A randomized combined modality trial in small cell carcinoma of the lung comparison of combination chemotherapy-radiation therapy versus cyclophosphamide-radiation therapy effects of maintenance chemotherapy and prophylactic whole brain irradiation

Abstract

A randomized trial of combined modality therapy employing combination chemotherapy (cyclophosphamide (CTX) and methotrexate (MTX), CTX, MTX and Vincristine (VCR) and CTX, VCR and high-dose MTX with citrovorum rescue) and radiation therapy was compared to cyclophosphamide and radiation therapy in 258 patients with pulmonary small cell carcinoma. Patients were also rendomized: 1) to determine the effects of prophylactic whole brain irradiation; and 2) to establish the effects of maintenance chemotherapy. Survival, frequency of response and site of relapse were different in patients with limited disease (LD) (disease confined to lung, mediastinum and supraclavicular lymph nodes) when compared with disease spread beyond these sites (extensive disease) (ED). No survival advantage was seen in LD when combination chemotherapy was employed, although the frequency of complete remission was greater with three drugs than with one or two drugs (40% vs. 32%). In ED frequency of response was greater for three drugs than for one and two drugs (60% vs. 40%), but there was no survival advantage. The median survival time for complete responders was similar for limited or extensive disease (12.1 months), but 23.8% were alive at 24 months with LD compared to none with ED. Maintenance chemotherapy significantly prolonged survival by 16.8 months with 33% alive at 24 months compared to 9% who were unmaintained. Prophylactic while brain irradiation prevented brain metastases with only 4% developing this complication as compared to 18% of control subjects, but did not influence survival.

Pro‐gastrin–releasing peptide as a factor predicting the incidence of brain metastasis in patients with small cell lung carcinoma with limited disease receiving prophylactic cranial irradiation

“…15 However, the metaanalysis included various trials and often insufficient systemic chemotherapy regimens, different PCI techniques, and a mixed population of patients with limited and extensive disease. [12][13][14][15] Therefore, Kotalik et al 18 found there was insufficient evidence to make a definitive recommendation in terms of the total dose, fractionation, indication, and timing of PCI according to this metaanalysis. In the current study, 16.9% of patients had brain metastasis as a first site of failure, which is consistent with previous reports of 4 -24%.…”

“…In the current study, 16.9% of patients had brain metastasis as a first site of failure, which is consistent with previous reports of 4 -24%. 6,[12][13][14] The salvage treatment for brain metastasis after PCI would be restricted by the number of brain metastases, patient condition, and previous irradiation. To our knowledge, no report has described the predictive or prognostic factors for outcomes after PCI.…”

“…10,11 Although several randomized trials of prophylactic cranial irradiation (PCI) have attempted to reduce the risk of brain metastasis and to improve survival, to our knowledge its role in the management of patients with SCLC has remained controversial according to the results of each trial. [12][13][14] Recently, the metaanalysis of these trials comparing PCI with no-PCI found that PCI led to a small but significant absolute reduction in mortality (5.4%), and that PCI not only significantly reduced the risk of brain metastasis, but also improved both overall survival (OS) and disease-free survival among patients with SCLC in CR. 15 These results suggest that PCI should be considered as a part of the standard treatment for patients with limited disease SCLC who achieved CR or good partial remission (PR).…”

“…6,[12][13][14] Whole-brain irradiation (WBRT) for brain recurrence was often difficult because these patients had already received PCI to the whole brain. Therefore, we should strictly consider PCI for patients who could achieve a true CR, as assessed with diagnostic imaging.…”

Cranial irradiation in small cell lung cancer

“…Majority of the nine published randomised trials confirm that PCI in doses of about 30 Gy reduces significantly the incidence of brain relapse (Jackson, 1985;Cox, 1978;Beiler, 1979;Maurer, 1980;Hansen, 1980;Eagan, 1981;Katsenis, 1982;Seydel, 1983). There is regrettably only one published trial in patients with a complete response to chemotherapy (Aroney, 1983).…”