjuvant Treatment with Doxorubicin in Patients with Sarcomas: A Phase I Trial of the Spanish Group for Research on Sarcoma.

Purpose: Nilotinib plus doxorubicin showed to be synergistic regarding apoptosis in several sarcoma cell lines. A phase I/II trial was thus designed to explore the feasibility of nilotinib as coadjuvant of doxorubicin by inhibiting MRP-1/P-gp efflux activity. The phase I part of the study is presented here.Patients and Methods: Nilotinib 400 mg/12 hours was administered in fixed dose from day 1 to 6, and doxorubicin on day 5 of each cycle. Three dose escalation levels for doxorubicin at 60, 65, and 75 mg/m2 were planned. Cycles were repeated every 3 weeks for a total of 4 cycles. Eligible subtypes were retroperitoneal liposarcoma, leiomyosarcoma, and unresectable/metastatic high-grade chondrosarcoma.Results: Thirteen patients were enrolled: 7 chondrosarcoma, 4 liposarcoma, and 2 leiomyosarcoma. In 46 cycles administered, the most relevant grade 3/4 adverse effects per patient were neutropenia 54%, febrile neutropenia 15%, and asthenia 8%. No cardiac toxicity was observed. Only one dose-limiting toxicity (febrile neutropenia) was reported in the third dose level. With regard to efficacy, 1 partial response (1 liposarcoma), 9 stable diseases (5 chondrosarcoma, 2 liposarcoma, 1 leiomyosarcoma), and 3 progressive diseases (2 chondrosarcoma and 1 leiomyosarcoma) were present. ABCB1 and ABCC1 RNA expression levels decreased by 58.47-fold and 1.47-fold, respectively, on day 5 of the cycle.Conclusions: Combination of MRP-1/P-gp inhibitor, nilotinib, as coadjuvant with doxorubicin is feasible; it appears not to add substantial toxicity compared with doxorubicin alone. Pharmacodynamic study supports this concept. The recommended dose for the phase II part for doxorubicin was 75 mg/m2 Clin Cancer Res; 24(21); 5239-49. ©2018 AACR.

Phase II trial of ifosfamide in combination with the VEGFR inhibitor sorafenib in advanced soft tissue sarcoma: a Spanish group for research on sarcomas (GEIS) study.

Background Sorafenib is a potent targeted-therapy that blockades angiogenesis and has demonstrated activity against some sarcoma subtypes. Preclinical studies suggested that treatment with sorafenib plus cytotoxic agents could result in additive efficacy. Methods Patients with advanced soft tissue sarcoma, with or without anthracycline pretreatment were included. Patients received oral sorafenib 400 mg twice daily starting on Day +2, ifosfamide 2.0 g/m2 iv infusion lasting 4 h on days 1, 2 and 3 with concurrent mesna 400 mg/m2 every three weeks until disease progression or unacceptable toxicity or up to a maximum of 6 cycles of ifosfamide (sorafenib could be continued until progressive disease or unacceptable toxicity). Primary objective was progression-free rate (PFR) at 3 and 6 months; secondary objectives were overall response rate (ORR), Progression-free survival (PFS), Overall survival (OS) and safety. This article reports the phase II part of a phase I/II clinical trial. Results Thirty-five patients were enrolled. PFR at 3 and 6 months was 66% (95% CI 48-81) and 37% (95% CI 22-55). Six patients (17%) achieved partial response and 17 (49%) stable disease. Median PFS was 4.8 months (CI 95% 1.94-6.36) and overall survival 16.2 months (95% CI 8.75-NA). Conclusion Treatment with sorafenib plus ifosfamide achieved a significant clinical benefit with an acceptable safety profile in patients with advanced soft tissue sarcoma resistant to anthracyclines, which warrants a more detailed study in randomized clinical trials.

Sorafenib in metastatic thyroid cancer.

Although thyroid cancer usually has an excellent prognosis, few therapeutic options are available in the refractory setting. Based on the recent results of phase II studies with tyrosine kinase inhibitors, we designed a retrospective analysis of patients with metastatic thyroid cancer treated with sorafenib in seven Spanish referral centers. Consecutive patients with progressive metastatic thyroid cancer (papillary, follicular, medullary, and anaplastic) not suitable for curative surgery, radioactive-iodine therapy, or radiotherapy were treated with sorafenib 400 mg twice a day. The primary end point was objective response rate (RR). Secondary end points included toxicity, median progression-free survival (mPFS), median overall survival (mOS), and correlation between tumor marker levels (thyroglobulin, calcitonin, and carcinoembryonic antigen) and efficacy. Between June 2006 and January 2010, 34 patients were included in the study. Sixteen patients presented differentiated thyroid carcinomas (DTC) of which seven (21%) were papillary, nine (26%) follicular, 15 (44%) medullary (MTC), and three (9%) were anaplastic (ATC). Eleven (32%) patients achieved partial response and 14 (41%) had stable disease beyond 6 months. Regarding histological subtype, RRs were 47% (seven of 15) for MTC, 19% (three of 16) for DTC, and 33% (one of three) for ATC. With a median follow-up of 11.5 months, mPFS were 13.5, 10.5, and 4.4 months for DTC, MTC, and ATC respectively. Tumor markers were evaluated in 22 patients, and a statistically significant association was observed between RR and decrease in tumor marker levels >50% (P=0.033). In this retrospective trial, sorafenib showed antitumor efficacy in all histological subtypes of thyroid cancer, warranting further development in this setting.

Phase III study comparing cisplatin plus fluorouracil to paclitaxel, cisplatin, and fluorouracil induction chemotherapy followed by chemoradiotherapy in locally advanced head and neck cancer.

PURPOSE: To compare the antitumor activity and toxicity of the two induction chemotherapy treatments of paclitaxel, cisplatin, and fluorouracil (FU; PCF) versus standard cisplatin and FU (CF), both followed by chemoradiotherapy (CRT), in locally advanced head and neck cancer (HNC). PATIENTS AND METHODS: Eligibility criteria included biopsy-proven, previously untreated, stage III or IV locally advanced HNC. Patients received either CF (cisplatin 100 mg/m2 on day 1 plus FU 1000 [corrected] mg/m2 continuous infusion on days 1 through 5) or PCF (paclitaxel 175 mg/m2 on day 1, cisplatin 100 mg/m2 on day 2, and FU 500 mg/m2 continuous infusion on days 2 through 6); both regimens were administered for three cycles every 21 days. Patients with complete response (CR) or partial response of greater than 80% in primary tumor received additional CRT (cisplatin 100 mg/m2 on days 1, 22, and 43 plus 70 Gy). RESULTS: A total of 382 eligible patients were randomly assigned to CF (n = 193) or PCF (n = 189). The CR rate was 14% in the CF arm v 33% in the PCF arm (P < .001). Median time to treatment failure was 12 months in the CF arm compared with 20 months in the PCF arm (log-rank test, P = .006; Tarone-Ware, P = .003). PCF patients had a trend to longer overall survival (OS; 37 months in CF arm v 43 months in PCF arm; log-rank test, P = .06; Tarone-Ware, P = .03). This difference was more evident in patients with unresectable disease (OS: 26 months in CF arm v 36 months in PCF arm; log-rank test, P = .04; Tarone-Ware, P = .03). CF patients had a higher occurrence of grade 2 to 4 mucositis than PCF patients (53% v 16%, respectively; P < .001). CONCLUSION: Induction chemotherapy with PCF was better tolerated and resulted in a higher CR rate than CF. However, new trials that compare induction chemotherapy plus CRT versus CRT alone are needed to better define the role of neoadjuvant treatment.