Crizotinib in the Treatment of Non-Small-Cell Lung Carcinoma.

Crizotinib in the treatment of non-small-cell lung carcinoma.

Contemp Oncol (Pozn). 2012; 16(6): 480-484
P?u?a?ski A, Piórek A, Krzakowski M

Recent studies have demonstrated the benefit of EGFR tyrosine kinase inhibitors in the treatment of advanced non-small-cell lung cancer (NSCLC). The role of activation of the anaplastic lymphoma kinase (ALK) pathway and the presence of the fusion gene EML4-ALK are new molecular targets in studies into the pathogenesis and treatment of NSCLC. ALK gene rearrangement is observed in 3-5% of NSCLC patients. Crizotinib is an oral inhibitor of ALK kinase activity, approved for the treatment of NSCLC patients with ALK gene rearrangement. Crizotinib treatment has resulted in a progression-free survival of 7-10 months with 50-60% objective response rate. The present paper gives an overview of literature reports on the role of crizotinib in the treatment of NSCLC patients harbouring a molecular defect in the ALK gene. Molecular diagnosis of ALK-associated aberrations, results of clinical trials of different phases assessing the efficacy and safety profile of crizotinib are also discussed. Attention is given to the likely causes of drug resistance and management strategies in patients with treatment failure. HubMed – drug


Thrombocytosis in patients with pancreatic cancer treated with gemcitabine – does it have clinical significance? Description of 6 cases.

Contemp Oncol (Pozn). 2012; 16(4): 353-355
Swieboda-Sadlej A, Kraj L, Krawczyk J, Nita E, Dwilewicz-Trojaczek J

Gemcitabine is a cytostatic drug from the pyrimidine antimetabolite group. It is used in treatment of some neoplasms, among them inoperable pancreatic cancer. The most common undesirable effects of gemcitabine include pancytopenia, with thrombocytopenia associated with gemcitabine’s myelosuppressive activity. This study contains a description of six cases of patients with pancreatic cancer treated with gemcitabine, who – contrary to expectations – showed increased levels of thrombocytes. The number of thrombocytes ranged from 424 to 1059 × 109 (mean 470 × 109). It was highest during the 2(nd) and 3(rd) chemotherapy cycles and it normalized after completion of treatment. One patient suffered from a cardiac infarction on the 15(th) day of the 3(rd) cycle of treatment, despite a normal level of thrombocytes on the day; however, the patient indicated thrombocytosis on the 1(st) day of the cycle. No thromboembolic complications were observed in the remaining patients. These patients were not subjected to any antithrombotic prophylaxis. The mechanism by which thrombocytosis occurs after administration of gemcitabine and the clinical significance of this fact remain unknown. HubMed – drug


Bortezomib has little ex vivo activity in chronic myeloid leukemia: individual tumor response testing comparative study in acute and chronic myeloid leukemia.

Contemp Oncol (Pozn). 2012; 16(3): 210-214
Styczy?ski J, Gil L, Czy?ewski K, Ko?odziej B, Kury?o-Rafi?ska B, Lewandowski K, Gniot M, Lewandowska M, Komarnicki M, Wysocki M

Resistance to imatinib is one of the most important issues in treatment of chronic myeloid leukemia (CML) patients. The objective of the study was to analyze the ex vivo drug resistance profile to bortezomib and 22 other antileukemic drugs, including three tyrosine kinase inhibitors (TKIs), in CML in comparison to acute myeloid leukemia (AML).A total of 82 patients entered the study, including 36 CML and 46 AML adults. Among CML patients, 19 had advanced disease, 16 were resistant to imatinib, and 6 had ABL-kinase domain mutations. The ex vivo drug resistance profile was studied by the MTT assay.CML CELLS WERE MORE RESISTANT THAN AML BLASTS TO THE FOLLOWING DRUGS: prednisolone, vincristine, doxorubicin, etoposide, melphalan, cytarabine, fludarabine, thiotepa, 4-HOO-cyclophosphamide, thioguanine, bortezomib, topotecan, and clofarabine. CML cells were 2-fold more sensitive to busulfan than AML cells. CML patients with clinical imatinib resistance had higher ex vivo resistance to vincristine, daunorubicin, etoposide, and busulfan. No significant differences to all tested drugs, including TKIs, were observed between CML patients with non-advanced and advanced disease. CML patients with mutation had higher ex vivo resistance to vincristine, idarubicin, thiotepa, and busulfan.CML cells are ex vivo more resistant to most drugs than acute myeloid leukemia blasts. Busulfan is more active in CML than AML cells. In comparison to AML cells, bortezomib has little ex vivo activity in CML cells. No differences between CML subgroups in sensitivity to 3 tested TKIs were detected. HubMed – drug


Chemotherapy-induced polyneuropathy. Part I. Pathophysiology.

Contemp Oncol (Pozn). 2012; 16(1): 72-78
Brzezi?ski K

Chemotherapy-induced peripheral neuropathy (CIPN) is a toxic neuropathy, a syndrome consisting of highly distressing symptoms of various degrees of severity. It includes numbness of distal extremities, long-term touch, heat, and cold dysaesthesia and, in more severe cases, motor impairment affecting daily functioning. Each form of the syndrome may be accompanied by symptoms of neuropathic stinging, burning, and tingling pain. In the case of most chemotherapeutic agents, the incidence and severity of CIPN are dependent on the cumulative dose of the drug. The syndrome described is caused by damage to the axons and/or cells of the peripheral nervous system. Chemotherapeutic agents have distinct mechanisms of action in both neoplastic tissue and the peripheral nervous system; therefore, CIPN should not be regarded as a homogeneous disease entity. The present article is an attempt to systematize the knowledge about the toxic effects of chemotherapy on the peripheral nervous system. HubMed – drug