2014-12-16-国际肺癌辅助试验- The International Adjuvant Lung Cancer Trial (IALT)

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G. Buccheri, D. Ferrigno. Hospital, Cuneo, Ma/y
Combination chemotherapy with anti-proliferative agents is the usual treatment for patients with advanced non-small cell lung cancer (NSCLC), good performance status, and no major clinical contraindications. Since the early eighties, platinum-based regimens are the milestone of this treatment. Otder combinations with long-acting alkylating agents, are now practically abandoned representing a sort of historical treatment. Nevertheless, convincing evidence that cis-platinum containing programs does ensure longer survivals is still scarce (Lung Cancer 1994; 11: 115-117). Herein, we report the first randomized trial comparing two classic platinum (MVP) and non-platinum (MACC) regimens. One-hundred and fifty-six patients with advanced NSCLC were assigned at random to the two treatment arms. MACC and MVP treatments were given as originally described and continued until progression of disease, unacceptable toxicity, or refusal by the patient. Actual median dose intensities (Dls) of MVP and MACC were, respectively, 95% and 100% of the intended (p = 0.0132). In all, 16 partial responses in patients allocated to MVP and 10 in patients on MACC were observed. Median progressionfree times were 21 weeks for the group on MVP and 20 for the group on MACC (p = NS). Median survival after MVP was 34 weeks (31 after MACC, p = NS). Also in multivariate analysis, the type of chemotherapy assigned was unrelated with survival. Toxicity was similar in both arms, except for the more severe anemia, thrombocytopenia, nausea, and vomiting observed in the group on MVP. Alopecia occurred more often in MACC patients. Subjective tolerance to treatment, perception of physical and psychological well-being were rated similarly by patients of both groups (however, subjective tolerance tended to worse more rapidly in MVP patients). We conclude that MVP is more active than MACC in NSCLC, and shows a foreseeable and reversible toxicity of low-medium grade. However, we have failed to substantiate any survival benefit from the use of this platinum-based combination.
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)14*1 A randomized study of CODE plus thoracic irradiation versus alternating CAWEP for extensive stage small cell lung cancer (ESCLC): An intergroup study of the national cancer institute of Canada and the southwest oncology group
T. Le Chevalier. /AL7 Collaborative Chevalier; lnsfitut Gustave-Roussy Group, to be presented Wejuif France by 7: Le
Tuesday, 12 August 1997
ORAL SESSION
N. Murray, R. Livingston, F. Shepherd, K. James, B. Zee, A. Langleben, M. Kraut, J. Bearden, J. Goodwin, C. Grafton, A. Turrisi, D. Walde, H. Croft, J. Ottaway. Kingston, Ontario, Canada The CODE regimen (J Clin Oncol9: 1632, 1991) was designed to deliver in 9 weeks as much cisplatin (225 mg/ms vs 225 mg/m*) and more: vincrtstine (5.0 mgfm2 vs 3.6 mg/m*), doxorubicin (200 mg/m2 vs 150 mg/m2) and etoposide (1080 mg/m2 vs 900 mgIm2) as alternating CAV and EP (Ann Intern Med 107:451,1987) administers in 18 weeks. Thoracic irradiation (30Gy/lOF) and cranial irradiation (25Gy/lOF) was recommended for patients (pts) without extrathoracic disease after CODE. Radiotherapy was optional for CAV/EP pts. Eligible ESCLC pts were ~68 years (yrs), PS O-2 and free of brain metastases. The arms were well matched for prognostic factors (median age 59.3 yrs). Both regimens were equally well delivered as over 70% of all pts actually received the intended protocol chemotherapy. Despite supportive prednisone, co-trimoxazole, and ketoconazole, febrile neutropenia occurred in 20% of CODE pts. Febrile neutropenia occurred in 17% of CAWEP pts. However, lo/110 (9.1%) pts on CODE died during chemotherapy whereas only l/109 died on CAWEP. Regimen CODE CAV/EP Response Rate CR PR 26.4% 40.0% 17.4% 04 9% Median ProgressionFree Survival 0.66 yrs 0.66 vrs Median Survival 0.96 yrs 0.69 “KS
Lung cancer is now the major cause of death among adult malignancies. The 5-year survival rate of patients with non small-cell lung cancer (NSCLC) who undergo complete surgical resection is only 40 to 50%. The individual data based meta-analysis recently performed (BMJ 1995) suggests a survival benefit of 5% at 5 years for patients treated with a cisplatin based chemotherapy. The IALT aims to determine the impact on overall survival of 3 or 4 cycles of chemotherapy including cisplatin and either vinca alkaloid or etoposide compared to no chemotherapy after complete surgery in patients with stage I, II and IIIA NSCLC. The trial started in 1995. At the end of 1996, 92 centers from 30 different countries throughout the world participated actively and 578 patients had been included. Among the patients included, median age is 59 years. Distribution by pathological stage is 36% for stage I, 23% for stage II and 41% for stage III. Two-thirds of patients have had a lobectomy. The patient accrual rate has been steadily increasing. Nevertheless, in order to randomize the more than 3000 patients needed to clarify the issue of adjuvant chemotherapy, a widespread collaboration and more participating centers are required. In breast and colorectal cancer, adjuvant systemic therapy has been widely recognized with trials randomizing more than 1000 patients and the benefit on survival is around 4%. If the beneficial effect of cisplatin based chemotherapy is confirmed with a reduction of mortality of 5 to lo%, adjuvant chemotherapy could become a standard and save several thousands of lives among the hundreds of thousand newly diagnosed lung cancer patients worldwide each year.