Phase I/II study of cetuximab in combination with cisplatin or carboplatin and fluorouracil in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

PURPOSE: This was an open, randomized, multicenter, phase I/II study to investigate the safety and tolerability of cetuximab in the first-line treatment of recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Treatment comprised cetuximab (initial dose 400 mg/m2 with subsequent weekly doses of 250 mg/m2) in combination with 3-week cycles of either cisplatin (100 mg/m2) or carboplatin (area under the curve, 5), each in combination with a 5-day infusion of fluorouracil (FU) at escalating doses of 600, 800, and 1,000 mg/m2/d. The study was divided into two phases: A, the first two cycles (6 weeks) focusing on the safety and tolerability of combination therapy; and B, the remaining time for those benefiting from therapy until disease progression or intolerable toxicity. RESULTS: Fifty-three patients were enrolled onto the study. The incidence of dose-limiting toxicities in phase A was acceptable. The most common grade 3/4 adverse events in both groups were leucopenia (38%), asthenia (25%), vomiting (14%), and thrombocytopenia (15%), which are consistent with the known safety profiles of cetuximab, cisplatin/carboplatin, and FU. The overall response rate among patients was 36%, with no clear trend toward an increased efficacy at the highest dose of FU, and no impact of the concomitant chemotherapy regimens on cetuximab pharmacokinetics. CONCLUSION: The combination of cetuximab, cisplatin/carboplatin, and FU was reasonably well tolerated and active in recurrent/metastatic SCCHN, and merits additional investigation. An FU dose of 1,000 mg/m2/d in combination with cisplatin or carboplatin can be recommended for additional studies.Clinical Trial, Phase IClinical Trial, Phase IIJournal ArticleMulticenter StudyRandomized Controlled Trialinfo:eu-repo/semantics/publishe

Cost-effectiveness Analysis of Innovative Therapy for Patients with Newly Diagnosed Hormone-Sensitive Metastatic Prostate Cancer

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Phase II study of figitumumab in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck : clinical activity and molecular response (GORTEC 2008-02)

BACKGROUND: Preclinical studies suggest that insulin-like growth factor-1 receptor (IGF-1R) blockage could be a promising therapeutic target in squamous cell carcinoma of the head and neck (SCCHN). Therefore, we investigated the efficacy and toxicity of figitumumab, an anti-IGF-1R monoclonal antibody, in palliative SCCHN. PATIENTS AND METHODS: Patients with palliative SCCHN progressing after platinum-based therapy were treated with figitumumab i.v. 20 mg/kg, every 3 weeks. The primary end point was the disease control rate at 6-8 weeks after treatment initiation. Tumor biopsies and plasma samples were collected before and after figitumumab administration to monitor the molecular response. RESULTS: Seventeen patients were included. Only two patients achieved stable disease at 6-8 weeks. Median overall survival and progression-free survival were 63 and 52 days, respectively. The main grade 3-4 adverse event was hyperglycemia (41%). Translational research showed that figitumumab downregulated IGF-1R at the surface of tumor cells with activation of the epidermal growth factor receptor (EGFR) pathway, as shown by the upregulation of p-EGFR in tumor cells (P = 0.016), and an increase in the plasma level of tumor growth factor-alpha (P = 0.006). CONCLUSION: Figitumumab monotherapy has no clinically significant activity in unselected palliative SCCHN

Axitinib in first-line for patients with metastatic papillary renal cell carcinoma: Results of the multicentre, open-label, single-arm, phase II AXIPAP trial

International audienceIntroduction: Papillary renal cell carcinoma (PRCC) represents 10%e15% of renal carcinomas. No standard treatments exist for metastatic PRCC (mPRCC) patients. Axitinib is indicated as second-line treatment in metastatic clear cell renal carcinoma, and we aim to assess the efficacy of this vascular endothelial growth factor receptor inhibitor in front line for mPRCC. Methods: This French multicentre phase II study AXIPAP enrolled untreated mPRCC patients, with measurable disease, Eastern Cooperative Oncology Group performance status 1 and Vascular endothelial growth factor; VEGF inhibitor; Targeted therapy adequate organ functions. PRCC had to be confirmed by histology expert central review. Axi-tinib was administered orally 5 mg twice daily. Primary end-point was progression-free rate at 24 weeks (24w-PFR) by central review. Results: Fifty-six patients were screened, and 44 included (13 type 1, 30 type 2 and 1 non-specified). The median follow-up was 32.0 (13.1e39.9) months. The 24w-PFR was 45.2% (95% confidence interval [CI], 32.6% to þN), the objective response rate was 28.6% (95% CI, 15.7%e44.6%) (type 1: 7.7%; type 2: 35.7%). The overall median progression free survival was 6.6 months (95% CI, 5.5e9.2), 6.7 months (95% CI, 5.5e9.2) and 6.2 months (95% CI, 5.4 e9.2) for type 1 and 2, respectively. Median overall survival was 18.9 months (95% CI, 12.8enot reached). Adverse events were as expected; grade 3e4 treatment-related adverse events were rare except hypertension (27%). Conclusions: Axitinib demonstrated encouraging efficacy in mPRCC patients, especially in type 2 PRCC. Toxicity was manageable. Axitinib appears as an interesting option for first-line treatment and to be worth further investigation in combination with immunotherapy in these patients. Expert pathology review should be recommended in this setting. Clinical trial registration: ClinicalTrials.gov, NCT02489695

Complete remission with tyrosine kinase inhibitors in renal cell carcinoma

Complete remission (CR) is uncommon during treatment for metastatic renal cell carcinoma (mRCC) with tyrosine kinase inhibitors (TKIs), but it may occur in some patients. It remains a matter of debate whether therapy should be continued after CR

Clinical and economic burden of head and neck cancer : a nationwide retrospective cohort study from France

International audienceObjectives: To evaluate the clinical and economic burden of head and neck squamous cell carcinoma (HNSCC) in France.Methods: All 53,255 incident adult patients discharged with a first diagnosis of HNSCC in 2010–2012 were identified from the 2008–2013 French National Hospital Discharge (PMSI) database. We conducted a retrospective longitudinal analysis of prognosis and direct costs attributable to HNSCC.Results: Direct medical costs attributable to HNSCC care amounted to 665 million euros in 2012 in France. The majority (62%) of incident patients were 64 years old or less at HNSCC diagnosis and incurred 1.3-fold higher mean direct costs as compared to elderly patients (41,909 vs 32,221 euros over 3 years, respectively; p<0.001). HNSCC stage at initial treatment was the major driver of mean (SD) direct costs over 3 years (p<0.001): 19,819 (23,150) euros in 31% patients diagnosed at early stage; 46,791 (34,841) euros in 60% patients diagnosed at locally advanced stage; and 43,377 (33,953) euros in 9% patients diagnosed with distant metastasis. About half patients died over 3 years at a median (IQR) age of 63 (56–75) years resulting in 10.9 years-of-life lost on average per incident patient.Conclusion: The present study suggests that the clinical and economic burden of HNSCC is substantial in France

Standard or accelerated methotrexate, vinblastine, doxorubicin and cisplatin as neoadjuvant chemotherapy for locally advanced urothelial bladder cancer: Does dose intensity matter?

International audienceBackground There is continuing controversy regarding the optimal regimen for neoadjuvant chemotherapy (NAC) in bladder cancer. Patients and methods We performed a retrospective analysis of 241 consecutive bladder cancer patients who received a combination of methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) using a standard (52 patients) or an accelerated schedule (189 patients) as NAC before radical cystectomy in 17 centres of the French GEnito-urinary TUmour Group from March 2004–May 2013. Results The median age was 62 years. As expected, the median number of cycles, the median total dose of cisplatin and the median cisplatin dose intensity were higher in patients treated with the accelerated regimen. Conversely, the median duration of chemotherapy was shorter. Regarding toxicity, grade III/IV neutropenia, grade III thrombocytopenia and grade III anaemia as well were more frequently observed in patients treated with the standard regimen. Among 211 (88%) patients who proceeded to cystectomy, 75 (35%) patients achieved an ypT0 pN0 status (no pathologic residual tumour cells) with no significant difference according to the MVAC schedule. Three-year overall survival rates were 66.5% (95% confidence interval [CI], 56–79) and 72% (95% CI, 59.5–88) in the standard and accelerated cohorts, respectively. In the multivariate analysis, two independent prognostic parameters were retained: the ypT0 stage and the ypN0 stage. Heterogeneity test did not show any interaction with NAC regimens. Conclusion Similar pathological response and survival rates were observed whatever the chemotherapy regimen used. Haematological toxicity was greater in patients who received standard MVA