Chemotherapy combinations in the treatment of patients with extensive small-cell lung cancer

This phase III study compared the benefit of three chemotherapy combinations as first line treatment (the first choice of treatment) for extensive disease small-cell lung cancer (ED-SCLC) patients. Topotecan–cisplatin (TP) combination treatment, topotecan–etoposide (TE) combination treatment, and cisplatin-etoposide (PE) combination treatment, were compared to investigate both the efficacy and safety of these therapy strategies.

Chemotherapy (including drugs such as cisplatin, carboplatin, paclitaxel, gemcitabine, topotecan and etoposide) is to date the most effective treatment strategy for delaying the progression of ED-SCLC, and extending survival. For many years, the cisplatin and etoposide (PE) combina­tion has represented the standard of care first-line treatment for ED-SCLC worldwide. However, the vast majority of patients treated with PE chemotherapy experience a relapse after 6 to 8 months. For most patients, overall survival rates range from 8.4 to 10.2 months. In addition, since chemotherapy drugs are toxic to both cancer and healthy cells, treatment is often associated with severe side effects. This emphasizes the need for the examination of new treatment strategies.

Topotecan is approved for the treatment of ED-SCLC patients who have already relapsed after first-line therapy. However, as first-line treatment, the topotecan-cisplatin combination chemotherapy has never been examined in a large trial.

795 previously untreated patients with extensive disease SCLC were randomly assigned to receive one of three different chemotherapy combinations. 358 patients received TP (topotecan and cisplatin) therapy, 345 patients received PE (cisplatin and etoposide) therapy and 92 patients received TE (topotecan and etoposide) therapy. Recruitment to the TE combination group was stopped prematurely due to safety concerns.

After 1 year, the survival rate of TP treated patients was 39.7%, compared to 36.1% for PE treated patients. However, results regarding survival varied widely, rendering them statistically inconclusive despite the trend towards better survival with TP treatment.

Overall tumor response rates were significantly higher for TP treatment. 55.5% of patients treated with TP showed some response to treatment (as measured by the change in tumor size), compared to 45.5% of patients treated with PE. The time to pro­gression of the disease (the average time between treatment and until the disease worsens) was also significantly longer with TP treatment. Average time to progression was 27.4 weeks for patients treated with TP, compared to 24.3 weeks for patients treated with PE.

Serious side effects were also slightly more common with TP treatment compared to PE. These included neutropenia (dangerously low immune cell count), thrombocytopenia (low platelet count which could increase the risk of bleeding), anemia (reduced capacity of the blood to carry oxygen requiring blood transfusions).

In conclusion, this trial showed that topotecan–cisplatin (TP) combination was better than the standard of care cisplatin–etoposide (PE) combination in the treatment of extensive disease small-cell lung cancer. However, this combination also raises the risk for severe toxic side effects.

Due to the increased risk of severe toxic side effects, TP combination treatment is unlikely to replace PE as the standard of care, first line therapy in the treatment of SCLC patients.

Consult with your physician regarding the benefits and risks of the different chemotherapy combinations available for the treatment of extensive small-cell lung cancer.