Adjuvant chemotherapy after neoadjuvant chemo-radiotherapy and surgery in locally advanced rectal cancer. A systematic review of literature with a meta-analysis of randomized clinical trials.

HIGHLIGHTS: Although no definitive data exist in literature, adjuvant chemotherapy is usually recommended in patients with radically resected stage III rectal cancer treated with neo-adjuvant chemo-radiotherapy. We performed a systematic review of literature with direct and indirect comparisons to assess the role of adjuvant mono- or poli-chemotherapy in radically resected rectal cancer treated with neoadjuvant chemo-radiotherapy. Neither chemotherapy (mono-or poli-chemotherapy) nor polichemotherapy with oxaliplatin-containing regimens seems to improve Overall Survival and Disease-Free Survival in patients with radically resected rectal cancer treated with neoadjuvant chemo-adiotherapy. Neither the entire population of patients radically resected after neoadjuvant chemotherapy, nor high risk patients seem to benefit from adjuvant chemotherapy. Our data seem to suggest the need of review the actual international guidelines that suggest the need of adjuvant chemotherapy at least in high risk rectal cancer treated with surgery and neoadjuvant chemo-radiotherapy.

Eribulin Mesylate as Third or Subsequent Line Chemotherapy for Elderly Patients with Locally Recurrent or Metastatic Breast Cancer: A Multicentric Observational Study of GIOGer (Italian Group of Geriatric Oncology)-ERIBE.

BACKGROUND: Metastatic breast cancer (MBC) is highly prevalent in middle-aged or elderly patients. Eribulin is a nontaxane microtubule inhibitor, approved for the treatment of pretreated MBC. This multicentric study (sponsored by GIOGer, Italian Group for Geriatric Oncology) was designed to assess the efficacy and tolerability of eribulin, according to parameters usually used in geriatric oncology. SUBJECTS, MATERIALS, AND METHODS: An observational study was conducted on 50 consecutive elderly patients with MBC. The primary endpoint was to evaluate the change in items score of comprehensive geriatric assessment (CGA) and health-related quality of life (HRQL). Italian versions of the CGA and HRQL questionnaires were administered at baseline, before the third and fifth cycles, and then every three cycles until treatment discontinuation. Secondary endpoints were efficacy and safety. RESULTS: Overall, both EQ-5D scores and EQ-5D-3 L visual analogic scale did not significantly change from baseline; the percentage of subjects without problems doing usual activities tended to decrease during treatment (p for linear trend .018), and the percentage of patients with minor problems performing usual activities tended to increase (p for linear trend.012). Among CGA items, Instrumental Activities of Daily Living tended to decrease during treatment and Geriatric Depression Scale tended to increase. After 12 months follow-up, 24 patients (out of 47) showed clinical benefits; median progression-free survival was 4.49 months (2.10-10.33) and median OS was 7.31 months (3.70-14.03). The treatment was associated with mild toxicity. CONCLUSION: Eribulin treatment preserved quality of life and geriatric parameters included in the CGA, except for instrumental functioning and geriatric depression, in elderly patients with MBC. IMPLICATIONS FOR PRACTICE: A collaboration between oncologist and geriatric specialists is essential in the management of patients with metastatic breast cancer, who are frequently elderly or frail. The assessment of geriatric parameters in the decision-making process can contribute to direct toward the most appropriate therapeutic plan and preserve the quality of life of patients. Eribulin does not seem to affect quality of life or worsen the overall geriatric status; therefore, it can be considered a suitable option for elderly patients with metastatic breast cancer.

Dose intensity and efficacy of the combination of everolimus and exemestane (EVE/EXE) in a real-world population of hormone receptor-positive (ER+/PgR+), HER2-negative advanced breast cancer (ABC) patients: a multicenter Italian experience.

AIM: This retrospective analysis focused on the effect of treatment with EVE/EXE in a real-world population outside of clinical trials. We examined the efficacy of this combination in terms of PFS and RR related to dose intensity (5 mg daily versus 10 mg daily) and tolerability. METHODS: 163 HER2-negative ER+/PgR+ ABC patients, treated with EVE/EXE from May 2011 to March 2016, were included in the analysis. The primary endpoints were the correlation between the daily dose and RR and PFS, as well as an evaluation of the tolerability of the combination. Secondary endpoints were RR, PFS, and OS according to the line of treatment. Patients were classified into three different groups, each with a different dose intensity of everolimus (A, B, C). RESULTS: RR was 29.8% (A), 27.8% (B) (p = 0.953), and not evaluable (C). PFS was 9 months (95% CI 7-11) (A), 10 months (95% CI 9-11) (B), and 5 months (95% CI 2-8) (C), p = 0.956. OS was 38 months (95% CI 24-38) (A), median not reached (B), and 13 months (95% CI 10-25) (C), p = 0.002. Adverse events were stomatitis 57.7% (11.0% grade 3-4), asthenia 46.0% (6.1% grade 3-4), hypercholesterolemia 46.0% (0.6% grade 3-4), and hyperglycemia 35.6% (5.5% grade 3-4). The main reason for discontinuation/interruption was grade 2-3 stomatitis. CONCLUSIONS: No correlation was found between dose intensity (5 vs. 10 mg labeled dose) and efficacy in terms of RR and PFS. The tolerability of the higher dose was poor in our experience, although this had no impact on efficacy.

Prognostic model for advanced breast carcinoma with luminal subtype and impact of hormonal maintenance: Implications for post-progression and conditional survival.

BACKGROUND: The aim of this analysis was to develop and validate a prognostic model for advanced breast cancer (ABC) with luminal subtype based on the combination of clinical, pathological and therapeutic predictors to provide a practical tool to evaluate patients' prognosis. METHODS: Clinical and pathological data were retrospectively correlated to progression-free and overall survival (PFS/OS) using a Cox model. Significant treatment variables were adjusted with the propensity score analysis. A continuous score to identify risk classes was derived according to model ratios. The performance of the risk-class model was tested for post-progression survival (PPS) and conditional survival (CS) as well. RESULTS: Data from 335 patients (3 institutions) were gathered (median follow-up 58 months). At multivariate analysis Ki67, Performance Status (PS) and number of metastatic sites were significant predictors for PFS, whereas Ki67, PS, brain metastases, PFS after 1st-line therapy, number of chemotherapy lines, hormonal therapy and maintenance were significant predictors for OS. The hormonal maintenance resulted to be prognostic after adjustment with propensity score analysis. A two-class model significantly differentiated low-risk and high-risk patients for 2-year PFS (31.5% and 11.0%, p < 0.0001), and 3-years OS (57.1% and 4.8%, p < 0.0001). A three-class model separated low risk, intermediate-risk, and high-risk patients for 2-year PFS (40.8%, 24.4%, and 11.0%, p < 0.0001) and 3-year OS (68.1%, 24.8%, and 4.8%, p < 0.0001). Both models equally discriminate the luminal ABC prognosis in terms of PPS and CS. CONCLUSIONS: A risk stratification model including 'easy-to-obtain' clinical, pathological and therapeutic parameters accurately separates luminal ABC patients into different risk classes.

Antiemetic efficacy of single-dose palonosetron and dexamethasone in patients receiving multiple cycles of multiple day-based chemotherapy.

INTRODUCTION: The goal of pharmacological prophylaxis of chemotherapy-induced nausea and vomiting (CINV) should be the elimination of both nausea and vomiting symptoms during all planned chemotherapy cycles. The aim of this study was to assess the efficacy of a single dose of palonosetron and dexamethasone to prevent CINV and to guarantee an adequate food intake (FI) in patients receiving several cycles of multiple day-based chemotherapy (MD-CT). METHODS: Patients with advanced cancer but without a compromised nutritional status (bone mass index ≥ 18.5) were treated with 0.25 mg palonosetron plus 20 mg dexamethasone before MD-CT. The MD-CT regimen was either epirubicin plus ifosfamide or paclitaxel plus cisplatin and ifosfamide. Nausea, vomiting, and FI were monitored in a 7-day diary. Complete response (CR: no vomiting and no rescue therapy) was the primary endpoint, while complete control (CC: CR and no more than mild nausea) and the evaluation of FI were secondary endpoints. The endpoints were evaluated during the overall timescale (0-168 h) of the chemotherapy regimen. RESULTS: Fifty patients were enrolled, 80% of whom achieved CR and 78% achieved CC. During the six chemotherapy cycles, CR and CC ranged from 76% to 88% and from 62% to 88%, respectively. Moreover, patients with CR had a significantly (p < 0.0001) higher weekly food intake compared with patients not achieving CR. CONCLUSIONS: This trial was the first to assess the efficacy of palonosetron and dexamethasone for the prevention of both nausea and vomiting in patients receiving multiple cycles of MD-CT. In this trial, the ability of patients to intake an adequate amount of food each week was correlated with nausea, thus providing clinicians with an objective parameter for the measurement of the effects of nausea. A single dose of palonosetron and dexamethasone was able to prevent CINV in most patients receiving 3 days of chemotherapy during all planned chemotherapy cycles.