Prophylactic Cranial Irradiation for Patients With Small-Cell Lung Cancer in Complete Remission

Institut Gustave-Roussy, Radiotherapy Department, Villejuif, France.
JNCI Journal of the National Cancer Institute (Impact Factor: 15.16). 03/1995; 87(3):183-90. DOI: 10.1093/jnci/87.3.183
Source: PubMed

ABSTRACT Prophylactic cranial irradiation in patients with small-cell lung cancer decreases the overall rate of brain metastases without an effect on overall survival. It has been suggested that this treatment may increase neuropsychological syndromes and brain abnormalities indicated by computed tomography scans. However, other retrospective data suggested a beneficial effect on overall survival for patients in complete remission.
Our purpose was to evaluate the effects of prophylactic cranial irradiation on brain metastasis, overall survival, and late-occurring toxic effects in patients with small-cell lung cancer in complete remission.
We conducted a prospective study of 300 patients who had small-cell lung cancer that was in complete remission. The patients were randomly assigned to receive either prophylactic cranial irradiation delivering 24 Gy in eight fractions during 12 days (treatment group) or no prophylactic cranial irradiation (control group). A neuropsychological examination and a computed tomography scan of the brain were performed at the time of random assignment and repeatedly assessed at 6, 18, 30, and 48 months. Patterns of failure were analyzed according to total event rates and also according to an isolated first site of relapse, using a competing-risk approach.
Two hundred ninety-four patients who did not have brain metastases at the time of random assignment were analyzed. The 2-year cumulative rate of brain metastasis as an isolated first site of relapse was 45% in the control group and 19% in the treatment group (P < 10(-6)). The total 2-year rate of brain metastasis was 67% and 40%, respectively (relative risk = 0.35; P < 10(-13)). The 2-year overall survival rate was 21.5% in the control group and 29% in the treatment group (relative risk = 0.83; P = .14). There were no significant differences between the two groups in terms of neuropsychological function or abnormalities indicated by computed tomography brain scans.
Prophylactic cranial irradiation given to patients with small-cell lung cancer in complete remission decreases the risk of brain metastasis threefold without a significant increase in complications. A possible beneficial effect on overall survival should be tested with a higher statistical power.
The results of the trial favor, at present, the indication of prophylactic cranial irradiation for patients who are in complete remission. A longer follow-up and confirmatory trials are needed to fully assess late-occurring toxic effects. The possible effect on overall survival needs to be evaluated with a larger number of patients in complete remission, and a meta-analysis of similar trials is recommended.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This randomised trial compared platinum-based to anthracycline-based chemotherapy in patients with small-cell lung cancer (limited or extensive stage) and <or=2 adverse prognostic factors. Patients were randomised to receive six cycles of either ACE (doxorubicin 50 mg/m(2) i.v., cyclophosphamide 1 g/m(2) i.v. and etoposide 120 mg/m(2) i.v. on day 1, then etoposide 240 mg/m(2) orally for 2 days) or PE (cisplatin 80 mg/m(2) and etoposide 120 mg/m(2) i.v. on day 1, then etoposide 240 mg/m(2) orally for 2 days) given for every 3 weeks. For patients where cisplatin was not suitable, carboplatin (AUC6) was substituted. A total of 280 patients were included (139 ACE, 141 PE). The response rates were 72% for ACE and 77% for PE. One-year survival rates were 34 and 38% (P=0.497), respectively and 2-year survival was the same (12%) for both arms. For LD patients, the median survival was 10.9 months for ACE and 12.6 months for PE (P=0.51); for ED patients median survival was 8.3 months and 7.5 months, respectively. More grades 3 and 4 neutropenia (90 vs 57%, P<0.005) and grades 3 and 4 infections (73 vs 29%, P<0.005) occurred with ACE, resulting in more days of hospitalisation and greater i.v. antibiotic use. ACE was associated with a higher risk of neutropenic sepsis than PE and with a trend towards worse outcome in patients with LD, and should not be studied further in this group of patients.
    British Journal of Cancer 09/2008; 99(3):442-7. DOI:10.1038/sj.bjc.6604480 · 4.82 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Patients who are treated within clinical trials may have a survival benefit dependent on being a trial participant. A number of factors may produce such beneficial outcome including more rigorous adherence to a peer reviewed trial protocol, management by an experienced treatment team, being treated in a specialist centre etc. The current investigation compared patients treated on and off trial with the same standard arm treatment regimen. The results could then be interpreted without the confounding factors of differing treatment regimens, treatment teams or treatment hospitals. The results demonstrated given these circumstances that survival was no different for patients participating in a randomised trial compared with a group of patients similarly treated who were not eligible for trial entry or who declined randomisation. These results were obtained by the rigorous adherence to a defined protocol with the invaluable assistance of designated lung cancer staff. British Journal of Cancer (2002) 87, 562–566. doi:10.1038/sj.bjc.6600433 © 2002 Cancer Research UK
    British Journal of Cancer 09/2002; 87(5):562-6. DOI:10.1038/sj.bjc.6600433 · 4.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chemotherapy is the backbone in the treatment of small cell lung cancer (SCLC) and radiotherapy is an important adjunct in limited stage disease. The role of chest irradiation is now documented in three meta-analysis, based on the same body of data. Trials on timing, scheduling and fractionation could have followed a more stringent development line but altogether, the highest efficacy seems to be obtained with early, concurrent twice-daily chest irradiation. Patients in complete remission should have prophylactic cranial irradiation, which reduces the risk of brain metastases and of death from SCLC. Four series of chemotherapy seem to be sufficient in limited-stage disease while six is recommended in extensive disease. The combination of etoposide plus cis- or carboplatin is appropriate in both stages and addition of other agents has no clinically important impact on the survival. Use of haematological growth factors such as granulocyte colony stimulating factor (G-CSF) and granulocyte macrophage colony stimulating factor (GM-CSF) may enable higher doses or more frequent dosage. Three randomized trials on GM-CSF showed a negative outcome while G-CSF support may result in better survival rates, but a more cost-efficient policy must be found. High-dose chemotherapy plus haematological stem-cell support is still under investigation but disappointing long-term survival rates means there is not much optimism for this strategy. New strategies in general are requested in the treatment of extensive-stage disease and of elderly patients. Phase II trials suggest that good-risk patients with extensive disease should be treated aggressively, intermediate-risk patients more gently, and palliation must be the primary aim in the treatment of poor-risk patients. In elderly patients impressive survival rates are obtained with 3-4 series of chemotherapy and radiation delivered in 5-10 fractions. A number of new agents are active but more trials are required before each has found a place, if any, in the treatment of small cell lung cancer. To conclude, the randomized trial is still an important instrument in clinical oncology, and trials in small cell lung cancer must be large, which is why the cooperation of organizations and multicentres is urgent.
    European Respiratory Journal 01/2002; 18(6):1026-43. DOI:10.1183/09031936.01.00266101 · 7.13 Impact Factor