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Stage IIIA NSCLC Treatment

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    The addition of sequential and concurrent chemotherapy to radiation therapy has been evaluated in prospective randomized trials and meta-analyses. Overall, concurrent treatment may provide the greatest benefit in survival with increase in toxic effects.

    Concomitant platinum-based radiation chemotherapy may improve survival of patients with locally advanced NSCLC. However, the available data are insufficient to accurately define the size of such a potential treatment benefit and the optimal schedule of chemotherapy.[29]

    Evidence (chemoradiation therapy):

    1. A meta-analysis of patient data from 11 randomized clinical trials showed the following:[30]
      • Cisplatin-based combinations plus radiation therapy resulted in a 10% reduction in the risk of death compared with radiation therapy alone.[30][Level of evidence: 1iiA]
    2. A meta-analysis of 13 trials (based on 2,214 evaluable patients) showed the following:[31]
      • The addition of concurrent chemotherapy to radical radiation therapy reduced the risk of death at 2 years (relative risk [RR], 0.93; 95% CI, 0.88–0.98; P = .01).
      • For the 11 trials with platinum-based chemotherapy, RR was 0.93 (95% CI, 0.87–0.99; P = .02).[31]
    3. A meta-analysis of individual data from 1,764 patients was based on nine trials and showed the following:[29]
      • The HR of death among patients treated with radiation therapy and chemotherapy compared with radiation therapy alone was 0.89 (95% CI, 0.81–0.98; P = .02), corresponding to an absolute benefit of chemotherapy of 4% at 2 years.
      • The combination of platinum with etoposide seemed more effective than platinum alone.

    Concurrent versus sequential chemoradiation therapy

    The results from two randomized trials (including RTOG-9410) and a meta-analysis indicate that concurrent chemotherapy and radiation therapy may provide greater survival benefit, albeit with more toxic effects, than sequential chemotherapy and radiation therapy.[32,33,34][Level of evidence: 1iiA]

    Evidence (concurrent vs. sequential chemoradiation therapy):

    1. In the first trial, the combination of mitomycin C, vindesine, and cisplatin were given concurrently with split-course daily radiation therapy to 56 Gy compared with chemotherapy followed by continuous daily radiation therapy to 56 Gy.[32]
      • Five-year OS favored concurrent therapy (27% vs. 9%).
      • Myelosuppression was greater among patients in the concurrent arm, but treatment-related mortality was less than 1% in both arms.[32]
    2. In the second trial, 610 patients were randomly assigned to sequential chemotherapy with cisplatin and vinblastine followed by 60 Gy of radiation therapy, concurrent chemotherapy, or concurrent chemotherapy with cisplatin and vinblastine with twice-daily radiation therapy.[33]
      • Median and 4-year survival were superior in the concurrent chemotherapy with daily radiation therapy arm (17 mo vs. 14.6 mo and 21% vs. 12% for sequential regimen [P = .046]).[33]
    3. Two smaller studies also reported OS results that favored concurrent over sequential chemotherapy and radiation, although the results did not reach statistical significance.[34,35][Level of evidence: 1iiA]
    4. A meta-analysis of three trials evaluated concurrent versus sequential treatment (711 patients).[31]
      • The analysis indicated a significant benefit of concurrent over sequential treatment (RR, 0.86; 95% CI, 0.78–0.95; P = .003). All studies used cisplatin-based regimens and once-daily radiation therapy.[31]
      • More deaths (3% OS rate) were reported in the concurrent arm, but this did not reach statistical significance (RR, 1.60; CI, 0.75–3.44; P = .2).
      • There was more acute esophagitis (grade 3 or worse) with concurrent treatment (range = 17%–26%) compared with sequential treatment (range = 0%–4%; RR, 6.77; P = .001). Overall, the incidence of neutropenia (grade 3 or worse) was similar in both arms.
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