A randomised trial comparing preoperative to perioperative chemotherapy in early-stage non-small-cell lung cancer (IFCT 0002 trial).

HYPOTHESIS: There will be a detectable increase in overall survival (OS) using preoperative (PRE) as opposed to perioperative (PERI) chemotherapy in resectable StageI-II non-small-cell lung cancer (NSCLC). METHODS: This multicenter, open-label, randomised trial with a 2×2 factorial design first compared two chemotherapy strategies (PRE versus PERI), then two chemotherapy regimens (gemcitabine-cisplatin [GP] versus paclitaxel-carboplatin [TC]). The PRE group received two preoperative cycles followed by two additional preoperative cycles, while the PERI group underwent two preoperative cycles followed by two postoperative cycles, the 3rd and 4th cycles being given only to responders in both cases. RESULTS: A total of 528 patients were randomised, 267 of which were assigned to the PRE group and 261 to the PERI group. Three-year OS did not differ between the two groups (67.4% and 67.7%, respectively; hazard ratio (HR)=1.01 [0.79-1.30], p=0.92), nor did 3-year disease-free survival, response rates, toxicity, or postoperative mortality. Pathological complete response was observed in 22 (8.2%) and 16 patients (6.1%), respectively. Although quality of life did not differ significantly, chemotherapy compliance was significantly higher in the PRE group. The proportion of responders who received Cycles 3 and 4 was significantly higher in the PRE group (90.4% versus 75.2%, p=0.001). In responders, the dose intensity of Cycles 3 and 4 was higher in the PRE group than in the PERI group (mean relative dose intensity of 90.4% versus 82.6%, respectively; p=0.0007). There was no difference between GP and TC in 3-year OS (HR=0.97 [95% confidence interval (CI): 0.76-1.25], p=0.80) or response rates. However, the regimens' toxicity profiles differed. CONCLUSIONS: This study failed to demonstrate any difference in survival between patients receiving preoperative and perioperative chemotherapy in early-stage NSCLC. The increase from two to four preoperative chemotherapy cycles did not increase the pathological response rate.

Pathologic complete response to preoperative chemotherapy predicts cure in early-stage non-small-cell lung cancer: combined analysis of two IFCT randomized trials.

INTRODUCTION: Our study aimed to evaluate whether pathologic complete response (pCR) in early-stage non-small-cell lung cancer (NSCLC) after neoadjuvant chemotherapy resulted in improved outcome, and to determine predictive factors for pCR. METHODS: Eligible patients with stage-IB or -II NSCLC were included in two consecutive Intergroupe Francophone de Cancérologie Thoracique phase-III trials evaluating platinum-based neoadjuvant chemotherapy, with pCR defined by the absence of viable cancer cells in the resected surgical specimen. RESULTS: Among the 492 patients analyzed, 41 (8.3%) achieved pCR. In the pCR group, 5-year overall survival was 80.0% compared with 55.8% in the non-pCR group (p = 0.0007). In multivariate analyses, pCR was a favorable prognostic factor of overall survival (relative risk = 0.34; 95% confidence interval = 0.18-0.64) in addition to squamous-cell carcinoma, weight loss less than or equal to 5%, and stage-IB disease. Five-year disease-free survival was 80.1% in the pCR group compared to 44.8% in the non-pCR group (p < 0.0001). Two patients (4.9%) in the pCR group experienced disease recurrence compared to 193 patients (42.8%) in the non-pCR group. SCC subtype was the only independent predictor of pCR (odds ratio [OR] = 4.30; 95% confidence interval = 1.90-9.72). CONCLUSION: Our results showed that pCR after preoperative chemotherapy was a favorable prognostic factor in stage-IB-II NSCLC. Our study is the largest published series evaluating pCRs after preoperative chemotherapy. The only factor predictive of pCR was squamous-cell carcinoma. Identifying molecular predictive markers for pCR may help in distinguishing patients likely to benefit from neoadjuvant chemotherapy and in choosing the most adequate preoperative chemotherapy regimen.

Third-line chemotherapy in advanced non-small cell lung cancer: identifying the candidates for routine practice.

BACKGROUND: The interest of first- and second-line treatments in non-small cell lung cancer (NSCLC) has been demonstrated by successive randomized trials. Improvements in lung cancer care have routinely allowed a significant proportion of patients to be considered for third-line treatment. METHODS: A retrospective analysis was performed, including all consecutive patients with advanced NSCLC, who received at least three lines of systemic antineoplastic treatment at our institution. RESULTS: From a population of 613 patients treated with first-line treatment, a total of 173 patients received third-line treatment (cytotoxic chemotherapy in 131 patients; epidermal growth factor (EGFR) tyrosine kinase inhibitors in 42 patients). Only 13 patients (8%) received less than 75% of the theoretical dose intensity; 22 patients (13%) presented with severe toxicities. Symptom relief and performance status (PS) improvement were observed in 121 (92% of the 131 patients with symptoms) and 90 patients (52%), respectively. Using multivariate analysis, survival after third-line treatment was significantly increased in patients younger than 70 years-old (hazard ratio [HR] = 0.73, 95% confidence interval [CI]: 0.53-0.99, p = 0.047), who smoked less than 10 pack-years (HR = 0.82, 95% CI: 0.57-0.93, p = 0.036), with no cancer-related symptoms (HR = 0.75, 95% CI: 0.61-0.92, p = 0.007), a weight loss inferior to 5 kg since the beginning of second-line (HR = 0.63, 95% CI: 0.52-0.75, p = 0.013), a PS 0 to 1 (HR = 0.81, 95% CI: 0.76-0.86, p = 0.008), and no extrathoracic tumor spread at initiation of third-line treatment (HR = 0.67, 95% CI: 0.47-0.94, p = 0.042). Disease control after both first- and second-line treatments was the strongest predictor of prolonged survival after third-line treatment (HR = 0.47, 95% CI: 0.33-0.67, p = 0.001). CONCLUSIONS: Patients with advanced NSCLC may benefit from third-line treatment. The best candidates can be identified using standard prognostic factors, such as PS, and disease control after first- and second-line treatments.

Negative impact of rurality on lung cancer survival in a population-based study.

INTRODUCTION: Several studies have suggested that rurality is a risk factor for worse prognosis in cancer. METHODS: The study population included the 2268 lung cancer cases collected between 1981 and 1996 in the Doubs Cancer Registry (France). RESULTS: The numbers of patients were 849 (31.8%) in rural areas and 89 (3.3%) in very rural areas. The relative 5-year survival was 15.2% in rural areas and 13.4% in urban areas (p = 0.5), and 2.7% in very rural areas and 14.4% in extended urban areas (p = 0.02). Multivariate analyses of observed and relative survival showed that patients living in very rural areas (p < 0.0001), 65 years of age and older and having small cell carcinoma had a significantly shorter survival. CONCLUSIONS: This study showed that the multidimensional definition of rurality identified a population with unfavorable prognoses.

[Appropriate cytotoxic drug usages in solid tumors: conformity to official labelling and level of scientific evidence]. / Bon usage du médicament dans les tumeurs solides: conformité à l'AMM et niveau de preuve scientifique.

The definition of appropriate use of drugs is questioned in oncology. Daily therapeutic practices were compared to official labelling and to published scientific data in this retrospective study. It was carried out in two respective specialised centers, from January to September 2004. All chemotherapies administered for adult solid tumours and including one of the eleven studied drugs were evaluated. The analysis of use was performed by drug : conformity to the validated labelling and level of scientific evidence (at the period study). The study included 1,561 drug uses in 1,211 patients. The overall rate of conformity to official labelling was 81.7 % (67.1 % of strict conformity). In 73.8 % of cases, the indications were supported by at least one randomized phase III trial. The results appeared to be significantly different in rare tumours. The potential economic stake of the "contrat de bon usage" was estimated as less than 5 % in our study. This analysis showed an appropriate and controlled use of onerous drugs in solid tumours. The official labelling of drugs are unable to answer to all clinical situations. The definition of a sufficient level of evidence is mandatory for the use of scientific data in clinical practice. This process has to be adapted for rare tumours.

Weekly paclitaxel combined with monthly carboplatin in elderly patients with advanced non-small cell lung cancer: a multicenter phase II study.

INTRODUCTION: We designed this phase II trial to evaluate the efficacy and safety of weekly paclitaxel in combination with monthly carboplatin as first-line treatment in elderly patients with advanced non-small cell lung cancer (NSCLC). METHODS: Main eligibility criteria were histologically or cytologically proven stage IIIB or IV NSCLC, age > or =70 years, Eastern Cooperative Oncology Group performance status 0-2, and measurable disease. The 4-week-based chemotherapy regimen consisted of carboplatin infusion (area under the concentration-time curve 6 mg/ml/min) on day 1 and paclitaxel 90 mg/m as a 1-hour infusion on days 1, 8, and 15. Tumor response was evaluated using Response Evaluation Criteria in Solid Tumors criteria, and symptoms were evaluated using the Lung Cancer Symptoms Scale. Analyses were performed on an intention-to-treat basis. RESULTS: From February 2002 to August 2003, 51 patients (median age, 74 years) participated in the study. One complete and 21 partial responses were reported by the independent review committee, leading to an intention-to-treat objective response rate of 43% (95% confidence interval, 30-57%). The median progression-free and overall survivals were 7.5 (95% confidence interval, 6.2-9.4) and 13.6 (95% confidence interval, 7.5-17) months, respectively. Longitudinal evaluation of the Lung Cancer Symptoms Scale demonstrated lack of quality of life modification during the treatment period. Neurotoxicity was mild to moderate, with 6% of patients suffering from a grade 3 or 4 neuropathy. Myelosuppression was the main toxicity; 39% of patients experienced grade 3 or 4 neutropenia, 18% experienced grade 3 anemia, and 8% experienced grade 3 or 4 thrombocytopenia. There was no treatment-related death. CONCLUSIONS: The combination of weekly paclitaxel 90 mg/m administered on days 1, 8, and 15 plus monthly carboplatin area under the curve 6 on day 1 of a 4-week cycle was feasible and active as a first-line treatment for elderly patients with NSCLC with a good safety profile. These results deserve further analysis to compare the standard care for these patients (monotherapies) with this doublet.

Complete response following preoperative chemotherapy for resectable non-small cell lung cancer: accuracy of clinical assessment using the French trial database.

BACKGROUND: Pathologic complete response (CR) to preoperative chemotherapy has been shown to be a strong prognostic factor in resected non-small cell lung cancer (NSCLC). This preoperative setting offers the opportunity to evaluate the clinical prediction of CR by investigators and an evaluation committee (EC) using the "gold standard" pathologic examination as the reference. The only published large randomized trial of preoperative chemotherapy (to our knowledge), the French neoadjuvant study, constitutes an interesting database to evaluate CT scan-based CR assessment. STUDY OBJECTIVES AND DESIGN: The French trial compared mitomycin-ifosfamide-cisplatin followed by surgery with surgery alone in stage I (except T1N0) to IIIa resectable NSCLC. Response was prospectively assessed in all patients receiving preoperative chemotherapy by the investigator in charge of the patient and by an EC, and was compared with pathologic postoperative data. RESULTS: In the preoperative chemotherapy study, 167 patients were operated on. Nineteen patients were found to have a pathologic CR. Only seven patients were classified as having a CR by investigators and five patients by the EC. Evaluation of CR was correct in six of these seven cases and in three of these five cases, respectively. Sensitivity of the CR diagnosis was 31.6% for investigators and 15.8% for the EC. Specificities of the CR diagnosis were 99.4% and 98.8%, respectively. Positive predictive values were 85.7% and 60%, respectively. Negative predictive values were 91.9% and 90.1%, respectively. Accuracies were 91.6% and 89.2%, respectively. CONCLUSION: Investigator assessment of CR was highly predictive of pathologic CR. However, this study showed that clinical CT scan-based assessment, whether performed by investigators or the EC, underestimated the frequency of CR after preoperative chemotherapy in resectable NSCLC.

Randomized study of maintenance vinorelbine in responders with advanced non-small-cell lung cancer.

BACKGROUND: Prolongation of chemotherapy duration, usually referred to as maintenance chemotherapy, has been considered as an approach to improve survival of patients with advanced non-small-cell lung cancer (NSCLC). If the maintenance regimen differs from the induction regimen, patients will receive not only higher total doses of chemotherapy but also earlier delivery of non-cross-resistant agents. We conducted a randomized trial to compare maintenance vinorelbine therapy with observation in previously untreated patients who responded to induction treatment with mitomycin-ifosfamide-cisplatin (MIC). METHODS: Patients with stage IIIB NSCLC were treated with two monthly MIC cycles followed by radiotherapy; those with "wet" stage IIIB (pleural or pericardial involvement), with stage IIIB with supraclavicular node involvement, or stage IV (i.e., metastatic) NSCLC were treated with four monthly MIC cycles. Patients who responded to induction treatment were randomly assigned to receive intravenous vinorelbine at a dose of 25 mg x m(-2) x wk(-1) for 6 months or no further treatment. Survival comparisons used the log-rank test and the Cox regression adjusted for stage. All statistical tests were two-sided. RESULTS: A total of 573 patients were registered, of whom 227 responded to induction treatment and 181 were randomly assigned (91 to maintenance vinorelbine and 90 to observation) between January 1994 and March 2000. One- and 2-year survival rates were 42.2% and 20.1% in the vinorelbine arm and 50.6% and 20.2% in the observation arm, respectively (log-rank P = .48). The hazard ratio of survival after adjustment on stage, in the vinorelbine arm relative to the observation arm, was 1.08 (95% confidence interval = 0.79 to 1.47; P = .65). There was also no difference between arms in progression-free survival (log-rank P = .32). CONCLUSION: Maintenance vinorelbine did not improve survival of patients with advanced NSCLC who responded to induction MIC treatment. Nevertheless, other agents, including docetaxel and targeted agents, should be evaluated as maintenance agents before the concept is abandoned.

Randomized phase III study of matrix metalloproteinase inhibitor BMS-275291 in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: National Cancer Institute of Canada-Clinical Trials Group Study BR.18.

PURPOSE: To determine whether BMS-275291, a broad-spectrum matrix metalloproteinase inhibitor (MMPI), added to systemic chemotherapy improved survival in advanced non-small-cell lung cancer (NSCLC). In early phase studies, BMS- 275291 was not associated with dose-limiting joint toxicity seen with other MMPIs. PATIENTS AND METHODS: Chemotherapy-naive patients with stage IIIB/IV NSCLC, performance status (PS) 0 to 2, and adequate organ function were eligible. All patients received paclitaxel 200 mg/m2 plus carboplatin (area under the curve, 6 mg/mL-min) intravenously every 21 days for up to 8 cycles, and were randomly assigned to receive BMS-275291, 1,200 mg orally daily, or placebo until disease progression. The primary study end point was survival (OS); secondary end points included progression-free survival (PFS), response rates (RR), toxicity, and quality of life. RESULTS: From 2000 to 2002, 774 patients were randomly assigned. Pretreatment characteristics were well balanced between arms: median age, 61 years; male sex, 73%; stage IV, 79%; PS 0 to 1, 88%. Interim safety analysis revealed no survival advantage and increased toxicity in the experimental arm, and study treatment was stopped. Median OS, PFS and RR in the final analysis in the BMS-275291 arm were 8.6 months, 4.9 months, and 25.8% respectively, and in the control arm 9.2 months, 5.3 months, 33.7%. Toxicity was significantly higher in the BMS-275291 arm, including flu-like symptoms, rash, hypersensitivity reactions (8.6% v 2.4%), and febrile neutropenia (9.7% v 5.5%). CONCLUSION: BMS-275291 added to chemotherapy increases toxicity and does not improve survival in advanced NSCLC.

First line chemotherapy with gemcitabine in advanced non-small cell lung cancer elderly patients: a randomized phase II study of 3-week versus 4-week schedule.

PURPOSE: This randomized phase II multicenter trial aimed at evaluating the efficacy and safety of the 4-week versus 3-week schedules of gemcitabine monotherapy in previously untreated elderly patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemonaive patients with stage IIIB or IV NSCLC, and age between 70 and 90 years, were randomized to receive gemcitabine dose of either 1000 mg/m2 on days 1, 8, 15, every 28 days (arm Q4W), or 1125 mg/m2 on days 1 and 8, every 21 days (arm Q3W). RESULTS: From June 1999 to January 2001, 81 patients (42 on arm Q4W; 39 on arm Q3W) were included. The median age was 75 on both arms; most patients (82.7%) were male, and had a Karnofsky performance status of 80 or 90 (76.5%). For arms Q4W and Q3W, respectively, the median time to treatment failure was 83 days (95% CI, 69-98 days) versus 92 days (95% CI, 63-113), and the median survival was 154 days (95% CI, 108-227) versus 205 days (95% CI, 125-344). The objective response rate was higher on arm Q3W (28.2%) than on arm Q4W (14.3%). Total number of cycles administered was 132 on arm Q4W (median 3, range 1-10 cycles) and 169 on arm Q3W (median 4, range 1-9 cycles). Patients on arm Q4W and Q3W, respectively, received 100.1 and 99.8% of the planned weekly mean dose. The most common grade, three to four toxicities, was neutropenia (17.1% on arm Q4W versus 18.9% on arm Q3W) and thrombocytopenia (12.2% on arm Q4W versus 2.6% on arm Q3W). CONCLUSION: Although both 3- and 4-week gemcitabine regimens were safely and effectively administered in chemonaive elderly patients with advanced NSCLC, the 3-week schedule appears to be the more convenient for this population. Moreover, even if this is only a phase II study this 3-week schedule appears to be at least as efficient as the 4-week regimen.

[Standards, Options and Recommendations for the management of non-small cell lung carcinoma patients]. / Standards, Options et Recommandations 2000 pour la prise en charge des patients atteints d'un cancer bronchopulmonaire non á petites cellules (rapport abrégé).

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French cancer centers and specialists from French public university and general hospitals and private clinics. Its main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop, according to the definitions of the Standards, Options and Recommendations, clinical practice guidelines for the management of non small cell lung carcinoma patients. METHODS: Data were identified by searching Medline and the personal reference lists of members of the expert groups, then submitted for review to independent reviewers. This is a short version of the SOR guideline covering diagnosis, treatment and follow-up and includes the algorithms for the management of patients with non-small cell lung cancer.

Combined modality treatment of non-small-cell lung cancer.

Among all nonmetastatic non-small-cell lung cancer (NSCLC) patients, the best survival rates are observed in patients who undergo surgery. Nevertheless, 5-year survival rates vary between 20% and 60% depending on the stage of the disease. Several combined modality treatments have been investigated to improve outcome in localized NSCLC. These include local treatment, systemic before local treatment, concomitant systemic and local treatments, and systemic after local treatment. Preoperative irradiation was shown to be of no benefit on local recurrence rates or overall survival. Even doses of radiation >/=40 grays (Gy) were associated with lower survival rates. Postoperative irradiation did not influence survival in stage III disease and seemed to be deleterious in stages I and II disease. Modern radiotherapy techniques might be of interest in this setting but have been insufficiently tested. The early phase III studies of preoperative chemotherapy versus primary surgery in stage III NSCLC showed a tremendous difference in favor of chemotherapy. A larger study did not confirm these results but suggested that preoperative chemotherapy might have a greater effect in stages I and II of the disease. In locally advanced disease, chemotherapy followed by radiotherapy was shown to increase survival when compared with radiotherapy alone. Studies comparing concurrent chemoradiation with radiotherapy only were in favor of the concomitant schedule, which improved local control. Promising results have been reported with chemoradiation followed by surgery in stage IIIa and even stage IIIb disease. Randomized studies of postoperative chemotherapy demonstrated a 5% improvement in 5-year survival over adjuvant-free treatment. Postoperative chemoradiation showed no advantage over postoperative radiotherapy. Several trials that are ongoing or whose accrual was recently completed should further define the role of perioperative chemotherapy in resectable NSCLC and of trimodality treatments in advanced disease. Targeted agents are being developed in the postoperative setting. New schedules of chemoradiation with higher therapeutic indexes are also being investigated in nonresectable stage III NSCLC.

[New neoadjuvant approaches using gemcitabine in non-small-cell lung cancer]. / Nouvelles approches néoadjuvantes avec la gemcitabine dans le cancer bronchique non à petites cellules.

Preoperative chemotherapy is a real challenge in the treatment of non-small cell lung cancer. From the first phase II studies, we have learned that response rates to preoperative chemotherapy were high, around 70% with approximately 10% of complete responses. Although toxicity seemed acceptable, increased morbidity and mortality were observed and have to be taken into account for the choice of the preoperative chemotherapy regimen. Two randomized trials were initially conducted in stage IIIA disease and showed highly positive survival results. However, only few patients had been included in both studies, and their statistical value has been considered as questionable. The French MIP91 study, whose results have been published in 2002, argues in favour of preoperative chemotherapy but could not demonstrate a clear-cut advantage. New studies are ongoing. In the search of effective and less toxic combinations, cisplatin-gemcitabine has a role to play. Several phase II studies of this regimen have been presented at the last meeting of the American Society of Clinical Oncology (ASCO) in the preoperative setting or in combination with radiotherapy, and confirmed its efficacy and good tolerability. Chemoradiation is important as part of the trimodality strategy including chemotherapy, radiotherapy, and surgery, which might become standard of care in the treatment of stage IIIa disease.

[2000 Standards, Options and Recommendations for prognostic value of oncogenes and tumor suppressor genes in non small cell lung cancer]. / Standards, Options et Recommandations 2000 pour l'intérêt pronostique des oncogènes et gènes suppresseurs de tumeurs dans les cancers bronchopulmonaires non à petites cellules.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French cancer centers (FNCLCC), the 20 French cancer centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines for non small cell lung cancer patients according to the definitions of the Standards, Options and Recommendations project. METHODS: Data were identified by searching Medline , web sites, and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers. RESULTS: This article presents the chapter "Prognosis significance of oncogenes and tumor suppressor genes" from the full report "Standards, Options and Recommendation for non small cell lung cancer" validated in August 2000. The main recommendations are: 1) No clear clinical prognostic value of oncogenes and tumor suppressor genes (p53, bcl-2, Ki-ras, c-erbB-2, Rb, p16) in non small cell lung cancer, can be established from the available evidences (standard, level of evidence C). 2) Prospective multicenter studies should be performed to assess prognostic significance of oncogenes and tumor suppressor genes in non small cell lung cancer.

[Neo-adjuvant chemotherapy of non-small cell bronchial cancers (NSCLC)]. / La chimiothérapie néo-adjuvante des cancers bronchiques non à petites cellules (CBNPC).

TO PROLONG SURVIVAL: Systemic neo-adjuvant chemotherapy attempts to reduce the development of metastases. Data available on neoadjuvant chemotherapy of NSCLC come from three types of clinical trials. NEO-ADJUVANT CHEMOTHERAPY PHASE II TRIALS: Many trials have demonstrated that the neo-adjuvant approach is feasible, that it leads to a high rate of response, to the order of 50 to 70%, that it does not compromise surgery, and exhibits acceptable toxicity. High survival rates have been obtained, notably in total responders. NEO-ADJUVANT CHEMO-RADIOTHERAPY PHASE II TRIALS: Have essentially demonstrated that this approach is feasible, exhibits acceptable toxicity, worse in pneumonectomy. High response rates have been obtained and relative improved survival, since most of the cases concerned extensive forms that could not be treated surgically. RANDOMIZED PHASE III TRIALS: Gave varying results: two of them only concerned small series of patients (60 in all) with stage IIIA NSCB, with positive results. The third study concerned 373 patients with stage I, II and IIIA cancers: survival at 3 years was increased by 11%, but this difference is not yet significant. Benefits were essentially apparent for stage I and II patients. IN THE FUTURE: Continued active clinical research, oriented differently, on stage I and II, and stage IIIA is necessary.

Gemcitabine induction chemotherapy in non-small cell lung cancer.

Surgery has long been considered standard treatment in early stage non-small cell lung cancer. Preoperative chemotherapy is a real challenge in the treatment of these stages. Some conclusions can be drawn from the first phase II studies in stage IIIA tumors. Response rates were higher than those observed in stage IV tumors, reaching approximately 70%. Although toxicity seemed acceptable, increased morbidity and mortality have to be taken into account for the choice of preoperative regimens. Two randomized studies that included only a few patients were conducted in stage IIIA disease and showed highly positive survival results. The French randomized study argued in favor of preoperative chemotherapy with an absolute difference in survival rates that remains constant beyond the third year. New studies are ongoing to evaluate the role of the gemcitabine/cisplatin combination. Several phase II studies of this regimen in the preoperative setting or in combination with radiotherapy have been presented at the most recent meetings of the American Society of Clinical Oncology. These studies confirmed both its efficacy and good tolerability. In several ongoing randomized studies, this combination has been chosen to test the concept of preoperative chemotherapy. One such study, which compares two different strategies of preoperative chemotherapy, is by the Intergroupe Francophone de Cancérologie Thoracique.

[To be cured of lung cancer]. / Guéri d'un cancer bronchique.

Pronostic of lung carcinoma is very poor but, every year in Europe and North America, thousands of patients are offered a chance of cure. However only a long period of time without relapse allows to state the reality of cure. Sequelae generated by cancer treatments are potentially increased by the use of treatments combinations. In operated patients, chronic respiratory insufficiency is the most common late complication often interfering with professionnal activity especially for manual workers. Late toxicity after radiotherapy for lung cancer has been little studied. Thoracic irradiation especially affects lung and cardiac functions. Late toxicity of chemotherapy may be more frequent with the increasing use of neoadjuvant chemotherapy before surgery or radiotherapy in patients potentially cure.

Preoperative chemotherapy followed by surgery compared with primary surgery in resectable stage I (except T1N0), II, and IIIa non-small-cell lung cancer.

PURPOSE: To evaluate whether preoperative chemotherapy (PCT) could improve survival in resectable stage I (except T1N0), II, and IIIA non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A randomized trial compared PCT to primary surgery (PRS). PCT consisted of two cycles of mitomycin (6 mg/m(2), day 1), ifosfamide (1.5 g/m(2), days 1 to 3) and cisplatin (30 mg/m(2), days 1 to 3), and two additional postoperative cycles for responding patients. In both arms, patients with pT3 or pN2 disease received thoracic radiotherapy. RESULTS: Three hundred fifty-five eligible patients were randomized. Overall response to PCT was 64%. There were two preoperative toxic deaths. Postoperative mortality was 6.7% in the PCT arm and 4.5% in the PRS arm (P =.38). Median survival was 37 months (95% confidence interval [CI], 26.7 to 48.3) for PCT and 26.0 months (95% CI, 19.8 to 33.6) for PRS (P =.15). Survival differences between both arms increased from 3.8% (95% CI, 1.3% to 25.1%) at 1 year to 8.6% (95% CI, 2.64% to 24.4%) at 4 years. A quantitative interaction between N status and treatment was observed, with benefit confined to N0 to N1 disease (relative risk [RR], 0.68; 95% CI, 0.49 to 0.96; P =.027). After a nonsignificant excess of deaths during treatment, the effect of PCT was significantly favorable on survival (RR, 0.74; 95% CI, 0.56 to 0.99; P =.044). Disease-free survival time was significantly longer in the PCT arm (P =.033). CONCLUSION: Although impressive differences in median, 3-year, and 4-year survival were observed, they were not statistically significant, except for stage I and II disease.