Phase III Study of Oral Compared With Intravenous Topotecan As Second-Line Therapy in Small-Cell Lung Cancer

• Published in: Journal of clinical oncology Vol. 25; no. 15; pp. 2086 - 2092
• Main Authors: ECKARDT, John R, VON PAWEL, Joachim, PUJOL, Jean-Louis, PAPAI, Zsolt, QUOIX, Elisabeth, ARDIZZONI, Andrea, POULIN, Ruth, PRESTON, Alaknanda J, DANE, Graham, ROSS, Graham
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 20-05-2007; Lippincott Williams & Wilkins
• Subjects: Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Agents - administration & dosage; Biological and medical sciences; Carcinoma, Small Cell - drug therapy; Carcinoma, Small Cell - pathology; Female; Humans; Liver Neoplasms - drug therapy; Liver Neoplasms - secondary; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Medical sciences; Middle Aged; Pneumology; Salvage Therapy; Survival Rate; Topotecan - administration & dosage; Tumors; Tumors of the respiratory system and mediastinum; Antineoplastic agent; Phase III trial; Lung disease; Intravenous administration; Respiratory disease; Enzyme; Lung cancer; Bonchopulmonary small cell carcinoma; DNA topoisomerase; Enzyme inhibitor; Topotecan; Malignant tumor; Isomerases; Cancerology; Bronchus disease; Second line treatment; Comparative study
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2006.08.3998

Single-agent intravenous (IV) topotecan is an effective treatment for small-cell lung cancer (SCLC) after failure of first-line chemotherapy. This open-label, randomized, phase III study compared oral and IV topotecan in patients with SCLC sensitive to initial chemotherapy.
Patients with limited- or extensive-disease SCLC, documented complete or partial response to first-line therapy, Eastern Cooperative Oncology Group performance status < or = 2, and measurable recurrent disease (WHO criteria) with a treatment-free interval of > or = 90 days were assigned to treatment with either oral topotecan 2.3 mg/m2/d on days 1 through 5 or IV topotecan 1.5 mg/m2/d on days 1 through 5 every 21 days. Primary end point was response rate as confirmed by an external reviewer blinded to treatment.
A total of 309 patients were randomly assigned. In intent-to-treat analysis, response rates were 18.3% with oral topotecan (n = 153) and 21.9% with IV topotecan (n = 151), with a difference (oral -IV) of -3.6% (95% CI, -12.6% to 5.5%). Median survival time was 33.0 weeks for oral and 35.0 weeks for IV topotecan; 1- and 2-year survival rates were 32.6% and 12.4% for oral topotecan, respectively, and 29.2% and 7.1% for IV topotecan, respectively. Third-line chemotherapy was similar for both groups (33% for oral; 35% for IV). Incidence of grade 4 toxicity in patients who received oral and IV topotecan was as follows: neutropenia in 47% and 64%, thrombocytopenia in 29% and 18%, grade 3 or 4 anemia in 23% and 31%, and sepsis in 3% and 3%, respectively. The most frequent nonhematologic adverse events (all grades) included nausea (43% oral; 42% IV), alopecia (26% oral; 30% IV), fatigue (31% oral; 36% IV), and diarrhea (36% oral; 20% IV).
Oral topotecan demonstrates activity and tolerability similar to IV topotecan in chemotherapy-sensitive SCLC patients and offers patients a convenient alternative to IV therapy.