Francesca Rancati's scientific contributions

Publications (11)

Publications citing this author (174)

    • The final article related to the use of nilotinib in a non-randomised cohort of individuals and was thus excluded from the meta-analysis. Five of the included studies compared imatinib at standard (400 mg daily) and high dose (600 mg/ 800 mg daily)323334394041 and these were included in the evidence network for reasons of completeness. Two studies compared dasatinib 100 mg daily to imatinib 400 mg daily [13,29303138] and one compared nilotinb 600 mg/800 mg daily to imatinib 400 mg daily [12,353637.
    [Show abstract] [Hide abstract] ABSTRACT: Dasatinib 100 mg daily and nilotinib 600/800 mg daily have been compared to imatinib as first line treatments for CML in two recent randomised studies. However, no head to head evidence exists of the relative efficacy of dasatinib and nilotinib. We conducted a systematic literature review and used the data extracted to perform an indirect comparison meta-analysis of the three interventions. Data from eight clinical studies (3,520 individuals) were included, all of which were of good quality (low risk of bias). At six months, the odds of complete cytogenetic response (CCyR) for dasatinib and nilotinib were approximately three times those for imatinib (range 2.77 to 3.06, all values not significant). At twelve months datatinib and nilotinib were significantly better than imatinib for both CCyR and major molecular response (MMR) (CCyR odds range 2.06 to 2.41, MMR odds range 2.09 to 2.87). At eighteen months dasatinib and nilotinib were again significantly better in terms of CCyR than imatinib (response odds 1.55 to 2.01). When dasatinib and nilotinib were compared to each other, for both clinical endpoints at all time points the response odds were not significantly different. On the basis of a systematic review of the current literature base, dasatinib 100 mg, nilotinib 600 mg and nilotinib 800 mg should be viewed as equivalent in terms of complete cytogenetic and major molecular response.
    Full-text · Article · Feb 2013
    • The response to kinase inhibitors (eg imatinib) may not be driven exclusively by the KIT expression level. Studies have shown that not all KIT-expressing solid and hematological malignancies will benefit from imatinib therapy383940. They indicate that the response rate may depend on the presence of KIT mutations in the tumor and potentially also on the location and type of mutation as well as the interaction with other signal pathways.
    [Show abstract] [Hide abstract] ABSTRACT: c-kit functions as a tyrosine kinase receptor and represents a target for small molecule kinase inhibitors. The expression pattern for c-kit was studied in different human tumor types to their correlation with prognosis. Paraffin-embedded tumor tissues from 282 patients were analyzed immunohistochemically for c-kit expression. Survival and follow-up data were available from 192/282 (68%) patients. c-kit immunopositivity was found in 62/282 (22%) cases. c-kit expression was found in 14/83 (17%) colorectal cancers, in 13/62 (21%) breast cancers, in 7/20 sarcomas (35%), in 5/14 (36%) renal cell carcinomas, in 2/12 ovarian cancers (17%) and in 2/12 (17%) hepatocellular carcinomas. We found no significant correlation between c-kit expression and prognosis although a trend to a worse prognosis in patients with c-kit positive tumors could be observed. Expression of c-kit was found in tumor samples with varying intensities and infrequently.
    Full-text · Article · Feb 2010
    • With the advent of targeted therapies such as imatinib in chronic myeloid leukemia (CML) [20,21,22] and trastuzumab in breast cancer [23], there has been an effort to identify subsets of cancer patients with tumors reliant on pathways that can be disrupted without intolerable collateral damage to the cells responsible for tissue maintenance and regeneration. The type III receptor tyrosine kinase KIT is a highly conserved signaling protein involved in the regulation of apoptosis, proliferation, differentiation and adhesion [17].
    [Show abstract] [Hide abstract] ABSTRACT: We have previously described the expression of CD44, CD90, CD117 and CD133 in NSCLC tumors, adjacent normal lung, and malignant pleural effusions (MPE). Here we describe the unique subset of tumors expressing CD117 (KIT), a potential therapeutic target. Tumor and adjacent tissue were collected from 58 patients. Six MPE were obtained before therapy. Tissue was paraffin embedded for immunofluorescent microscopy, disaggregated and stained for flow cytometry or cryopreserved for later culture. The effect of imatinib on CD117(high)/KIT+ tumors was determined on first passage cells; absolute cell counts and flow cytometry were readouts for drug sensitivity of cell subsets. Primary tumors divided into KIT(neg) and KIT(+) by immunofluorescence. By more sensitive flow cytometric analysis, CD117+ cytokeratin+ cells were detected in all tissues (1.1% of cytokeratin+ cells in normal lung, 1.29% in KIT "negative" tumors, 40.7% in KIT(+) tumors, and 0.4% in MPE). In KIT(+)/CD117(high), but not KIT(+)/CD117(low) tumors, CD117 was overexpressed 3.1-fold compared to normal lung. Primary cultures of CD117(high) tumors were sensitive to imatinib (5 µM) in short term culture. We conclude that NSCLC tumors divide into CD117(low) and CD117(high). Overexpression of CD117 in CD117(high) NSCLC supports exploring KIT as a therapeutic target in this subset of patients.
    Full-text · Article · Dec 2012
    • These serious complications typically require a multidisciplinary group of clinicians. The benefit of imatinib in F/P fusion gene positive CEL has since been confirmed in numerous studies, and imatinib is recommended as a clear first-line therapy in patients with F/P-positive CEL [7][8][9][10][11]. One hundred mg/day is sufficient to induce a CMR and histological response in most patients with an F/P fusion gene, and 100-200 mg/week may be sufficient to maintain a durable remission in some patients.
    [Show abstract] [Hide abstract] ABSTRACT: Background: The FIP1L1/PDGFRA (F/P) fusion gene is the most common clonal genetic abnormality of chronic eosinophilic leukemia (CEL). Tyrosine kinase inhibitors (TKI), such as imatinib, have been demonstrated to be effective therapies for F/P mutated disease. The aim of this study was to analyze the treatment response and long term prognosis in patients with F/P mutated CEL. Methods: The clinical features and treatment responses of 33 consecutive patients with F/P mutated CEL between August 2006 and October 2014 were analyzed. The 33 cases received imatinib therapy at an initial dose of 100 mg/day (30 patients) or 200 mg/day (3 patients); the maintenance dose depended on the response condition and patient willingness. Through the follow up, the molecular responses were regularly monitored. Results: With a median follow up of 64 months, 94% of the 33 patients with F/P mutated CEL achieved a complete hematologic remission (CHR), and 97% achieved a complete molecular remission (CMR) after a median of 3 (1.5-12) months. Twenty-four cases received maintenance therapy, with a median CMR duration of 43 (5-88) months. Imatinib therapy was discontinued in 8 cases, including 4 cases who experienced relapse, and 4 patients who maintained CHR or CMR after discontinuing therapy with a median time of 47 (2-74) months. One case exhibited primary resistance with a PDGFRA T674I mutation. Conclusions: F/P mutated CEL has an excellent long-term prognosis following imatinib therapy. A 100 mg daily dose of imatinib is sufficient to induce remission, and a single 100 mg weekly dose maintains a durable remission. A subgroup of patients may maintain a durable remission after discontinuing therapy with a CMR.
    Full-text · Article · Apr 2016