Purpose 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 and Methods Patients with limited- or extensive-disease SCLC, documented complete or partial response to first-line therapy, Eastern Cooperative Oncology Group performance status :5 2, and measurable recurrent disease (WHO criteria) with a treatment-free interval of ! 90 days were assigned to treatment with either oral topotecan 2.3 mg/m(2) /d on days 1 through 5 or IV topotecan 1.5 mg/m(2) /d on days I through 5 every 21 days. Primary end point was response rate as confirmed by an external reviewer blinded to treatment. Results 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% Cl, -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). Conclusion Oral topotecan demonstrates activity and tolerability similar to IV topotecan in chemotherapy-sensitive SCLC patients and offers patients a convenient alternative to IV therapy.
Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer / Eckardt JR; von Pawel J; Pujol JL; Papai Z; Quoix E; Ardizzoni A; Poulin R; Preston AJ; Dane G; Ross G. - In: JOURNAL OF CLINICAL ONCOLOGY. - ISSN 0732-183X. - ELETTRONICO. - 25:15(2007), pp. 2086-2092. [10.1200/JCO.2006.08.3998]
Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer
ARDIZZONI, ANDREA;
2007
Abstract
Purpose 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 and Methods Patients with limited- or extensive-disease SCLC, documented complete or partial response to first-line therapy, Eastern Cooperative Oncology Group performance status :5 2, and measurable recurrent disease (WHO criteria) with a treatment-free interval of ! 90 days were assigned to treatment with either oral topotecan 2.3 mg/m(2) /d on days 1 through 5 or IV topotecan 1.5 mg/m(2) /d on days I through 5 every 21 days. Primary end point was response rate as confirmed by an external reviewer blinded to treatment. Results 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% Cl, -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). Conclusion Oral topotecan demonstrates activity and tolerability similar to IV topotecan in chemotherapy-sensitive SCLC patients and offers patients a convenient alternative to IV therapy.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
