Combination of three cytotoxic agents in small-cell lung cancer

Purpose

The established treatment for small-cell lung cancer has been a cisplatin–etoposide combination, as the most effective chemotherapy regimen. Paclitaxel has also been used in combination with cisplatin and etoposide but this has been unacceptable due to the toxicity. This toxicity could be attributed to the three consequent days of treatment with etoposide plus the doses of each of the three drugs. Our objectives were to determine an equal or longer survival and lower toxicity by administering all 3 drugs with low dosage on day one, compared to the established guideline of 3-day administration.

Methods

We tested the aforementioned three-drug combination and avoided the toxicity in the majority of patients by administering all 3 drugs on day one. Fifty-one patients (50 evaluable) were recruited from 4 oncology clinics. All patients had histologically or cytologically confirmed small-cell lung cancer with limited and extensive disease in 40 and 60 % of the patients, respectively. The treatment was: cisplatin 75 mg/m², etoposide 120 mg/m² (maximum 200 mg), and paclitaxel 135 mg/m². The agents were administered on day one and repeated every 3 weeks for 6 cycles.

Results

The median survival was 15 months (95 % CI 13.6–16.4) (mean 16 months). Forty-five (90 %) patients achieved a response: 20 (40 %) patients, a complete response and 25 (50 %), a partial response. Adverse reactions included grade 3 and 4 neutropenia in 12 and 2 % of the patients, respectively. Other side effects were of very low toxicity.

Conclusion

The 1-day, three-agent (cisplatin–etoposide–paclitaxel) treatment of small-cell lung cancer is beneficial with respect to response rate and survival, and the toxicity is low and well-tolerated.