Old Tyrosine Kinase Inhibitors and Newcomers in Gastrointestinal Cancer Treatment.

Gastrointestinal cancer treatment is based more on molecular biology that has provided increasing knowledge about cancer pathogenesis on which targeted therapy is being developed. Precisely, targeted therapy is defined as a "type of treatment that uses drugs, such as monoclonal antibodies or tyrosine kinase inhibitors, to identify and attack specific cancer cells". Nowadays, the United States Food and Drug Administration has approved many targeted therapies for gastrointestinal cancer treatment, as many are in various phases of development as well. In a previous review we discussed the main monoclonal antibodies used and studied in gastrointestinal cancer. In addition to monoclonal antibodies, tyrosine kinase inhibitors represent another class of targeted therapy and following the approval of imatinib for gastrointestinal stromal tumours, other tyrosine kinase inhibitors have been approved for gastrointestinal cancers treatment such as sunitinib, regoragenib, sorafenib and erlotinib. Moving forward, the purpose of this review is to focus on the efficacy data of main tyrosine kinase inhibitors commonly used in the personalized treatment of each gastrointestinal tumour and to provide a comprehensive overview about experimental targeted therapies ongoing in this setting.

An unusual case of spleen metastasis from carcinoma ex pleomorphic adenoma of the parotid gland.

Carcinoma ex pleomorphic adenoma is a rare tumor arising from the salivary glands that spreads through direct extension, through the lymphatic vessels, and, rarely, hematogenously. When distant metastases have been found, they have been reported mainly in the lung. We present an unusual case of carcinoma ex pleomorphic adenoma of the parotid gland with splenic metastases. The patient presented with a primary carcinoma ex pleomorphic adenoma of the parotid gland and he underwent a total parotidectomy with laterocervical lymphadenectomy ipsilateral and adjuvant radiation therapy to the right parotid area. One year later, the patient showed an ipsilateral supraclavicular lymph node recurrence, treated with surgery and radiation therapy. Two more years later, the patient developed lung and splenic lesions, detected through CT and PET. He underwent splenectomy and pathologic assessment of the specimen showed metastatic carcinoma ex pleomorphic adenoma. To our knowledge, there is no reported case of a carcinoma ex pleomorphic adenoma metastasizing to the spleen. Patients treated for carcinoma ex pleomorphic adenoma should be investigated for distant metastases with a long-term follow-up examination for local and distant metastases and new splenic lesions in these patients should be investigated.

Efficacy and safety analysis of once per cycle pegfilgrastim and daily lenograstim in patients with breast cancer receiving adjuvant myelosuppressive chemotherapy FEC 100: a pilot study.

BACKGROUND: Neutropenia is a common toxicity in patients receiving myelosuppressive chemotherapy. In this prospective pilot study, we compared the efficacy and safety profiles of pegfilgrastim administered subcutaneously once per cycle and lenograstim administered subcutaneously daily six times per cycle, for primary neutropenia prophylaxis in women with breast cancer receiving adjuvant anthracycline-based chemotherapy. MATERIALS AND METHODS: Twenty women were enrolled. All patients received epirubicin 100 mg/m(2) with 5-fluorouracil 500 mg/m(2) and cyclophosphamide 500 mg/m(2) on day 1 and every 21 days thereafter, according to the FEC 100 chemotherapy regimen. Eight patients received a single dose of pegfilgrastim on day 2, while 12 patients were treated with daily administration of lenograstim from days five to ten. Absolute neutrophil count and duration of grade 3-4 neutropenia were monitored using seriated blood samples. The incidence of bone pain was evaluated using the visual analog scale (VAS). RESULTS: The incidence of grade 3-4 neutropenia was 75% in patients who received pegfilgrastim, and 25% in patients who received lenograstim. One case of febrile neutropenia was shown in pegfilgrastim patients. The mean duration of grade 3-4 neutropenia was 2 days in pegfilgrastim group versus 1.4 days in the lenograstim group. Bone pain was present in 37.5% of pegfilgrastim patients versus 58.3% of lenograstim patients. The mean duration of bone pain in the pegfilgrastim group was 4 days versus 6 days in the lenograstim group. CONCLUSION: In our experience, a single injection of pegfilgrastim was less effective for controlling neutropenia than six daily injections of lenograstim. The safety profiles of pegfilgrastim and lenograstim were similar with a lower incidence of bone pain in patients treated with pegfilgrastim.

Critical appraisal of bevacizumab in the treatment of metastatic colorectal cancer.

Colorectal cancer is one of the most common cancers worldwide. The prognosis of patients with metastatic colorectal cancer in recent years has increased from 5 months with best supportive care to nearly 2 years with chemotherapy combined with bevacizumab, an antivascular endothelial growth factor monoclonal antibody. New prognostic and predictive biomarkers have been identified to guide chemotherapy in metastatic colorectal cancer, such as KRAS and BRAF oncogenes. However, the status of these oncogenes does not affect the efficacy of bevacizumab, and biomarkers predicting response to treatment with bevacizumab are still lacking. Addition of bevacizumab to regimens based on fluoropyrimidines or irinotecan has been shown to improve overall survival in treatment-naïve patients with metastatic colorectal cancer. Similarly, a significant increase in overall survival rate is achieved by adding bevacizumab to fluoropyrimidines and oxaliplatin in patients with disease progression. Bevacizumab has been found to be effective even when used as third-line therapy and later. In addition, cohort studies have shown that bevacizumab improves survival significantly despite disease progression. Finally, bevacizumab therapy in the neoadjuvant setting for the treatment of liver metastasis is well tolerated, safe, and effective.

Emerging role of cetuximab in the treatment of colorectal cancer.

CRC is the fourth most frequently diagnosed tumor and the second leading cause of cancer death in the United States. KRAS mutations occur in 35-45% of metastatic-CRC and preclude responsiveness to cetuximab or panitumumab. However, less than 20% of KRAS wild-type (wt) patients achieve objective response. Alterations of BRAF/NRAS/ PIK3CA/PTEN, have independently been found to give rise to resistance. The first-line trials with cetuximab chemotherapy are conflicting, because of the many differences among prospective and retrospective evaluations. In neoadjuvant regimens, cetuximab with CT obtained a significant and early increase of the RR. In second-line studies cetuximab improved RR and PFS. In third-line studies cetuximab-irinotecan is associated with a significant advantage in ORR, mTTP and OS. Cetuximab has not reported any benefit neither in adjuvant nor in trials with bevacizumab. In third-line studies cetuximab-irinotecan is associated with a significant advantage in ORR, mTTP and OS. Value of KRAS is questioned, since a high percentage of KRAS-wt patients has no benefit with cetuximab. More and more data on the molecular patterns of these tumors underline their biological complexity. Cetuximab treatment is usually well tolerated. Moreover, toxicity seems to correlate with response to treatment. This patents review focuses on recent advances in the treatment of CRC with cetuximab including several novel therapeutic protocols of intervention.