Guy Vandermoten

A randomized study comparing cisplatin or carboplatin with etoposide in patients with advanced non-small-cell lung cancer: European Organization for Research and Treatment of Cancer Protocol 07861.

The European Organization for Research and Treatment of Cancer (EORTC) Lung Cancer Working Party conducted a randomized trial comparing cisplatin (CDDP; 120 mg/m2, day 1) and carboplatin (CBDCA; 325 mg/m2, day 1) in combination with etoposide (VP16; 100 mg/m2, days 1, 2, and 3) in advanced non-small-cell lung cancer (NSCLC). Two hundred twenty-eight patients were eligible for survival and 202 assessable for response. We obtained 27 of 100 objective responses (ORs; 27%) in the CDDP arm and 16 of 102 (16%) in the CBDCA arm (P = .07). There was no significant difference in survival. Toxicity, consisting mainly of myelosuppression and renal function impairment, was significantly increased in the patients receiving the CDDP treatment. We conclude that CDDP plus VP16 was more active but also more toxic than CBDCA plus VP16 in advanced NSCLC.

A randomized study comparing a high and a standard dose of cisplatin in combination with etoposide in the treatment of advanced non-small-cell lung carcinoma.

We conducted a randomized trial comparing a high (120 mg/m2 day 1) v a standard (60 mg/m2 day 1) dose of cisplatin in combination with etoposide (120 mg/m2 days 3, 5, and 7) in advanced non-small-cell lung carcinoma (NSCLC). Two hundred forty-one patients were evaluable for survival and 207 for response. We obtained a 25% objective response rate in the standard-dose arm and 29% in the high-dose arm; this difference was not statistically significant. There was no significant improvement in the overall survival or survival of responders with the high-dose regimen. However, toxicity (mainly myelosuppression) was significantly increased in the patients receiving the higher dose of cisplatin. An analysis of prognostic factors showed that disease progression, loss of body weight, performance status, and prior therapy were predictive parameters of survival.

Cisplatin versus cisplatin plus etoposide in the treatment of advanced non-small-cell lung cancer. Lung Cancer Working Party, Belgium.

We conducted a randomized study comparing the survival after treatment with cisplatin (120 mg/m2) or cisplatin plus etoposide (100 mg/m2 on days 1, 2, and 3) in 162 evaluable patients with advanced non-small-cell lung cancer (NSCLC). No statistically significant difference in survival was detected; the median survival was 26 and 22 weeks, respectively, for patients receiving cisplatin and for those receiving cisplatin plus etoposide. The objective response rate was 19% for cisplatin and 26% for the combination; the corresponding response rates were 17% and 43% in patients with limited disease. No significant differences were detected between the two study arms as far as toxicity was concerned, except for alopecia and granulocytopenia, which occurred more frequently in patients treated with cisplatin plus etoposide.

Multiple-drug weekly chemotherapy versus standard combination regimen in small-cell lung cancer: a phase III randomized study conducted by the European Lung Cancer Working Party.

PURPOSE A randomized trial was conducted in patients with small-cell lung cancer (SCLC) to determine if survival can be improved by a weekly chemotherapy regimen combining various drugs. PATIENTS AND METHODS Two hundred twenty-three patients were randomized to receive either six courses of a multiple-drug combination (MDC) regimen (Adriamycin [ADR; doxorubicin; Farmitalia Carlo Erba, Milan, Italy] 25 mg/m2 intravenously [i.v.] on day 1; etoposide [VP16] 120 mg/m2 i.v. on day 1; cyclophosphamide [CPA] 500 mg/m2 i.v. on day 1; cisplatin 60 mg/m2 i.v. on day 8; vindesine [VDS] 3 mg/m2 i.v. on day 8; vincristine [VCR] 2 mg i.v. on day 15; methotrexate [MTX] 100 mg/m2 i.v. on day 15), or a standard chemotherapy (SC) regimen (ADR 50 mg/m2 i.v. on day 1; CPA 1 g/m2 i.v. on day 1; VP16 80 mg/m2 i.v. on days 1 to 3). RESULTS In 98 MDC-treated and 101 SC-treated assessable patients, we observed 69% and 62% objective responses rates, respectively. There was no significant difference in survival, with median durations and 2-year overall survival rates of 49 and 43 weeks and 8.5% and 7.9%, respectively. There was a significant increase in response rate in favor of MDC patients with limited disease (84% v 62%). Toxicity was tolerable, although SC was more hematotoxic, with 76% (v 59%) experiencing leukopenia and 17% (v 7%) experiencing thrombocytopenia (grades III and IV). If the cumulative doses received were nearly equal to the scheduled cumulative doses in both arms, the total relative dose-intensity (RDI) was significantly higher in the SC arm. The difference was due to increased treatment delays in the MDC arm. CONCLUSION Weekly MDC failed to improve survival rates in patients with SCLC.

Combination chemotherapy with adriamycin, etoposide, and cyclophosphamide for small cell carcinoma of the lung. A study by the EORTC lung cancer working party (Belgium)

The current study reports the results of Adriamycin (doxorubicin), etoposide, and cyclophosphamide (AVE) in small cell bronchogenic carcinoma. The overall rate of response was 82% in patients with limited disease and 66% in patients with extensive disease; complete remissions have been achieved in 20% of the patients with limited disease and in 7% of those with extensive disease. The median duration of survival was 14 months in patients with limited disease and 8.3 months in those with extensive disease. The results, and the analysis of literature, suggest that survival rather than response should be used to compare studies of chemotherapy in small cell bronchogenic carcinoma.

A phase II study evaluating CAVi (cyclophosphamide, adriamycin, vincristine) potentiated or not by amphotericin B entrapped into sonicated liposomes, as salvage therapy for small cell lung cancer

Abstract Two consecutive trials were conducted, testing the CAVi (cyclophosphamide 1 g/m 2 ; doxorubicin (adriamycin) 45 mg/m 2 ; vincristine 1.4 mg/m 2 ; all i.v. on day 1; every 3 weeks) combination as salvage therapy for small cell lung cancer (SCLC) after first line treatment with etoposide plus vindesine with or without cisplatin. In the first study, CAVi was used alone. In 45 evaluable patients, 6 objective responses were observed (13%; Confidence Limits (C.L.): 5.1–20.8). In the second study, CAVi was potentiated with 2 mg/kg of ampholiposomes given i.v., 24 h prior to chemotherapy. Ampholiposomes consisted of amphotericin B entrapped into sonicated liposomes made of egg lecithin, cholesterol and stearylamine in the molar ratio 4:3:1 (lipid concentration: 20 mg/ml). Among 11 evaluable patients, 6 objective responses were observed (55%; Confidence Limits: 23.4–83.3) and toxicity was not increased. These preliminary results suggest that ampholiposomes might overcome resistance to chemotherapy in SCLC and should encourage controlled studies.