Rafał Czyżykowski

Nicotine-induced resistance of non-small cell lung cancer to treatment – possible mechanisms

Cigarette smoking is the leading risk factor of lung cancer. Data from several clinical studies suggest that continuation of smoking during therapy of tobacco-related cancers is associated with lower response rates to chemotherapy and/or radiotherapy, and even with decreased survival. Although nicotine--an addictive component of tobacco--is not a carcinogen, it may influence cancer development and progression or effectiveness of anti-cancer therapy. Several in vitro and in vivo trials have evaluated the influence of nicotine on lung cancer cells. The best known mechanisms by which nicotine impacts cancer biology involve suppression of apoptosis induced by certain drugs or radiation, promotion of proliferation, angiogenesis, invasion and migration of cancer cells. This effect is mainly mediated by membranous nicotinic acetylcholine receptors whose stimulation leads to sustained activation of such intracellular pathways as PI3K/Akt/mTOR, RAS/RAF/MEK/ERK and JAK/STAT, induction of NF-κB activity, enhanced transcription of mitogenic promoters, inhibition of the mitochondrial death pathway or stimulation of pro-angiogenic factors. We herein summarize the mechanisms underlying nicotines influence on biology of lung cancer cells and the effectiveness of anti-cancer therapy.

Synchronous primary ovarian and endometrial cancers: a series of cases and a review of literature.

Synchronous cancers account for 0.7-1.8% of all gynecologic cancers. Among them, synchronous ovarian and endometrial cancers are predominant (40-53%). Patients with synchronous cancers have better prognosis than those with single disseminated cancer. We present 10 patients with synchronous ovarian and endometrial cancers who were treated at the Chemotherapy Department of the Medical University of Lodz in 2009-2013. The most often reported symptom of the disease was abnormal vaginal bleeding (6 patients). The range of the patients’ age was 48-62 and the median age was 56. Five patients had stage I of ovarian cancer, single patients had stage IIA, IIB and IIIB, 2 patients had stage IIIC. Three patients had I, 5 – II, and 2 – III stage of endometrial cancer. All patients had endometrioid type of endometrial cancer, 7 of them had also the same histological type of ovarian cancer. All patients had adjuvant chemotherapy because of ovarian cancer, none of them had adjuvant radiotherapy. One patient was lost to follow up. For other patients a median follow up was 13 months (range: 3-53 months). One patient experienced relapse, all patients are alive. Synchronous ovarian and endometrial cancers are usually diagnosed at an earlier stage, have lower histological grade and better prognosis than single cancers. The most common histological type of both endometrial and ovarian cancers is endometrioid carcinoma. The first symptoms reported by our patients and the course of the disease were concordant with data from the literature.

The prognostic impact of neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio in patients with advanced colorectal cancer treated with first-line chemotherapy

Introduction Colorectal cancer is the second most frequently diagnosed malignancy and one of the leading causes of cancer-related death in Poland. Many reports of different types of cancer have indicated that blood count parameters may serve as a source of prognostic or predictive information. Aim To assess the association between these parameters and clinical outcome in patients with advanced colorectal cancer. Material and methods We retrospectively analysed a database of 295 patients with advanced colorectal cancer treated with first-line palliative chemotherapy at our institution from January 2008 to December 2012. Blood-based parameters were measured before the first cycle of treatment. Results The median progression-free survival (PFS) was 6.7 months, and the median overall survival was 17.6 months. A high neutrophil-to-lymphocyte ratio (NLR) and a high platelet-to-lymphocyte ratio (PLR) were associated with a shorter survival (hazard ratio (HR): 1.88, p < 0.0001 for the NLR and HR: 1.39, p = 0.0054 for the PLR), but for the PLR, we observed only a not significant trend toward a worse PFS (HR = 1.25, p = 0.07 for the PLR and HR = 1.55, p = 0.0004 for the NLR). A high lymphocyte-to-monocyte ratio (LMR) was associated with a better prognosis (HR = 0.58, p ≤ 0.0001) and a longer PFS (HR = 0.73, p = 0.011). Conclusions The blood-based parameters are readily available, reliable, and low-cost biomarkers, which can be easily incorporated into routine practice to predict the prognosis in patients with advanced colorectal cancer.

Palliative systemic treatment of patients with pancreatic cancer — should reimbursement of nab-paclitaxel change the current management paradigm?

Pancreatic cancer is associated with poor prognosis. In the majority of patients the disease is diagnosed at an inoperable stage, so palliative chemotherapy is the only possible management. In a highly clinically and biochemically selected subpopulation two chemotherapy multi-drug schemes: FOLFIRINOX regimen and combination of nab-paclitaxel with gemcitabine, are more effective than gemcitabine alone, being the current standard of treatment. As there is a lack of direct comparison between doublet and triplet chemotherapies and the prognosis of patients enrolled to ACCORD 11 and MPACT clinical trials is similar, an attempt at indirect analysis was undertaken. It seems that chemotherapy with the use of FOLFIRINOX regimen prolongs overall survival significantly more and mainly has a beneficial impact on quality of life. In the authors’ opinion, the possibilities of using chemotherapy containing nab-paclitaxel and gemcitabine are quite limited. In patients with worse performance status monotherapy with gemcitabine or best supportive care should remain a standard of management.

Bisphosphonates for the treatment of patients with cancer

Bisphosphonates inhibit osteoclasts activity and therefore reduce bone resorption. The main application of bisphosphonates in patients with cancer involves treatment of hypercalcemia, prevention of cancer treatment-induced bone loss, and decrease of the risk of skeletal-related events in patients with breast cancer or prostate cancer and bone metastases. For some time now there has been an increasing amount of data indicating that treatment with bisphosphonates improves survival of patients with early breast cancer. The activity is restricted to postmenopausal women or premenopausal patients whose treatment involves gonadotropin agonist.

A retrospective evaluation of associations between chronic obstructive pulmonary disease, smoking, and efficacy of chemotherapy and selected laboratory parameters in patients with advanced non-small cell lung cancer

Aim of the study To was to determine the impact of chronic obstructive pulmonary disease (COPD) and active smoking on the efficacy of chemotherapy and complete blood count (CBC) in patients with non-small cell lung cancer (NSCLC). Material and methods The retrospective evaluation included 50 patients with stage IIIB–IV NSCLC, who started cisplatin-based chemotherapy. Peripheral blood CBC values were collected for testing before chemotherapy and after the first and third cycles. Results COPD was diagnosed in 49% of patients, while 42% of those enrolled were current smokers. Current smoking (p = 0.92) and COPD (p = 0.91) status did not affect the response to treatment. The non-COPD population presented a significantly higher pretreatment absolute lymphocyte count (ALC) than the COPD population (2.31 vs. 1.81 × 109/l; p = 0.0374). Also, only the non-COPD group demonstrated an elevated absolute monocyte count (AMC) following the first and third cycles of chemotherapy (p = 0.004). In current smokers, pretreatment values for white blood cells (WBC), absolute neutrophil count (ANC), and platelets (PLT) were higher than in the ex-smoker population (WBC 9.94 vs. 8.7 (× 109/l); p = 0.01; ANC 6.47 vs. 5.61 (× 109/l); p = 0.037; PLT 316 vs. 266 (× 109/l); p = 0.049). Ex-smokers demonstrated AMC level elevation after the first cycle of chemotherapy and PLT level elevation after the third cycle, while current smokers also demonstrated an early decrease in LMR. Conclusions COPD and smoking induce chronic systemic inflammation and oxidative stress, which influence the results of standard laboratory tests, but do not change the response rate of lung cancer on chemotherapy.

Is cetuximab in combination with irinotecan as a third-line treatment for advanced colorectal cancer scientifically justified?

Palliative systemic therapy for advanced colorectal cancer involves cytotoxic and molecularly targeted agents, either in combination or as monotherapy. In Poland, patients with RAS wild-type tumours can receive epidermal growth factor receptor (EGFR) inhibitors after progression on fluoropyrimidine, irinotecan, and oxaliplatin-based chemotherapy. Monotherapy with cetuximab or panitumumab provides statistically significant survival benefit and improves quality of life. The role of cetuximab and irinotecan in combination, as a more intensive third-line treatment in irinotecan-resistant patients is a matter of controversy. To determine the benefit of this combination we analysed the available literature data (the results of the BOND trial and of two Canadian retrospective studies). In our opinion, the use of cetuximab in combination with irinotecan as the third-line of therapy is not based on reliable scientific evidence.

Tamoxifen-induced acute pancreatitis – a case report

Tamoxifen is a selective estrogen receptor modulator used for the treatment of oestrogen/progesterone receptor positive breast cancer. It has antagonistic or agonistic activity depending on the tissue location. Generally it causes mild and reversible side effects, however more serious ones including cardiovascular and thromboembolic adverse events, uterine cancer or acute pancreatitis can also occur. Tamoxifen, like oestrogens, increases the plasma level of TG and liver secretion of VLDL. Moreover, it inhibits the key enzymes of triglyceride metabolism. In this report we present a case of a 55-year-old woman with a history of a poorly controlled hypertriglyceridaemia diagnosed with breast cancer. She was treated with surgery and adjuvant chemotherapy, radiotherapy and hormonotherapy with tamoxifen. About three months after hormonal treatment, her triglyceride level increased. Five months later she developed an acute necrotic pancreatitis that required hospitalization. Her serum samples on admission were highly lipemic. An abdominal ultrasound showed no evidence of gallstones or dilation of the bile ducts. There was no history of alcohol abuse or abdominal trauma. Tamoxifen was suspected as a trigger factor for pancreatitis. After the drug withdrawal and administration of the conservative management the patients medical condition improved. Due to a postmenopausal status of the patient and no harmful effect on serum lipids, an adjuvant hormonotherapy with aromatase inhibitor was started.