Exploratory findings from a prematurely closed international, multicentre, academic trial: RAVELLO, a phase III study of regorafenib versus placebo as maintenance therapy after first-line treatment in RAS wild-type metastatic colorectal cancer.

BACKGROUND: In patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC), the role of maintenance therapy after first-line treatment with chemotherapy plus antiepidermal growth factor receptor (EGFR) monoclonal antibodies (MoAb) is still an object of debate. METHODS: We assessed the efficacy and safety of regorafenib as a switch maintenance strategy after upfront 5-fluorouracil-based chemotherapy plus an anti-EGFR MoAb in patients with RAS WT mCRC. RAVELLO was a phase III, international, double-blind, placebo-controlled, academic trial. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival and toxicity. Regorafenib or placebo were administered daily for 3 weeks of 4-week cycle until disease progression or unacceptable toxicity, up to 24 months. RESULTS: The study was stopped prematurely due to slow accrual and lack of funding after the randomisation of 21 patients: 11 in the regorafenib arm and 10 in the placebo arm. The small sample size precludes any statistical analysis. Toxicity was acceptable and consistent with the known regorafenib safety profile. Median PFS was similar in the two arms. However, a subgroup of patients treated with regorafenib experienced a remarkably long PFS. Three patients were progression free at 9 months in the regorafenib arm versus one patient in the placebo arm, whereas at 12 months two regorafenib-treated patients were still progression free versus none in the placebo arm. CONCLUSION: RAVELLO trial demonstrated that growing financial and bureaucratic hurdles affect the feasibility of independent academic research. Although stopped prematurely and within the limited sample size, RAVELLO suggests that regorafenib has not a major activity in maintenance setting after upfront chemotherapy and anti-EGFR MoAb. However, a subgroup of patients experienced a remarkable long PFS, indicating that a better refinement of the patient population would help to identify subjects that might benefit from a regorafenib personalised approach in the switch maintenance setting.

Adherence and safety of regorafenib for patients with metastatic colorectal cancer: observational real-life study.

AIM: In this prospective multicenter real-life observational cohort study, we investigated the acceptance, adherence and safety of regorafenib, in the treatment of metastatic colorectal cancer patients. PATIENTS & METHODS: A total of 136 patients were recruited at six oncological hospital sites in southern Italy. The adherence to the treatment was measured with patient-completed medication diaries, physician interviews and pill counts. RESULTS: We found a statistically significant improvement of therapy adhesion by the acceptance questionnaire. The Eastern Cooperative Oncology Group performance status, the level of acceptance, the educational level and the concomitant usage of oral medications influenced the adherence to the treatment. CONCLUSION: Patients' level of education, concomitant other oral medications and patients' general clinical condition may influence the adherence to regorafenib.

Response to eribulin in a difficult-to-treat, heavily pretreated breast cancer patient: a case report.

In this short paper, we report our experience with eribulin mesylate in a heavily pretreated breast cancer patient with multiple bone metastases. The patient had been treated with doxorubicin, cyclophosphamide, methotrexate, fluorouracil, tamoxifen, letrozole, LH-RH analogs, fulvestrant, bevacizumab and paclitaxel and liposomal doxorubicin. In November 2013 treatment with eribulin ready to use solution (1.23 mg/m(2) days 1 and 8 of a 21-day cycle) was started and administered for a total of 14 courses. After six cycles of eribulin, evaluation with MRI showed a marked decrease in neoplastic involvement and replacement of osteolytic lesions with osteoblastic ones. No unexpected acute toxicity was observed. Although with all the limitations of any anecdotal report, our experience documents the efficacy and safety of eribulin in this difficult-to-treat patient who had been treated with multiple lines of chemotherapy.

Treatment of gastric cancer.

The authors focused on the current surgical treatment of resectable gastric cancer, and significance of peri- and post-operative chemo or chemoradiation. Gastric cancer is the 4(th) most commonly diagnosed cancer and the second leading cause of cancer death worldwide. Surgery remains the only curative therapy, while perioperative and adjuvant chemotherapy, as well as chemoradiation, can improve outcome of resectable gastric cancer with extended lymph node dissection. More than half of radically resected gastric cancer patients relapse locally or with distant metastases, or receive the diagnosis of gastric cancer when tumor is disseminated; therefore, median survival rarely exceeds 12 mo, and 5-years survival is less than 10%. Cisplatin and fluoropyrimidine-based chemotherapy, with addition of trastuzumab in human epidermal growth factor receptor 2 positive patients, is the widely used treatment in stage IV patients fit for chemotherapy. Recent evidence supports the use of second-line chemotherapy after progression in patients with good performance status.

Emotional impact in beta-thalassaemia major children following cognitive-behavioural family therapy and quality of life of caregiving mothers.

BACKGROUND: Cognitive-Behavioural Family Therapy (CBFT) can be an effective psychological approach for children with beta-thalassaemia major, increasing compliance to treatment, lessening the emotional burden of disease, and improving the quality of life of caregivers. DESIGN AND METHODS: Twenty-eight beta-thalassaemic major children that followed CBFT for one year were compared with twenty-eight age-matched healthy children, focusing particularly on behavioural, mood, and temperamental characteristics as well as compliance with chelation, assessed using the Child Behaviour Checklist (CBCL), Children's Depression Inventory (CDI), Multidimensional Anxiety Scale for Children (MASC), and Emotionality, Activity, Sociability and Shyness Scale (EAS). We also monitored the quality of life of caregiving mothers using the World Health Organization Quality Of Life (WHOQOL-BREF) questionnaire. Data were analysed with non-parametric standard descriptive statistics. RESULTS: 90% of beta-Thalassaemic children showed good compliance with chelation therapy; however they had significantly increased somatic complains, physical symptoms and separation panic. Moreover, temperamental assessment revealed high emotionality and poor sociability in treated thalassaemic children and in their mothers. Physical and psychological domains concerning individual's overall perception of quality of life resulted impaired in mothers of beta-thalassaemic children. CONCLUSION: CBFT can be a valid tool to increase the compliance with chelation therapy in beta-thalassaemic children; however, treated children continue to show an important emotional burden; moreover, CBFT therapy seems not to have any positive impact on the quality of life of caregiving mothers, who may therefore need additional psychological support.