Leona Koubková

Cisplatin-Based Three Drugs Combination (NIP) as Induction and Adjuvant Treatment in Locally Advanced Non-small Cell Lung Cancer: Final Results

Introduction: This phase III trial was conducted in non-small cell lung cancer patients with locally advanced stage II B (only T3N0) III A and III B (only T4 N0). Primary endpoint was 2-year survival; secondary were toxicity, disease-free survival, and overall survival. Methods: After three cycles of vinorelbine (N) 25 mg/m2 on days 1 and 5, ifosfamide/mesna (I) 3 g/m2 on day 1, cisplatin (P) (NIP), patients were treated by surgery and within 45 days were randomized to two additional cycles of NIP versus observation. Results: Median tumor diameter was 5.5 cm (1.2–10.6). Overall, 155 of 156 patients received chemotherapy: 133 (85%) men, median age: 59 years (35–75). Sixty-five percentage of patients were stage III A, 28% II B, and 7% III B. The study has been closed prematurely because of the low inclusion rate. After three cycles of induction in 143 assessable patients, 82 reported an objective response (57.3%) (95% CI: 48.8–65.6), with 3.5% complete response and 53.8% partial response. Relative dose intensity during neoadjuvant NIP (%) was 97, 98, and 98.5 for vinorelbine, ifosfamide/mesna, and cisplatin, respectively. Tolerance: G3 to 4 neutropenia in 3% of patients and G3 to 4 anemia in 4%; nonhematological toxicities included G3 nausea/vomiting in 11%, G3 anorexia and G3 to 4 infection in 6.5%, G3 asthenia in 10% and G3 to 4 alopecia in 25.5%. After a median of 32 days after NIP, 107 patients (69%) underwent operation with complete resection (R0) in 74% (79 of 107 patients). Downstaging (N2 to N0) after surgery was 29%. Operative mortality rate was 2.8%. Twenty-one days (median) after surgery, 79 patients were randomized to adjuvant NIP (47%) or control (53%). Tolerance of adjuvant NIP: 12.5% G3 to 4 nausea/vomiting, 19% G3 alopecia, 6% G3 infection, and G3 asthenia. Overall median survival 32.3 versus 31.8 months in the observation and NIP arms, respectively. Conclusions: NIP allows 74% of R0 with no surgery delay. The few number of randomized patients did not allow to conclude on the efficacy of adjuvant chemotherapy.

Lung cancer in pregnancy: Report of nine cases from an international collaborative study

OBJECTIVE Lung cancer is an uncommon diagnosis during pregnancy. The combination of smoking in young women, increased maternal age during pregnancy, and increasing incidence of lung cancer worldwide may cause an increase of pregnancy associated lung cancer. The aim of this study was to describe all cases of lung cancer during pregnancy, registered in the international Cancer in Pregnancy registration study (CIP study; www.cancerinpregnancy.org). MATERIALS AND METHODS We present nine cases, all advanced lung cancer during the course of pregnancy. Collected data included demographic features of the study patients, cancer treatment, pregnancy outcome as well as maternal and fetal outcomes. RESULTS AND CONCLUSION Nine pregnant patients from 4 European centres with a median age of 33 years old (range, 26-42) were included. The median gestational age at diagnosis was 17 weeks (range, 6-28). All patients presented with metastatic disease including bone, lung, brain, spinal cord, pleura, lymph nodes, adrenal and liver. Histopathology was compatible with adenocarcinoma in 4 patients, non-small cell lung cancer with unidentified subtype in 2 patients and squamous-cell, large-cell and a poorly differentiated carcinoma in 3 patients, respectively. Eight patients were treated with systemic therapy, five of them during gestation. No responses were seen. The maternal postpartum outcome was poor with less than one year survival following delivery. One patient experienced a spontaneous abortion and three pregnancies were terminated. Five infants were all born premature due to poor maternal status by cesarean section, with a median gestational age of 30 weeks (range 26-33). To summarize, lung cancer in pregnancy has a dismal maternal outcome in our series. We add nine new cases and discuss both therapeutic and prognostic results.

Effects of Treatment with Crizotinib on Non-small Cell Lung Carcinoma with ALK Translocation in the Czech Republic

BACKGROUND Patients with advanced anaplastic lymphoma kinase (ALK) -positive non-small cell lung cancer (NSCLC) may gain significant benefit from treatment with the first-generation ALK inhibitor crizotinib. This study investigated the effects of crizotinib in advanced ALK-positive NSCLC patients via analyzing data submitted to the TULUNG registry by pneumo-oncology centers in the Czech Republic. PATIENTS AND METHODS We analyzed the data of 60 NSCLC patients submitted to the TULUNG registry by pneumo-oncology centers who had ALK translocation confirmed by fluorescence in situ hybridization and complete data records from 2011 to 2017. RESULTS The median age of patients was 58 years. A total of 53% of patients were men, 90% had adenocarcinomas, 61.7% were smokers or ex-smokers, and 65% had a performance status of 0. Upon initiation of crizotinib therapy, most patients were at stage IV (88.3%) and the remainder were at stage IIIA or IIIB. Crizotinib was the second-line therapy in 71.7% of patients. A total of 20% of patients suffered side effects, while 11.7% suffered grade 3 and 4 adverse effects. A total of, 6.7, 25, 21.7, and 25% of patients displayed a complete response, a partial response, stable disease, and progressive disease, resp. Progression-free survival (PFS) was 5.8 months. Overall survival (OS) was 27.9 months from the initiation of the first-line therapy and 12.6 from the initiation of crizotinib therapy. PFS and OS were longer among nonsmokers and ex-smokers than among smokers (PFS, 9.7 vs. 5.8 vs. 3.8 months, p = 0.029; OS, 26.8 vs. 15.3 vs. 7.0 months, p = 0.015). CONCLUSION Targeted crizotinib therapy is well tolerated and has significant benefit in patients with advanced ALK-positive NSCLC. Although international guidelines recommend that crizotinib is only used as a first-line therapy, it is used as a second-line and higher-line therapy in the Czech Republic. Clinical studies provide evidence that targeted therapy elicits better effects and less toxicity than routine chemotherapy. Key words: ALK translocation - crizotinib - targeted biological therapy - tyrosine kinase inhibitors This work was supported by AZV grant No. 17- 30748A. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 17. 1. 2018 Accepted: 20. 2. 2018.

Carboplatin with intravenous and subsequent oral administration of vinorelbine in resected non-small-cell-lung cancer in real-world set-up

Objectives Adjuvant cisplatin-based chemotherapy is recommended for routine use in patients with Stage IIA, IIB or IIIA non-small cell lung cancer (NSCLC) after complete resection. Results obtained for Stage IB were not conclusive. While vinorelbine plus cisplatin is the preferred choice after resection, combining vinorelbine with carboplatin promises improved compliance and delivery of drugs due to lower toxicity. We evaluated the impact of this option on treatment compliance and survival under real-world conditions. Material and methods A prospective, single-arm, multicenter, non-interventional study evaluated the tolerability, dose intensity and survival resulting from adjuvant use of intravenous carboplatin (AUC 5 on day 1) with vinorelbine administered both intravenously (25 mg/m2 on day 1) and orally (60 mg/m2 on day 8) within four cycles of 21 days each. A total of 74 patients with a median age of 64 years were observed. Results The mean number of accomplished cycles was 3.78, and 62 patients (83.7%) completed all four planned cycles. Relative dose intensity for carboplatin was 88.9%, for intravenous vinorelbine 93.1%, and for oral vinorelbine 83.2%. Median follow-up was 4.73 years. Median disease-specific survival (DSS) was 7.63 years, median overall survival (OS) was 5.90 years, median disease-free survival (DFS0) was 4.43 years, and five-year survival was 56.2%. TNM stage of disease significantly affected DSS and OS. Favorable survival was observed in females, nonsmokers, patients aged over 65 years, patient with prior lobectomy, patients with tumor of squamous histology, and those who finished the planned therapy, but the differences were non-significant. Conclusion Adjuvant carboplatin with vinorelbine switched from intravenous to oral administration was shown to be a favorable regimen with regard to tolerability and safety. Compliance to therapy was high, and survival parameters were promising, showing that applied regimen can be another potential option for adjuvant chemotherapy in patients with NSCLC.

Lung cancer, pulmonary emphysema and pleural effusion: An autopsy study

OBJECTIVES To determine the exact incidence of lung cancer, pulmonary emphysema and pleural effusion we decided to carry out an autopsy study. METHODS In this autopsy study carried out over two years, we compared the results of autopsy findings with the clinical data in accompanying records of the deceased. RESULTS Among the 708 deceased subjects, there were 398 males and 310 females with a median age of 71 years. At autopsy, 55 cases of lung carcinoma (BCA) were found, of which 24 have not been identified during life (44%). Among the deceased with BCA, emphysema was also observed at autopsy in 40% of the cases. Pulmonary emphysema was described macroscopically in 28% of the full set of 708 deceased, whereas the accompanying records of the deceased described this condition in only 12% of the cases. Microscopic changes compatible with emphysema were identified in 54% of the examined lungs. Pleural effusions were described in the accompanying records of 13% of the deceased, while the autopsies showed this condition in 33% of the deceased. BCA was accompanied by effusion in 25% of the cases. CONCLUSIONS The obtained results show that the studied conditions are present in more cases than are reported by clinicians. The study confirms the commonly accepted association between lung cancer and emphysema.

Pemetrexed in the Second Line Chemotherapy of Non-small Cell Lung Cancer. A Multicentre Prospective Analysis of Data From Clinical Practice

Non small cell lung cancer (NSCLC) is one of the most aggressive tumours with unsatisfactory prognosis and extremely high mortality. Pemetrexed became one of the standard chemotherapeutic options in advanced NSCLC. It is recommended both in the 1st line and in the 2nd line.