Factors influencing treatment with chemotherapy
More patients with ED SCLC have greatly impaired performance status at the time of diagnosis than patients with LD. Such patients have a poor prognosis and tolerate aggressive chemotherapy or combined-modality therapy poorly. Single-agent intravenous, oral, and low-dose biweekly regimens have been developed for these patients.[30,35,36,37,38,39,40,41]
Prospective randomized studies have shown that patients with a poor prognosis who are treated with conventional regimens live longer than those treated with the single-agent low-dose regimens or abbreviated courses of therapy. A study comparing chemotherapy every 3 weeks with treatment given as required for symptom control showed an improvement in QOL in those patients receiving regular treatment.[Level of evidence: 1iiDii]
Other studies have tested intensive one-drug or two-drug regimens. A study conducted by the Medical Research Council demonstrated similar efficacy for an etoposide plus vincristine regimen and a four-drug regimen. The latter regimen was associated with a greater risk of toxic effects and early death but was superior with respect to palliation of symptoms and psychological distress.[Level of evidence: 1iiC] Studies comparing a convenient oral treatment with single-agent oral etoposide versus combination therapy showed that the overall response rate and OS were significantly worse in the oral etoposide arm.[35,40][Level of evidence: 1iiA]
Subgroup analyses of phase II and phase III trials of SCLC patients by age showed that myelosuppression and doxorubicin-induced cardiac toxic effects were more severe in older patients than in younger patients and that the incidence of treatment-related death tended to be higher in older patients. About 80% of older patients, however, received optimal treatment, and their survival was comparable to that of younger patients. The standard chemotherapy regimens for the general population could be applied to older patients in good general condition (i.e., performance status of 0-1, normal organ function, and no comorbidity). There is no evidence of a difference in response rate, disease-free survival (DFS), or OS in older patients compared with younger patients.
Radiation therapy to sites of metastatic disease unlikely to be immediately palliated by chemotherapy, especially brain, epidural, and bone metastases, is a standard treatment option for patients with ED SCLC. Brain metastases are treated with whole-brain radiation therapy.
Chest radiation therapy is sometimes given for superior vena cava syndrome, but chemotherapy alone, with radiation reserved for nonresponding patients, is appropriate initial treatment. (Refer to the PDQ summary on Cardiopulmonary Syndromes for more information.)
Prophylactic cranial irradiation (PCI)
Patients with ED treated with chemotherapy who have achieved a response can be considered for administration of PCI.
- A randomized trial of 286 patients with response following four to six cycles of chemotherapy compared PCI versus no further therapy with symptomatic brain metastases.[Level of evidence: 1iiD
- The cumulative risk of brain metastases within 1 year was 14.6% in the radiation group (95% CI, 8.3-20.9) and 40.4% in the control group (95% CI, 32.1- 48.6).
- Radiation was associated with an increase in median DFS from 12.0 weeks to 14.7 weeks and in median OS from 5.4 months to 6.7 months after randomization.
- The 1-year survival rate was 27.1% (95% CI, 19.4-35.5) in the radiation group and 13.3% (95% CI, 8.1-19.9) in the control group.
- Radiation had side effects but did not have a clinically significant effect on global health status.