Topotecan: An evolving option in the treatment of relapsed small cell lung cancer

Figures & data

Figure 1 Mechanism of action of topotecan. Copyright © 1997. Reprinted with permission from Rothenberg ML. 1997. Topoisomerase I inhibitors: review and update. Ann Oncol, 8:837–55

Figure 2 Median neutrophil nadirs by treatment course, dose, and granulocyte-colony stimulating factor (G-CSF). After the first course, patients may have received G-CSF or reduced doses of topotecan; some patients may have discontinued topotecan because of myelosuppression. Copyright © 2005. Reprinted with permission from Armstrong DK, Spriggs D, Levin J, et al. 2005. Hematologic safety and tolerability of topotecan in recurrent ovarian cancer and small cell lung cancer: an integrated analysis. Oncologist, 10:686–94

Table 1 Topotecan SCLC trials included in an integrated analysis

Study	Phase	Patientsa, n
Ardizzoni et al (1997)	II	101
Eckardt et al (1996)	II	99
von Pawel et al (2001)	II	54b
Depierre et al (1997)	II	119
von Pawel et al (1999)	III	107

a Note: Patients from all trials received the US Food and Drug Administration approved dose and schedule of topotecan (1.5 mg/m² on days 1 to 5 of a 21-day cycle)

b Number of patients in the intravenous arm of a randomized study who were treated with the US Food and Drug Administration-approved dose of topotecan. Adapted with permission from Treat et al (2004).

Abbreviations: SCLC, Small cell lung cancer.

Table 2 Antitumor response in the intent-to-treat population in a pooled analysis of patients with SCLC

Response	Patients, n(%)
	Overall N = 479	Chemosensitive n = 330	Chemoresistant/Chemorefractory n = 149
Objective response	70 (14.6)	64 (19.4)	6 (4.0)
Complete response	14 (2.9)	12 (3.6)	2 (1.3)
Partial response	56 (11.7)	52 (15.8)	4 (2.7)
Stable disease	97 (20.3)	73 (22.1)	24 (16.1)
Progressive disease	257 (53.7)	158 (47.9)	99 (66.4)
Not determined	55 (11.5)	35 (10.6)	20 (13.4)

Abbreviations: SCLC, Small cell lung cancer.

Data from Treat et al (2004).

Table 3 Proportion of patients with SCLC treated with topotecan who had symptom improvement

Symptom	Patients showing improvement, n (%) N = 260a
Insomnia	51 (19.6)
Cough	46 (17.7)
Anorexia	45 (17.3)
Dyspnea	41 (15.8)
Chest pain	31 (11.9)
Hoarseness	30 (11.5)
Hemoptysis	9 (3.5)
Interference with daily activitiesb	26 (16.1)
Fatigueb	22 (13.7)

a Note: Symptom palliation was evaluated in only 3 of the 5 trials in this retrospective study

b Evaluated in only 2 of the 3 trials (N = 161)

Data from Treat et al (2004).

Figure 3 Overall response rates (ORRs) and stable disease (SD) responses to various topotecan treatment regimens.

Table 4 Efficacy and safety of various topotecan treatment regimens

Study	Regimen	Efficacy responses		Grade 3/4 hematologic toxicities, %
		ORR, %	mOS, weeks	Neutropenia	Thrombocytopenia	Anemia
von Pawel et al (1999)	1.5 mg/m^2 days 1–5 of 21-day cycle	24	25.0	70	29	41
Treat et al (2004)a	1.5 mg/m^2 days 1–5 of 21-day cycle	15	16.0–36.3b	90	55	33
Koschel et al (2000)	1.25 mg/m^2 days 1–5 of 21-day cycle	15	22.4	10c	5c	1c
Perez-Soler et al (1996)	1.25 mg/m^2 days 1–5 of 21-day cycle	11	20.0	NR	31c	NR
Ogawara et al (2000)	1.0 mg/m^2 days 1–5 of 21-day cycle	26	35.1	84	42	46
Takeda et al (2003)	1.0 mg/m^2 days 1–5 of 21-day cycle	26	37.4	92	40	46
Shipley et al (2006)	4.0 mg/m^2 weekly for 12 weeks	5	19.4	21	27	NR
Murphy et al (2006)	4.0 mg/m^2 weekly for 12 weeks	13	22.4 (in patients with PR/SD)	29	8	NR
Ardizzoni et al (2003)	Topotecan, 0.75 mg/m^2 on days 1–5; cisplatin, 60 mg/m^2 on day 1 every 21-days	27	S: 27.5, R: 26.2	S: 76, R: 74	S: 74, R: 63	S: 37, R: 40
Christodoulou et al (2006)	Topotecan, 0.9 mg/m^2; cisplatin, 20 mg/m^2 on days 1–3 every 21-days	18	28.0	42	15	15

a Note: Pooled retrospective analysis of 5 phase II and III trials

b Survival times were reported based on patient performance status

c Results reported as percentage of courses.

Abbreviations: ORR, Overall response rate; mOS, Median overall survival; NR, Not reported; S, Chemosensitive; R, Chemorefractory; PR, Partial response; SD, Stable disease.

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