H. de Cremoux

Competing events determining relapse-free survival in limited small-cell lung carcinoma. The French Cancer Centers' Lung Group.

PURPOSE We report results in terms of relapse-free survival (RFS), obtained in patients with limited small-cell lung carcinoma (SCLC) treated by four consecutive alternating protocols, using a competing risk approach with local recurrences, distant metastases, and death unrelated to cancer as competing events. PATIENTS AND METHODS Two hundred two patients with limited SCLC were included in four consecutive protocols alternating radiotherapy and chemotherapy (CT). The alternating schedule consisted of six cycles of CT (doxorubicin, etoposide [VP16213], and cyclophosphamide [CAVP16], plus methotrexate in the first protocol; cisplatin replaced methotrexate in the other three protocols) and three courses of thoracic radiotherapy at a total dose of 45, 55, 65, and 61 Gy in the four consecutive protocols, respectively (accelerated hyperfractionation was used in the first course of the fourth protocol). A 1-week rest followed each CT cycle and each course of radiotherapy. Seventy-six percent of patients were in complete remission at the end of the induction treatment. RFS variables were determined according to a model assuming competing risks to define the first cause of failure (local disease, distant metastasis, or intercurrent death). RESULTS No significant differences were observed between the four treatment groups. Overall results showed a 2-year cumulative incidence rate of failure of 75%. When analyzed, the first cause of failure was local recurrence only, 33%; distant only, 25%; distant and local simultaneously, 9%; and intercurrent death, 8%. CONCLUSIONS The methodology of competing risks allowed an unequivocal description of first events in limited SCLC. The extent of the local problem has been relatively overshadowed by the use of conventional descriptive methods.

Alternating radiotherapy and chemotherapy in 173 consecutive patients with limited small cell lung carcinoma

One-hundred seventy-three patients with limited small cell lung cancer were included in three consecutive protocols alternating radiotherapy and chemotherapy. The alternating schedule consisted of six courses of chemotherapy (doxorubicin, VP16213, cyclophosphamide, and methotrexate in the first protocol; methotrexate being replaced by cisplatinum in the other two protocols) and three series of thoracic radiotherapy delivering a total dose of 45, 55, and 65 Gy in each consecutive protocol. Radiotherapy was started after the second course of chemotherapy. A 1-week gap was respected between each course of chemotherapy and each series of radiotherapy. Seventy percent of patients were in complete remission at the end of the induction treatment. The actuarial 5-year local control was 60% and the 5-year overall survival was 18%. Sixty percent of patients developed distant metastases. The death rate unrelated to cancer was 10%. These results show that alternating radiotherapy and chemotherapy schedules are reproducible, and provide a consistent long-term local control and a long-term survival rate exceeding 15% in limited disease.

Dose intensity of initial chemotherapy may have an impact on survival in limited small cell lung carcinoma

Abstract The analysis of the outcome of 131 patients with limited small cell lung cancer (SCLC) from two consecutive phase II trials which used the same drugs suggested that the intensity of the first course of chemotherapy was a prognostic factor in SCLC. The T3 stage of the TNM classification was the only clinical factor found to be prognostic for overall survival. Irrespective if the T3 stage was controlled or not by multivariate analysis, we found that overall survival rate increased with the dose of cyclophosphamide administered during the first course. A U-shaped dose-response relationship was observed for cisplatinum; survival was ostensibly better for doses ranging from 85 to 105 mg/m 2 . When both drugs were taken into account in the analysis, the effect on overall survival remained significant.

Alternating radiotherapy and chemotherapy in limited small cell lung cancer: the IGR protocols

Two-hundred two patients with limited small cell lung cancer were tested by four consecutive alternating radiotherapy and chemotherapy protocols. The alternating schedule consisted of six cycles of chemotherapy (doxorubicin, etoposide, and cyclophosphamide, plus methotrexate in the first protocol; cisplatin replaced methotrexate in the other three protocols) and three courses of thoracic radiotherapy at a total dose of 45, 55, 65 and 61 Gy in the four consecutive protocols, respectively. A 1-week rest followed each chemotherapy cycle and each course of radiotherapy. Seventy-six percent of patients were in complete remission at the end of the induction treatment. Overall results showed a 2-year cumulative incidence rate of failure of 75%. The first cause of failure was local recurrence only, 33%; distant only, 25%; distant and local simultaneously, 9%; and intercurrent death, 8%. Overall survival rate at 5 years was 16%. No significant differences were observed between the four treatment groups. Alternating radio-chemotherapy approaches are feasible and currently included in Phase III trials.

An open phase II trial of gemcitabine, oxaliplatin and vinorelbine combination as first-line therapy in advanced non-small cell lung cancer patients.

The purpose of this multicentric Phase II study was to evaluate the safety and efficacy of a gemcitabine/oxaliplatin/vinorelbine combination as first-line therapy in advanced non-small cell lung cancer patients. Patients followed a fortnightly drug schedule, receiving on day 1, vinorelbine 25mg/m(2) (20-min infusion); gemcitabine 700 mg/m(2) (70-min infusion, fixed 10mg/m(2)/min); and on day 2, oxaliplatin 85 mg/m(2) (2-h infusion). Thirty-nine patients with a median age of 58 years received a total of 306 cycles (median 8 cycles); 67% were males. Most had adenocarcinoma (51%), large-cell (23%) and squamous cell carcinoma (21%); 15% had stage IIIB and 85% stage IV. There was one complete response (3%; 95% CI: 0.1-13%), 15 partial responses (PR) (38%; 95% CI: 23-55%), and 13 patients with stable disease (33%; 95% CI: 19-50%) of at least 2 months duration, for an overall non-progression rate of 74%. Median progression-free survival (PFS) was 4.1 months (95% CI: 3.1-8.7) and overall survival was 11.7 months (95% CI: 7.7-19.4). No treatment-related deaths occurred and very few grade 3-4 events were observed. Overall, the regimen was well tolerated and the planned recommended dose intensity was safely delivered to more than 95% of patients. This triple combination therapy study yielded favourable efficacy and toxicity results, which merit further evaluation in prospective randomised trials.