World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website http://www.wjon.org

Review

Volume 6, Number 5, October 2015, pages 429-436

Role of Topotecan in Non-Small Cell Lung Cancer: A Review of Literature

**Table 1.** Phase I Clinical Trials of Topotecan as Combination Therapy
Author and year	Phase	Patients	n	Drugs and dosage	Disease response	Median survival
PR: partial remission; SD: stable disease; n: number of patients.
Raymond et al, 1997 [14]	I	Untreated advanced NSCLC	14	TPT (0.75 mg/m²/day) as 30 min infusion daily for 5 days with cisplatin given at 75 mg/m² on day 1 every 3 weeks	4 (30.7%) had PR	Tumor response lasted for 12 weeks
Rinaldi et al, 2001 [15]	I/II	Previously treated advanced NSCLC	19	TPT (0.75 mg/m²/day) as 30 min infusion daily for 5 days and gemcitabine 400 mg/m² on days 1 and 5 only	3 (18%) had PR, 6 (32%) had SD	10 months
Stupp et al, 2001 [16]	I/II	Recurrent or metastatic NSCLC	29	IV TPT (0.5 - 1 mg/m²/day) for 5 days and IV vinorelbine (20 - 30 mg/m²/day) on days 1 and 5 only every 21 days	42% clinical response rate	13 months
Guarino et al, 2002 [17]	I	Untreated stage IIIb/IV NSCLC	30	IV TPT (1.75 mg/m²), cisplatin (20 mg/m²) on days 1, 8, and 15 and gemcitabine (1,000 mg/m²) on days 1 and 15 of a 28-day cycle	11 (38%) had PR	38 weeks. One-year survival rate was 33%.
Dabrow et al, 2003 [18]	I/II	Untreated stage IIIb/IV NSCLC	24	IV TPT (2 mg/m²) and gemcitabine (1,250 mg/m²) on days 1, 8, and 15 of a 28-day cycle	5 (21%) had PR	22 weeks
Beldner et al, 2007 [19]	I	Previously treated advanced NSCLC	18	IV vinorelbine (20 mg/m²) and TPT (2 - 4 mg/m²) on days 1 and 8 every 21 days	1 had PR, 4 (27%) had SD	10.5 months

Table 1. Phase I Clinical Trials of Topotecan as Combination Therapy

Author and year

Phase

Patients

Drugs and dosage

Disease response

Median survival

PR: partial remission; SD: stable disease; n: number of patients.

Raymond et al, 1997 [14]

Untreated advanced NSCLC

TPT (0.75 mg/m²/day) as 30 min infusion daily for 5 days with cisplatin given at 75 mg/m² on day 1 every 3 weeks

4 (30.7%) had PR

Tumor response lasted for 12 weeks

Rinaldi et al, 2001 [15]

I/II

Previously treated advanced NSCLC

TPT (0.75 mg/m²/day) as 30 min infusion daily for 5 days and gemcitabine 400 mg/m² on days 1 and 5 only

3 (18%) had PR, 6 (32%) had SD

10 months

Stupp et al, 2001 [16]

I/II

Recurrent or metastatic NSCLC

IV TPT (0.5 - 1 mg/m²/day) for 5 days and IV vinorelbine (20 - 30 mg/m²/day) on days 1 and 5 only every 21 days

42% clinical response rate

13 months

Guarino et al, 2002 [17]

Untreated stage IIIb/IV NSCLC

IV TPT (1.75 mg/m²), cisplatin (20 mg/m²) on days 1, 8, and 15 and gemcitabine (1,000 mg/m²) on days 1 and 15 of a 28-day cycle

11 (38%) had PR

38 weeks. One-year survival rate was 33%.

Dabrow et al, 2003 [18]

I/II

Untreated stage IIIb/IV NSCLC

IV TPT (2 mg/m²) and gemcitabine (1,250 mg/m²) on days 1, 8, and 15 of a 28-day cycle

5 (21%) had PR

22 weeks

Beldner et al, 2007 [19]

Previously treated advanced NSCLC

IV vinorelbine (20 mg/m²) and TPT (2 - 4 mg/m²) on days 1 and 8 every 21 days

1 had PR, 4 (27%) had SD

10.5 months

**Table 2.** Phase II Clinical Trials of Topotecan as Single-Agent Therapy
Author and year	Phase	Patients	n	Dose of topotecan	Disease response	Median survival
SD: stable disease; PR: partial remission; PRG: progression of disease; SCC: squamous cell cancer, n: number of patients.
Lynch et al, 1994 [6]	II	Untreated advanced NSCLC	20	2 mg/m²/day IV for 5 days every 21 days for two cycles	11 (55%) had SD, 9 (45%) had PRG.	7.6 months
Perez-Soler et al, 1996 [7]	II	Untreated advanced NSCLC	40	1.5 mg/m²/day for 5 days every 21 days	6 (15%) had PR, 10 had SD and 20 had PRG. 36% PR in patients with SCC.	38 weeks and 30% patients were alive at 1 year
Mainwaring et al, 1997 [9]	II	Untreated advanced NSCLC	12	0.6 mg/m²/day as continuous IV infusion for 21 days every 4 weeks	1 (8%) had PR.	Not reached
Kindler et al, 1998 [10]	II	Untreated advanced NSCLC	26	0.6 mg/m²/day as continuous IV infusion for 21 days every 4 weeks	1 (4%) had PR.	9 months and 1-year survival was 39%.
Weitz et al, 2000 [8]	II	Untreated advanced NSCLC	38	1.5 mg/m²/day over 30min for 5 days every 21 days	6 (16%) had PR.	257 days (37 weeks)
Weitz et al, 2000 [8]	II	Untreated advanced NSCLC	37	1.3 mg/m²/day as continuous infusion over 72 h every 21 days	3 (8%) had PR.	179 days (26 weeks)
White et al, 2000 [11]	II	Untreated advanced NSCLC	29	2.3 mg/m²/day orally for 5 days every 21 days for up to six cycles	13 (43.3%) had SD. No PR. 3 had radiological response.	39.9 weeks and 1-year survival of 33.3%
Gonzalez et al, 2011 [20]	II	Advanced NSCLC pre treated with platinum and taxanes	35	1.25 mg/m²/day IV daily for 5 days every 21 days for 73 cycles	1 (2.8%) had PR, 9 (25.7%) had SD, 23 (65.7%) had PRG.	70 days

Table 2. Phase II Clinical Trials of Topotecan as Single-Agent Therapy

Author and year

Phase

Patients

Dose of topotecan

Disease response

Median survival

SD: stable disease; PR: partial remission; PRG: progression of disease; SCC: squamous cell cancer, n: number of patients.

Lynch et al, 1994 [6]

Untreated advanced NSCLC

2 mg/m²/day IV for 5 days every 21 days for two cycles

11 (55%) had SD, 9 (45%) had PRG.

7.6 months

Perez-Soler et al, 1996 [7]

Untreated advanced NSCLC

1.5 mg/m²/day for 5 days every 21 days

6 (15%) had PR, 10 had SD and 20 had PRG. 36% PR in patients with SCC.

38 weeks and 30% patients were alive at 1 year

Mainwaring et al, 1997 [9]

Untreated advanced NSCLC

0.6 mg/m²/day as continuous IV infusion for 21 days every 4 weeks

1 (8%) had PR.

Not reached

Kindler et al, 1998 [10]

Untreated advanced NSCLC

0.6 mg/m²/day as continuous IV infusion for 21 days every 4 weeks

1 (4%) had PR.

9 months and 1-year survival was 39%.

Weitz et al, 2000 [8]

Untreated advanced NSCLC

1.5 mg/m²/day over 30min for 5 days every 21 days

6 (16%) had PR.

257 days (37 weeks)

Weitz et al, 2000 [8]

Untreated advanced NSCLC

1.3 mg/m²/day as continuous infusion over 72 h every 21 days

3 (8%) had PR.

179 days (26 weeks)

White et al, 2000 [11]

Untreated advanced NSCLC

2.3 mg/m²/day orally for 5 days every 21 days for up to six cycles

13 (43.3%) had SD. No PR. 3 had radiological response.

39.9 weeks and 1-year survival of 33.3%

Gonzalez et al, 2011 [20]

Advanced NSCLC pre treated with platinum and taxanes

1.25 mg/m²/day IV daily for 5 days every 21 days for 73 cycles

1 (2.8%) had PR, 9 (25.7%) had SD, 23 (65.7%) had PRG.

70 days

**Table 3.** Phase II Clinical Trials of Topotecan as Combination Therapy
Author and year	Phase	Patients	n	Drugs and dosage	Disease response	Median survival
RCT: randomized controlled trial; ORR: overall response rate; MR: minimal remission; PFS: progression-free survival.
Dowlati et al, 2001 [21]	II	Untreated advanced NSCLC	19	TPT at 0.85 mg/m²/day as a continuous 72-h infusion from days 1 to 3 and etoposide at 100 mg PO twice daily for 3 days on days 7 - 9. Total of 55 cycles.	1 PR and 2 SD	One-year survival rate was 33%.
Joppert et al, 2003 [22]	II	Untreated advanced NSCLC	51	TPT 1 mg/m² on days 1 - 5, and gemcitabine 1 g/m² on days 1 and 15 IV, every 28 days.	8 (17%) had PR, 11 (23%) had SD	7.6 months. One-year survival rate was 39%.
Lorusso et al, 2005 [23]	II	Previously treated advanced NSCLC	42	TPT (1.2 mg/m²) plus ifosfamide (1,200 mg/m²) IV for three consecutive days every 3 weeks. Total of three cycles.	6 (14.2%) had PR, 1 (2.4%) had MR, 14 (34%) had SD, 21 (51%) had PRG	26 weeks. One-year survival rate was 14%.
Stathopoulos et al, 2006 [24]	II	Untreated advanced NSCLC	45	TPT (1.75 mg/m²) infused over 30 min and paclitaxel (70 mg/m²) infused over 90 min, weekly for 3 weeks every 28 days up to three cycles.	2 (4.4%) had CR, 16 (35.6%) had PR, 21 (46.7%) had SD, 6 (13.3%) had PRG	9 months
Jones et al, 2008 [25]	II. RCT	Previously treated advanced NSCLC	80	39 received TPT (2 or 2.5 mg/day, for 5 of 7 days for 2 weeks) orally and 41 received docetaxel (75 mg/m²) every 21 days.	8% ORR with TPT and docetaxel	8.4 months with TPT and 7.6 months with docetaxel
Powell et al, 2013 [26]	II	Previously treated advanced NSCLC	42	TPT (4 mg/m²) on days 1, 8, and 15 and bevacizumab (10 mg/kg) on days 1 and 15 as IV infusion every 28 days.	14.3% had PR, 54.8% had SD, 28.6% had PRG	PFS was 5.1 months and overall survival was 11.5 months.

Table 3. Phase II Clinical Trials of Topotecan as Combination Therapy

Author and year

Phase

Patients

Drugs and dosage

Disease response

Median survival

RCT: randomized controlled trial; ORR: overall response rate; MR: minimal remission; PFS: progression-free survival.

Dowlati et al, 2001 [21]

Untreated advanced NSCLC

TPT at 0.85 mg/m²/day as a continuous 72-h infusion from days 1 to 3 and etoposide at 100 mg PO twice daily for 3 days on days 7 - 9. Total of 55 cycles.

1 PR and 2 SD

One-year survival rate was 33%.

Joppert et al, 2003 [22]

Untreated advanced NSCLC

TPT 1 mg/m² on days 1 - 5, and gemcitabine 1 g/m² on days 1 and 15 IV, every 28 days.

8 (17%) had PR, 11 (23%) had SD

7.6 months. One-year survival rate was 39%.

Lorusso et al, 2005 [23]

Previously treated advanced NSCLC

TPT (1.2 mg/m²) plus ifosfamide (1,200 mg/m²) IV for three consecutive days every 3 weeks. Total of three cycles.

6 (14.2%) had PR, 1 (2.4%) had MR, 14 (34%) had SD, 21 (51%) had PRG

26 weeks. One-year survival rate was 14%.

Stathopoulos et al, 2006 [24]

Untreated advanced NSCLC

TPT (1.75 mg/m²) infused over 30 min and paclitaxel (70 mg/m²) infused over 90 min, weekly for 3 weeks every 28 days up to three cycles.

2 (4.4%) had CR, 16 (35.6%) had PR, 21 (46.7%) had SD, 6 (13.3%) had PRG

9 months

Jones et al, 2008 [25]

II. RCT

Previously treated advanced NSCLC

39 received TPT (2 or 2.5 mg/day, for 5 of 7 days for 2 weeks) orally and 41 received docetaxel (75 mg/m²) every 21 days.

8% ORR with TPT and docetaxel

8.4 months with TPT and 7.6 months with docetaxel

Powell et al, 2013 [26]

Previously treated advanced NSCLC

TPT (4 mg/m²) on days 1, 8, and 15 and bevacizumab (10 mg/kg) on days 1 and 15 as IV infusion every 28 days.

14.3% had PR, 54.8% had SD, 28.6% had PRG

PFS was 5.1 months and overall survival was 11.5 months.