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406 Chapter 7: Solid Tumors<br />

SCLC have been treated with high-dose combination alkylating agents after<br />

response to conventional-dose induction therapy. Of the original cohort of 36<br />

limited-stage SCLC (all had stages III A or B disease), 29 were in or near complete<br />

response before treatment with high-dose cyclophosphamide, carmustine, <strong>and</strong><br />

cisplatin (CBP) with <strong>marrow</strong> ± PBPC support followed by chest <strong>and</strong> PCI. 62<br />

- 66<br />

For<br />

this group, the 5-year event-free survival is 53% (minimum follow-up 40 months,<br />

range to 11 years). Multivariate analysis suggests that response to induction is most<br />

important (CR or near CR vs. PR), but that short induction (four cycles or fewer)<br />

<strong>and</strong> the use of ifosfamide during induction also impart better prognosis. Of the<br />

extensive-stage patients, 17% remain progression free >2 years after high-dose<br />

therapy. Local regional relapse represents about 50% of all relapses.<br />

FUTURE DIRECTIONS<br />

Intensify involved field radiotherapy<br />

Meta-analyses of r<strong>and</strong>omized trials indicate that for LD SCLC, thoracic<br />

radiotherapy (TRT) provides a 25-30% improvement in local-regional control <strong>and</strong> a<br />

6 7 6 8<br />

5% increase in long-term progression-free survival for limited-stage SCLC.<br />

Local-regional relapse remains unacceptably high (about a 60% actuarial risk of local<br />

relapse by 3 years) with the routinely given 45-50 Gy TRT, 69-71<br />

<strong>and</strong> may be underestimated<br />

due to the competing risk of systemic relapse. 72<br />

Further enhancement of<br />

local-regional control might increase the proportion of long-term survivors.<br />

Dose intensity of chest radiotherapy has not been sufficiently studied. The<br />

Eastern Cooperative Oncology Group (ECOG) <strong>and</strong> the Radiation Therapy<br />

Oncology Group (RTOG) compared 45 Gy TRT given either daily over 5 weeks or<br />

twice a day over 3 weeks concurrent with cisplatin <strong>and</strong> etoposide chemotherapy. 73<br />

Two-year local-regional failure was reduced from 61 to 48% with the more intense<br />

TRT. With extended follow-up, a survival advantage for the more intensive<br />

radiotherapy is observed. 74<br />

In a prolonged phase I CALGB trial, Choi et al.<br />

escalated the dose of TRT in cohorts of five to six patients with limited-stage<br />

SCLC. 75<br />

Using a shrinking-field technique, TRT was given concurrently with<br />

cisplatin <strong>and</strong> etoposide either as daily 180 cGy fractions or as twice-a-day 150 cGy<br />

fractions. The maximal tolerated doses defined by acute esophagitis was 45 Gy for<br />

twice-a-day administration <strong>and</strong> 70 Gy when given once a day. Intensification of<br />

TRT dose is feasible <strong>and</strong> should be evaluated in a r<strong>and</strong>omized setting.<br />

Intensify induction<br />

The benefits of induction therapy include the reduction of tumor burden,<br />

stabilization of rapidly progressive systemic <strong>and</strong> local symptoms from SCLC,

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