Cette mise au point évoque le développement de l’immunothérapie, et notamment des inhibiteurs de point de contrôle immunitaire (IPCI) dans la prise en charge des cancers bronchiques neuroendocrines à petites cellules (CBPC). Compte-tenu de la pérennité d’une incidence relativement importante et d’un pronostic réservé, ces IPCI ont été les bienvenus pour enrichir l’arsenal thérapeutique permettant de lutter contre le CBPC. Si les IPCI ont d’abord été évalués en maintenance après radiochimiothérapie concomitante dans les stades limités et en mono/bithérapie en seconde ligne de traitement des stades étendus, les premières tentatives ne se sont pas avérées concluantes. C’est véritablement en première ligne, en association avec la chimiothérapie, que les anti-PD-(L)1 ont prouvé une amélioration de la survie globale des patients atteints de CBPC de stades étendus, en particulier dans les essais IMpower133 et CASPIAN qui ont donné lieu à une AMM européenne, respectivement de l’atézolizumab et du durvalumab en combinaison avec un doublet platine-étoposide. Si le signal est clairement en faveur d’un bénéfice des anti-PD-(L)1 dans cette indication, nous manquons encore à l’heure actuelle de biomarqueur prédictif de l’efficacité de ces molécules. La poursuite des avancées en terme de phénotypage moléculaire des CBPC devrait confirmer l’existence de sous-types de CBPC plus susceptibles de répondre à de telles associations et ainsi permettre d’individualiser plus encore la prise en charge thérapeutique des patients atteints de CBPC. © 2022 SPLF. Publié par Elsevier Masson SAS. Tous droits réservés. This article focuses on development and use of immunotherapy, namely immune checkpoint inhibitors (ICI), as the treatment of neuroendocrine small-cell lung cancer (SCLC). Considering both remaining quite-high incidence and poor prognosis, these ICI have successfully enriched the existing therapeutic armamentarium against SCLC. If ICI were initially evaluated as maintenance therapy of limited-stage SCLC after concomitant chemoradiotherapy, and as mono/bitherapies for second-line treatment of extensive-stage SCLC, first attempts were not really conclusive. PD-(L)1 inhibitors really proved to be relevant as first-line treatment of extensive-stage SCLC through combination with platine-etoposide chemotherapy. Thus, IMpower133 and CASPIAN studies granted a European marketing approval in this indication for atezolizumab and durvalumab, respectively. However, if the provided benefit might not be denied, an unequivocal predictive biomarker of ICI is still missing while the improvement of SCLC molecular phenotyping is going on. This may confirm that some SCLC subtypes are more likely to respond to ICI, either as combinations or with chemotherapy, and consequently push forward care individualisation of patients suffering from SCLC. © 2022 SPLF. Published by Elsevier Masson SAS. All rights reserved.

BACKGROUND:On the basis of a previous meta-analysis, the International Adjuvant Lung Cancer Trial was designed to evaluate the effect of cisplatin-based adjuvant chemotherapy on survival after complete resection of non-small-cell lung cancer.METHODS:We randomly assigned patients either to three or four cycles of cisplatin-based chemotherapy or to observation. Before randomization, each center determined the pathological stages to include, its policy for chemotherapy (the dose of cisplatin and the drug to be combined with cisplatin), and its postoperative radiotherapy policy. The main end point was overall survival.RESULTS:A total of 1867 patients underwent randomization; 36.5 percent had pathological stage I disease, 24.2 percent stage II, and 39.3 percent stage III. The drug allocated with cisplatin was etoposide in 56.5 percent of patients, vinorelbine in 26.8 percent, vinblastine in 11.0 percent, and vindesine in 5.8 percent. Of the 932 patients assigned to chemotherapy, 73.8 percent received at least 240 mg of cisplatin per square meter of body-surface area. The median duration of follow-up was 56 months. Patients assigned to chemotherapy had a significantly higher survival rate than those assigned to observation (44.5 percent vs. 40.4 percent at five years [469 deaths vs. 504]; hazard ratio for death, 0.86; 95 percent confidence interval, 0.76 to 0.98; P<0.03). Patients assigned to chemotherapy also had a significantly higher disease-free survival rate than those assigned to observation (39.4 percent vs. 34.3 percent at five years [518 events vs. 577]; hazard ratio, 0.83; 95 percent confidence interval, 0.74 to 0.94; P<0.003). There were no significant interactions with prespecified factors. Seven patients (0.8 percent) died of chemotherapy-induced toxic effects.CONCLUSIONS:Cisplatin-based adjuvant chemotherapy improves survival among patients with completely resected non-small-cell lung cancer.

PURPOSE: Topotecan, administered intravenously, is active in small-cell lung cancer (SCLC). In this study, the comparability of oral topotecan to IV topotecan was investigated. PATIENTS AND METHODS: Patients with SCLC that had relapsed 90 days or more after cessation of initial chemotherapy were randomized to receive either oral topotecan (Hycamtin) 2.3 mg/m2/d × 5 (52 patients) or IV topotecan 1.5 mg/m2/d × 5 (54 patients), every 21 days. RESULTS: Response rates in this phase II randomized study were 23% (12/52) in the oral topotecan arm and 15% (8/54) in the IV topotecan arm. All radiological responses were confirmed by an independent radiologist. Median survival was 32 weeks (oral) and 25 weeks (IV). Good symptom control, defined as sustained improvement or no deterioration, was evident in both treatment groups. Topotecan was generally well tolerated, with myelosuppression being the major toxicity. Grade 4 neutropenia occurred in 35.3% of patients on oral topotecan and in 67.3% of patients on IV topotecan, which was statistically significant (P = .001). Fever/infection more than or equal to grade 2 associated with grade 4 neutropenia, together with sepsis, occurred in only 5.1% of courses (oral) and 3.3% of courses (IV). Non-hematological toxicity consisted mainly of vomiting (oral: 36.5% of patients; IV: 31.5% of patients) and nausea (oral: 26.9% of patients; IV: 40.7% of patients). CONCLUSION: This study found oral topotecan to be similar in efficacy to IV topotecan in the treatment of patients with relapsed SCLC, sensitive to first-line chemotherapy, with less grade 4 neutropenia and greater convenience of administration.

Chemotherapy is the backbone of small-cell lung cancer therapy. However, optimal drug combinations and schedules remain to be defined and there is hitherto no world-wide accepted standard regimen. Cisplatin, an alkylating agent with high putative toxicity is currently widely used although its effectiveness in this disease has not been established firmly. We conducted a meta-analysis of published data reporting trials randomizing a cisplatin-containing regimen versus a regimen without this alkylating agent in order to determine possible differences in survival response and toxicity. Nineteen trials have been identified in medical literature (4054 evaluable patients). Ten trials randomized patients to receive a cisplatin-etoposide regimen versus a regimen without any of these two drugs. A subgroup analysis was, therefore, carried out in the nine remaining trials that randomly allocated patients between two regimens differing in the absence or presence of cisplatin, whereas etoposide was given (or not given) in both arms (1579 evaluable patients). The DerSimonian and Laird method was used to estimate the size effects and the Peto and Yusuf method was used in order to generate the odds ratios (OR) of reduction in risk of death and the increase in probability of being responders to chemotherapy. There was no significant difference between the cisplatin-containing regimen and the regimen without this drug when the risk of toxic-death was taken into account with respective probabilities of 3.1 and 2.7% (NS). Patients randomized in a cisplatin-containing regimen had an increase in probability of being responders with an OR of 1.35, 95% confidence interval (CI) of 1.18–1.55;P < 10–5 corresponding to an increase of objective (partial plus complete) response rate from 0.62 to 0.69 (a result taking into account a significant heterogeneity). Patients treated with a cisplatin-containing regimen benefited from a significant reduction of risk of death at 6 months and 1 year with respective OR 0.87, 95% CI 0.75–0.98, P = 0.03, and or 0.80, 95% CI 0.69–0.93, P = 0.002 (no statistical heterogeneity). This corresponded to a significant increase in the probability of survival of 2.6% and 4.4% at 6 months and 1 year respectively. The meta-analysis restricted to the subset of nine trials without etoposide treatment imbalance reached similar conclusions. A cisplatin-containing regimen yields a higher response rate and probability of survival than does a chemotherapy containing others alkylating agents without a perceptible increase in risk of toxic-death. © 2000 Cancer Research Campaign

Non small cell lung cancer (NSCLC) is the leading cause of cancer death while squamous cell carcinoma the world. The incidence of adenocarcinoma is rising multistep carcinogenesis. During the last years, changing in the management of NSCLC have occurred The lobectomy and mediastinal lymph node dissection are now the references. Postoperative radiotherapy has failed to improve survival, but hyperfractionated radiotherapy seems to be interesting for inoperable patients. The platin-based chemotherapy is now considered as standard treatment for stage IV Gene therapy and angiogenesis inhibitors are currently under development

This review presents a synthesis of published studies on the activity of the newer cytotoxic drugs in the treatment of bronchial cancer. It also touches on the early indications of recent results which until now have only been the subject of oral presentations. The taxanes form a new class of anti-cancer drug. Myelosuppression is their limiting factor. These are very active cytotoxic drugs but their toxological profile makes them difficult to use in polychemotherapy. The anti-tumour activity of docetaxel (Taxotere(R)) has been shown. For non-small cell cancer (CNPC) the objective response (OR) is of the order of 26% in new patients and 21% in those who have been pre-treated with a combination of drugs based on Cisplatine. For paclitaxel (Taxol(R)) the CIR. is around 25% in new patients. In association with a course of cis platine the efficacy would be dose dependent. For smal cell cancer (CPC) it enables a level of OR around 38% as monochemotherapy. Inhibitors of topoisomerase I (topotecan, irinotecan) form another new class of therapy. Myelosuppression again limits their toxicity. Diarrhoea is an additional toxicity of irinotecan (Campto(R)). The inhibitors of topoisomerase I seem particularly active as monochemotherapy in the treatment of small cell cancer. Haematological toxicity makes them difficult in, association The activity of topotecan (Hycantin(R)) in the treatment of nonsmall cell carcinoma remains to be studied For this indication irinotecan would enable an OR of 33% in new patients. The new anti-metabolite, gemcitabine (Gemzar(C)) is characterised by a different mode of action from other cytotoxics used in the treatment of bronchial cancer. For non-small cell carcinoma it is active as monotherapy and in association with cisplatine. Its activity is more modest in the treatment of CPC but few studies are available for this indication. Its toxic profile makes it promising to be used in association. The new spindle drug vinorelbine (Navelbine(R)) is active as monotherapy or associated with cisplatine in the treatment of non-small cell carcinoma. The limiting toxicity is haematological. Its neurotoxicity is moderate compared to agents in the same therapeutic class. These different cytotoxic drugs arouse a ligitimate interest but the optimal therapeutic schemas for their use remain poorly understood (with the exception of vinorelbine). Their place in the therapeutic arsenal remains to be defined whilst waiting for the results of Phase III studies, their routine use cannot be recommended.

Lung cancer is a major cause of concern since it is now the leading cause of cancer deaths throughout the world and is becoming increasingly common, especially in developing countries, women, and subjects younger than 45 years, due to the high prevalence of smoking in these groups. Although surgical excision remains the cornerstone of the treatment of lung cancer, advances have been made regarding chemotherapy used alone or in combination with radiation therapy. Treatment of nonresectable lung cancers is warranted since it provides small but indisputable increases in survival and, above all, substantial improvements in quality of life. A review of 640 patients showed that attempts at chemotherapy, warranted by the frequency of metastatic spread, were often stymied by chemoresistant relapses in patients with small cell carcinomas and by primary resistance in those with other cancer types. Recent advances in the management of lung cancer have led to radical changes in everyday practice. The efficacy of chemotherapy in small cell carcinomas is dose-dependent, and consequently induction therapy should be given using optimal, although not necessarily aggressive, protocols. Irradiation of the chest is beneficial in early lung cancer. Also, proof that chemotherapy is effective in non-small cell lung cancer has finally been obtained. Some chemotherapy protocols are designed to eradicate microscopic metastases (intensive chemotherapy in small cell cancer and neoadjuvant chemotherapy in non-small cell cancer), whereas others are aimed at maintaining the initial tumor response to chemotherapy (interferon therapy). Although no breakthroughs in lung cancer therapy are expected to occur In the near future, ongoing phase III studies of new anticancer drugs and new strategies offer room for hope.

The genetics of atopy and asthma is a fascinating area of research which has made tremendous progresses over the last couple of years. It has been known for ages that allergies and asthma are concentrating within families. Modern genetics has pinpointed some gene areas such as 5q31.1, 6p21.3, 11q13, 12q15 and 14q11.1. To do so, a crucial step is the definition of the phenotypes. Once the phenotype is set up (which is not an easy task), familial aggregation and segregation studies can be performed. These familial studies allow molecular genetics and linkage analysis. Both candidate gene approach and genome-wide search have been utilized in the genetic of atopy and asthma. Much of the information available today has been fragmentary and not always confirmed. Alleles at multiple loci are likely to be involved and the ultimate picture is most likely determined by many genetic and environmental factors.

The quest for an effective treatment for lung cancer is a major preoccupation for the medical community as it is now the leading cause of cancer mortality worldwide and its incidence continues to increase particularly in developing : countries, in women and in patients under the age of 45 due to the high incidence of tobacco smoking. The major form of treatment for lung cancer is surgery whenever possible followed by chemotherapy either alone or in association with radiotherapy. The treatment of non-operable tumours can today be justified both by the slight but undeniable amelioration of survival rates and more importantly by an increase in the quality of life. Our experience, based on the treatment of 640 patients, suggests that the use of chemotherapy, which is legitimized by the high incidence of metastatic spread associated with the disease, leads to chemoresistant relapses in the case of small cell cancers and primary resistances in non-small cell cancer. Recent advances in the treatment of bronchial cancers are worth underlining as they have led to radical changes in daily practice. The efficacity of chemotherapy in the treatment of small cell cancers is based on a dose-effect relationship which justifies the use of induction therapy which, even if not particularly intensive, should be given at an optimal level. Moreover, thoracic radiotherapy is beneficial in the early stages of the disease. Chemotherapy increases the survival rates for patients with non small cell cancers and although this was difficult to demonstrate the effect is, today, widely accepted. Certain types of chemotherapy are oriented towards the optimisation of initial treatment with the aim of eradicating the microscopic metastatic disease (this is the case for chemotherapy intensification for small cell cancers and neo-adjuvant chemotherapy for non small cell cancers). Other strategies are aimed at maintaining a chemotherapy-induced tumoral response : possibly involving the use of interferons. Whilst thoracic oncology cannot promise exciting breakthroughs in the short term, present phase III trials with new cytostatic drugs and new therapies give rise to real hopes for the future.

The aim of this study was to test cisplatinum and 5-FU chemotherapy. Thirty-five patients with epidermoid or undifferentiated lung carcinoma were entered in a multicentric phase II trial, in an attempt to further define the activity and toxicity of this association. None of them had been previously treated by chemotherapy. The dosage schedule was cisplatinum 100 mg/m2 D1 and 5-FU 1 g/m2 D1 to D5 every 3 weeks for 3 courses before evaluation. There were CR: 2, PR: 10, for a total response rate of 35%. Median survival was 7 months. Tolerance was acceptable. We conclude that this association can be safely administered, but that the results are not superior to others previously reported. Further studies are required to define the activity of a cisplatinum, 5-FU and radiotherapy association.