We have studied the clinical impact of elective brain irradiation (EBI) in patients with locally advanced, non-small cell lung cancer (LA-NSC). All patients received combination chemotherapy (cyclophosphamide + doxorubicin (Adriamycin) + cisplatin = CAP) or CAP plus radiotherapy as the initial treatment for their active tumor or as an adjuvant therapy. Of 97 evaluable patients, 46 were randomized to receive EBI (3 000 rad in 10 fractions given over two weeks). The characteristics of both groups were comparable by sex, age, performance status, pretherapy weight loss, histologic cell type, clinical staging, and type of prior therapy. EBI significantly decreased the incidence of central nervous system (CNS) metastasis in the treated group compared to the control group (4% vs 27%, p = .002). CNS involvement occurred in the treated group after failure at other sites whereas 12 of 14 control patients had CNS metastases as the first site of relapse. EBI decreased the incidence of CNS metastasis in all prognostic categories. Using multivariate analysis, the beneficial effect was shown to be significant in females, patients with good performance status, weight loss less than 6%, squamous cell histology, state III disease or no prior therapy. EBI significantly increased CNS metastasis-free interval with a beneficial effect that was significant in males, patients with weight loss less than 6%, squamous cell histology or responders. Although no survival benefit was observed for the treated group because of the adverse effect from other relapses, EBI will become more important as better treatment programs are developed.(ABSTRACT TRUNCATED AT 250 WORDS)

One hundred sixty-seven evaluable patients with non-small-cell lung cancer were randomized to receive high-dose cisplatin and vindesine (PVD), or cisplatin and VP-16-213 (etoposide epipodophyllotoxin) (PVP), or cisplatin with VP-16-213 and vindesine (PVPVD). The patient distribution and characteristics were similar in all the treatment arms. The response rate differences (35% in PVD arm, 30% in PVP arm, and 22% in PVPVD arm) were not statistically significant (P = .33). Response durations were 43 weeks in the PVD arm, 20 weeks in the PVP arm, and 27 weeks in the PVPVD arm. Median survival was 29 weeks in the PVD and PVP arms and 28 weeks in the PVPVD arm. Median survival time of responding patients was 76 weeks in the PVD arm and 65 weeks in the PVP arm; 78% of patients were alive at 22+ to 87+ weeks follow-up in the PVPVD arm. Myelosuppression was similar in all three treatment arms. Significantly more azotemia occurred in the PVD arm than in the PVP and PVPVD arms (P = .002), and significantly more neuropathy in the PVD and PVPVD arms than in the PVP arm (P = .003 and .005). All the treatment arms have similar antitumor activity in non-small-cell lung cancer, but the PVP combination is slightly less toxic than the PVD and PVPVD treatment arms.

The efficacy and toxicity of high-dose chemotherapy with autologous bone marrow transplantation (ABMT) was studied in 32 patients with untreated limited small-cell bronchogenic carcinoma (SCBC). Ten patients received three courses of induction therapy consisting of vincristine (VCR) (1.5 mg X 2), ifosfamide (5 g/m2), and Adriamycin (Ad; Adria Laboratories, Columbus, Ohio) (60 mg/m2). Patients then received two courses of intensification therapy with cyclophosphamide (CYT) (4.5 g/m2), 4' demethyl-epipodophyllotoxin-d-D-ethylidene glucoside (VP-16-213) (600 mg/m2) and VCR (2 mg) with ABMT. Another 22 patients received induction therapy with VCR, CYT (600 mg/m2), Ad (50 mg/m2), and VP-16-213 (180 mg/m2). All 22 patients also received intensification therapy of the same dose of CYT (4.5 g/m2) and VP-16-213 (600 mg/m2). Nine patients also received high-dose methotrexate (MTX), four patients received Ad (40 to 60 mg/m2), and two patients received both Ad and MTX. After intensification, patients received elective prophylactic brain irradiation (3,000 rad) and chest irradiation (5,000 rad). After induction therapy, there were 13 (41%) complete remissions (CR) and 17 (53%) partial remissions (PR). After intensification therapy, there were 22 CRs (69%) and 10 PRs (31%). Median survival for all patients was 14 months (range, 5 to 59+). Of the 13 patients who received intensification therapy in CR, five remain disease free (DF), four for 4 years or longer. Of the nine patients to achieve CR with intensification, only one is DF. No patient died during intensification. In conclusion, intensification with high-dose chemotherapy can increase the CR rate, and this approach is most likely to show long-term benefits in patients with minimal disease (CR) at the beginning of intensification therapy.

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