Gastrosplenic Fistula From Hodgkin's Lymphoma

Background: Recent data suggest that capecitabine may have little efficacy in women with metastatic triple negative breast cancer (TNT). We have therefore retrospectively analysed capecitabine outcome in the TN subgroup of patients with locally advanced or metastatic breast cancer treated in our unit. Patients and Methods: All TNT patients on our prospectively maintained database with locally advanced or metastatic breast cancer who were given capecitabine as 1st-, 2nd- or 3rd-line chemotherapy were assessed for response and outcome. Results: In total, 363 patients with locally advanced or metastatic breast cancer treated with capecitabine were identified. Eighty-nine (24.5%) patients had TNT and of these, 47 (53%) patients received capecitabine as 1st-line treatment and 42 (47%) as 2nd- or 3rd-line treatment. The overall response rate was 21% (95% CI: 13–31%), including 1 (1%) complete response (CR) and 18 (20%) partial responses (PR). Another 11 (12%) patients maintained stable disease (SD) for ≥6 months. An overall disease control (CR + PR + SD) was, therefore, achieved in 30 (33%) patients. The median time to disease progression was 11 weeks (95% CI: 9–13) and the median overall survival was 39 weeks (95% CI: 33–45). Median response duration was 22 weeks (95% CI: 18–25). No significant difference in efficacy was seen between 1st- and 2nd-/3rd-line treatment. Conclusion: Capecitabine is a treatment option for patients with TN tumours in advanced disease including 1st line and 2nd/3rd line.

Section: Discussionmentioning

confidence: 99%

Is Capecitabine Efficacious in Triple Negative Metastatic Breast Cancer?

Kotsori¹,

Dolly²,

Sheri³

et al. 2010

“…Brivanib has demonstrated activity against several types of solid tumors in clinical trials and is currently under investigation in many cancer types [35]. Data from a single-arm phase II study in advanced HCC have demonstrated brivanib’s antitumor activity in both frontline [36] and second-line [37] settings (table 3). Phase III trials with brivanib are ongoing, including a study comparing brivanib with sorafenib in the frontline setting, a study in patients who have failed prior sorafenib and a study combining brivanib treatment with transarterial chemoembolization in patients with unresectable HCC.…”

Section: Novel Fgfr-targeted Multikinase Inhibitors For the Treatmentmentioning

confidence: 99%

Targeting Fibroblast Growth Factor Receptor Signaling in Hepatocellular Carcinoma

Cheng¹,

Shen²,

Zhu

2011

Hepatocellular carcinoma (HCC) is the primary type of liver cancer, and both the age-adjusted incidence and mortality of HCC have steadily increased in recent years. Advanced HCC is associated with a very poor survival rate. Despite accumulating data regarding the risk factors for HCC, the mechanisms that contribute to HCC tumorigenesis remain poorly understood. Signaling through the fibroblast growth factor (FGF) family is involved in fibrosis and its progression to cirrhosis of the liver, which is a risk factor for the development of HCC. Furthermore, several alterations in FGF/FGF receptor (FGFR) signaling correlate with the outcomes of HCC patients, suggesting that signaling through this family of proteins contributes to the development or progression of HCC tumors. Currently, there are no established systemic treatments for patients with advanced HCC in whom sorafenib treatment has failed or who were unable to tolerate it. Recently, several multikinase inhibitors that target FGFRs have demonstrated some early evidence of antitumor activity in phase I/II trials. Therefore, this review discusses the molecular implications of FGFR-mediated signaling in HCC and summarizes the clinical evidence for novel FGFR-targeted therapies for HCC currently being studied in clinical trials.

“…Molecular-target- ing drugs for liver cancer and their target molecules are shown in figure 4[15]. The results of clinical trials of molecular-targeted agents for HCC are summarized in table 3[16,17,18,19,20,21,22,23,24,25,26,27]. …”

Section: Clinical Trial Status Of Molecular-targeted Agents For Hccmentioning

confidence: 99%

Positioning of a Molecular-Targeted Agent, Sorafenib, in the Treatment Algorithm for Hepatocellular Carcinoma and Implication of Many Complete Remission Cases in Japan

Kudo

Ueshima

2010

Sorafenib, a molecular-targeted agent that inhibits tumor cell proliferation and angiogenesis by inhibiting RAF serine-threonine kinase and VEGF, PDGF, Flt-3, c-Kit receptor tyrosine kinase, was approved in Europe and North America in 2007 and in Japan on May 20, 2009. In the 10 months since its approval, sorafenib has been prescribed for more than 3,700 patients with advanced hepatocellular carcinoma (HCC), and its efficacy has been confirmed in many cases. According to the consensus statements of the Japan Society of Hepatology in 2010, sorafenib is recommended for advanced HCC with extrahepatic spread or major vascular invasion such as invasion of the 1st branch of the portal vein or the main portal branch of the portal vein in patients with Child-Pugh A liver function. In addition to that, transcatheter arterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) refractory HCC patients with Child-Pugh A liver function are also candidates of sorafenib monotherapy as a second-line treatment option. To date, 15 cases with complete remission (CR) to sorafenib in metastatic advanced HCC patients have been reported in Japan, an event that is rarely reported in other countries. Of the 90 cases treated by ourselves, 2 achieved CR. Factors indicating systemic cancer spread, including multiple liver lesions, lymph node metastases, adrenal metastases, lung metastases and vascular invasion, were completely absent in both cases of CR by 2 and 1 year, respectively. Similarly, three tumor markers (AFP, PIVKA-II, and AFP-L3) completely returned to normal values. Although cases of CR are rare, it seems that there might be racial differences in terms of gene mutations. Clinical trials for other molecular-targeted agents, including sunitinib, brivanib, or linifanib, are ongoing and their outcomes are eagerly awaited. According to a subanalysis of the SHARP study, it is expected that sorafenib in combination with resection, ablation, TACE or HAIC will markedly prolong the overall survival in early-, intermediate- and advanced- stage HCCs.