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Introduction: the emergence of new molecules for the treatment of metastatic cutaneous melanoma with a significant benefit on the survival brings new therapeutic perspectives. Nevertheless, their respective use and place in the therapeutic strategy are still debated by healthcare professionals. Objective: the French National Cancer Institute leads a national clinical practice guidelines project since 2008. It realized a review of these modalities of treatment and established recommendations. Methods: the clinical practice guidelines development process is based on systematic literature review and critical appraisal by experts. The recommendations are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines are reviewed by independent practitioners in cancer care delivery. Results: this article presents recommendations for first-line and second-line systemic treatment of metastatic cutaneous melanoma (without brain metastatis). [ABSTRACT FROM AUTHOR]

Background Recent studies have shown that interleukin-2 (IL2) is less toxic when administered subcutaneously than intravenously. Moreover interferon a and Dacarbazine could increase the efficiency of IL2. Patients and methods Nineteen ambulatory patients with metastatic melanoma (I stage III and 18 stage IV) were treated with an association of dacarbazine 400 mg/m[sup2], interferon α[sub2a] (Roferon) 9 × 10[sup6] IU 3 times per week administered subcutaneously and recombinant interleukin-2 (IL-2) (Eurocetus) 3 × 10[sup6] IU five days per week for two weeks per month subcutaneously. The treatment consisted of 2 induction cures separated by a one-month interval followed by evaluation studies. Results At the end of the induction phase, 2 complete and 3 partial responses (response rate 26.2%) were observed. These responses were obtained in patients with sinus (1 case), skin (3 cases), lymph node (2 cases), bone (1 case) and liver (1 case) targets. The mean response period was 10 months for the 2 complete responses. No patients had grade 4 toxicity, and treatment was stopped for only one patient. Painful subcutaneous nodules frequently (23%) formed at the injection site. Conclusion The association of subcutaneously administered dacarbazine, interferon α and IL2 would thus seem of interest for the treatment of metastatic melanoma. Moreover, toxicity is tolerable and compatible with ambulatory treatment ensuring the patient a decent quality of life. [ABSTRACT FROM AUTHOR]

The French Sarcoma Group assessed the efficacy, safety, and quality of life (QoL) of trabectedin versus best supportive care (BSC) in patients with advanced soft tissue sarcoma (STS). This randomized, multicenter, open-label, phase III study included adults with STS who progressed after 1-3 prior treatment lines. Patients were randomized (1 : 1) to receive trabectedin 1.5 mg/m2 every 3 weeks or BSC, stratified into L-STS (liposarcoma/leiomyosarcoma) and non-L-STS groups (other histotypes). Patients from the BSC arm were allowed to cross over to trabectedin at progression. The primary efficacy endpoint was progression-free survival (PFS) confirmed by blinded central review and analyzed in the intention-to-treat population. Between 26 January 2015 and 5 November 2015, 103 heavily pre-treated patients (60.2% with L-STS) from 16 French centers were allocated to receive trabectedin (n = 52) or BSC (n = 51). Median PFS was 3.1 months [95% confidence interval (CI) 1.8-5.9 months] in the trabectedin arm versus 1.5 months (0.9-2.6 months) in the BSC arm (hazard ratio = 0.39, 95% CI 0.24-0.64, P < 0.001) with benefits observed across almost all analyzed subgroups, but particularly in patients with L-STS (5.1 versus 1.4 months, P = 0.0001). Seven patients (13.7%) in the trabectedin arm (all with L-STS) achieved a partial response, while no objective responses were observed in the BSC arm (P = 0.004). The most common grade 3/4 adverse events were neutropenia (44.2% of patients), leukopenia (34.6%), and transaminase increase (32.7%). Health-related 30-item core European Organization for the Research and Treatment of Cancer Quality-of-Life Questionnaire evidenced no statistical differences between the arms for any domain and at any time point. After progression, 91.8% of patients crossed over from BSC to trabectedin. Trabectedin demonstrates superior disease control to BSC without impairing QoL in patients with recurrent STS of multiple histologies, with greater impact in patients with L-STS. • In adults with STS, trabectedin significantly prolonged PFS as compared to BSC. • Overall, 13.7% achieved a partial response in the trabectedin arm, while no objective response was observed in the BSC arm. • Benefits were observed across most of analyzed subgroups, but particularly in patients with liposarcoma/leiomyosarcoma. • QoL questionnaire evidenced no statistical difference between the arms for any domain or time point. • Trabectedin has superior disease control to BSC in patients with recurrent STS of multiple histologies. [ABSTRACT FROM AUTHOR]

Afatinib, an oral irreversible ErbB family blocker, showed comparable activity to cetuximab in patients with recurrent/metastatic head and neck squamous cell carcinoma in this phase II trial. Further, sequential EGFR/ErbB treatment provided sustained clinical benefit in some patients, suggesting a lack of cross-resistance.Background Afatinib is an oral, irreversible ErbB family blocker that has shown activity in epidermal growth factor receptor (EGFR)-mutated lung cancer. We hypothesized that the agent would have greater antitumor activity compared with cetuximab in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients, whose disease has progressed after platinum-containing therapy. Patients and methods An open-label, randomized, phase II trial was conducted in 43 centers; 124 patients were randomized (1 : 1) to either afatinib (50 mg/day) or cetuximab (250 mg/m2/week) until disease progression or intolerable adverse events (AEs) (stage I), with optional crossover (stage II). The primary end point was tumor shrinkage before crossover assessed by investigator (IR) and independent central review (ICR). Results A total of 121 patients were treated (61 afatinib, 60 cetuximab) and 68 crossed over to stage II (32 and 36 respectively). In stage I, mean tumor shrinkage by IR/ICR was 10.4%/16.6% with afatinib and 5.4%/10.1% with cetuximab (P = 0.46/0.30). Objective response rate was 16.1%/8.1% with afatinib and 6.5%/9.7% with cetuximab (IR/ICR). Comparable disease control rates were observed with afatinib (50%) and cetuximab (56.5%) by IR; similar results were seen by ICR. Most common grade ≥3 drug-related AEs (DRAEs) were rash/acne (18% versus 8.3%), diarrhea (14.8% versus 0%), and stomatitis/mucositis (11.5% versus 0%) with afatinib and cetuximab, respectively. Patients with DRAEs leading to treatment discontinuation were 23% with afatinib and 5% with cetuximab. In stage II, disease control rate (IR/ICR) was 38.9%/33.3% with afatinib and 18.8%/18.8% with cetuximab. Conclusion Afatinib showed antitumor activity comparable to cetuximab in R/M HNSCC in this exploratory phase II trial, although more patients on afatinib discontinued treatment due to AEs. Sequential EGFR/ErbB treatment with afatinib and cetuximab provided sustained clinical benefit in patients after crossover, suggesting a lack of cross-resistance. [ABSTRACT FROM AUTHOR]

Options in second-line therapy after doxorubicin-based chemotherapy for metastatic/advanced leiomyosarcoma include gemcitabine (G), trabectedin and pazopanib (P) monotherapy. Currently, no combination therapy is better than monotherapy. LMS03 is an open-label multicentre single-group phase II study designed to assess the efficacy and tolerance of G + P in the second-line setting. Patients (pts), ECOG ≤2, with metastatic leiomyosarcomas (LMS) after first-line doxorubicin chemotherapy failure were eligible. Pts were treated with G 1000 mg/m2 on days 1 and 8 of each 21 days (maximum eight cycles), in combination with oral daily P (800 mg), until disease progression/toxicity. 9-month progression-free survival (PFS) rate was the primary endpoint. Inacceptable and promising 9-month PFS rates were defined, in the intent-to-treat population, as 32% and 44%. 106 pts were included with a mean age of 59.8 years and an ECOG 0 in 63.5%; the primary tumour site was uterus in 61%. Pts were treated with P + G for a median of 3.8 mo, and P for a median of 4.2 mo. The 9-month PFS rate was 32.1% (95% CI 23.1–41.1). After a median follow-up of 14.2 months, the PFS was 6.5 months (95% CI 5.6–8.2), and the overall survival was 22.4 months (95% CI 16.9–26.5). The best response was 23.8%. The most frequent reported grade 3–4 adverse events were haematological. LMS03 failed to show that second-line therapy, with gemcitabine combined with pazopanib, followed by pazopanib alone, was beneficial for advanced LMS patients. Eudract N°2011-001308-36 and NCT01442662. • Gemcitabine combined with pazopanib in second-line leiomyosarcoma after doxorubicine failure is feasible without limiting toxicity. • The 12-week disease control rate was 83.6%, and the best response during the treatment was 23.8%. • The LMS03 study failed to meet its primary objective but is nearly positive when considering per-protocol results with a median PFS 7.1 months. [ABSTRACT FROM AUTHOR]

Background: Sarcomas are rare but aggressive diseases. Specialized multidisciplinary management is not implemented for all patients in most countries. We investigated the impact of a multidisciplinary tumor board (MDTB) presentation before treatment in a nationwide study over 5 years. Patients and methods: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized MDTB, funded by the French National Cancer Institute to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and second pathological review are mandatory for sarcoma patients in France. Patients' characteristics and follow-up are collected in a database regularly monitored and updated. The management and survival of patients presented to these MDTB before versus after initial treatment were analyzed. Results: Out of the 12 528 patients aged ≥15 years, with a first diagnosis of soft tissue and visceral sarcoma obtained between 1 January 2010 and 31 December 2014, 5281 (42.2%) and 7247 (57.8%) were presented to the MDTB before and after the initiation of treatment, respectively. The former group had generally worse prognostic characteristics. Presentation to a MDTB before treatment was associated with a better compliance to clinical practice guidelines, for example, biopsy before surgery, imaging, quality of initial surgery, and less reoperations (all P<0.001). Local relapse-free survival and relapse-free survival were significantly better in patients presented to a MDTB before initiation of treatment, both in univariate and multivariate analysis. Conclusion: The compliance to clinical practice guidelines and relapse-free survival of sarcoma patients are significantly better when the initial treatment is guided by a pre-therapeutic specialized MDTB. [ABSTRACT FROM AUTHOR]

Background: Solitary fibrous tumors (SFT) are rare unusual ubiquitous soft tissue tumors that are presumed to be of fibroblastic differentiation. At present, the challenge is to establish accurate prognostic factors. Patients and methods: A total of 214 consecutive patients with SFT diagnosed in 24 participating cancer centers were entered into the European database (www.conticabase.org) to perform univariate and multivariate analysis for overall survival (OS), local recurrence incidence (LRI) and metastatic recurrence incidence (MRI) by taking competing risks into account. A prognostic model was constructed for LRI and MRI. Internal and external validations of the prognostic models were carried out. An individual risk calculator was carried out to quantify the risk of both local and metastatic recurrence. Results: We restricted our analysis to 162 patients with local disease. Twenty patients (12.3%) were deceased at the time of analysis and the median OS was not reached. The LRI rates at 10 and 20 years were 19.2% and 38.6%, respectively. The MRI rates at 10 and 20 years were 31.4% and 49.8%, respectively. Multivariate analysis retained age and mitotic count tended to significance for predicting OS. The factors influencing LRI were viscera localization, radiotherapy and age. Mitotic count, tumor localization other than limb and age had independent values for MRI. Three prognostic groups for OS were defined based on the number of unfavorable prognostic factors and calculations were carried out to predict the risk of local and metastatic recurrence for individual patients. Conclusion: LRI and MRI rates increased between 10 and 20 years so relapses were delayed, suggesting that long-term monitoring is useful. This study also shows that different prognostic SFT sub-groups could benefit from different therapeutic strategies and that use of a survival calculator could become standard practice in SFTs to individualize treatment based on the clinical situation. [ABSTRACT FROM AUTHOR]

Background: In the phase III LUX-Head & Neck 1 (LHN1) trial, afatinib significantly improved progression-free survival (PFS) versus methotrexate in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients progressing on/after platinum-based therapy. This report evaluates afatinib efficacy and safety in prespecified subgroups of patients aged ≥65 and <65 years. Patients and methods: Patients were randomized (2:1) to 40 mg/day oral afatinib or 40 mg/m²/week intravenous methotrexate. PFS was the primary end point; overall survival (OS) was the key secondary end point. Other end points included: objective response rate (ORR), patient-reported outcomes, tumor shrinkage, and safety. Disease control rate (DCR) was also assessed. Results: Of 483 randomized patients, 27% (83 afatinib; 45 methotrexate) were aged ≥65 years (older) and 73% (239 afatinib; 116 methotrexate) <65 years (younger) at study entry. Similar PFS benefit with afatinib versus methotrexate was observed in older {median 2.8 versus 2.3 months, hazard ratio (HR) = 0.68 [95% confidence interval (CI) 0.45-1.03], P = 0.061} and younger patients [2.6 versus 1.6 months, HR = 0.79 (0.62-1.01), P = 0.052]. In older and younger patients, the median OS with afatinib versus methotrexate was 7.3 versus 6.4 months [HR = 0.84 (0.54-1.31)] and 6.7 versus 6.2 months [HR = 0.98 (0.76-1.28)]. ORRs with afatinib versus methotrexate were 10.8% versus 6.7% and 10.0% versus 5.2%; DCRs were 53.0% versus 37.8% and 47.7% versus 38.8% in older and younger patients, respectively. In both subgroups, the most frequent treatment-related adverse events were rash/acne (73%-77%) and diarrhea (70%-80%) with afatinib, and stomatitis (43%) and fatigue (31%-34%) with methotrexate. Fewer treatment-related discontinuations were observed with afatinib (each subgroup 7% versus 16%). A trend toward improved time to deterioration of global health status, pain, and swallowing with afatinib was observed in both subgroups. Conclusions: Advancing age (=65 years) did not adversely affect clinical outcomes or safety with afatinib versus methotrexate in second-line R/M HNSCC patients. [ABSTRACT FROM AUTHOR]

Background We previously demonstrated that interruption of imatinib mesylate (IM) in responding patients (pts) with advanced gastrointestinal stromal tumours (GISTs) results in rapid reprogression. The impact of interruption on residual tumour, quality of response and secondary resistance has not been fully investigated. Patients and methods Within the BRF14 study, 71 non-progressing patients were randomly assigned in the interruption arms after 1, 3 or 5 years. IM was resumed in the case of progressive disease (PD). Tumour status at randomisation, relapse and after IM rechallenge, progression-free survival (PFS) and time to secondary resistance were analysed. Results At data cut-off, 51 of 71 patients had restarted IM following documented PD. Eighteen patients (35%) progressed on known lesions only, while 33 patients (65%) had new lesions, with concomitant progression of known lesions in 17 patients. Only 8 (42%) of complete remission (CR) patients and 12 (52%) of partial response (PR) patients at randomisation achieved a new CR and PR. Patients progressing rapidly after interruption had a poorer prognosis. Tumour status at randomisation influenced time to progression after rechallenge. Conclusion In advanced GIST patients interrupting IM, quality of response upon reintroduction did not reach the tumour status observed at randomisation. Rapid progression after imatinib interruption is associated with poor PFS after reintroduction. [ABSTRACT FROM PUBLISHER]

Background: Metastatic soft tissue sarcoma (STS) prognosis remains poor and few cytotoxic agents offer proven efficacy. This randomized open phase III study examines whether high-dose (HD) chemotherapy with peripheral blood stem cells (PBSCs) could improve overall survival (OS) of chemosensitive patients. Patients and methods: Advanced STS patients aged 18–65 years received four courses of standard mesna, adryamycin, ifosfamide and dacarbazine (MAID) treatment. Chemotherapy-responding patients and patients with at least stable disease amenable to complete surgical resection were randomized to receive standard dose (SD) with two successive MAID cycles or HD treatments of one MAID then MICE intensification: mesna (3.6 g/m2, day 1–5), ifosfamide (2.5 g/m2, day 1–4), carboplatin [area under the curve (AUC) 5/day 2–4] and etoposide (300 mg/m2, day 1–4) with PBSC reinjection at day 7. Results: From 2000 to 2008, 207 patients received four cycles of MAID and 87 assessable patients were randomly assigned to receive the following: 46 SD, 41 HD, with 45 and 38 maintained for analyses after secondary centralized histological review. Futility analyses led to study closure in November 2008. Three-year OS was 49.4% for the SD group versus 32.7% for HD arm, hazard ratio= 1.26, 95% confidence interval 0.70–2.29; progression-free survival was 32.4% and 14.0%, respectively. HD treatment led to higher grades 3–4 toxicity. Conclusion: This study failed to show an OS advantage for advanced STS patients treated with dose-intensified chemotherapy with PBSC. [ABSTRACT FROM PUBLISHER]

Background: Angiosarcomas are a rare but aggressive form of soft tissue sarcoma. At metastatic stage, the clinical benefit of therapeutic intervention remains debatable. Patients and methods: We have carried a retrospective analysis of 149 cases treated between 1996 and 2009 in the French Sarcoma Group. Results: The median age was 60; the sex ratio was 0.80. Sixty-two percentage of cases presented with metastasis at the diagnosis. About 20% arose in irradiated fields. The median overall survival was 11 months. Treatment consisted in metastasectomy (5.4%), doxorubicin-based regimen (46.9%), weekly paclitaxel (Taxol) (31.5%), other chemotherapy regimens (10.7%) or exclusive palliative care (10.9%). Clinical prognostic factors identified by univariate analysis were presence of bone metastasis (P = 0.0107), presence of other metastasis (P = 0.0327) and performance status (P < 0.0001). The Cox model retained a performance status of two or more as the sole independent prognostic factor (HR [hazard ratio] = 2.49, P < 0.0001). After adjustment to the performance status and compared with exclusive palliative care, the following treatments significantly improve the outcome: doxorubicin-based regimen as first-line chemotherapy (HR = 0.38, P = 0.0165), weekly paclitaxel as first-line regimen (HR = 0.36, P = 0.0146) and metastasectomy (HR = 0.09, P = 0.0221). Conclusions: This retrospective analysis indicates that some therapeutic interventions may significantly improve the outcome of this aggressive disease. Doxorubicin-based regimens and weekly paclitaxel seem to provide the same range of efficacy. [ABSTRACT FROM PUBLISHER]

Background: Lapatinib is a dual inhibitor of epidermal growth factor receptor (EGFR) and human EGFR-2 (HER-2) tyrosine kinases. This study investigated the pharmacodynamic and clinical effects of lapatinib in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN).Methods: In total, 107 therapy-naive patients with locally advanced SCCHN were randomised (2 : 1) to receive lapatinib or placebo for 2-6 weeks before chemoradiation therapy (CRT). Endpoints included apoptosis and proliferation rates, clinical response, and toxicity.Results: Versus placebo, lapatinib monotherapy did not significantly increase apoptosis detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labelling or caspase-3 assays. A statistically significant decrease in proliferation using Ki67 assay was observed (P=0.030). In a subset of 40 patients that received 4 weeks of lapatinib or placebo, objective response rate (ORR) was 17% (n=4/24) vs 0% (n=0/16). In the lapatinib single-agent responders, all had EGFR overexpression, 50% had EGFR amplification, and 50% had HER2 expression by immunohistochemistry (including one patient with HER2 amplification). However, these patients showed variable modulation of apoptosis, proliferation, and phosphorylated EGFR on drug treatment. Following CRT, there was a statistically non-significant difference in ORR between lapatinib (70%) and placebo (53%). There was no clear correlation between changes in apoptosis or proliferation and response to chemoradiation. Mucosal inflammation, asthenia, odynophagia, and dysphagia were the most commonly reported adverse events with lapatinib.Conclusion: Short-term lapatinib monotherapy did not demonstrate apoptotic changes, but provided evidence of clinical activity in locally advanced SCCHN, and warrants further investigation in this disease. [ABSTRACT FROM AUTHOR]

Background: Imatinib evaluated as a new treatment option in patients with recurrent or established progressive aggressive fibromatosis/desmoid tumor (AF/DT).Patients and methods: Forty patients with unresectable and progressive symptomatic AF/DT were treated with imatinib (400 mg/day for 1 year) in a Simon's optimal two-stage phase II study (P0 = 10%, P1 = 30%, α = 5%, β = 10%). The primary end point was non-progressive at 3 months (RECIST).Results: The study population consisted of 28 women and 12 men, with a mean age of 41 (range 20–72 years). Most of the primary sites were extra-abdominal (24, 54.5%). Familial adenomatous polyposis was observed in six (15%) cases. The median follow-up was 34 months. Imatinib toxicity was similar to that previously reported in literature. Tumor assessment was validated by a central independent radiology committee for 35 patients At 3 months, one (3%) complete and three (9%) partial confirmed responses were observed. The non-progression rates at 3, 6 and 12 months were, respectively, 91%, 80% and 67%. The 2-year progression-free and overall survival rates were 55% and 95%, respectively. Two patients with mesenteric AF/DT died from progressive disease.Conclusion: Imatinib is active in the treatment of recurrent and progressive AF/DT, providing objective response and long-term stable disease in a large proportion of patients. [ABSTRACT FROM AUTHOR]

Background: A phase III trial demonstrated that cetuximab is the first agent in 30 years to improve survival when added to platinum-based chemotherapy (platinum-fluorouracil) first line for recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN). This analysis of the trial assessed the impact of treatment on quality of life (QoL).Patients and methods: The European Organisation for Research and Treatment of Cancer QoL Questionnaire-Core 30 (QLQ-C30) and QLQ-Head and Neck 35 (QLQ-H&N35) module were used to assess QoL.Results: Of 442 patients randomly assigned, 291 (QLQ-C30) and 289 (QLQ-H&N35) patients completed at least one evaluable questionnaire. For QLQ-C30, cycle 3 and month 6 mean scores for platinum–fluorouracil plus cetuximab were not significantly worse than those for platinum–fluorouracil. Pattern-mixture analysis demonstrated a significant improvement in the global health status/QoL score in the cetuximab arm (P = 0.0415) but no treatment differences in the social functioning scale. For QLQ-H&N35, the mean score for the cetuximab arm was not significantly worse than that for the chemotherapy arm for all symptom scales at all post-baseline visits. At cycle 3, some symptom scores significantly favored the cetuximab arm (pain, swallowing, speech problems, and social eating).Conclusion: Adding cetuximab to platinum–fluorouracil does not adversely affect the QoL of patients with recurrent and/or metastatic SCCHN. [ABSTRACT FROM AUTHOR]

Background: Imatinib induces responses and disease stabilisations in non-resectable patients with aggressive fibromatosis (AF). The precise target of imatinib in AF and predictive factors for response to treatment are unknown.Methods: We investigated factors potentially predictive of response to imatinib in a series of 40 patients with progressive AF included in a phase II trial of imatinib: we tested the presence of KIT exon 10 variant (M541L), the expression of imatinib-sensitive kinases and cell cycle proteins by immunohistochemistry (IHC), and other clinical and biological factors.Results: Of 10 patients for whom DNA could be extracted, 3 had a KIT exon 10 variant (30%), with no correlation with response or progression-free survival (PFS). The expression of other imatinib targets (PDGFRA/B, macrophage colony-stimulating factor receptor (M-CSFR)) and of downstream components of the cell cycle, cell proliferation and proliferation pathway (cyclin D1, ERK, MEK 1-2) did not correlate with PFS. Pre-treatment lymphopenia (<1500/microl) and tumour size >120 mm correlated with shorter PFS in univariate and multivariate analyses.Conclusion: Our findings show that a baseline biological characteristic of the patient is the major parameter influencing response to imatinib in aggressive fibromatosis. Tumour characteristics, including the presence of a KIT exon 10 M541L variant, may influence tumour control but this needs to be confirmed and better explained. [ABSTRACT FROM AUTHOR]

We report the results of a randomised phase II trial of docetaxel tested as a single agent in patients with recurrent head and neck cancer using methotrexate as a control arm to validate the results. Eligibility criteria included: histologically-confirmed squamous cell carcinoma, measurable disease, adequate haematological, renal and hepatic functions, no prior chemotherapy for recurrent cancer, signed informed consent. 40 mg/m2 methotrexate was given as a short weekly bolus i.v. injection, and 40 mg/m2 docetaxel was administered as a one hour weekly infusion. A total of 57 patients were randomised based on a ratio of 2/1:37 and 20 patients received docetaxel and methotrexate, respectively. Patient characteristics included 49 males and 8 females; the median age was 59 years (range: 43–82 years). Twenty-eight patients had a local-regional relapse and 29 had distant metastasis, the median disease-free interval was 7.9 months (range: 0–165 months). For patients treated with docetaxel, the following grade 3–4 toxicities occurred: neutropenia (12.5%) with febrile neutropenia in one patient (1%), anaemia (19%) mucositis (9%) and ungueal toxicity (9%). In the methotrexate arm, the grade 3–4 toxicities were: anaemia (15%) and mucositis (5%). The response rate was significantly higher in the docetaxel arm with 27% (95% confidence interval (CI): 21.7–32.3%) of objective responses versus 15% (95% CI: 11.2–18.8%) in the methotrexate arm. Overall survival and time to progression were super-imposable between the docetaxel and methotrexate treatments. Docetaxel given as a weekly infusion has a high activity in patients with head and neck cancer. A phase III trial is needed to test if this translates into a survival benefit for docetaxel use. [Copyright &y& Elsevier]

Purpose. – The main objective of this prospective multicenter randomised phase III study was to compare a combined regimen of fotemustine plus whole brain irradiation versus fotemustine alone in terms of cerebral response and time to cerebral progression in patients with melanoma brain metastases.Patients and methods. – Seventy-six patients (instead of the 106 planned patients; study was stopped after the interim analysis) were randomised receiving either fotemustine (arm A, n = 39) or fotemustine and whole brain irradiation (arm B, n = 37). Fotemustine was administered intravenously at 100 mg m–2 on day 1, 8 and 15, followed by a 5-week rest period, then every 3 weeks in non-progressive patients. In arm B, a concomitant whole brain irradiation was performed at the total dose of 37.5 Gy (2.5 Gy/d–1, days 1–5, 3 consecutive weeks).Results. – Although patients who received fotemustine alone had worse prognostic factors, there was no significant difference in brain response (arm A: 7.4%, B: 10.0%) or control rates (objective response plus stable disease) after seven weeks (arm A: 30%, B: 47%) and overall survival (arm A: 86d, B: 105d). However, there was a significant difference in favour of arm B for the time to brain progression (p = 0.028, Wilcoxon test).Conclusion. – Fotemustine plus whole brain irradiation delayed the time to brain progression of melanoma cerebral metastases compared to fotemustine alone but without a significant improvement in terms of objective control or overall survival. [Copyright &y& Elsevier]

Studies the treatment for the disease cutaneous melanoma. Clinical diagnosis and histopathological assessment of the disease; Need for removal of cutaneous lesion instead of a biopsy; Description of therapeutic strategies followed for the disease.

Background: Owing to the limited efficacy of therapy on melanoma at the stage of distant metastases, a well-tolerated adjuvant therapy is needed for patients with high-risk primary melanoma. Our hypothesis was that an adjuvant treatment with low doses of interferon alpha could be effective in patients with localised melanoma.Methods: After resection of a primary cutaneous melanoma thicker than 1.5 mm, patients without clinically detectable node metastases were randomly assigned to receive either 3x10(6) IU interferon alpha-2a, three-times weekly for 18 months, or no treatment. The primary endpoint was the relapse-free interval.Findings: 499 patients were enrolled, of whom 489 were eligible. When used as part of a sequential procedure, interferon alpha-2a was of significant benefit for relapse-free interval (p=0.038). A long-term analysis, after a median follow-up of 5 years, showed a significant extension of relapse-free interval (p=0.035) and a clear trend towards an increase in overall survival (p=0.059) in interferon alpha-2a-treated patients compared with controls. There were 100 relapses and 59 deaths among the 244 interferon alpha-2a-treated patients compared with 119 relapses and 76 deaths among the 245 controls. The estimated 3-year-relapse rates were 32% in the interferon alpha-2a group and 44% in controls; the 3-year death rates were 15% and 21%, respectively. Only 10% of patients experienced WHO grade 3 or 4 adverse events. Treatment was compatible with normal daily life.Interpretation: Adjuvant therapy of high-risk melanoma with low doses of interferon alpha-2a for 18 months is safe and is beneficial when started before clinically detectable node metastases develop. [ABSTRACT FROM AUTHOR]

Introduction et but de l’étude Un essai prospectif de phase 2 objectivait qu’une pharmaconutrition par voie orale en cours de chimioradiothérapie (CRT) des cancers de la tête et du cou, pourrait réduire les mucites sévères et améliorer la survie (Assenat 2011). Nous avons mis en place une étude phase III dans l’objectif de confirmer ces résultats. Matériel et méthodes Cent quatre-vingt patients issus de 20 centres étaient randomisés après chirurgie et avant une CRT adjuvante. Une randomisation en double insu était effectuée entre une pharmaconutrition (3 sachets/j d’une formule enrichie en l -arginine, oméga-3 et acides ribonucléiques vs un placébo isocalorique et isoazoté). L’analyse statistique était réalisée en intention de traiter (ITT) et en per protocole (PP). Les toxicités muqueuses aiguës (RTOG et WHO) étaient analysées en double aveugle ainsi que la survie à 2 ans. Résultats L’étude en ITT incluait 172 patients et, en PP, 109 patients avec une compliance au produit supérieure ou égale à 75 %. Les toxicités muqueuses grade 3 et 4 étaient identiques dans les deux bras, en ITT ou PP, avec les deux échelles, RTOG ( p = NS) et WHO ( p = NS). En PP, dans le bras avec pharmaconutrition, la survie sans maladie était significativement améliorée ( p = 0,004), et une tendance statistique significative était observée en survie globale ( p = 0,07). En ITT, la survie globale n’était pas significative ( p = 0,22), mais une tendance statistique significative était observée en survie sans maladie ( p = 0,07). La médiane de la survie sans maladie et de la survie globale n’était pas atteinte. Conclusion Cette pharmaconutrition orale n’est pas efficiente sur les mucites aiguës sévères. Cependant, ce traitement améliore de façon significative la survie sans maladie pour les patients compliants. Le suivi à plus long terme des patients traités est nécessaire pour confirmer ces résultats. Ce traitement pourrait alors devenir le nouveau standard en CRT adjuvante des cancers de la tête et du cou. Remerciements Ligue nationale contre le cancer, Nestlé International pour les produits, les membres du Groupe oncologie radiothérapie tête et cou (GORTEC). [ABSTRACT FROM AUTHOR]

Objectifs Évaluation de la radiothérapie conformationnelle avec modulation d’intensité (RCMI) en pratique de routine pour les cancers du cavum. Patients et méthodes Entre mars 2004 et juillet 2013, 49 patients, dont 82 % atteints d’un cancer du cavum indifférencié et 88 % d’une infection par le virus d’Epstein Barr, ont reçu une RCMI pour dans notre institution. L’âge moyen était de 51 ans (21–82 ans). La majorité des cancers (45 %) était de stade III, 33 % étaient de stade II, 20 % de stade IVA et 2 % de stade IVB (selon la classification de l’American Joint Committee on Cancer, AJCC, de 2010). Une chimiothérapie néoadjuvante par taxotère, cisplatine et 5-fluoro-uracile (TPF) a été délivrée à 37 % des patients. Une chimiothérapie concomitante a été administrée à 86 % des patients, il s’agissait essentiellement de cisplatine à la dose 100 mg/m 2 les première, quatrième et septième semaines de l’irradiation (deux tiers des patients). Résultats Durant l’irradiation, il a été observé 35 % de cas de toxicité de grade II, 35 % de grade III et 8 % de grade IV. La perte de poids moyenne était de 6,5 kg. Alors que 96 % des patients avaient une alimentation orale avant radiothérapie, ils n’étaient plus que 14 % à la fin du traitement (86 % des patients supplémentés l’étaient par gastrostomie endoscopique percutanée, 7 % par sonde nasogastrique et 7 % par voie parentérale). Le suivi médian est de 37 mois. À 5 ans, la probabilité de survie globale estimée était de 91 % et celle de survie sans progression de 79 %. Sept cancers ont rechuté, trois localement et cinq à distance. Deux récidives locales ont été rattrapées par irradiation stéréotaxique. La toxicité tardive observée était de grade II dans 16 % des cas, de grade III dans 16 % et 0 % de grade IV. À distance, 94 % des patients ont repris une alimentation orale normale. Conclusion L’analyse de ces résultats a confirmé l’excellent taux de contrôle offert par la RCMI dans les cancers du cavum au prix d’un taux de toxicité tardive acceptable. Le suivi nutritionnel en cours et au décours du traitement apparaît essentiel. [ABSTRACT FROM AUTHOR]