Second-line paclitaxel in non-small cell lung cancer initially treated with cisplatin: a study by the European Lung Cancer Working Party

In the context of a phase III trial comparing in advanced non-small cell lung cancer (NSCLC) sequential to conventional administration of cisplatin-based chemotherapy and paclitaxel, we evaluated the activity of paclitaxel as second-line chemotherapy and investigated any relation of its efficacy with the type of failure after cisplatin. Patients received three courses of induction GIP (gemcitabine, ifosfamide, cisplatin). Non-progressing patients were randomised between three further courses of GIP or three courses of paclitaxel. Second-line paclitaxel was given to patients with primary failure (PF) to GIP and to those progressing after randomisation to further GIP (secondary failure or SF). One hundred sixty patients received second-line paclitaxel. Response rates were 7.7% for PF and 11.6% for SF (P=0.42). Median survival times (calculated from paclitaxel start) were 4.1 and 7.1 months for PF and SF (P=0.002). In multivariate analysis, three variables were independently associated with better survival: SF (hazard ratio (HR)=1.55, 95% confidence interval (CI) 1.08–2.22; P=0.02), normal haemoglobin level (HR=1.56, 95% CI 1.08–2.26; P=0.02) and minimal weight loss (HR=1.79, 95% CI 1.26–2.55; P=0.001). Paclitaxel in NSCLC patients, whether given for primary or for SF after cisplatin-based chemotherapy, demonstrates activity similar to other drugs considered active as second-line therapy

Prophylactic cranial irradiation in small cell lung cancer: a systematic review of the literature with meta-analysis

PURPOSE: A systematic review of the literature was carried out to determine the role of prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC) . METHODS: To be eligible, full published trials needed to deal with SCLC and to have randomly assigned patients to receive PCI or not. Trials quality was assessed by two scores (Chalmers and ELCWP). RESULTS: Twelve randomised trials (1547 patients) were found to be eligible. Five evaluated the role of PCI in SCLC patients who had complete response (CR) after chemotherapy. Brain CT scan was done in the work-up in five studies and brain scintigraphy in six. Chalmers and ELCWP scores are well correlated (p < 0.001), with respective median scores of 32.6 and 38.8 %. This meta-analysis based on the available published data reveals a decrease of brain metastases incidence (hazard ratio (HR): 0.48; 95 % confidence interval (CI): 0.39 - 0.60) for all the studies and an improvement of survival (HR: 0.82; 95 % CI: 0.71 - 0.96) in patients in CR in favour of the PCI arm. Unfortunately, long-term neurotoxicity was not adequately described . CONCLUSIONS: PCI decreases brain metastases incidence and improves survival in CR SCLC patients but these effects were obtained in patients who had no systematic neuropsychological and brain imagery assessments. The long-term toxicity has not been prospectively evaluated. If PCI can be recommended in patients with SCLC and CR documented by a work-up including brain CT scan, data are lacking to generalise its use to any CR situations

Admission of advanced lung cancer patients to intensive care unit: A retrospective study of 76 patients

<p>Abstract</p> <p>Background</p> <p>Criteria for admitting patients with incurable diseases to the medical intensive care unit (MICU) remain unclear and have ethical implications.</p> <p>Methods</p> <p>We retrospectively evaluated MICU outcomes and identified risk factors for MICU mortality in consecutive patients with advanced lung cancer admitted to two university-hospital MICUs in France between 1996 and 2006.</p> <p>Results</p> <p>Of 76 included patients, 49 had non-small cell lung cancer (stage IIIB n = 20; stage IV n = 29). In 60 patients, MICU admission was directly related to the lung cancer (complication of cancer management, n = 30; cancer progression, n = 14; and lung-cancer-induced diseases, n = 17). Mechanical ventilation was required during the MICU stay in 57 patients. Thirty-six (47.4%) patients died in the MICU. Three factors were independently associated with MICU mortality: use of vasoactive agents (odds ratio [OR] 6.81 95% confidence interval [95%CI] [1.77-26.26], p = 0.005), mechanical ventilation (OR 6.61 95%CI [1.44-30.5], p = 0.015) and thrombocytopenia (OR 5.13; 95%CI [1.17-22.5], p = 0.030). In contrast, mortality was lower in patients admitted for a complication of cancer management (OR 0.206; 95%CI [0.058-0.738], p = 0.015). Of the 27 patients who returned home, four received specific lung cancer treatment after the MICU stay.</p> <p>Conclusions</p> <p>Patients with acute complications of treatment for advanced lung cancer may benefit from MCIU admission. Further studies are necessary to assess outcomes such as quality of life after MICU discharge.</p

Identification of patients at risk for early death after conventional chemotherapy in solid tumours and lymphomas

1–5% of cancer patients treated with cytotoxic chemotherapy die within a month after the administration of chemotherapy. Risk factors for these early deaths (ED) are not well known. The purpose of this study was to establish a risk model for ED after chemotherapy applicable to all tumour types. The model was delineated in a series of 1051 cancer patients receiving a first course of chemotherapy in the Department of Medicine of the Centre Léon Bérard (CLB) in 1996 (CLB-1996 cohort), and then validated in a series of patients treated in the same department in 1997 (CLB-1997), in a prospective cohort of patients with aggressive non-Hodgkin's lymphoma (NHL) (CLB-NHL), and in a prospective cohort of patients with metastatic breast cancer (MBC series) receiving first-line chemotherapy. In the CLB-1996 series, 43 patients (4.1%) experienced early. In univariate analysis, age > 60, PS > 1, lymphocyte (ly) count ≤ 700 μl−1 immediately prior to chemotherapy (d1), d1-platelet count ≤ 150 Gl−1, and the type of chemotherapy were significantly correlated to the risk of early death (P ≤ 0.01). Using logistic regression, PS > 1 (hazard ratio 3.9 (95% Cl 2.0–7.5)) and d1-ly count ≤ 700 μl−1 (3.1 (95% Cl 1.6–5.8)) were identified as independent risk factors for ED. The calculated probability of ED was 20% (95% Cl 10–31) in patients with both risk factors, 6% (95% Cl 4–9) for patients with only 1 risk factor, and 1.7% (95% Cl 0.9–3) for patients with none of these 2 risk factors. In the CLB-97, CLB-NHL and MBC validation series, the observed incidences of early death in patients with both risk factors were 19%, 25% and 40% respectively and did not differ significantly from those calculated in the model. In conclusion, poor performance status and lymphopenia identify a subgroup of patients at high risk for early death after chemotherapy. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

APACHE III outcome prediction in patients admitted to the intensive care unit after liver transplantation: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>The Acute Physiology and Chronic Health Evaluation (APACHE) III prognostic system has not been previously validated in patients admitted to the intensive care unit (ICU) after orthotopic liver transplantation (OLT). We hypothesized that APACHE III would perform satisfactorily in patients after OLT</p> <p>Methods</p> <p>A retrospective cohort study was performed. Patients admitted to the ICU after OLT between July 1996 and May 2008 were identified. Data were abstracted from the institutional APACHE III and liver transplantation databases and individual patient medical records. Standardized mortality ratios (with 95% confidence intervals) were calculated by dividing the observed mortality rates by the rates predicted by APACHE III. The area under the receiver operating characteristic curve (AUC) and the Hosmer-Lemeshow C statistic were used to assess, respectively, discrimination and calibration of APACHE III.</p> <p>Results</p> <p>APACHE III data were available for 918 admissions after OLT. Mean (standard deviation [SD]) APACHE III (APIII) and Acute Physiology (APS) scores on the day of transplant were 60.5 (25.8) and 50.8 (23.6), respectively. Mean (SD) predicted ICU and hospital mortality rates were 7.3% (15.4) and 10.6% (18.9), respectively. The observed ICU and hospital mortality rates were 1.1% and 3.4%, respectively. The standardized ICU and hospital mortality ratios with their 95% C.I. were 0.15 (0.07 to 0.27) and 0.32 (0.22 to 0.45), respectively.</p> <p>There were statistically significant differences in APS, APIII, predicted ICU and predicted hospital mortality between survivors and non-survivors. In predicting mortality, the AUC of APACHE III prediction of hospital death was 0.65 (95% CI, 0.62 to 0.68). The Hosmer-Lemeshow C statistic was 5.288 with a p value of 0.871 (10 degrees of freedom).</p> <p>Conclusion</p> <p>APACHE III discriminates poorly between survivors and non-survivors of patients admitted to the ICU after OLT. Though APACHE III has been shown to be valid in heterogenous populations and in certain groups of patients with specific diagnoses, it should be used with caution – if used at all – in recipients of liver transplantation.</p

Ifosfamide, cisplatin and etoposide combination in locally advanced inoperable non-small-cell lung cancer: a phase II study

From March 1993 to February 1997, 43 eligible patients with inoperable stage IIIA (ten patients) and stage IIIB (33 patients), histologically confirmed NSCLC received 3 courses of the ICE combination (ifosfamide 1.5 g m−2 and mesna 750 mg m−2 two times a day, cisplatin 25 mg m−2 and etoposide 100 mg m−2, all administered intravenously (i.v.) on days 1–3 every 3 weeks) with G-CSF support. After three cycles, patients were submitted to radical surgery or received two additional courses of the ICE regimen and/or curative radiotherapy. Grade 3–4 neutropenia occurred in 21% of 114 evaluable courses, but was of short duration, leading to neutropenic fever in 5% of the courses. Severe thrombocytopenia and anaemia were observed in 13% and 3% of the courses respectively. Non-haematological toxicity was generally mild with only two episodes of reversible renal impairment. The overall response rate after three chemotherapy courses was 69% (28 partial responses, one complete response). Ten patients (8/10 patients in stage IIIA, 2/33 patients in stage IIIB) underwent radical surgery. Median TTP for patients not undergoing surgery (n = 33) was 8 months (range 3–34+); median DFS for patients rendered NED by surgery (n = 10) was 26 months (range 1–54+). Median OS for the entire group was 12.5 months (range 2–57+). The ICE regimen is active in locally advanced NSCLC with acceptable toxicity and warrants further exploration as induction chemotherapy in larger series. © 1999 Cancer Research Campaig

Adaptive intrapatient dose escalation of cisplatin in combination with low-dose vp16 in patients with nonsmall cell lung cancer

The objective of this phase II and pharmacologic study was to explore the feasibility toxicity and activity of adaptive intrapatient dose escalation of cisplatin in a dose-intensive weekly schedule using predefined levels of exposure, with the ultimate aim to improve the antitumour activity of the therapy in patients with nonsmall cell lung cancer (NSCLC). Platinum DNA-adduct levels in peripheral white blood cells during treatment were used as the primary parameter for adaptive dosing. If DNA-adduct levels were not available, the area under the concentration-time curve (AUC) of unbound platinum in plasma was used for dose adaptation. Target levels for DNA-adducts and AUC have been defined in a previously performed pharmacologic study. The feasibility of adaptive dosing was tested in 76 patients with stage IIIB and IV NSCLC, who were planned to receive 6 weekly courses of cisplatin at a starting dose of 70 mg m-2, together with daily low oral dose of 50 mg VP16. In total, 37 patients (49%) who were given more than one course received a dose increase varying from 10 to 55%. The majority of patients reached the defined target levels by a dose increase during course two. Relevant grade 2 neurotoxicity was observed in eight (10%) patients and reversible ototoxicity grade 2 in 14 (18%) patients. The strategy of adaptive intrapatient dose adjustment of cisplatin is practically feasible in a research setting even when results for dose adaptation have to be reported within a short time-period of I week. The toxicity appeared to be manageable in this cohort of patients. In some patients, exposure after the standard dose was substantially lower than the defined target level and significant dose escalations of more than 50% had to be applied. The response rate (RR) was relatively high: overall 40% (29 out of 72 patients) partial remission (PR), in patients with stage IIIB the RR was 60% (15 out of 25 patients) and with stage IV 30% (14 out of 47 patients). Randomised studies are needed to determine whether the adaptive dosing strategy results in better efficacy than standard dosing

Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis

Among new biological markers that could become useful prognostic factors for lung carcinoma, Ki-67 is a nuclear protein involved in cell proliferation regulation. Some studies have suggested an association between Ki-67 and poor survival in lung cancer patients. In order to clarify this point, we have performed a systematic review of the literature, using the methodology already described by our Group, the European Lung Cancer Working Party. In total, 37 studies, including 3983 patients, were found to be eligible. In total, 49% of the patients were considered as having a tumour positive for the expression of Ki-67 according to the authors cutoff. In all, 29 of the studies dealt with non-small-cell lung carcinoma (NSCLC), one with small-cell carcinoma (SCLC), two with carcinoid tumours and five with any histology. In terms of survival results, Ki-67 was a bad prognosis factor for survival in 15 studies while it was not in 22. As there was no statistical difference in quality scores between the significant and nonsignificant studies evaluable for the meta-analysis, we were allowed to aggregate the survival results. The combined hazard ratio for NSCLC, calculated using a random-effects model was 1.56 (95% CI: 1.30-1.87), showing a worse survival when Ki-67 expression is increased. In conclusion, our meta-analysis shows that the expression of Ki-67 is a factor of poor prognosis for survival in NSCLC.Journal ArticleMeta-AnalysisResearch Support, Non-U.S. Gov'tSCOPUS: re.jinfo:eu-repo/semantics/publishe

Non-small-cell lung cancer in a French department, (1982–1997): management and outcome

Addition of chemotherapy to the treatment of non-small-cell lung cancer (NSCLC) resulted in a modest but clear improvement in the survival of selected patients. To ascertain if this translates to improved survival in the whole population of patients, we conducted a retrospective population-based study of a sample of 1738 patients diagnosed with primary NSCLC in a French department between 1982 and 1997. The proportion of women, metastatic cases and adenocarcinoma changed significantly over time, as did their management: use of chemotherapy alone increased from 9.7 to 28.1% (P<0.0001), while the use of radiotherapy alone decreased from 32.2 to 9.4% (P<0.0001). The 5-year survival probability was 15.7 % for all patients and 32.6% for those with resectable disease. The 1- and 2-year survival probabilities were 38.2 and 15.6% in locally advanced disease, and were, respectively, 16.8 and 5.2% in metastatic disease. Disease extent and histological subtype were significant independent prognostic factors. Survival of resectable disease was longer among patients treated with surgery or surgery plus chemotherapy, while better outcomes for locally advanced disease were associated with radiation plus chemotherapy. In metastastic disease, patients treated by classical agent without platin or palliative care only had the shortest survival. Despite changes in treatment in accordance with the state-of-the-art, overall survival did not improve over time. It is not unlikely that more patients with bad PS were diagnosed during the latter end of the study period. This could at least partially explain the absence of detection of an overall improvement in survival