M. Tarayre

Astro plenary: Effect of chemotherapy on locally advanced non-small cell lung carcinoma: A randomized study of 353 patients

Abstract Most patients with locally advanced non small cell lung carcinoma are treated with external thoracic radiotherapy. Because of the high incidence of distant metastasis the addition of chemotherapy has been proposed. The present randomized study was conducted from June 1983 to February 1989 and included 353 patients. The trial compared arm A, thoracic megavoltage radiotherapy alone at a total dose of 65 Gy in 26 fractions and 45 days, to arm B that comprised the same radiotherapy preceded and followed by 3 monthly cycles of VCPC (vindesine 1.5 mg/m 2 d 1–2, cyclophosphamide 200 mg/m 2 d 2–4, cisplatinum 100 mg/m 2 d 2 and lomustine 75 mg/m 2 d 3). Disease was deemed unresectable but non-metastasic after bronchoscopic, radiologic, CAT, and nuclear scans and physical examinations. Only patients in clinical, radiological, endoscopic, and histological complete remission were considered as locally controlled; these patients were monitored by fiberoptic bronchoscopy and systematic biopsies to the primary site. One hundred seventy-seven patients received thoracic radiotherapy alone and 176 received the combined modality. Twenty-seven percent of arm B patients had an objective response after 2 VCPC cycles. At the time of final assessment, performed 3 months after the end of thoracic radiotherapy in both arms, there were 20% of complete responders in arm A versus 16% in arm B. The two-year survival rate was 14% in arm A versus 21% in arm B ( p = 0.08 logrank test). The distant metastasis rate was 67% in arm A versus 45% in arm B ( p

Long-Term Results of the International Adjuvant Lung Cancer Trial Evaluating Adjuvant Cisplatin-Based Chemotherapy in Resected Lung Cancer

PURPOSE Based on 5-year or shorter-term follow-up data in recent randomized trials, adjuvant cisplatin-based chemotherapy is now generally recommended after complete surgical resection for patients with non-small-cell lung cancer (NSCLC). We evaluated the results of the International Adjuvant Lung Cancer Trial study with three additional years of follow-up. PATIENTS AND METHODS Patients with completely resected NSCLC were randomly assigned to three or four cycles of cisplatin-based chemotherapy or to observation. Cox models were used to evaluate treatment effect according to follow-up duration. Results The trial included 1,867 patients with a median follow-up of 7.5 years. Results showed a beneficial effect of adjuvant chemotherapy on overall survival (hazard ratio [HR], 0.91; 95% CI, 0.81 to 1.02; P = .10) and on disease-free survival (HR, 0.88; 95% CI, 0.78 to 0.98; P = .02). However, there was a significant difference between the results of overall survival before and after 5 years of follow-up (HR, 0.86; 95% CI, 0.76 to 0.97; P = .01 v HR, 1.45; 95% CI, 1.02 to 2.07; P = .04) with P = .006 for interaction. Similar results were observed for disease-free survival. The analysis of non-lung cancer deaths for the whole period showed an HR of 1.34 (95% CI, 0.99 to 1.81; P = .06). CONCLUSION These results confirm the significant efficacy of adjuvant chemotherapy at 5 years. The difference in results beyond 5 years of follow-up underscores the need for the long-term follow-up of other adjuvant lung cancer trials and for a better identification of patients deriving long-term benefit from adjuvant chemotherapy.

Radiotherapy alone versus combined chemotherapy and radiotherapy in unresectable non-small cell lung carcinoma

We report the results observed in a large randomized study comparing radiotherapy alone to combined radiotherapy and chemotherapy in unresectable squamous cell and large cell lung carcinoma. Radiation dose was 65 Gy in both groups and chemotherapy included vindesine, cyclophosphamide, cisplatin and lomustine. One hundred seventy-seven patients received radiotherapy alone, and 176 received the combined treatment. The 2-year survival rate was 14% for patients receiving radiotherapy vs. 21% for patients receiving the combined treatment (P = 0.02). The distant metastasis rate was significantly lower in the group receiving the combined treatment (P < 0.001). Local control at 1 year was poor in both groups (17% and 15%, respectively) and remains a major problem in locally advanced non-small cell lung cancer.

Controlled clinical trial of prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission

We conducted a randomised clinical trial on 211 patients with small-cell lung cancer in complete remission (CR). The aim of this trial was to evaluate the effect of prophylactic cranial irradiation (PCI) on overall survival. Eligible patients were randomly assigned to receive either PCI (100 patients) or no PCI (111 patients). Each centre was allowed to use its own PCI protocol as long as the total dose was within the range of 24-30 Gy and delivered in less than 3 weeks with fractions of 3 Gy or less. The mean follow-up is 5 years. The survival curves do not differ significantly (P = 0.25) between the two groups. The 4-year overall survival rate (95% confidence interval) is 22% [15-32%] in the PCI group versus 16% [10-25%] in the control group. The relative risk of death in the PCI group compared to the control group is 0.84 (95% CI = [0.62-1.13]). The incidence of brain metastasis is lower in the PCI group, but the difference is not statistically significant (P = 0.14). The 4-year cumulative rate of brain metastasis is 44% [32-57%] in the PCI group compared to 51% [38-63%] in the control group. In conclusion, in this study, which had to be closed prematurely, no significant difference was found in terms of the incidence of brain metastases nor in survival.

Alternating radiotherapy and chemotherapy in 173 consecutive patients with limited small cell lung carcinoma

One-hundred seventy-three patients with limited small cell lung cancer were included in three consecutive protocols alternating radiotherapy and chemotherapy. The alternating schedule consisted of six courses of chemotherapy (doxorubicin, VP16213, cyclophosphamide, and methotrexate in the first protocol; methotrexate being replaced by cisplatinum in the other two protocols) and three series of thoracic radiotherapy delivering a total dose of 45, 55, and 65 Gy in each consecutive protocol. Radiotherapy was started after the second course of chemotherapy. A 1-week gap was respected between each course of chemotherapy and each series of radiotherapy. Seventy percent of patients were in complete remission at the end of the induction treatment. The actuarial 5-year local control was 60% and the 5-year overall survival was 18%. Sixty percent of patients developed distant metastases. The death rate unrelated to cancer was 10%. These results show that alternating radiotherapy and chemotherapy schedules are reproducible, and provide a consistent long-term local control and a long-term survival rate exceeding 15% in limited disease.

Dose intensity of initial chemotherapy may have an impact on survival in limited small cell lung carcinoma

Abstract The analysis of the outcome of 131 patients with limited small cell lung cancer (SCLC) from two consecutive phase II trials which used the same drugs suggested that the intensity of the first course of chemotherapy was a prognostic factor in SCLC. The T3 stage of the TNM classification was the only clinical factor found to be prognostic for overall survival. Irrespective if the T3 stage was controlled or not by multivariate analysis, we found that overall survival rate increased with the dose of cyclophosphamide administered during the first course. A U-shaped dose-response relationship was observed for cisplatinum; survival was ostensibly better for doses ranging from 85 to 105 mg/m 2 . When both drugs were taken into account in the analysis, the effect on overall survival remained significant.

Modalités de la radiothérapie dans les carcinomes bronchiques à petites cellules : radiothérapie thoracique et irradiation prophylactique cérébrale

Resume Les cancers bronchiques a petites cellules (CPC) representent 20 % de l’ensemble des cancers bronchiques. Apres le bilan d’extension initial, seul un tiers de ces patients aura finalement une forme limitee. Le traitement des CPC limites repose actuellement sur les associations chimiotherapie-radiotherapie qui ont permis une amelioration de la survie globale et de la survie sans metastases au cours des dernieres annees. Neanmoins, meme dans les formes limitees, la survie a 5 ans varie entre 10 et 15 % et ne depasse guere 25 % dans les meilleures series. Le risque de rechute est en effet eleve : si pres de 70 % des patients avec une forme limitee parviennent a une reponse complete, seul 15 a 20 % d’entre eux survivront de facon prolongee. En effet, la plupart rechutent, et le risque de dissemination cerebrale par exemple est particulierement eleve, puisqu’il atteint pres de 50 % a 2 ans meme chez des patients mis en reponse complete. Ainsi, l’irradiation prophylactique cerebrale a egalement pris place dans la prise en charge standard des patients ayant un CPC en reponse complete suite aux resultats d’une meta-analyse ayant montre que la survie a 3 ans etait amelioree de 5 %. Malgre l’amelioration de la survie globale grâce aux traitements combines, les resultats mediocres observes en termes de survie a long terme devraient stimuler plus d’essais therapeutiques, afin de trouver les chimiotherapies et les modalites de radiotherapie optimales, la meilleure facon d’associer ces deux traitements ainsi que la place de nouvelles therapeutiques.

Alternating radiotherapy and chemotherapy in limited disease small cell lung cancer

In a pilot study of 29 patients treated for localized small cell lung cancer, three new approaches were introduced, i.e. an increased initial drug dose, an early alternation of chemotherapy and thoracic radiotherapy and initial accelerated and hyperfractionated irradiation. The results were interesting. However, a high rate of fatal toxicity (21%) was observed.

1055 From the results of the meta-analysis evaluating the role of chemotherapy in non-small cell lung cancer (NSCLC) to the IALT project

A recent meta-analysis using individual data from 54 trials included more than 9000 NSCLC patients in three adjuvant settings (surgery + chemotherapy (CT), surgery ± radiotherapy (RT) ± CT, radical RT ± CT) and in the supportive care setting. Of the 14 trials analysing the first adjuvant setting, only 7 including 1062 patients, used a cisplatin based regimen. Even if the CT protocols would be now considered sub-optimal, the results suggested a relative benefit of CT of 13% in terms of death reduction. This is equivalent to an absolute improvement of survival of 5% at 5 years (from 47% to 52%). Chemotherapy after curative resection of NSCLC could therefore improve survival. The main objective of IALT is to evaluate the effect on overall survival of 3 or 4 cycles of cisplatin-based CT at a dose ranging from 80 to 120mg/m 2 combined with a vinca-alkaloid or etoposide compared with no adjuvant CT. in stage I to IIIA completely resected lung cancer. This hypothesis deserves to be tested in a large-scale trial in order to obtain clear evidence on the value of adjuvant CT With widespread collaboration, it will be possible to include the necessary 3000 patients for randomisation in only a few years.