Roberta Granata

Outcome of recurrent and metastatic head and neck squamous cell cancer patients after first line platinum and cetuximab therapy

OBJECTIVES Second-line chemotherapy in recurrent and/or metastatic head and neck cancer (r/mHNSCC) patients showed dismal results with limited tumor response and reduced life expectancy. Outside of clinical trials, data on efficacy of second line treatment after first line anti-EGFR-AB combination therapy are not available. MATERIAL AND METHODS Data regarding r/mHNSCC consecutive pts treated with cetuximab and platinum from 2009 to 2014 at our center were retrospectively collected. The analyses of response, Progression-Free Survival (PFS) and Overall Survival (OS), each evaluated starting from first and second-line treatment, were performed. Survival curves were estimated with the Kaplan-Meier method and compared using the log-rank test. RESULTS We identified 117 patients treated with first-line platinum and cetuximab-based therapy. Sixty-four (55%) patients did not receive second-line treatment due to worsening in performance status, 2 were not assessable for response thus 51 patients were included for analysis. Fifty-six percent were smokers/former smokers and 78% were male. Primary tumor sites were oropharynx (39%), oral cavity (31%), larynx/hypopharynx (24%) and others (6%). Regimens used in second-line were mostly monotherapies. Twenty-one % of the patients were treated within a clinical trial. Response rate (PR, CR) was 6% with 45% showing SD as best response. Median PFS was 2.2months (95%CI:1.5-2.8months) and OS 6.1months (95%CI:3.7-7.2months). CONCLUSIONS Within our single center experience only half of the patients with r/mHNSCC were able to receive second-line treatment. Response rate was unsatisfactory, but median OS seems higher than previously reported in an anti-EGFR-AB naïve population (Leon 2005).

Weekly paclitaxel infusion in elderly patients with solid tumors.

Paclitaxel is a recent cytotoxic agent with significant clinical activity in a considerable number of solid tumors, most notably in breast and ovarian cancer and in non-small cell lung cancer when given at dose of 135175 mg/m? every 3 weeks. Considering the cellular mode of action of paclitaxel, which is predominantly cytotoxic for dividing cells and preferably acts on cells in the late G2 and M phase, more frequent application might result in increased antitumor activity. Thus a weekly schedule seems to offer an advantage over application every 3-4 weeks. Paclitaxel, given in a weekly 1 hour infusion was safe and showed mild toxicity in heavily pretreated breast and ovarian cancer patients in published phase I trial. In a multicenter phase II study (211 patients) weekly paclitaxel therapy in advanced breast cancer patients obtained an overall response rate of 21,5%; disease stabilization occurred in 41,8% of patients, thus it may be considered that 63,3% of the patients who received weekly paclitaxel had some benefit from therapy. The treatment was well tolerated by the majority of patients; few patients (15%) encountered serious hematological toxicity. Grade 3 neuropathy, occurring in 9% of patients, developed after a median of 20 weeks of therapy. Other serious toxicity were uncommon. Patients ~65 years of age had an equivalent overall response rate and no greater incidence of toxicity compared with younger patients. Overall quality of life was reasonably well maintained throughout the course of therapy; quality of life scores improved with therapy for patients achieving complete or partial responses. This trial confirms the tolerability of weekly paclitaxel therapy in women with advanced breast cancer noted in several trials. The mild toxicity profile also makes weekly paclitaxel a viable candidate for combination with other agents. Studies evaluating weekly paclitaxel in combination with agents such trastuzumab and carboplatin are currently underway. Ongoing studies comparing the efficacy and tolerability of weekly paclitaxel versus every 3-4 weeks administration schedules will help further define the role of this taxane in breast cancer therapy. The relative lack of

Prognostic role of PIK3CA and TP53 in human papillomavirus–negative oropharyngeal cancers:

Background: Human papilloma virus (HPV)–negative oropharyngeal squamous cell carcinomas (OPCs) have a poorer prognosis and best management is an unmet need. We studied the prognostic role of epidermal growth factor receptor (EGFR) and PIK3CA amplifications and TP53 functional status. Methods: Between 1992 and 2000, 90 consecutive patients with OPCs were treated with surgery, followed by radiotherapy in case of high-risk pathologic features. Of those, 73 cases were HPV-negative and therefore were selected for molecular analysis (PIK3CA and EGFR fluorescent in situ hybridization [FISH] analysis and TP53 mutation analysis). Results: FISH analyses of EGFR and PIK3CA were successfully conducted on 69 and 63 of 73 tumor samples, respectively. EGFR alterations were detected in 43% of patients but just 7% showed amplification. Seven cases (11%) carried PIK3CA amplification and 18 (29%) gene gain or high polysomy. TP53 was detected as nonfunctional in 24 of 67 (36%) successfully analyzed cases. Both univariable and multivariable analysis showed statistically significantly worse disease-free survival (DFS) for patients with PIK3CA disomy compared to those with gene gain or high polysomy. No differences in overall survival or DFS for EGFR and TP53 alteration were evident. The combined evaluation of PIK3CA and TP53 showed that PIK3CA gene copy number gain separated a population with better outcome, defining an overall worse prognosis population (disomy) now clearly further divided according to TP53 functional status. Conclusion: PIK3CA gene copy number increase is associated with a favorable clinical outcome in HPV-negative OPCs treated with surgery ± postoperative radiotherapy. In patients without PIK3CA alteration, TP53 nonfunctional mutations are associated with poor prognosis.

Circulating miR-375 as a novel prognostic marker for metastatic medullary thyroid cancer patients

This study aimed to identify circulating miRNAs as novel non-invasive biomarkers for prognosis and vandetanib response in advanced medullary thyroid cancer (MTC) patients. We prospectively recruited two independent cohorts of locally advanced/metastatic MTC patients including a subgroup of vandetanib-treated subjects: a discovery cohort (n = 20), including matched plasma/tissue samples (n = 17/20), and a validation cohort, yielding only plasma samples (n = 17). Plasma samples from healthy subjects (n = 36) and MTC patients in remission (n = 9) were used as controls. MTC (n = 17 from 8 patients included in discovery cohort) and non-neoplastic thyroid specimens (n = 3) were assessed by microarray profiling to identify candidate circulating miRNAs. qRT-PCR and in situ hybridization were carried out to validate the expression and localization of a selected miRNA within tissues, and qRT-PCR was also performed to measure miRNA levels in plasma samples. By microarray analysis, we identified 51 miRNAs differentially expressed in MTC. The most overexpressed miR, miR-375, was highly expressed by C cells compared to other thyroid cells, and more expressed in MTC than in reactive C-cell hyperplasia. MTC patients had significantly higher miR-375 plasma levels than healthy controls (P < 0.0001) and subjects in remission (P = 0.0004) as demonstrated by qRT-PCR analysis. miR-375 plasma levels were not predictive of vandetanib response, but, notably, high levels were associated with significantly reduced overall survival (HR 10.61, P < 0.0001) and were a strong prognostic factor of poor prognosis (HR 6.24, P = 0.00025) in MTC patients. Overall, our results unveil plasma miR-375 as a promising prognostic marker for advanced MTC patients, to be validated in larger cohorts.

Comment on ‘Human papillomavirus association is the most important predictor for surgically treated patients with oropharyngeal cancer’

Comment on ‘Human papillomavirus association is the most important predictor for surgically treated patients with oropharyngeal cancer’

Safety of combination treatment with imatinib mesylate, carboplatin, and cetuximab in a patient with multiple cancers: a case report.

Purpose Therapies directed against multiple signaling pathways have been validated in the clinical setting as effective anticancer treatments. The combination of different agents is particularly helpful in patients with multiple cancer diagnoses, while data on cross-toxicity are frequently missing, as for imatinib and cetuximab plus platinum drugs. Methods We present the case of a 76-year-old man with advanced laryngeal squamous cell carcinoma and chronic myeloid leukemia (CML). Combined treatment with imatinib mesylate and cetuximab plus carboplatin was well-tolerated by the patient, who did not develop neutropenia. By an interdisciplinary approach with hematology specialists, the anticipated neutropenia was managed by the temporary interruption of imatinib treatment when the white blood cell (WBC) count nadir was expected to occur. Results Although treatment with imatinib, carboplatin, and cetuximab can be associated with hematologic toxicities, a combination regimen based on the concomitant administration of these 3 drugs and on the discontinuation of imatinib at the predicted nadir of WBC count was feasible and well-tolerated in a patient with concomitant CML and locally advanced laryngeal squamous cell carcinoma. Conclusions Our report indicates the feasibility of combination imatinib and cetuximab plus carboplatin in a case of multiple cancer diagnoses, provided that the treatment with imatinib is modulated according to the expected bone marrow depression.

A Patient with Advanced Differentiated Radioactive Iodine-Refractory Thyroid Cancer Receiving Tyrosine Kinase Inhibitor Treatment: Managing Hypertension, QTc Prolongation, Dermatologic and Gastrointestinal Adverse Events

We report our experience with a patient with metastatic differentiated radioactive iodine-refractory thyroid cancer treated with vandetanib. We describe the potential side effects of this drug and the treatment of toxicities. The goal is to allow patients to remain on their full dose of vandetanib for as long as their treatment is indicated. A combination of early recognition and intervention for adverse events, patient education, and an open dialogue between patients and their multidisciplinary healthcare team, with timely reporting of adverse events, will allow for effective management of side effects and minimize the need for dose reduction or discontinuation of tyrosine kinase inhibitor therapy.

Carcinoma anaplastico della tiroide

RiassuntoIl carcinoma anaplastico della tiroide è considerato uno dei più aggressivi e letali tra i tumori solidi, con una mortalità del 90% e una sopravvivenza mediana di 6 mesi. Non esistono trattamenti standard per questa malattia che tende ad avere un comportamento loco-regionale molto aggressivo, oltre a dare metastasi a distanza molto rapidamente quando non già presenti all’esordio. Sono in corso, infatti, numerosi studi che prevedono l’utilizzo di nuovi farmaci per cercare di ridurre la velocità di progressione della malattia. Scopo di questo articolo è analizzare retrospettivamente gli studi più importanti che ci permettano di capire quali sono stati i trattamenti utilizzati e quali potrebbero essere i futuri trattamenti di questa malattia ancora poco conosciuta.