Metastatic melanoma: results of 'classical' second-line treatment with cytotoxic chemotherapies.

BACKGROUND: Metastatic melanoma is one of the most aggressive tumours, with a median survival that does not exceed 12 months. None of the cytotoxic first-line therapies have shown survival benefit in randomised clinical trials. OBJECTIVE: To describe clinical benefit of second-line cytotoxic chemotherapy in the second line of treatment for metastatic melanoma. METHODS: In a retrospective study, we analyse the outcome of patients with metastatic melanoma who had received two lines or more of cytotoxic treatments in four French dermato-oncology departments between 1999 and 2009. RESULTS: We describe the outcomes for 109 patients. Most of these patients received dacarbazine for the first line of chemotherapy and fotemustine for the second line of chemotherapy (67.0 and 64.2%, respectively). A clinical benefit was observed in 24.1% of the patients and overall survival was 4.1 months after the second-line treatment. At least 23.8% of patients suffered from grade 3 or 4 toxicities. The presence of more than two sites of metastasis and an M1c staging according to the AJCC classification represented negative predictive factors of clinical benefit. CONCLUSION: This study shows the modest benefit of a second line of cytotoxic chemotherapy in a nonselected population. If eligible, these patients should be proposed for ongoing clinical trials or for targeted therapies.

In vitro demonstration of synergy/additivity between (188)rhenium and sorafenib on hepatoma lines: preliminary results.

BACKGROUND: Hepatocellular carcinoma is generally diagnosed at advanced stages, for which only palliative treatments are possible by intra-arterial route or by targeted therapies. Among these treatments, metabolic radiotherapy using (90)-yttrium or (188)Re and sorafenib are two options adopted in monotherapy. MATERIALS AND METHODS: We address the question of a possible synergy arising from the combination of these two treatments. Two primary malignant hepatoma cell lines, N1S1 (murine HCC) and HepG2 (human hepatoblastoma) were treated in media containing increasing concentrations of sorafenib with/without (188)Re to assess the cellular toxicities of each treatment alone and in combination. The combination index method was used to look for synergy or additivity. RESULTS: A synergistic advantage of a treatment combining (188)Re and sorafenib is shown in vitro on hepatoma cell lines. CONCLUSION: This combined approach is promising and now needs to be confirmed by more complex in vitro models integrating the tumoral stroma, as well as by in vivo studies.

Chemotherapy for inoperable advanced or metastatic cholangiocarcinoma: retrospective analysis of 78 cases in a single center over four years.

BACKGROUND: Systemic chemotherapy is the treatment of choice for inoperable (advanced or metastatic) cholangiocarcinoma. According to phase II and III trials, regimens combining 5-fluorouracil (5FU) or gemcitabine with a platinum salt have provided an overall response rate of 12-50% with a median overall survival of 5-16 months. METHODS: This was a retrospective analysis of 78 consecutive cases of inoperable cholangiocarcinoma treated by palliative chemotherapy from July 2005 to November 2009 in one center. We firstly aimed to evaluate the impact of palliative chemotherapy in terms of survival and secondly to analyze possible related prognostic factors. RESULTS: This cohort included 25 female and 53 male patients, with a mean age of 60.8 ± 11.4 years. Intrahepatic and extrahepatic cholangiocarcinoma were observed in 57 and 21 patients, respectively. First-line chemotherapy regimens were as follows: gemcitabine (n = 7), gemcitabine plus oxaliplatin (with or without cetuximab; n = 62) and 5FU plus cisplatin (n = 9). None of the patients achieved a complete response. The partial response rate was 35.9% (27/78), and the stable disease rate was 26.9% (21/78), giving a disease control rate of 62.8%. At the time of this analysis, with a median follow-up of 18 months, 13 patients were survivors. Median overall survival was 10 months [95% confidence interval (CI) 7-12], and median progression-free survival was 7 months (95% CI 6-8). Upon univariate analysis, only the distribution of the disease was significantly linked with prognosis, with a median overall survival of 10 months (95% CI 10-24) for solitary tumors versus 7 months (95% CI 6-11) in the case of infiltrative or multifocal tumors (p = 0.039). CONCLUSION: The disease control rate, overall survival and progression free-survival in this single-center retrospective study were in agreement with earlier reports. Specific features of this cohort were a large proportion of cholangiocarcinoma with associated cirrhosis (n = 30/78, 38.5%), mostly intrahepatic (n = 25/30, 83.5%). This confirms the increasing incidence of intrahepatic localization and the epidemiological link recently reported between intrahepatic biliary tract carcinoma and cirrhosis.

[Retrospective analysis of 24 recurrent glioblastoma after chemoradiation and treated with nitrosoureas or irinotecan and bevacizumab]. / Analyse rétrospective de 24 glioblastomes récidivant après radiochimiothérapie concomitante et traités par nitrosourées ou par l'association irinotécan et bévacizumab.

Despite progress in the initial management of glioblastoma (GB), the vast majority of patients will experience recurrence within 2-3 years. The medical treatment of these recurrences is being modified by the use of antiangiogenic therapies. Twenty-four patients, who relapsed from GB after chemoradiation followed by adjuvant temozolomide in Rennes, were treated by conventional chemotherapy (nitrosourea) or by the combination of irinotecan and bevacizumab. In this retrospective analysis, overall survival from diagnosis of recurrence was significantly longer in patients treated with the combination of bevacizumab and irinotecan than with nitrosourea (5 months versus 11.5 months). The combination of irinotecan and bevacizumab appeared to provide clinical benefit to patients with recurrent GB.

Cementoplasty for painful bone metastases: a series of 42 cases.

The aim of this study is to assess the interest of cementoplasty in the management of bone metastases, based on a retrospective study involving 42 cementoplasty procedures. The median age of the patients is 59 years, with 24 women (57%) and 18 men, all of them presenting with an advanced disease. The cementoplasty was situated in long bones (ten patients), dorsal or lumbar vertebrae (13) and flat bones (20). The principal indication was pain, sometimes with consolidation. The intensity of pain decreases between the day before and the month following the treatment (P = 0.04) among the 25 patients who had pain assessment before and after the procedure. We note 57% good results (24 patients), 9.5% failures (4 patients), and 31% with partial results (13 patients), that is, a total of 88% with "partial or full" alleviation. 16 patients out of 22 (73%) who were no longer able to walk (because of the pain or risk of fracture) were able to resume walking. We observed in this series 40.5% of complications, all of them benign. Cementoplasty improves the quality of life of patients with bone metastases, by decreasing the pain in 88% of cases and allowing the resumption of walking in almost three-quarters of the patients who had lost the ability to walk.

[Breast carcinoma metastasis into a renal cell carcinoma]. / Métastase d'un carcinome mammaire dans un carcinome rénal.

We report the case of a patient carrying a right breast carcinoma whose imaging exams showed lung and bone metastasic release, and incidentally synchronous right renal tumor. Histologic examination of the renal tumor found a mammary carcinoma metastasis into a clear renal cell carcinoma. This is the second case report of breast cancer with metastasis in a resected renal clear cell carcinoma.

Impressive efficacy of sorafenib in a patient with an hepatocellular carcinoma and a portal vein thrombosis associated with a metastatic ENT cancer.

Sorafenib, a new antiangiogenic and antiproliferative agent, is currently used for hepatocellular and renal cell carcinoma. We report here the case of a patient with two cancers, a locally advanced cancer of the piriform sinus and a hepatocellular carcinoma, who was given sorafenib. Tumor response of both cancers might suggest that sorafenib could be effective against head and neck cancer.

Clubbing and hypertrophic osteoarthropathy in two patients taking long-term bevacizumab for metastatic colorectal cancer.

INTRODUCTION: The authors report two cases of young patients who developed clubbing and hypertrophic osteoarthropathy in one case or lung diffusion disorder in the second, after a long-term use of bevacizumab plus chemotherapy in a palliative setting of metastatic colorectal cancer. DISCUSSION: We propose that patients on long-term bevacizumab be examined for clubbing and undergo respiratory function tests and that this would be studied prospectively before beginning trials in evaluating this monoclonal antibody given for 2 years in an adjuvant setting.

Usefulness of chemotherapy beyond the second line for metastatic breast cancer: a therapeutic challenge.

PURPOSE: Several lines of chemotherapy can be proposed for patients with metastatic breast cancer, but beyond the second line, agreement is lacking concerning the most appropriate therapeutic strategy. METHODS: We conducted a retrospective analysis of the files of 162 patients, who had received at least 3 lines of chemotherapy (CT3) for metastatic breast cancer during a 5-year period (2000-2004), in order to analyze management practices and search for factors affecting survival from CT3 and predictive factors of non-progressive disease (NPD) after CT3. RESULTS: Multivariate analysis identified seven factors which had a positive influence on survival from CT3 (SBR grade I, absence of adjuvant hormone therapy, free interval >or=2 years, absence of cerebromeningeal metastasis before CT, unique focus at initiation of CT3, use of polychemotherapy for CT2, and complete response to CT1 or CT2) and two predictive factors of NPD (histology and drug group used for CT3). CONCLUSIONS: These factors should help determine the appropriate strategy for proposing a third line of chemotherapy.

Prognosis for isolated skin recurrence after breast cancer treated by mastectomy.

UNLABELLED: Isolated skin recurrence after mastectomy (ISRAM) for breast cancer is a rare event for which treatment is difficult and subject to debate. PATIENTS AND METHODS: The records of 75 patients presenting with ISRAM were reviewed retrospectively. The factors liable to affect recurrence prognosis were analyzed, and included both factors related to the primary tumor and its treatment and those related to the recurrence itself. RESULTS: The size of the primary tumor is correlated with the inflammatory nature of the recurrence as well as overall survival. Metastatic lymph node involvement also affects the risk of inflammatory recurrence and is correlated with overall survival. Salvage mastectomy for local recurrence after primary breast-conserving surgery followed by ISRAM has a poor prognosis in terms of recurrence-free survival, and chest wall radiotherapy after primary mastectomy reduces the risk of metastatic development after ISRAM. When confronted with ISRAM, 2 factors affect prognosis: the inflammatory nature of the recurrence impairs overall survival and chest wall radiotherapy reduces the risk of secondary systemic disease. CONCLUSION: these results underline the importance of good local control when treating the primary tumor (to reduce the risk of ISRAM occurrence, and improve its prognosis if it occurs) and the advantage of locoregional and systemic treatment in the presence of ISRAM and in particular its inflammatory presentation.

Management of esophageal carcinoma associated with cirrhosis: a retrospective case-control analysis.

Objectives. Esophageal carcinoma and cirrhosis have the overlapping etiologic factors. Methods. In a retrospective analysis conducted in 2 Breton institutions we wanted to asses the frequency of this association and the outcome of these patients in a case-control study where each case (cirrhosis and esophageal cancer) was paired with two controls (esophageal cancer). Results. In a 10-year period, we have treated 958 esophageal cancer patients; 26 (2.7%) had a cirrhosis. The same treatments were proposed to the 2 groups; cases received nonsignificantly different radiation and chemotherapy dose than controls. Severe toxicities and deaths were more frequent among the cases. At the end of the treatment 58% of the cases and 67% of the controls were in complete remission; median and 2-year survival were not different between the 2 groups. All 4 Child-Pugh B class patients experienced severe side effects and 2 died during the treatment. Conclusions. This association is surprisingly infrequent in our population! Child-Pugh B patients had a dismal prognosis and a bad tolerance to radiochemotherapy; Child-Pugh A patients have the same tolerance and the same prognosis as controls and the evidence of a well-compensated cirrhosis has not modified our medical options.