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Phase III Trial Comparing Supportive Care Alone With Supportive Care With Oral Topotecan in Patients With Relapsed Small-Cell Lung Cancer

Mary E.R. O'Brien, Tudor-Eliade Ciuleanu, Hristo Tsekov, Yaroslav Shparyk, Branka ueviá, Gabor Juhasz, Nicholas Thatcher, Graham A. Ross, Graham C. Dane, Theresa Crofts

From the Royal Marsden Hospital, Sutton; Christie Hospital, Manchester; GlaxoSmithKline, Harlow, United Kingdom; Institutul Oncologic, Cluj-Napoca, Romania; Active Treatment Hospital, Varna, Bulgaria; Lviv State Oncology, Lviv, Ukraine; Klinika za plune bolesti Jordanovac, Zagreb, Croatia; and Margit Kórház, Csorna, Hungary

Address reprint requests to Mary O'Brien, MD, FRCP, Royal Marsden Hospital, National Health System Trust, Sutton Surrey, SM2 5 PT, England; e-mail: mary.o'brien{at}rmh.nhs.uk

PURPOSE: For patients with small-cell lung cancer (SCLC), further chemotherapy is routinely considered at relapse after first-line therapy. However, proof of clinical benefit has not been documented.

PATIENTS AND METHODS: This study randomly assigned patients with relapsed SCLC not considered as candidates for standard intravenous therapy to best supportive care (BSC) alone (n = 70) or oral topotecan (2.3 mg/m²/d, days 1 through 5, every 21 days) plus BSC (topotecan; n = 71).

RESULTS: In the intent-to-treat population, survival (primary end point) was prolonged in the topotecan group (log-rank P = .0104). Median survival with BSC was 13.9 weeks (95% CI, 11.1 to 18.6) and with topotecan, 25.9 weeks (95% CI, 18.3 to 31.6). Statistical significance for survival was maintained in a subgroup of patients with a short treatment-free interval ( 60 days). Response to topotecan was 7% partial and 44% stable disease. Patients on topotecan had slower quality of life deterioration and greater symptom control. Principal toxicities with topotecan were hematological: grade 4 neutropenia, 33%; grade 4 thrombocytopenia, 7%; and grade 3/4 anemia, 25%. Comparing topotecan with BSC, infection grade 2 was 14% versus 12% and sepsis 4% versus 1%; other grade 3/4 events included vomiting 3% versus 0, diarrhea 6% versus 0, dyspnea 3% versus 9%, and pain 3% versus 6%. Toxic deaths occurred in four patients (6%) in the topotecan arm. All cause mortality within 30 days of random assignment was 13% on BSC and 7% on topotecan.

CONCLUSION: Chemotherapy with oral topotecan is associated with prolongation of survival and quality of life benefit in patients with relapsed SCLC.

Supported by GlaxoSmithKline, Middlesex, United Kingdom.

Presented in part at the International Association for the Study of Lung Cancer’s 11th World Conference on Lung Cancer, Barcelona, Spain, July 3-6, 2005.

The trial was designed by the sponsor (G.S.K.) who held and analyzed the data. The contents of this article were reviewed and approved by all authors.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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