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Non-small cell lung cancer (NSCLC) is associated with IL-2-dependent cell-mediated immunodeficiency. As IL-2 is the main lymphocyte growth factor, a phase III randomized multicenter trial was conducted to evaluate the impact of subcutaneous low-dose IL-2 added to standard chemotherapy (CT) on overall survival (OS) in advanced NSCLC patients. Patients (n=241) with histologically confirmed stage IIIb or IV non-operable NSCLC underwent stratified randomization on the basis of center, ECOG PS, stage of disease and percentage of weight loss. Patients received gemcitabine (1000 mg/m2) on days 1 and 8 + cisplatin (100 mg/m2) on day 2 every 21 days for a maximum of 6 cycles [chemotherapy (CT) arm]. In the CT+IL-2 arm, patients also received low-dose subcutaneous IL-2 3,000,000 IU/die on days 3-5, 9-11, 15-17. The study had 90% power to detect a 20% absolute increase in 1-year OS with 118 patients/arm. An overall response (OR) rate of 12.8% (14% in the CT+IL-2 arm and 11.4% in CT arm) was observed. Stable disease was 70 and 66.7%, and progressive disease 16 and 21.8% in the CT+IL-2 and CT arms, respectively. No differences in response were found in any subgroup analysis. At a median follow-up of 32 months, 1-year OS was 45% for the CT+IL-2 arm vs. 51% for the CT arm (p=0.456 log-rank). Median progression-free survival was 6.6 months in the CT+IL-2 arm vs. 6.9 months in the CT arm (p=0.573, log-rank). A higher number of grade 4 toxicities were reported with CT+IL-2. The most common grade ≥3 adverse events were gastrointestinal toxicity (mainly nausea and diarrhea) and myelosuppression. No relevant differences in clinical outcome were observed from the addition of IL-2 to CT. Future studies investigating the role of T-regulators in chemoimmunotherapeutic regimens could be performed.

A total of 45 patients with advanced non-small-cell lung carcinoma were treated with a combination of cisplatin, teniposide, and mitomycin C. Most subjects exhibited good prognostic factors (performance status, 0-1; minimal weight loss; locoregional disease). Toxicity consisted mainly of myelosuppression and nausea and vomiting. Four patients died of sepsis due to chemotherapy-induced leukopenia. The response rate was 39.5%, with no complete responses being observed; the median duration of partial responses was 231 days and median survival was 243 days. Although the response rate and durations of both response and survival were comparable with those obtained using other cisplating-containing regimens, myelotoxicity was rather pronounced in the present study. Further studies of teniposide in this type of combination are not warranted.

Fifty patients with small-cell lung cancer (SCLC) were treated with teniposide (VM26) at 120 to 140 mg/m2 on days 1, 3, and 5, every 3 weeks. Twelve elderly patients were administered VM26 as first-line chemotherapy. Toxicity was manageable, myelosuppression being the major side effect. The response rate for 44 evaluable patients was 34% (36% for untreated patients); the median durations of response and survival were 230 and 208 days, respectively. Effectiveness of prior chemotherapy and time from last administration was found to influence patient response to VM26: 42% of responders to prior chemotherapy responded to VM26, while 0% of the nonresponders to prior chemotherapy responded to the new agent. Moreover, among patients pretreated with chemotherapy, 12% of those recently treated (earlier chemotherapy ending less than or equal to 2.6 months before administration of VM26) responded to VM26, while 53% of patients treated greater than 2.6 months earlier responded to VM26. Survival was influenced by common prognostic factors (performance status, weight loss, prior chemotherapy exposure). Selection of pretreated patients by type of exposure to prior chemotherapy may help in the testing of new drugs in this disease.

Fifty-one patients with advanced non-small cell lung carcinoma were treated with a combination of mitomycin C, vinblastine and cis-platin (MVP). Most cycles were given on an out-patient basis. Major side effects were leukopenia and peripheral neurotoxicity; one patient died of sepsis while leukopenic. In 44 evaluable patients the response rate was 50%, with one complete response. Overall median survival time was 280 days and median duration of responses was 232 days. A better performance status, disease limited to one hemithorax and no prior exposure to chemotherapy positively influenced the survival. MVP is an effective chemotherapy for non-small cell lung cancer and further experience with this combination is warranted.

Despite good results of chemotherapy in small cell lung cancer (SCLC), occurrence of brain metastases is frequent and unaffected by commonly employed antineoplastic drugs, mainly because they do not cross the blood-brain barrier. We treated eight patients with SCLC and cerebral metastases with VM26 at 120 mg/m2 given on days 1, 3 and 5 and repeated every 3 weeks. Two patients achieved complete response and one had partial response. Mean response duration was 8.2 months and survival was more than 9 months in responding patients. Toxicity was manageable. VM26 is an active drug in SCLC with brain metastases.

Thirteen patients with small cell lung cancer responsive to chemotherapy were retreated with the same regimen at relapse, after a median off-therapy time of 30 weeks. Fifty per cent responded to reinduction; two out of six patients who had complete response to first chemotherapy obtained complete response again at reinduction. Median survival time from start of any therapy was 94 weeks. When induction chemotherapy has been effective and of short duration, the same chemotherapy can be attempted again with success at relapse and it may affect survival of relapsing small cell lung cancer patients.