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Background Results from a phase 2 trial of the TPEx chemotherapy regimen (docetaxel-platinum-cetuximab) showed promising results, with a median overall survival of 14.0 months in first-line recurrent or metastatic head and neck squamous-cell carcinoma (HNSCC). We therefore aimed to compare the efficacy and safety of the TPEx regimen with the standard of care EXTREME regimen (platinum-fluorouracil-cetuximab) in this setting. Methods This was a multicentre, open-label, randomised, phase 2 trial, done in 68 centres (cancer centres, university and general hospitals, and private clinics) in France, Spain, and Germany. Eligible patients were aged 18-70 years with histologically confirmed recurrent or metastatic HNSCC unsuitable for curative treatment; had at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1; and had an Eastern Cooperative Oncology Group (ECOG) performance status of 1 or less. Participants were randomly assigned (1:1) using the TenAlea website by investigators or delegated clinical research associates to the TPEx regimen or the EXTREME regimen, with minimisation by ECOG performance status, type of disease evolution, previous cetuximab treatment, and country. The TPEx regimen consisted of docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2), both intravenously on day 1, and cetuximab on days 1, 8, and 15 (intravenously 400 mg/m(2) on day 1 of cycle 1 and 250 mg/m(2) weekly subsequently). Four cycles were repeated every 21 days with systematic granulocyte colony-stimulating factor (G-CSF) support at each cycle. In case of disease control after four cycles, intravenous cetuximab 500 mg/m(2) was continued every 2 weeks as maintenance therapy until progression or unacceptable toxicity. The EXTREME regimen consisted of fluorouracil 4000 mg/m(2) on day 1-4, cisplatin 100 mg/m(2) on day 1, and cetuximab on days 1, 8, and 15 (400 mg/m(2) on day 1 of cycle 1 and 250 mg/m(2) weekly subsequently) all delivered intravenously. Six cycles were delivered every 21 days followed by weekly 250 mg/m(2) cetuximab as maintenance therapy in case of disease control. G-CSF support was not mandatory per the protocol in the EXTREME regimen. The primary endpoint was overall survival in the intention-to-treat population; safety was analysed in all patients who received at least one dose of chemotherapy or cetuximab. Enrolment is closed and this is the final analysis. This study is registered at ClinicalTrials.gov, NCT02268695. Findings Between Oct 10, 2014, and Nov 29, 2017, 541 patients were enrolled and randomly assigned to the two treatment regimens (271 to TPEx, 270 to EXTREME). Two patients in the TPEx group had major deviations in consent forms and were not included in the final analysis. Median follow-up was 34.4 months (IQR 26.6-44.8) in the TPEx group and 30.2 months (25.5-45.3) in the EXTREME group. At data cutoff, 209 patients had died in the TPEx group and 218 had died in the EXTREME group. Overall survival did not differ significantly between the groups (median 14.5 months [95% CI 12.5-15.7] in the TPEx group and 13.4 months [12.2-15.4] in the EXTREME group; hazard ratio 0.89 [95% CI 0.74-1.08]; p=0.23). 214 (81%) of 263 patients in the TPEx group versus 246 (93%) of 265 patients in the EXTREME group had grade 3 or worse adverse events during chemotherapy (p

International audience; Spermatic cord sarcomas are rare tumors for which the most important is the initial diagnostic procedure. They are frequently misdiagnosed after surgery for inguinal hernia, inguinal lymphadenectomy or testicular malignancy. Any clinical suspicion has to lead to perform imaging with MRI and a core needle biopsy in order to obtain an accurate preoperative diagnosis. Liposarcoma and leiomyosarcoma are the most common histological subtypes in elderly adults, rhabdomyosarcoma in children or in young adults. A CT scan will precede the treatment in order to look for distant metastasis and abdominal involvement. The therapeutic strategy as well as the surgical planning are then adapted to the histological, morphological and prognostic factors. Surgery is the cornerstone for the treatment of spermatic cord sarcoma. The minimum requirements for the surgical procedure are a wide excision of the tumor en bloc with radical orchidectomy, excision of the ipsilateral scrotum and high spermatic cord ligation. It could be enlarged to the anterior abdominal wall and adjacent organs some required a soft tissue flap. Spermatic cord sarcoma and trunk wall sarcoma have the same prognosis for which local recurrence could significantly decrease survival. Consequently, surgeon in charge with these tumors has to be familiar with soft tissue sarcoma and the management of these patients must be carried out under the supervision of a multidisciplinary team within the Netsarc network.; Le sarcome du cordon spermatique est une pathologie rare pour laquelle la prise en charge initiale est d’importance primordiale. Le diagnostic est souvent découvert a posteriori après une chirurgie pour cure de hernie inguinale, pour suspicion de cancer du testicule ou après exérèse d’une adénopathie inguinale. Toute suspicion clinique doit donc faire l’objet d’une imagerie par résonance magnétique (IRM) et d’une biopsie percutanée sous contrôle radiologique dans le but d’obtenir un diagnostic préopératoire précis. Les histologies les plus fréquentes sont le liposarcome et le léiomyosarcome chez l’adulte âgé, le rhabdomyosarcome chez l’enfant et l’adulte jeune. Un bilan d’extension intra-abdominal et à distance par scanner précédera le traitement. La stratégie thérapeutique de même que la planification chirurgicale sont ensuite adaptées aux paramètres histologiques, morphologiques et pronostiques. La chirurgie est la pierre angulaire du traitement des sarcomes du cordon spermatique. Le geste minimal requis est l’exérèse de la tumeur en bloc avec la réalisation d’une orchidectomie totale, l’exérèse du cordon spermatique et la ligature des vaisseaux spermatiques à l’orifice inguinal profond. Elle peut être élargie à la paroi abdominale et aux organes de voisinage et nécessiter si besoin une reconstruction par lambeau. Le pronostic des sarcomes du cordon spermatique est équivalent à celui des sarcomes du tronc dont l’évolutivité locale est péjorative pour la survie des patients. De fait, l’exérèse doit être réalisée par un chirurgien ayant l’expertise des problématiques liées à la chirurgie des sarcomes au sein d’un centre spécialisé du réseau Netsarc.

International audience

In the LUX-Head & Neck 1 study, older age (≥65 years) did not adversely affect the benefit in patient-reported outcomes and antitumor activity observed with afatinib over methotrexate, which was consistent with findings from the overall population. Safety in older patients was also consistent with the overall population, favoring afatinib in terms of fewer dose reductions and discontinuations., 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

BACKGROUND The objective of the current study was to evaluate the response rate, survival, and toxicity of treatment with cisplatin and high dose intravenous continuous infusion interleukin-2 (IL-2) with or without interferon-α-2a (IFN) in patients with metastatic melanoma. METHODS One hundred and seventeen patients with metastatic melanoma randomly were assigned to receive cisplatin, 100 mg/m2, followed after a 3-day rest period by IL-2, 18 × 106 IU/m2, on Days 3-6 and Days 17-21 (Arm 1) or cisplatin and IL-2 using an identical schedule plus subcutaneous IFN, 9 × 106 U, 3 times a week during IL-2 administration (Arm 2). In the absence of disease progression or undue toxicity, the cycle could be repeated on Day 29. Patients who responded after two cycles eventually could receive a third cycle. One hundred and one patients were evaluable for toxicity and efficacy. RESULTS On treatment Arm 1, 3 patients (6%) achieved a complete response (CR) and 5 patients (10%) achieved a partial response (PR) with a median response duration of 3.8 months for the CRs and 8.7 months for the PRs. On treatment Arm 2, 2 patients (3%) achieved a CR (durations of 5.9 and 33.1 months, respectively) and 11 patients (21%) a PR with a median response duration of 8.3 months. The median durations of overall survival were 10.4 months (range, 1.1-39.7+ months) and 10.9 months (range, 0.5-38.1+ months) for treatment Arms 1 and 2, respectively. The toxicity profile was consistent with the known side effects of this IL-2 intravenous regimen combined with cisplatin chemotherapy and IFN. Toxicity was more pronounced in treatment Arm 2 compared with treatment Arm 1. There were 2 and 4 patients, respectively, in treatment Arms 1 and 2 who died within 28 days after completion of treatment. CONCLUSIONS The observed overall response rates of 16% and 25% in treatment Arms 1 and 2, respectively, is lower than that expected with biochemotherapy; despite the fact that the objective of the trial was not to show any difference between the 2 treatment arms, our results indicate that the addition of IFN, at the dose and schedule used in this trial, fails to improve the activity of a cisplatin/IL-2 regimen significantly in patients with metastatic melanoma. Although response rates were relatively low, the median overall survival was nearly 1 year in both groups. Cancer 1999;85:1060–6. © 1999 American Cancer Society.

International audience; 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/m(2), day 1-5), ifosfamide (2.5 g/m(2), day 1-4), carboplatin [area under the curve (AUC) 5/day 2-4] and etoposide (300 mg/m(2), 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.

Carcinomas of unknown primary (CUP) are highly malignant diseases which have poor prognosis. We report in the present study the impact on survival and toxicity of a salvage chemotherapy with 5-Fluorouracil (5-FU) and leucovorin (LV) in 25 patients with CUP who failed first-line treatment with cisplatin-based regimens. Chemotherapy was a bimonthly regimen of intravenous LV 200 mg/m2 as a 2-hour infusion followed by a 1-hour bolus 5-FU 400 mg/m2 and a 22-hour continuous infusion 5-FU 600 mg/m2 for 2 consecutive days every 2 weeks. The median number of cycles per patient was 4. Overall toxicity was mild. No objective response was observed. From the start of second-line chemotherapy, the median overall survival was 3 months. The median overall survival from diagnosis was 9 months. Second-line chemotherapy with 5-FU/LV has no impact on survival in patients with CUP.