"Twice-Daily versus Once-Daily Thoracic Radiotherapy in Limited Small-Cell Lung Cancer Treated with Cisplatin and Etoposide". New England Journal of Medicine. 1999. 340(4):265-271. PubMed • Full text • PDF

Contents

1 Clinical Question
2 Bottom Line
3 Major Points
4 Design
5 Population
5.1 Inclusion Criteria
5.2 Exclusion Criteria
5.3 Baseline Characteristics
6 Interventions
7 Outcomes
7.1 Primary Outcome
7.2 Secondary Outcomes
8 Funding
9 Further Reading

Clinical Question

In patients with limited small-cell lung cancer, does twice-daily thoracic radiotherapy improve survival compared with once-daily thoracic radiotherapy when both are combined with cisplatin and etoposide?

Bottom Line

In patients with limited small-cell lung cancer, twice-daily thoracic radiotherapy significantly improved survival compared with once-daily therapy when combined with cisplatin and etoposide, but increased the risk of grade 3 esophagitis.

Major Points

Twice-daily accelerated thoracic radiotherapy, when combined with cisplatin and etoposide, offers a survival advantage over once-daily radiotherapy in limited small-cell lung cancer, with a 10% higher 5-year survival rate.

Design

- Multicenter, randomized, controlled trial
- N=417 patients with limited small-cell lung cancer
- Once-daily thoracic radiotherapy (n=206)
- Twice-daily thoracic radiotherapy (n=211)
- Setting: Multiple institutions
- Enrollment: May 1989 to July 1992
- Mean follow-up: Almost 8 years
- Analysis: Intention-to-treat
- Primary outcome: Overall survival

Population

Inclusion Criteria
- Small-cell lung cancer clinically confined to one hemithorax (limited)
- Adequate organ function and performance status

Exclusion Criteria
- Pleural effusions visible on chest films, symptomatic cardiac disease, previous chemotherapy or radiotherapy, prior cancer

Baseline Characteristics
- Median age: 63 years (once-daily), 61 years (twice-daily)
- Sex: 40% female

Interventions

- Four cycles of chemotherapy with cisplatin (60 mg/m² on day 1) and etoposide (120 mg/m² on days 1-3) every 21 days
- Thoracic radiotherapy 45 Gy total dose, delivered as
- Once-daily (1.8 Gy per day) over five weeks
- Twice-daily (1.5 Gy per treatment) over three weeks
- Prophylactic cranial irradiation offered to patients with complete response

Outcomes

Primary Outcome
- Median survival: 19 months for once-daily, 23 months for twice-daily
- 2-year survival rate: 41% for once-daily, 47% for twice-daily
- 5-year survival rate: 16% for once-daily, 26% for twice-daily

Secondary Outcomes
- Grade 3 esophagitis: 11% for once-daily, 27% for twice-daily

Funding

- Public Health Service grants from the National Cancer Institute, National Institutes of Health, and Department of Health and Human Services

Further Reading

- Full text article available on the New England Journal of Medicine website