Chemotherapy in epithelial ovarian cancer.

Epithelial ovarian cancer is the most common type of ovarian cancer; usually occurs in women older than 50years, and because 75% of cases are diagnosed at stage III or IV it is associated with a poor prognosis. Treatment of ovarian cancer is based on the integration of surgery and chemotherapy. Chemotherapy plays a major role both in the adjuvant treatment and in the care of patients with advanced disease. Several active drugs have been introduced in the treatment of ovarian cancer in the last decades and novel targets and agents are under evaluation.

First-line treatment of advanced ovarian cancer: current research and perspectives.

Epithelial ovarian cancer is the fourth biggest cause of cancer-related death in women. Over recent decades, improvements have been made in treatment outcome in terms of response rate and survival. To date, intensive surgical staging and cytoreduction, followed by primary chemotherapy with the carboplatin-paclitaxel regimen, are considered the gold standard for the management of this disease. Nevertheless, despite good initial response to systemic therapy after optimal debulking surgery, the long-term survival remains poor, with a high risk of recurrence. Furthermore, medical therapy of ovarian cancer impacts quality of life owing to the common occurrence of chemotherapy side effects, such as alopecia, neurotoxicity and fatigue. In order to improve the efficacy and reduce the toxicity of first-line chemotherapy, more than 10,000 women have been involved in worldwide randomized trials in the last 10 years. Several treatment alternatives have been investigated, such as intraperitoneal chemotherapy, alternative doublets and triplet regimens, in the effort to find an optimal first-line treatment strategy. In this review we discuss the results of these trials, the recent progresses and the most important ongoing studies, including those with emerging target and biological agents.

Second-line intra-arterial chemotherapy in advanced pancreatic adenocarcinoma.

The present study was conducted to evaluate activity and toxicity of the FLEC (folinic acid 100 mg/m2; 5-fluorouracil 1000 mg/m2; carboplatin 300 mg/m2; epirubicin 60 mg/m2) schedule as second-line treatment for progressive locally advanced or metastatic pancreatic cancer (LAMPC). FLEC was administered every 3 weeks with an angiographic catheter introduced into the tumor vascular bed. Thirty-two patients were enrolled. Twenty patients had a PS of 2. Twenty-five patients had metastatic disease to liver. Seven (21.9%) partial responses were observed (WHO criteria). Fifteen patients (46.9%) had stable disease and ten patients (31.2%) had progressive disease. The median OS from the diagnosis was 11.8 months. PS (p=0.0308) and pain (WHO scale, p=0.0222; analogic scale, p=0.0446) significantly improved after therapy. No patient discontinued treatment because of toxicity (NCI-CTC criteria). The current study shows that intraarterial chemotherapy is a good therapeutic option in second-line treatment of LAMPC.

Medical treatment of gastrointestinal stromal tumors: state of the art and future perspectives.

Gastrointestinal Stromal Tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract, and it is characterized by the occurrence, in > 90 % of cases, of a gain of function mutation in the c-kit proto-oncogene. STI-571 (imatinib mesylate), a selective KIT tyrosine kinase inhibitor, has changed the natural history of this disease, since it has shown high effectiveness in metastatic GIST, and it is currently under investigation also in the adjuvant and neoadjuvant setting. Mechanisms of resistance to imatinib mesylate include both de novo, and, more frequently, acquired resistance, which may occur after several months of drug administration and possibly depends, in most cases, upon an acquired second mutation. In order to overcome imatinib mesylate resistance, the addition of other drugs may be considered in patients who have less than an optimal response to imatinib mesylate monotherapy. Investigational agents that are being studied in this setting include the mammalian target of rapamycin (mTOR) inhibitor RAD 001 and the protein kinase C inhibitor PKC412. In addition, other KIT tyrosine kinase inhibitors with anti-VEGF receptor inhibitory activity, such as SU11248, PTK787/ZK787 and AMG 706, are currently being explored as second line monotherapy for imatinib mesylate-resistant GIST. Finally, another new drug, ecteinascidin (ET-743), that blocks cell cycle progression in G2/M phase through a p53-independent apoptotic mechanism, has shown important preclinical and clinical activity against a number of human solid tumors, including GIST.