Gefitinib (ZD1839, Iressa) in non-small-cell lung cancer: a review of clinical trials from a daily practice perspective.

Gefitinib (ZD1839) is the most widely studied targeting agent in the area of non-small-cell lung cancer (NSCLC). Gefitinib is an orally active epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitor. In order to assess the role of gefitinib in the management of NSCLC patients, we systematically reviewed published clinical trials from a daily practice perspective. A systematic research was made in the international medical literature. Gefitinib demonstrated a good tolerance and an encouraging efficacy in pretreated NSCLC patients in preclinical studies. These results were then confirmed in two phase II trials (IDEAL 1 and 2) involving more than 400 patients mostly pretreated with a platinum-containing regimen and docetaxel. All these results were reinforced by those of retrospective studies on patients enrolled in a compassionate use programme. Thus, two phase III trials in chemo-naive patients were initiated (INTACT 1 and 2). Unfortunately, the use of gefitinib with standard combination chemotherapy provided no survival benefit nor response rate or progression-free survival improvement over placebo. Furthermore, we also reviewed the results of studies interested in the characterization of predictive clinical or biological markers for response to gefitinib and discussed the results obtained with other EGFR inhibitors. The efficacy of gefitinib in the first-line setting of each stage of NSCLC has to be further studied through clinical trials. Furthermore, translational studies characterizing the molecular features involved in the response to anti-EGFR-targeted therapies are needed.

Multiple pulmonary nodules and underlying head and neck cancer.

We describe a 66-year-old woman with recently diagnosed cT2N0 mouth cancer and multiple hypo-dense pulmonary nodules discovered on a computed tomographic chest scan. These nodules were located in the anterior part of the right upper and middle lobe and were resected thoracoscopically. Histologic examination of these nodules revealed a lipoid pneumonia. Exogenous lipoid pneumonia is a rare but described pulmonary disease that typically presents as consolidations. An exclusive presentation such as multiple pulmonary nodules is very unusual.

[Impact of a brochure on pain destined for thoracic oncology patients]. / Impact d'un livret d'information sur la douleur destiné aux patients en oncologie thoracique.

OBJECTIVE: To assess the impact of a brochure supplied on pain and analgesic treatment on the knowledge, attitude, belief and perception of patients consulting oncology departments. METHOD: A prospective, comparative, study on patients consulting a thoracic oncology and a general oncology department, suffering from pain and motivating a treatment level > or = to 2 (WHO scale). A group of patients having been given a brochure (case) was compared with a group who had not been given the brochure (controls). The assessment questionnaire, developed according to the KABP (Knowledge, Attitudes, Belief, Practice) method, was distributed to the 2 groups. A second assessment was made 4 weeks after the patients having received the brochure. Visual analog scales (VAS) followed the intensity of the pain. RESULTS: Twenty-one cases and 33 controls were assessed. There was no modification in their belief (risk of addiction) but an improvement in their knowledge (duration of action of morphine agents, management of treatment, multi-disciplinary management). This improvement in knowledge was accompanied by improved control of pain: 2/3 of the patients exhibited a VAS < 1 at the time of the second assessment versus 1/3 during the initial assessment. CONCLUSION: Improvement, if only partial, in the patients' knowledge of pain and its treatment using a brochure, is one of the routes for optimising the management of pain.

Prognostic value of combination of Cyfra 21-1, CEA and NSE in patients with advanced non-small cell lung cancer.

OBJECTIVE: To assess the value of Cyfra 21-1, carcino-embryonic antigen (CEA) and neuron-specific enolase (NSE) combined, all three together as prognostic factors in advanced stage non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Serum samples from untreated NSCLC patients were prospectively collected. All assays were performed using commercial kits blind to clinical information. Serum levels of CEA, NSE and Cyfra 21-1 higher than 10, 13 and 3.5 ng/ml, respectively, were considered as elevated. RESULTS: 264 patients (men, 87%), with Performans Status (PS) of 0/1 in 80% and stage IV disease in 65% were studied. Cyfra 21-1, CEA and NSE were elevated in 52.5%, 41.8% and 33.2% of patients, respectively. Median survival was 9 months (range, 1-77). Cyfra 21-1, age, PS, stage as well as the combination of the three markers together correlated with prognosis in univariate analysis. Multivariate analysis demonstrated that age > or = 65 years (HR = 1.3 [1.02-1.70], p = 0.03), PS 2 (HR = 4.3 [3.13-6.11], p < 0.0001), Cyfra 21-1 > or = 3.5 ng/ml (HR = 1.3 [1.06-1.78], p = 0.01) and the combination of the three markers (HR = 1.06 [1.009-1.13], p = 0.02) remained prognostic determinants. CONCLUSION: Combining Cyfra 21-1, NSE and CEA correlated with prognosis in a significant and independent manner.

Vascular stenting for palliation of superior vena cava obstruction in non-small-cell lung cancer patients: a future 'standard' procedure?

BACKGROUND: Stenting is a relatively new option in the management of superior vena cava obstruction (SVCO), but available data often concern non-malignant and/or various malignant diseases. OBJECTIVE: The aim of this study was to assess the efficacy of vascular stenting as a first-choice treatment in SVCO in the exclusive setting of NSCLC. PATIENTS AND METHODS: Retrospective study of NSCLC patients with SVCO treated in the past year. Demographic data, disease characteristics, etiologic and palliative treatment (use of vascular stenting) were recorded as well as treatment outcome and survival. RESULTS: 17 patients were recruited. Eight had vascular stenting while 9 did not. Except for stenting, there was no difference between the two groups (median age 54 years; 80% men; 53% stage IIIB and 47% stage IV). Stenting (median length 60 mm) achieved complete resolution of SVCO more frequently (75 vs. 25%, p = 0.05) and faster (2 vs. 21 days, p = 0.002) without immediate or delayed complication. All patients with stents received anticoagulation therapy. Relapse rate after complete response (33 g, 50%, p = 0.6) was lower and time to relapse (6.5 g, 2 months) was longer for patients undergoing stenting, without reaching statistical significance. Median overall survival was not statistically different (8 and 5 months, p = 0.06). CONCLUSIONS: This study demonstrated the effectiveness of vascular stenting for SVCO in NSCLC patients. The high response rate, quick effect and safety of vascular stenting make this palliative treatment a candidate as a potential standard procedure. The results, however, must be confirmed in a prospective randomized trial including quality of life assessment.

Gemcitabine-induced severe pulmonary toxicity.

Gemcitabine is a relatively new deoxycytidine analog (2',2'-difluorodeoxycytidine) with structural similarities to cytosine arabinoside (Ara-C). Activity of gemcitabine is demonstrated in the treatment of many solid tumors, like pancreas, ovarian and nonsmall cell lung cancer (NSCLC). Although gemcitabine is considered as a drug with a good safety profile, cases of gemcitabine-induced severe pulmonary toxicity (GISPT) were reported as for Ara-C. We performed a systematic review of reported cases on the GISPT. Twenty-nine clinical trials especially interesting NSCLC patients (21) and 21 reported cases recording 40 patients were analyzed. The incidence of the GISPT varies from 0 to 5%. The clinical presentation is a subacute clinical syndrome and is frequently nonspecific. The predominant radiographic pattern on chest X-ray are reticulo-nodular interstitial infiltrates. It was postulated that the physio-pathological mechanism of the GISPT was an inflammatory reaction of the alveolar capillary wall cytokine-mediated, which created an abnormal permeability of its membrane. After the differential diagnosis were ruled out, the discontinuation of the drug and the early initiation of steroids and diuretics are the most frequently performed treatments. Under these conditions, the outcome was favorable in a delay of few days generally for a majority of patients but 20% of patients died. Some risk factors, as a previous pulmonary disease or a previous thoracic irradiation, for the occurrence of the GISPT were proposed. GISPT is rare but sometimes fatal. Its a necessity to increase awareness about it to enhanced an early and suitable management of patients developing such a toxicity after gemcitabine administration.

Bronchioloalveolar carcinoma: myths and realities in the surgical management.

Bronchioloalveolar carcinoma (BAC) of the lung is a subtype of adenocarcinoma with pure bronchoalveolar growth pattern and no evidence of stromal, vascular or pleural invasion (1999 WHO criteria), that seems to increase in incidence actually. BAC has its proper clinical spectrum, occurring more frequently in women and in younger patients. BAC also seems to be less dependent on tobacco exposure. Furthermore, original feature of this type of lung cancer is its intrapulmonary spreading and being infrequently systemic. Thus, surgical resection appears to have a pivotal role. This review of the literature attempted to assess whether or not patients with BAC should be treated according to the same oncological principles as those recommended for other non-small cell lung cancers, i.e. performance of anatomical resection combined with lymphadenectomy, and development of multimodality therapeutic strategies. Unilateral multinodular or pneumonic forms are best removed by lobectomy, or pneumonectomy when appropriate, combined with lymphadenectomy. Segmentectomy or wedge resection is a valuable option for the treatment of solitary lung nodules with pure pathological BAC patterns, provided specific conditions based upon computed tomography scan findings are present. The place of multimodality strategies is still unexplored. Treatment of bilateral BAC is challenging. Incomplete resection may be performed to palliate a severe intrapulmonary shunting. However, one hope of cure is provided by lung transplantation, even though disappointing results with disease recurrence on the grafts have been reported. The lack of large studies including only pure BAC gives a place for future biological and clinical research on this cancer.

Survival and postoperative complication in daily practice after neoadjuvant therapy in resectable stage IIIA-N2 non-small cell lung cancer.

Regarding persisting controversies about neoadjuvant treatment (NT), we studied the impact of neoadjuvant therapy in daily practice. Patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) resected after NT were eligible. Data on preoperative treatments, surgical procedure, postoperative complications and survival were collected. Overall, 71 (60 men, median age of 60 years) patients met inclusion criteria. All patients received a two-drug platinum-based regimen (median of 2.5 cycles [2-4 cycles]) and 15 (21%) had an associated radiotherapy (20-40 Gy). Nine complete and 27 partial responses were achieved. Surgical procedure principally was a lobectomy (44%), a left (15.5%) or a right (27%) pneumonectomy. Operative mortality was 4.2% while 21 patients (29%) experienced postoperative complications. Median survival was 17 months (95% CI, 13-21 months) with 3- and 5-year survival rates of 24 and 13%, respectively. Five-year survival was worse if postoperative complication occurred (18 versus 0%, p=0.09). Multivariate analysis showed male gender (RR=0.37, 95% CI, 0.16-0.81, p=0.013) and postoperative positive lymph node (RR=2.7, 95% CI, 1.4-5.2, p=0.002) to influence survival. In conclusion, achievement of a clinical and pathological response after NT for stage IIIA-N2 NSCLC patients enables a better survival. More efficient but also less toxic regimens of chemotherapy should be developed regarding its impact on long-term survival.

[Recent progress and perspectives in the management of patients with lung cancer]. / Progeés récents et perspectives dans la prise en charge des patients porteurs d'un cancer bronchique.

Lung cancer is still actually a leading cause of death in industrial countries, while the major etiologic agent, the tobacco smoke, is clearly identified. Primary or secondary prevention's strategies are frequently unsuccessful. The main survival chance is an early diagnosis of the disease. Efforts in the lung cancer screening have to be continued. Therapeutic strategies improved but progress in terms of survey are disappointing. Hopes relies on new drugs development coming from fundamental research, for whom first clinical trials are ongoing.